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Hamasaki MY, Mendes C, Batagello DS, Hirata MH, Britto LRGD, Nogueira MI. Pathophysiological aspects of neonatal anoxia and temporal expression of S100β in different brain regions. Neuroreport 2023; 34:575-582. [PMID: 37384931 DOI: 10.1097/wnr.0000000000001927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/01/2023]
Abstract
The aim of this study was to investigate the temporal variations of S100β in the hippocampus, cerebellum and cerebral cortex of neonatal rats (Wistar strain) under anoxic conditions. Real-time PCR and western blotting techniques were used for gene expression and protein analysis. Animals were divided into two groups, a control group and an anoxic group, and further separated at different time points for analysis. After anoxia, S100β gene expression showed a significant peak in the hippocampus and cerebellum after 2 h, followed by a decline compared to the control group at other time points. The increased gene expression in these regions was also accompanied by an increase in S100β protein levels in the anoxia group, observable 4 h after injury. In contrast, S100β mRNA content in the cerebral cortex never exceeded control values at any time point. Similarly, the protein content of S100β in the cerebral cortex did not show statistically significant differences compared to control animals at any assessment time point. These results suggest that the production profile of S100β differs by brain region and developmental stage. The observed differences in vulnerability between the hippocampus, cerebellum and cerebral cortex may be attributed to their distinct developmental periods. The hippocampus and cerebellum, which develop earlier than the cerebral cortex, showed more pronounced effects in response to anoxia, which is supported by the gene expression and protein content in this study. This result reveals the brain region-dependent nature of S100β as a biomarker of brain injury.
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Affiliation(s)
| | - Caroline Mendes
- Department of Anatomy and Physiology, Institute of Biomedical Sciences
| | | | - Mario Hiroyuki Hirata
- Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, Universitdade de São Paulo, São Paulo, SP, Brazil
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2
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Gong B, Guo D, Zheng C, Ma Z, Zhang J, Qu Y, Li X, Li G, Zhang L, Wang Y. Complement C3a activates astrocytes to promote medulloblastoma progression through TNF-α. J Neuroinflammation 2022; 19:159. [PMID: 35725556 PMCID: PMC9208237 DOI: 10.1186/s12974-022-02516-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 06/05/2022] [Indexed: 12/16/2022] Open
Abstract
Background Medulloblastoma (MB) is the most common malignant brain tumor in children. Approximately one-third of MB patients remain incurable. Understanding the molecular mechanism of MB tumorigenesis is, therefore, critical for developing specific and effective treatment strategies. Our previous work demonstrated that astrocytes constitute the tumor microenvironment (TME) of MB and play an indispensable role in MB progression. However, the underlying mechanisms by which astrocytes are regulated and activated to promote MB remain elusive. Methods By taking advantage of Math1-Cre/Ptch1loxp/loxp mice, which spontaneously develop MB, primary MB cells and astrocytes were isolated and then subjected to administration and coculture in vitro. Immunohistochemistry was utilized to determine the presence of C3a in MB sections. MB cell proliferation was evaluated by immunofluorescent staining. GFAP and cytokine expression levels in C3a-stimulated astrocytes were assessed by immunofluorescent staining, western blotting, q-PCR and ELISA. C3a receptor and TNF-α receptor expression was determined by PCR and immunofluorescent staining. p38 MAPK pathway activation was detected by western blotting. Transplanted MB mice were treated with a C3a receptor antagonist or TNF-α receptor antagonist to investigate their role in MB progression in vivo. Results We found that complement C3a, a fragment released from intact complement C3 following complement activation, was enriched in both human and murine MB tumor tissue, and its receptor was highly expressed on tumor-associated astrocytes (TAAs). We demonstrated that C3a activated astrocytes and promoted MB cell proliferation via the p38 MAPK pathway. Moreover, we discovered that C3a upregulated the production of proinflammatory cytokines, such as IL-6 and TNF-α in astrocytes. Application of the conditioned medium of C3a-stimulated astrocytes promoted MB cell proliferation, which was abolished by preincubation with a TNF-α receptor antagonist, indicating a TNF-α-dependent event. Indeed, we further demonstrated that administration of a selective C3a receptor or TNF-α receptor antagonist to mice subcutaneously transplanted with MB suppressed tumor progression in vivo. Conclusions C3a was released during MB development. C3a triggered astrocyte activation and TNF-α production via the p38 pathway, which promoted MB cell proliferation. Our findings revealed the novel role of C3a-mediated TNF-α production by astrocytes in MB progression. These findings imply that targeting C3a and TNF-α may represent a potential novel therapeutic approach for human MB. Supplementary Information The online version contains supplementary material available at 10.1186/s12974-022-02516-9.
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Affiliation(s)
- Biao Gong
- Laboratory of Molecular Neuropathology, Pediatric Cancer Center, College of Pharmaceutical Sciences, Soochow University, Suzhou, China
| | - Duancheng Guo
- Laboratory of Molecular Neuropathology, Pediatric Cancer Center, College of Pharmaceutical Sciences, Soochow University, Suzhou, China
| | - Chaonan Zheng
- Laboratory of Molecular Neuropathology, Pediatric Cancer Center, College of Pharmaceutical Sciences, Soochow University, Suzhou, China
| | - Zhen Ma
- Laboratory of Molecular Neuropathology, Pediatric Cancer Center, College of Pharmaceutical Sciences, Soochow University, Suzhou, China
| | - Jie Zhang
- Laboratory of Molecular Neuropathology, Pediatric Cancer Center, College of Pharmaceutical Sciences, Soochow University, Suzhou, China
| | - Yanghui Qu
- Laboratory of Molecular Neuropathology, Pediatric Cancer Center, College of Pharmaceutical Sciences, Soochow University, Suzhou, China
| | - Xinhua Li
- Laboratory of Molecular Neuropathology, Pediatric Cancer Center, College of Pharmaceutical Sciences, Soochow University, Suzhou, China
| | - Gen Li
- Laboratory of Molecular Neuropathology, Pediatric Cancer Center, College of Pharmaceutical Sciences, Soochow University, Suzhou, China
| | - Li Zhang
- Laboratory of Molecular Neuropathology, Pediatric Cancer Center, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
| | - Yuan Wang
- Laboratory of Molecular Neuropathology, Pediatric Cancer Center, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
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Forensic biomarkers of lethal traumatic brain injury. Int J Legal Med 2022; 136:871-886. [PMID: 35226180 PMCID: PMC9005436 DOI: 10.1007/s00414-022-02785-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 01/21/2022] [Indexed: 11/01/2022]
Abstract
AbstractTraumatic brain injury (TBI) is a major cause of death and its accurate diagnosis is an important concern of daily forensic practice. However, it can be challenging to diagnose TBI in cases where macroscopic signs of the traumatic head impact are lacking and little is known about the circumstances of death. In recent years, several post-mortem studies investigated the possible use of biomarkers for providing objective evidence for TBIs as the cause of death or to estimate the survival time and time since death of the deceased. This work systematically reviewed the available scientific literature on TBI-related biomarkers to be used for forensic purposes. Post-mortem TBI-related biomarkers are an emerging and promising resource to provide objective evidence for cause of death determinations as well as survival time and potentially even time since death estimations. This literature review of forensically used TBI-biomarkers revealed that current markers have low specificity for TBIs and only provide limited information with regards to survival time estimations and time since death estimations. Overall, TBI fatality-related biomarkers are largely unexplored in compartments that are easily accessible during autopsies such as urine and vitreous humor. Future research on forensic biomarkers requires a strict distinction of TBI fatalities from control groups, sufficient sample sizes, combinations of currently established biomarkers, and novel approaches such as metabolomics and mi-RNAs.
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Liu HL, Wang YN, Feng SY. Brain tumors: Cancer stem-like cells interact with tumor microenvironment. World J Stem Cells 2020; 12:1439-1454. [PMID: 33505594 PMCID: PMC7789119 DOI: 10.4252/wjsc.v12.i12.1439] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Revised: 10/07/2020] [Accepted: 10/27/2020] [Indexed: 02/06/2023] Open
Abstract
Cancer stem-like cells (CSCs) with potential of self-renewal drive tumorigenesis. Brain tumor microenvironment (TME) has been identified as a critical regulator of malignancy progression. Many researchers are searching new ways to characterize tumors with the goal of predicting how they respond to treatment. Here, we describe the striking parallels between normal stem cells and CSCs. We review the microenvironmental aspects of brain tumors, in particular composition and vital roles of immune cells infiltrating glioma and medulloblastoma. By highlighting that CSCs cooperate with TME via various cellular communication approaches, we discuss the recent advances in therapeutic strategies targeting the components of TME. Identification of the complex and interconnected factors can facilitate the development of promising treatments for these deadly malignancies.
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Affiliation(s)
- Hai-Long Liu
- Department of Neurosurgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Ya-Nan Wang
- Department of Pathology, Affiliated Hospital of Hebei University, Baoding 071000, Hebei Province, China
| | - Shi-Yu Feng
- Department of Neurosurgery, Chinese PLA General Hospital, Beijing 100853, China
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Liu Y, Yuelling LW, Wang Y, Du F, Gordon RE, O'Brien JA, Ng JMY, Robins S, Lee EH, Liu H, Curran T, Yang ZJ. Astrocytes Promote Medulloblastoma Progression through Hedgehog Secretion. Cancer Res 2017; 77:6692-6703. [PMID: 28986380 DOI: 10.1158/0008-5472.can-17-1463] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Revised: 08/10/2017] [Accepted: 09/26/2017] [Indexed: 12/30/2022]
Abstract
Astrocytes, the most abundant type of glial cells in the brain, play critical roles in supporting neuronal development and brain function. Although astrocytes have been frequently detected in brain tumors, including medulloblastoma (MB), their functions in tumorigenesis are not clear. Here, we demonstrate that astrocytes are essential components of the MB tumor microenvironment. Tumor-associated astrocytes (TAA) secrete the ligand sonic hedgehog (Shh), which is required for maintaining MB cell proliferation despite the absence of its primary receptor Patched-1 (Ptch1). Shh drives expression of Nestin in MB cells through a smoothened-dependent, but Gli1-independent mechanism. Ablation of TAA dramatically suppresses Nestin expression and blocks tumor growth. These findings demonstrate an indispensable role for astrocytes in MB tumorigenesis and reveal a novel Ptch1-independent Shh pathway involved in MB progression. Cancer Res; 77(23); 6692-703. ©2017 AACR.
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Affiliation(s)
- Yongqiang Liu
- Cancer Biology Program, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania
| | - Larra W Yuelling
- Cancer Biology Program, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania
| | - Yuan Wang
- Laboratory of Molecular Neuropathology, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China
| | - Fang Du
- Cancer Biology Program, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania
| | - Renata E Gordon
- Cancer Biology Program, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania
| | - Jenny A O'Brien
- Cancer Biology Program, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania
| | - Jessica M Y Ng
- Children's Research Institute, Children's Mercy Kansas City, Kansas City, Missouri
| | - Shannon Robins
- Cancer Biology Program, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania
| | - Eric H Lee
- Cancer Biology Program, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania
| | - Hailong Liu
- Cancer Biology Program, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania
| | - Tom Curran
- Children's Research Institute, Children's Mercy Kansas City, Kansas City, Missouri
| | - Zeng-Jie Yang
- Cancer Biology Program, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania.
- Laboratory of Molecular Neuropathology, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China
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See J, Mamontov P, Ahn K, Wine-Lee L, Crenshaw EB, Grinspan JB. BMP signaling mutant mice exhibit glial cell maturation defects. Mol Cell Neurosci 2007; 35:171-82. [PMID: 17391983 PMCID: PMC1950488 DOI: 10.1016/j.mcn.2007.02.012] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2006] [Revised: 01/16/2007] [Accepted: 02/13/2007] [Indexed: 10/23/2022] Open
Abstract
Bone morphogenetic proteins have been implicated in the development of oligodendrocytes and astrocytes, however, a role for endogenous BMP signaling in glial development has not been demonstrated in a genetic model. Using mice in which signaling via type I BMP receptors Bmpr1a and Bmpr1b have been inactivated in the neural tube, we demonstrate that BMP signaling contributes to the maturation of glial cells in vivo. At P0, mutant mice exhibited a 25-40% decrease in GFAP+ or S100beta+ astrocytes in the cervical spinal cord. The number of oligodendrocyte precursors and the timing of their emergence was unchanged in the mutant mice compared to the normals, however myelin protein expression and mature oligodendrocyte numbers were significantly reduced. These data indicate that BMP signaling promotes the generation of astrocytes and mature, myelinating oligodendrocytes in vivo but does not affect oligodendrocyte precursor development, thus suggesting tight regulation of BMP signaling to ensure proper gliogenesis.
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Affiliation(s)
- Jill See
- Department of Research Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
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Raponi E, Agenes F, Delphin C, Assard N, Baudier J, Legraverend C, Deloulme JC. S100B expression defines a state in which GFAP-expressing cells lose their neural stem cell potential and acquire a more mature developmental stage. Glia 2007; 55:165-77. [PMID: 17078026 PMCID: PMC2739421 DOI: 10.1002/glia.20445] [Citation(s) in RCA: 286] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
During the postnatal development, astrocytic cells in the neocortex progressively lose their neural stem cell (NSC) potential, whereas this peculiar attribute is preserved in the adult subventricular zone (SVZ). To understand this fundamental difference, many reports suggest that adult subventricular GFAP-expressing cells might be maintained in immature developmental stage. Here, we show that S100B, a marker of glial cells, is absent from GFAP-expressing cells of the SVZ and that its onset of expression characterizes a terminal maturation stage of cortical astrocytic cells. Nevertheless, when cultured in vitro, SVZ astrocytic cells developed as S100B expressing cells, as do cortical astrocytic cells, suggesting that SVZ microenvironment represses S100B expression. Using transgenic s100b-EGFP cells, we then demonstrated that S100B expression coincides with the loss of neurosphere forming abilities of GFAP expressing cells. By doing grafting experiments with cells derived from beta-actin-GFP mice, we next found that S100B expression in astrocytic cells is repressed in the SVZ, but not in the striatal parenchyma. Furthermore, we showed that treatment with epidermal growth factor represses S100B expression in GFAP-expressing cells in vitro as well as in vivo. Altogether, our results indicate that the S100B expression defines a late developmental stage after which GFAP-expressing cells lose their NSC potential and suggest that S100B expression is repressed by adult SVZ microenvironment.
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Affiliation(s)
- Eric Raponi
- Department of Medicine, Palade Cellular and Molecular medicine
University of California, San DiegoLa Jolla, CA 92093-0644,US
- Transduction du signal: signalisation calcique et phosphorylation
INSERM : EMI0104CEA : DRDCFR
| | - Fabien Agenes
- Contrôle moléculaire de la réponse immune specifique
INSERM : U548CEA : DSV/IRTSVUniversité Joseph Fourier - Grenoble IFR
| | - Christian Delphin
- Transduction du signal: signalisation calcique et phosphorylation
INSERM : EMI0104CEA : DRDCFR
| | - Nicole Assard
- Transduction du signal: signalisation calcique et phosphorylation
INSERM : EMI0104CEA : DRDCFR
| | - Jacques Baudier
- Transduction du signal: signalisation calcique et phosphorylation
INSERM : EMI0104CEA : DRDCFR
| | - Catherine Legraverend
- IGF, Institut de génomique fonctionnelle
CNRS : UMR5203INSERM : U661Université Montpellier IUniversité Montpellier II - Sciences et Techniques du Languedoc141, Rue de la Cardonille 34094 MONTPELLIER CEDEX 5,FR
| | - Jean-Christophe Deloulme
- Transduction du signal: signalisation calcique et phosphorylation
INSERM : EMI0104CEA : DRDCFR
- * Correspondence should be adressed to: Jean-Christophe Deloulme
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8
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de Barry J, Ghandour MS, Gombos G. Developing rat cerebellum: Glutamine and glutamate influx correlated to the cellular distribution of glutamine synthetase. Int J Dev Neurosci 2003; 1:351-60. [DOI: 10.1016/0736-5748(83)90016-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/25/1983] [Indexed: 11/29/2022] Open
Affiliation(s)
- J. de Barry
- Unité 44 de l'INSERM and Centre de Neurochimie du CNRS; 5, rue Blaise Pascal 67000 Strasbourg France
| | - M. S. Ghandour
- Unité 44 de l'INSERM and Centre de Neurochimie du CNRS; 5, rue Blaise Pascal 67000 Strasbourg France
| | - G. Gombos
- Unité 44 de l'INSERM and Centre de Neurochimie du CNRS; 5, rue Blaise Pascal 67000 Strasbourg France
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9
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Ghandour MS, Langley OK, Clos J. Immunohistochemical and biochemical approaches to the development of neuroglia in the CNS, with special reference to cerebellum. Int J Dev Neurosci 2003; 1:411-25. [DOI: 10.1016/0736-5748(83)90023-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/10/1983] [Indexed: 01/28/2023] Open
Affiliation(s)
- M. S. Ghandour
- Centre de Neurochimie du CNRS; 5 rue Blaise Pascal 67084 Strasbourg Cédex France
| | - O. K. Langley
- Centre de Neurochimie du CNRS; 5 rue Blaise Pascal 67084 Strasbourg Cédex France
| | - J. Clos
- Laboratoire de Physiologie Comparée; Université des Sciences et Techniques du Languedoc; Place E. Bataillon 34060 Montpellier Cédex France
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10
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Bastianelli E. Distribution of calcium-binding proteins in the cerebellum. CEREBELLUM (LONDON, ENGLAND) 2003; 2:242-62. [PMID: 14964684 DOI: 10.1080/14734220310022289] [Citation(s) in RCA: 201] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Calcium plays a fundamental role in the cell as second messenger and is principally regulated by calcium-binding proteins. Although these proteins share in common their ability to bind calcium, they belong to different subfamilies. They present, in general, specific developmental and distribution patterns. Most Purkinje cells express the fast and slow calcium buffer proteins calbindin-D28k and parvalbumin, whereas basket, stellate and Golgi cells the slow buffer parvalbumin only. They are, almost all, calretinin negative. Granule, Lugaro and unipolar brush cells present an opposite immunoreactivity profile, most of them being calretinin positive while lacking calbindin-D28k and parvalbumin. The developmental pattern of appearance of these proteins seems to follow the maturation of neurons. Calbindin-D28k appears early, shortly after cessation of mitosis when neurons become ready to start migration and differentiation while parvalbumin is expressed later in parallel with an increase in neuronal activity. The other proteins are generally detected later. During development, some of these proteins, like calretinin, are transiently expressed in specific cellular subpopulations. The function of these proteins is not fully understood, although strong evidence supports a prominent role in physiological settings with altered calcium concentrations. These proteins regulate and are regulated by intracellular calcium level. For example, they may directly or indirectly enable sensitization or desensitization of calcium channels, and may further block calcium entry into the cells, like the calcium-sensor proteins, that have been shown to be potent and specific modulators of ion channels, which may allow for feedback control of current function and hence signaling. The absence of calcium buffer proteins results in marked abnormalities in cell firing; with alterations in simple and complex spikes or transformation of depressing synapses into facilitating synapses. Calcium-binding protein implication in resistance to degeneration is still a controversial issue. Neurons rich in calcium-binding proteins, especially calbindin-D28k and parvalbumin, seem to be relatively resistant to degeneration in a variety of acute and chronic disorders. However other data support that an absence of calcium-binding proteins may also have a neuroprotective effect. It is not unlikely that neurons may face a dual action mechanism where a decrease in calcium-binding proteins has a first short-term beneficial effect while it becomes detrimental for the cell over the long term.
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Abstract
The identification of glial cells and neurons in brain slices is often difficult or uncertain. We have previously found that cultured rat cerebellar astrocytes and presumed astrocytes in acute brain slices, but not neurons, respond with cytosolic Ca(2+) transients following Ca(2+) influx in low external K+ concentrations (<1 mM; Cell Calcium 28 (2000) 247). We have now studied the possibility whether this Ca(2+) response can be employed to identify astrocytes during calcium imaging experiments. The Ca(2+) responses to low and high (50 mM) K+ were investigated in cells in culture and in hippocampal slices. In the stratum radiatum of hippocampal slices, S-100B-positive cells, presumed to be astrocytes, preferentially accumulated Fluo-4, while pyramidal neurons, identified by neuron-specific enolase, showed much lower Fluo-4 fluorescence, fixed with ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDAC). 81% of the cells with prominent Fluo-4 fluorescence showed responses to low K+, and 86% of these cells were S-100B-positive. Our results suggest that the responsiveness to low K+ can help to identify astrocytes in acute brain slices.
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Affiliation(s)
- Roger Dallwig
- Abteilung für Allgemeine Zoologie, FB Biologie, Universität Kaiserslautern, Postfach 3049, D-67653 Kaiserslautern, Germany
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Althaus HH, Richter-Landsberg C. Glial cells as targets and producers of neurotrophins. INTERNATIONAL REVIEW OF CYTOLOGY 2000; 197:203-77. [PMID: 10761118 DOI: 10.1016/s0074-7696(00)97005-0] [Citation(s) in RCA: 57] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Glial cells fulfill important tasks within the neural network of the central and peripheral nervous systems. The synthesis and secretion of various polypeptidic factors (cytokines) and a number of receptors, with which glial cells are equipped, allow them to communicate with their environment. Evidence has accumulated during recent years that neurotrophins play an important role not only for neurons but also for glial cells. This brief update of some morphological, immunocytochemical, and biochemical characteristics of glial cell lineages conveys our present knowledge about glial cells as targets and producers of neurotrophins under normal and pathological conditions. The chapter discusses the presence of neurotrophin receptors on glial cells, glial cells as producers of neurotrophins, signaling pathways downstream Trk and p75NTR, and the significance of neurotrophins and their receptors for glial cells during development, in cell death and survival, and in neurological disorders.
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Affiliation(s)
- H H Althaus
- AG Neural Regeneration, Max Planck Institute for Experimental Medicine, Göttingen, Germany
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13
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Abstract
The existence of multipotent progenitor populations in the adult forebrain has been widely studied. To extend this knowledge to the adult spinal cord we have examined the proliferation, distribution, and phenotypic fate of dividing cells in the adult rat spinal cord. Bromodeoxyuridine (BrdU) was used to label dividing cells in 13- to 14-week-old, intact Fischer rats. Single daily injections of BrdU were administered over a 12 d period. Animals were killed either 1 d or 4 weeks after the last injection of BrdU. We observed frequent cell division throughout the adult rodent spinal cord, particularly in white matter tracts (5-7% of all nuclei). The majority of BrdU-labeled cells colocalized with markers of immature glial cells. At 4 weeks, 10% of dividing cells expressed mature astrocyte and oligodendroglial markers. These data predict that 0.75% of all astrocytes and 0.82% of all oligodendrocytes are derived from a dividing population over a 4 week period. To determine the migratory nature of dividing cells, a single BrdU injection was given to animals that were killed 1 hr after the injection. In these tissues, the distribution and incidence of BrdU labeling matched those of the 4 week post injection (pi) groups, suggesting that proliferating cells divide in situ rather than migrate from the ependymal zone. These data suggest a higher level of cellular plasticity for the intact spinal cord than has previously been observed and that glial progenitors exist in the outer circumference of the spinal cord that can give rise to both astrocytes and oligodendrocytes.
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Vilette D, Madelaine MF, Laude H. Establishment of astrocyte cell lines from sheep genetically susceptible to scrapie. In Vitro Cell Dev Biol Anim 2000; 36:45-9. [PMID: 10691040 DOI: 10.1290/1071-2690(2000)036<0045:eoaclf>2.0.co;2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Primary cultures of the brain from sheep embryos were used to establish cell lines after transfection by the simian virus 40 (SV40) large T gene. Two of the lines (A15 and 4A6) displayed astroglial properties. They expressed the glial fibrillary acidic protein (GFAP), intermediate filament protein vimentin, and S-100 (beta-subunit) protein. While numerous rodent and human glial cell lines are available, this is to our knowledge the first description of ovine cell lines with astrocyte features. In addition, these cell lines were derived from sheep embryos chosen for their genetic susceptibility to scrapie (PrP genotype: VV136, QQ171). Therefore, they could be attractive tissue culture models for the study of propagation and pathogenesis of the scrapie agent ex vivo.
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Affiliation(s)
- D Vilette
- Unité de Virologie Immunologie Moléculaires, Institut National de la Recherche Agronomique, Jouy-en-Josas, France.
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15
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Rietze R, Poulin P, Weiss S. Mitotically active cells that generate neurons and astrocytes are present in multiple regions of the adult mouse hippocampus. J Comp Neurol 2000. [DOI: 10.1002/1096-9861(20000828)424:3<397::aid-cne2>3.0.co;2-a] [Citation(s) in RCA: 123] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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16
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Pérez-Torrero E, Durán P, Granados L, Gutiérez-Ospina G, Cintra L, Díaz-Cintra S. Effects of acute prenatal ethanol exposure on Bergmann glia cells early postnatal development. Brain Res 1997; 746:305-8. [PMID: 9037511 DOI: 10.1016/s0006-8993(96)01235-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
The effects of acute ethanol exposure during the prenatal phase of Bergmann glia cell (Bgc) generation were evaluated in three postnatal days. Ethanol exposed rats showed Bgc with reduced soma size, decreased number and width of their fibers, and increased fiber length, when compared with control animals. These differences, however, were significant at postnatal day 12. Our results demonstrate that acute, prenatal exposure to ethanol during critical stages of brain development disrupts Bgc early postnatal development.
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Affiliation(s)
- E Pérez-Torrero
- Centro de Neurobiología, Universidad Nacional Autónoma de México, Ciudad Universitaria, México D.F
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Vecino E, Velasco A, Caminos E, Aijón J. Distribution of S100 immunoreactivity in the retina and optic nerve head of the teleost Tinca tinca L. Microsc Res Tech 1997; 36:17-25. [PMID: 9031258 DOI: 10.1002/(sici)1097-0029(19970101)36:1<17::aid-jemt2>3.0.co;2-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
The distribution of S100 immunoreactivity within the normal and regenerating retina and optic nerve head of the teleost Tinca tinca L. has been investigated using the avidin-biotin complex (ABC) method and a polyclonal antibody against S100. Astrocytes and Müller cells were labeled with this antibody. This represents the first description of astrocytes localized in the optic nerve head and in the nerve fiber layer of the fish retina displaying a typical bipolar morphology. Horizontal cells in the inner nuclear layer were immunolabeled; we also observed species-specific S100 labeling of horizontal cells of the H1 subtype. No significant changes were seen in the S100 immunoreactive Müller cells, astrocytes, or horizontal cells in the tench retina after optic nerve crushing and during regeneration. These results might help to understand the function of glial cells in the normal and experimentally induced regenerating fish visual system.
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Affiliation(s)
- E Vecino
- Dpto. Biología Celular y Ciencias Morfológicas, Facultad de Medicina, Universidad del País Vasco, Vizcaya, Spain
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18
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Marks A, O'Hanlon D, Lei M, Percy ME, Becker LE. Accumulation of S100 beta mRNA and protein in cerebellum during infancy in Down syndrome and control subjects. BRAIN RESEARCH. MOLECULAR BRAIN RESEARCH 1996; 36:343-8. [PMID: 8965656 DOI: 10.1016/0169-328x(95)00293-2] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
S100 protein is a 20 kDA calcium-binding protein that accumulates during CNS maturation in mammals. The human gene coding for the beta subunit of S100 protein (S100 beta) is located on chromosome 21, in a subtelomeric position in 21q22.3. In order to investigate the effect of trisomy 21 on S100 beta gene expression, we performed Southern, Northern and Western blot analysis on DNA, RNA and protein, respectively, extracted from the cerebellum of control and Down syndrome (DS) subjects aged 1-18 months. Southern blot analysis revealed a novel EcoRI polymorphism in the S100 beta gene in two of 15 DNA samples examined, and a 1.5 gene dosage for S100 beta in DS. Northern and Western blot analysis showed an approximately 10-fold increase in S100 beta mRNA and protein levels between 1 and 18 months. No differences in the rates of accumulation of S100 beta mRNA and protein were observed between DS and normal subjects. These results demonstrate an increase in S100 beta mRNA and protein levels during infancy indicative of postnatal astrocytic maturation and show that there is no gross deregulation in the expression of the S100 beta gene in DS as a consequence of trisomy 21.
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Affiliation(s)
- A Marks
- Banting and Best Department of Medical Research, University of Toronto, Ont., Canada
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19
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Yang Q, Hamberger A, Wang S, Haglid KG. Appearance of neuronal S-100 beta during development of the rat brain. BRAIN RESEARCH. DEVELOPMENTAL BRAIN RESEARCH 1996; 91:181-9. [PMID: 8852368 DOI: 10.1016/0165-3806(95)00180-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
In addition to being an astroglial protein, S-100 beta is localised in distinct populations of neurons in the adult rat hindbrain. We report, here, the expression of S-100 beta in both neurons and glia of the rat brain during development. Prenatally, S-100 beta immunoreactivity was confined to glial cells close to the germinal zone. After birth, S-100 beta positive glial cells were seen mainly in the brainstem and cerebellum, while only a few were detected in cerebral cortex and hippocampus. The number of S-100 beta containing glial cells increased steadily during the first 2 postnatal weeks after which the adult pattern was attained. No S-100 beta containing neurons were present prenatally. The first S-100 beta containing neurons were seen in the mesencephalic trigeminal nucleus at postnatal day 1 (P1), and in the motor trigeminal nucleus at P3. Neuronal S-100 beta immunoreactivity in other nuclei was mostly attained from the 10th to the 21st postnatal day. The neuronal S-100 beta immunoreactivity was first detected in the cell nuclei during development, then increased in the cytoplasm with ages. A nuclear staining in many immunoreactive neurons persisted until the adult. It usually took 1 to 2 weeks for neuronal S-100 beta to attain the adult staining pattern, i.e., heavy staining of the cytoplasm and processes, after its appearance. The forebrain never contained S-100 beta positive neurons. The S-100 beta is first expressed in glial cells, suggesting it is primarily of the glial origin. Coupled with neurotrophic effects of the protein, the time course of neuronal S-100 beta expression during the critical period of neuronal development implies that it may be involved in neuronal differentiation and maturation.
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Affiliation(s)
- Q Yang
- Department of Anatomy and Cell Biology, University of Göteborg, Sweden. Qiner.
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20
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Shetty AK, Burrows RC, Wall KA, Phillips DE. Combined pre- and postnatal ethanol exposure alters the development of Bergmann glia in rat cerebellum. Int J Dev Neurosci 1994; 12:641-9. [PMID: 7900546 DOI: 10.1016/0736-5748(94)90016-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
The development and maturation of Bergmann glial cells in the rat cerebellum was evaluated on postnatal day 15 by glial fibrillary acidic protein (GFAP) immunocytochemistry, following combined gestational and 10-day postnatal ethanol exposure (a full three trimester human equivalency). GFAP-positive Bergmann glial fibers of lobules I, III, VIb, VII and X of the cerebellar vermis were examined and counted in the molecular layer (ML), the external granular layer (EGL) and the external limiting membrane (ELM). Ethanol exposure reduced: (1) the number of GFAP-positive fibers (per unit length of folia surface) at all three levels; (2) the percentage of mature fibers; and (3) the cross-sectional area in all lobules examined. When data from the five lobules were pooled, there were 7% fewer GFAP-positive fibers in the ML, 15% fewer in the EGL and 20% fewer in the ELM; the percentage of mature fibers was reduced by 16%; and the cross-sectional areas of lobules were reduced by 16%. The altered development of Bergmann glia could be one of the factors causing delayed migration of granular neurons and reductions in the number of granule cells reported in other studies following developmental ethanol exposures and could help to explain some of the motor dysfunctions reported in FAS victims.
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Affiliation(s)
- A K Shetty
- Department of Biology, Montana State University 59717-0346
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21
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Korr H, Horsmann C, Schürmann M, Delaunoy JP, Labourdette G. Problems encountered when immunocytochemistry is used for quantitative glial cell identification in autoradiographic studies of cell proliferation in the brain of the unlesioned adult mouse. Cell Tissue Res 1994; 278:85-95. [PMID: 7525071 DOI: 10.1007/bf00305780] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
We have used sections of adult mouse brain to determine whether antibodies specific for oligodendroglia (anti-carbonic anhydrase II, CA II; anti-galactocerebroside, GC; anti-myelin basic protein, MBP) and astroglia (anti-glial fibrillary acidic protein, GFAP; anti-S 100 protein) are suitable for quantitative studies of the proliferation and subsequent differentiation of these cells. Unlesioned adult mice received a single injection of 3H-thymidine (TdR) and were killed between 1 h and 70 days later. Quantitative evaluations of autoradiographs of 2-microns-thick serial sections stained immunocytochemically with the antibodies mentioned above or with Richardson's method for histological control led to the following conclusions. Anti-GC and anti-MBP stained only the oligodendrocytic processes and, thus, cannot be used in well-myelinated brain areas. Anti-CA II stained only a portion of the differentiated oligodendrocytes, but no proliferating cells. Anti-S 100 protein recognized all the astrocytes, but also many (interfascicular) oligodendrocytes. Anti-GFAP stained only a few astrocytes in the unlesioned mouse; all astrocytes may become GFAP-immunopositive only after wounding the brain. Thus, in contrast to in vitro studies, immunocytochemical studies with these antibodies on sections of adult animals cannot be recommended for the quantitative analysis of cell proliferation. In addition, our results show that differentiated glial cells proliferate in adult mice. Astro- and oligodendrocytes divide with the same cell cycle parameters and mode of proliferation up to about 1 month after 3H-TdR injection. In contrast to oligodendrocytes, some astrocytes might re-enter the cycle after a few weeks of quiescence.
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Affiliation(s)
- H Korr
- Institute of Anatomy, RWTH Aachen, Germany
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22
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Malagon M, Vaudry H, Van Strien F, Pelletier G, Gracia-Navarro F, Tonon MC. Ontogeny of diazepam-binding inhibitor-related peptides (endozepines) in the rat brain. Neuroscience 1993; 57:777-86. [PMID: 8309536 DOI: 10.1016/0306-4522(93)90023-9] [Citation(s) in RCA: 60] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Benzodiazepine receptors are expressed very early in the brain during embryonic life, suggesting that endogenous ligands for these receptors may play an important role during ontogenesis in the central nervous system. In the present study, the distribution and characterization of diazepam-binding inhibitor-related peptides (endozepines) in the rat brain was investigated during embryonic and postnatal development using an antibody raised against the biologically active region of the precursor molecule. Immunohistochemical labelling showed that, in newborn rats, endozepine-like immunoreactivity was present in ependymal cells of the hypothalamus. Although the number of positive cells increased by day 5, the intensity of the immunoreaction in each cell diminished. In 15-day-old rats, both the number of endozepine positive cells and the intensity of the immunoreaction increased in the ependymal layer. At day 40, a dense accumulation of immunoreactive tanycytes and glial cells was observed in the median eminence and the arcuate nucleus. Endozepines were detected by radioimmunoassay in all regions of the brain as early as embryonic day 18. The concentration of endozepine-related peptides increased in the hypothalamus and olfactory bulb during late gestation. Between birth and postnatal day 5, the levels of endozepines decreased two- to four-fold in all brain regions studied. Thereafter, endozepine concentration increased gradually until day 25. Reversed-phase high-performance liquid chromatography analysis of tissue extracts revealed that the olfactory bulb, pituitary, hypothalamus and cerebellum contained only one immunoreactive peak eluting at 39 min (peak C). In the telencephalon two peaks were observed: peak C and a second one eluting at 34 min (peak B). Peak B was present as early as embryonic day 20 and the ratio peak B/peak C gradually increased until day 25. At day 25 peak B was also detected in hippocampus, medulla oblongata, cortex and striatum extracts. In any brain region, no immunoreactivity co-eluting with the octadecaneuropeptide was observed. Sephadex G-50 gel filtration of hypothalamus extracts of 25-day-old animals, confirmed the existence of only one immunoreactive compound with an apparent molecular weight of 10,000. In the telencephalon two major species were resolved, with apparent molecular weights of 10,000 and 8800, and a minor one of 6500 mol. wt. In conclusion, the present study shows that endozepines are expressed in the rat brain as early as embryonic day 18 and the amount of endozepine-like material increases rapidly during the two days preceding birth. The results also indicate that diazepam-binding inhibitor is processed to different molecular forms depending on the brain region.(ABSTRACT TRUNCATED AT 400 WORDS)
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Affiliation(s)
- M Malagon
- European Institute for Peptide Research, CNRS URA 650, UA INSERM, University of Rouen, Mont-Saint-Aignan, France
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23
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Shetty AK, Phillips DE. Effects of prenatal ethanol exposure on the development of Bergmann glia and astrocytes in the rat cerebellum: an immunohistochemical study. J Comp Neurol 1992; 321:19-32. [PMID: 1613136 DOI: 10.1002/cne.903210103] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The consequences of prenatal ethanol exposure on the postnatal development of Bergmann glia and astrocytes in the rat cerebellum were investigated by using glial fibrillary acidic protein (GFAP) immunolabeling. Pregnant rats were either fed with an ethanol containing liquid diet (6.7% v/v) or pair-fed with an isocaloric diet throughout gestation. On postnatal day (PD) 15 and 22, parasagittal sections of the cerebellar vermis from female offspring were processed for GFAP immunohistochemistry to assess the development of Bergmann glia and astrocytes in lobules I, VII, and X and astrocytes in the central core of white matter. On PD 15, compared to control animals, ethanol exposed animals had fewer GFAP positive Bergmann glial fibers per unit length of molecular layer; a significantly greater percentage of morphologically immature Bergmann fibers; a significantly greater GFAP positive astrocytic area per unit area of internal granular layer and central white matter; and the astrocytic processes were wider and more closely packed. These glial changes were associated with significantly thicker external granular layer in all 3 lobules. However, no significant differences were seen between the ethanol exposed and control animals on PD 22, indicating "catch-up growth" in the ethanol exposed animals during the third postnatal week. These results suggest that prenatal ethanol exposure causes (1) delayed maturation of Bergmann glia, which in turn contributes to the delayed migration of granule cells; and (2) alterations in the normal postnatal development of astrocytes.
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Affiliation(s)
- A K Shetty
- Department of Biology, Montana State University, Bozeman 59717-0346
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24
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Pfeiffer B, Meyermann R, Hamprecht B. Immunohistochemical co-localization of glycogen phosphorylase with the astroglial markers glial fibrillary acidic protein and S-100 protein in rat brain sections. HISTOCHEMISTRY 1992; 97:405-12. [PMID: 1500296 DOI: 10.1007/bf00270387] [Citation(s) in RCA: 42] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Immunofluorescence double-labelling and immunoenzyme double-staining methods were used to examine the location of glycogen phosphorylase brain isozyme with the astrocyte markers glial fibrillary acidic protein (GFAP) and S-100 protein in formaldehyde-fixed, paraffin-embedded slices from adult rat brain. Astrocytes in the cerebellum and the hippocampus, which express GFAP or S-100 protein immunoreactivity, show glycogen phosphorylase immunoreactivity. Regional intensity and intracellular distribution of the three antigens vary characteristically. In ependymal cells, glycogen phosphorylase immunoreactivity is co-localized with S-100 protein immunoreactivity, but not with GFAP immunoreactivity. These findings confirm that glycogen phosphorylase in the rat brain is exclusively localized in astrocytes and ependymal cells. All astrocytes, as far as they express GFAP or S-100 protein, do contain glycogen phosphorylase.
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Affiliation(s)
- B Pfeiffer
- Physiologisch-Chemisches Institut, University of Tübingen, Federal Republic of Germany
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25
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Paden CM, Cranston H, Hapner SJ. Expression of a novel nuclear protein is correlated with neuronal differentiation in vivo. JOURNAL OF NEUROBIOLOGY 1992; 23:231-51. [PMID: 1624932 DOI: 10.1002/neu.480230304] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
We report the production of a monoclonal antibody (MAb 526) that recognizes a novel, developmentally regulated nuclear protein expressed in neurons throughout the rat nervous system. Analysis of whole brain and cell nuclear extracts by SDS-PAGE and immunoblotting determined that MAb 526 recognizes a single nuclear protein (np) of apparent molecular weight 42 kD, designated np526, as well as a slightly larger (ca. 44 kD) cytoplasmic protein. Light microscopic immunocytochemistry showed np526 to be present in neurons of all types throughout the central and peripheral nervous systems. Nuclei of both fibrous and protoplasmic astrocytes were also immunoreactive, but oligodendrocyte nuclei were negative. Positive, but highly variable immunocytochemical staining of nonneural cell nuclei in a variety of other tissues was also observed. Electron microscopic (EM) immunocytochemistry using pre-embedding peroxidase methods revealed that np526 is associated with euchromatin or with the edges of condensed chromatin bundles in neurons, indicating that it is likely to be a chromosomal protein. Most interestingly, the expression of np526 was found to be developmentally regulated in brain. Immunocytochemical analysis of the developing cerebral cortex from embryonic day (E) 16 to postnatal day (P) 4 and cerebellum from P4 to P18 revealed that np526 first appears in central neurons following the cessation of mitosis and that the intensity of nuclear staining increases during subsequent neuronal maturation. To our knowledge, np526 is the first presumptive chromosomal protein whose expression has been precisely correlated with the early postmitotic differentiation of mammalian neurons.
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Affiliation(s)
- C M Paden
- Department of Biology, Montana State University, Bozeman 59717
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26
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Marshak DR, Pesce SA, Stanley LC, Griffin WS. Increased S100β neurotrophic activity in Alzheimer's disease temporal lobe. Neurobiol Aging 1992; 13:1-7. [PMID: 1371849 DOI: 10.1016/0197-4580(92)90002-f] [Citation(s) in RCA: 148] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The confirming diagnosis of Alzheimer's disease includes an assessment of the concentration of neuritic plaques in the temporal lobe of the brain. The presence of abnormal levels of neurotrophic factors in Alzheimer's disease is one possible explanation for the increased concentration of aggregates of overgrown neurites in the neuritic plaques of Alzheimer's disease. The protein S100 beta, a neurotrophic factor produced by astroglia in the brain, induces neurite outgrowth in cerebral cortical neurons. The generation of specific S100 beta antibodies, the cloning of a full-length cDNA encoding the S100 beta mRNA, and the development of a neurite extension assay system for S100 beta allowed testing of the hypothesis that Alzheimer's disease S100 beta expression is elevated in brain temporal lobe where neuritic plaques are concentrated. The levels of S100 beta protein, mRNA, and specific neurotrophic activity were elevated 10-20-fold in extracts of temporal lobe from autopsy samples of Alzheimer's disease patients compared to those of aged control patients. The cells containing the increased S100 beta were reactive astrocytes; the neuritic plaques were surrounded by S100 beta-containing astrocytes. The elevated levels of S100 beta provides a link between the prominent reactive gliosis and neuritic plaque formation in this common disease of the elderly and raises the possibility that S100 beta contributes to Alzheimer's disease neuropathology.
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Affiliation(s)
- D R Marshak
- Cold Spring Harbor Laboratory, NY 11724-2220
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27
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Wilkinson M, Hume R, Strange R, Bell JE. Glial and neuronal differentiation in the human fetal brain 9-23 weeks of gestation. Neuropathol Appl Neurobiol 1990; 16:193-204. [PMID: 2402329 DOI: 10.1111/j.1365-2990.1990.tb01156.x] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Nineteen human fetal brains ranging from 9-23 weeks of gestation were examined immunocytochemically for evidence of glial and neuronal differentiation. Radial glia were positive for vimentin and glial fibrillary acidic protein (GFAP) throughout the age range. S100-positive cells which were presumed to be astrocytes were present from 9 weeks; they were always more widespread in the cerebrum and the brainstem than GFAP-positive mature astrocytes, which could be detected with certainty only at 14 weeks. Carbonic anhydrase II (CA II)-positive oligodendrocytes were present in the brainstem in small numbers from 17 weeks. Neuronal fibre tracts in the cerebrum were positive for 160 kD phosphorylated neurofilament protein (BF10) from 9 weeks, but negative for 200 kD phosphorylated neurofilament protein (RT97) and for 70 and 200 kD non-phosphorylated neurofilament protein (NFP) whereas most tracts in the brainstem were positive for BF10 from 9 weeks and positive for the other neurofilament proteins from 14 weeks. Corticospinal tracts differed in remaining negative for neurofilament proteins other than BF10, which showed positive reaction throughout. Perikarya of differentiated neurons in all areas of the brain were neurofilament-negative but neuron specific enolase (NSE)-positive. Germinal eminence cells were focally vimentin-positive from 15 weeks, focally GFAP-positive from 17 weeks, and negative for all NFP and for NSE. The value of a short fixation time and pretreatment with trypsin in the immunocytochemical demonstration of GFAP is stressed.
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Affiliation(s)
- M Wilkinson
- Department of Pathology, University of Edinburgh
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28
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Landry CF, Ivy GO, Dunn RJ, Marks A, Brown IR. Expression of the gene encoding the beta-subunit of S-100 protein in the developing rat brain analyzed by in situ hybridization. BRAIN RESEARCH. MOLECULAR BRAIN RESEARCH 1989; 6:251-62. [PMID: 2593780 DOI: 10.1016/0169-328x(89)90071-5] [Citation(s) in RCA: 51] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
To investigate patterns of expression of the gene encoding the beta-subunit of S-100 protein during development of the rat brain we have used Northern blotting and in situ hybridization histochemistry. During late prenatal development beta-S-100 mRNA was observed first in the germinal zone lining the 4th ventricle. In the postnatal cerebellum this mRNA accumulated primarily in Bergmann glia and astrocytes of the deep white matter. In the hindbrain, expression of S-100 mRNA increased steadily in specific regions during the first postnatal week while levels remained low in more anterior brain regions. By the end of the second postnatal week, a dense punctate signal was distributed throughout the midbrain and hindbrain. Expression in forebrain, first observed at E18, was confined to cells lining the ventricle until the second postnatal week when accumulation of mRNA was observed in specific regions of the hippocampus, neocortex and olfactory bulb. The adult brain pattern of beta-S-100 mRNA distribution is attained during the third postnatal week. These results demonstrate a caudal-rostral gradient in expression of the beta-S-100 gene during rat brain development, as well as pronounced regional differences which may reflect the differentiation of subpopulations of astrocytes.
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Affiliation(s)
- C F Landry
- Department of Zoology, University of Toronto, Ont., Canada
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29
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Ono K, Yanagihara M, Mizukawa K, Yuasa S, Kawamura K. Monoclonal antibody that binds to both the prenatal and postnatal astroglia in rodent cerebellum. BRAIN RESEARCH. DEVELOPMENTAL BRAIN RESEARCH 1989; 50:154-9. [PMID: 2582606 DOI: 10.1016/0165-3806(89)90136-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
A monoclonal antibody (MAb), generated by immunizing mice with homogenized guinea pig cerebellum, labeled cerebellar astroglia including perikarya, radial fibers and veil-like processes in adult rats, mice and guinea pigs. Cell bodies and processes of the immature radial glia in the ventricular neuroepithelium of fetal mice cerebellum were definitely stained by the MAb on the 14th day of gestation. The astroglial components continued to show selective immunoreactivity to the MAb after the 14th day of gestation.
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Affiliation(s)
- K Ono
- Third Department of Anatomy, Okayama University Medical School, Japan
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30
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Abstract
Brain tumors containing undifferentiated cells were selected from a series of 504 childhood brain tumors; 117 were analyzed. Most tumors were medulloblastomas, followed by cerebral neuroblastomas, pineocytomas-blastomas, ependymoblastomas, and polar spongioblastomas. Of each oncotype, the main histological features were evaluated, including differentiation and the most important prognostic factors. The terminology and different tumor entities are discussed in light of the recent PNET system. The usefulness of its application is evaluated in relation to prognosis.
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Affiliation(s)
- D Schiffer
- II. Department of Neurology, University of Turin, Italy
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31
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Bell JE, Sandison A, Boddy J, Franks AJ, Batcup G, Calvert R, Gordon A. Development of the cerebellum with particular reference to cellular differentiation in the external granular layer. Early Hum Dev 1989; 19:199-211. [PMID: 2505998 DOI: 10.1016/0378-3782(89)90080-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Immunocytochemical evidence of differentiation in developing human cerebellum is presented in this study. Antibodies to neuron specific enolase, neurofilament protein, glial fibrillary acidic protein, vimentin, cytokeratin, epithelial membrane antigen and lymphoid markers, DLC and Leu 7 were used. The external granular layer showed positivity with neuronal markers between 27 weeks gestation and 4 months postnatal, but was negative for all other markers including glial fibrillary acidic protein. Characteristic staining reactions were noted in the other cerebellar layers. Monoclonal antibodies, UJ13A (pan-neuroectodermal marker) and G10 (localising microtubule-associated protein MAP1x) were also used in a limited number of cryostat sections and were positive and negative, respectively, in the external granular layer. The results of this study are discussed in relation to the theory that the external granular layer may be one source of medulloblastomas.
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Affiliation(s)
- J E Bell
- Neuropathology Laboratory, University of Edinburgh, U.K
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32
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Nona SN, Shehab SA, Stafford CA, Cronly-Dillon JR. Glial fibrillary acidic protein (GFAP) from goldfish: its localisation in visual pathway. Glia 1989; 2:189-200. [PMID: 2526081 DOI: 10.1002/glia.440020308] [Citation(s) in RCA: 73] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
An intermediate filament fraction, isolated from goldfish brain, contains a prominent protein having a molecular weight of 51 kDa. In normal goldfish visual pathway, this protein is present in tectum and tract, but not in optic nerve. A polyclonal antibody raised to this protein clearly labels ependymal glial profiles in tectum and parallel processes in the tract, whereas optic nerve is unlabelled; Müller fibres in the retina are also labelled. A similar, but less prominent, pattern of staining is observed with antibodies, raised elsewhere, against glial fibrillary acidic protein from human and porcine. These results suggest that the 51 kDa protein is a GFAP, demonstrate the heterogeneity of astrocytes in goldfish visual pathway, and are consistent with the idea that GFAP is well conserved in vertebrate phylogeny.
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Affiliation(s)
- S N Nona
- Department of Optometry and Vision Sciences, University of Manchester Institute of Science & Technology, England
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33
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Alliot F, Delhaye-Bouchaud N, Geffard M, Pessac B. Role of astroglial cell clones in the survival and differentiation of cerebellar embryonic neurons. BRAIN RESEARCH. DEVELOPMENTAL BRAIN RESEARCH 1988; 44:247-57. [PMID: 2906278 DOI: 10.1016/0165-3806(88)90223-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
To investigate the role of astrocytes in the survival and differentiation of cerebellar neurons during development, we have used astroglial cell clones, derived from 8-day postnatal cerebellar explants and which might be the in vitro equivalents of the 3 main types of cerebellar astrocytes, the Golgi epithelial cells and their Bergmann processes, the velate protoplasmic and the fibrous astrocytes (F. Alliot and B. Pessac, Brain Res., 306 (1984) 283-291). Nearly all single cells, dissociated from 15-day embryonic mouse cerebella and seeded at low density, adhered to layers of each of the cerebellar astroglial cell clones as well as to other glial lines or artificial substrates. However, the cerebellar embryonic neurons survived well only on monolayers of either the 'Golgi-Bergmann'-like or the 'velate protoplasmic'-like clones. On these layers, 60-80% of the neurons were still present after 5 days of co-culture, while only less than 5% survived on the other types of substrates. The differentiation pattern of the neurons surviving on the 'Golgi-Bergmann' and the 'velate protoplasmic' astroglial clones was studied with markers of postmitotic granule cells, the major neuronal population in adult cerebellum. The velate protoplasmic-like clone was the only one able to support the coordinate acquisition by most surviving neurons of the phenotypic characteristics of granule cells, i.e. a distinct morphology, a specific epitope binding the monoclonal antibody 7-8 D2 and immunoreactivity to glutamate. These data show a broad heterogeneity in the capacity of astroglial cell clones to support embryonic cerebellar neurons. In addition, they indicate that neuronal survival per se is not sufficient for the acquisition of a differentiated neuronal phenotype.
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Affiliation(s)
- F Alliot
- INSERM U 178, Ivry-sur-Seine, France
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Hillman DE, Chen S, Chen V. Ectopic glial cells in rat cerebella following neonatal administration of methylazoxymethanol acetate. Brain Res 1988; 447:353-9. [PMID: 3390704 DOI: 10.1016/0006-8993(88)91139-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Immunological and ultrastructural studies of adult cerebella following neonatal injection of methylazoxymethanol acetate revealed ectopic glial cells in the molecular layer and at the pial surface. This finding strengthens the view that the external granular layer might give rise to Bergmann glia.
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Affiliation(s)
- D E Hillman
- Department of Physiology and Biophysics, New York University Medical Center, NY 10016
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Koppel H, Pilkington GJ, Lantos PL. Tumorigenicity of six clones of a cultured neoplastic cell line derived from a spontaneous murine astrocytoma: morphology and immunocytochemistry of tumours. J Neurol Sci 1988; 83:227-42. [PMID: 3356990 DOI: 10.1016/0022-510x(88)90071-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Six clones obtained from the neoplastic, astrocytic murine cell line VMDk P497 were injected intracerebrally into syngeneic hosts and the tumorigenicity of each clone was established. Five of the 6 clones produced tumours with incidences ranging from 25% to 100% and mean latencies of 43-100 days, according to the clone injected. Histological, immunocytochemical and electron microscopical examination of the resulting tumours revealed differences in the degree of invasiveness, but otherwise only slight variations in phenotype between the clones. Generally, the tumours were glioblastoma-like, showing a pleomorphic histoarchitectural pattern; the predominant cell types throughout were poorly differentiated, and lacked both antigenic and morphological characteristics, particularly the presence of intermediate filaments, of mature astrocytes. The basal lamina proteins, fibronectin and laminin, were, however, expressed in all tumours examined. This phenotypic change on cloning and syngeneic transplantation may be of considerable significance in future therapeutic studies using this glioma model.
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Affiliation(s)
- H Koppel
- Department of Neuropathology, Institute of Psychiatry, Denmark Hill, London, U.K
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Seregi A, Keller M, Hertting G. Are cerebral prostanoids of astroglial origin? Studies on the prostanoid forming system in developing rat brain and primary cultures of rat astrocytes. Brain Res 1987; 404:113-20. [PMID: 3567558 DOI: 10.1016/0006-8993(87)91361-8] [Citation(s) in RCA: 64] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Prostanoid forming capacity in vitro and convulsion-induced prostanoid formation in vivo were studied in the developing rat brain. For comparison, prostanoid synthesis in homogenates of primary astrocyte cultures of different ages was also examined. There was no significant prostanoid production in homogenates from primary astrocyte cultures prepared one week after cultivation. Two-week-old astrocyte cultures possessed a prostanoid synthesizing system of high specific activity. The relative proportions of the products were similar to those obtained in brain homogenates of adult rats, prostaglandin D2 (PGD2) being the major product. Prostanoid forming capacity of brain homogenates was low at birth, increased during development and nearly reached adult values by day 21. Generalized convulsions could be evoked by pentylenetetrazol (PTZ) irrespective of age, but convulsion-induced prostanoid formation characteristic of adult rodents did not take place before the third week of postnatal life. The close similarities between the characteristic features of prostanoid synthesis in both brain and astroglial homogenates, together with the coincidence during brain development of the expression of cerebral prostanoid synthesis with the appearance of mature astrocytes suggest that astrocytes are an important source of brain prostanoids.
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Hesketh J, Baudier J. Evidence that S100 proteins regulate microtubule assembly and stability in rat brain extracts. THE INTERNATIONAL JOURNAL OF BIOCHEMISTRY 1986; 18:691-5. [PMID: 3743875 DOI: 10.1016/0020-711x(86)90391-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Microtubule re-assembly in rat brain extracts was inhibited by antibodies to S100 proteins. Anti-S100 antibodies caused an increase in the cold-stability of microtubules and this effect was abolished by the presence of short lengths of microtubules formed under control conditions. Anti-S100 antibodies had no effect on the stimulation of assembly or the increase in microtubule stability caused by low zinc concentrations. Addition of exogenous S100a and S100b to brain extracts had different effects on assembly; S100a caused an inhibition of assembly while S100b stimulated the early phase of assembly. The data suggest that endogenous S100b is involved in the regulation of microtubule assembly in brain extracts.
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Evidence that mouse astrocytes may be derived from the radial glia. An immunohistochemical study of the cerebellum in the normal and reeler mouse. J Neuroimmunol 1985; 9:87-97. [PMID: 2409110 DOI: 10.1016/s0165-5728(85)80009-6] [Citation(s) in RCA: 47] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Astrocytic cells of unusual aspect can be detected in the cerebellum of normal mice during the first 4 weeks of life. They are visualized with anti-GFAP (glial fibrillary acidic protein), anti-S100 and anti-vimentin immune sera. Their perikaryons, located in the white matter or in the granular layer, extend long processes which are inserted onto the pial surface. These cells may be transitional forms between the radial glial cells and some of the differentiated astroglial elements. These unusual astrocytes are more numerous and heavily stained in the reeler mutant than in the normal mouse and it is suggested that our observations signify some degree of glial immaturity in the cerebellum of the mutant.
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Weir MD, Patel AJ, Hunt A, Thomas DG. Developmental changes in the amount of glial fibrillary acidic protein in three regions of the rat brain. Brain Res 1984; 317:147-54. [PMID: 6148128 DOI: 10.1016/0165-3806(84)90092-0] [Citation(s) in RCA: 46] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Glial fibrillary acidic (GFA) protein, extractable in 50 mM phosphate buffer, pH 8, was measured in the olfactory bulbs, forebrain and cerebellum of the rat during development using a double antibody radioimmunoassay. Each brain region showed a different pattern of development for GFA protein. At birth GFA protein per mg protein was highest in olfactory bulbs followed by forebrain and cerebellum, and these amounted to 15, 10 and 8% of the adult values, respectively. The relative increase in GFA protein was more marked during the first 2 postnatal weeks than in the following 7 weeks after birth. When values were expressed per brain region, the developmental increase in the amount of GFA protein from birth to adulthood was about 100-fold in olfactory bulbs, 85-fold in forebrain and 485-fold in cerebellum. The patterns of developmental increases in GFA protein and in glutamine synthetase activity, another protein enriched in astrocytes, were similar in the forebrain and olfactory bulbs, but differed markedly in the cerebellum. The major increase in content of the GFA protein during development was found to correspond with the maturation of astrocytes rather than with their proliferation; however, a small but significant amount of GFA protein acquired at an early age may be related to increase in astroglial cell numbers in the cerebellum.
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Marks A, Law J, Mahony J. Synthesis of a brain-specific protein (S100 protein) in a lectin-resistant mutant of a rat glial cell line (C6). Biochimie 1983; 65:609-18. [PMID: 6673740 DOI: 10.1016/s0300-9084(84)80024-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
The synthesis of S100 protein increases toward the end of the exponential phase of growth of clonal rat glial cells C6 in monolayer culture. Moreover the synthesis of this protein can be increased by treatment of C6 cells with the lectin succinylated concanavalin A (succinyl ConA). In order to study the relationship between these two inductions of S100 protein we have isolated a cell line resistant to ConA from a population of C6 cells. The resistant cells (C6-ConAR) have less succinyl ConA receptors than C6 cells. In contrast to C6 cells, the synthesis of S100 protein does not increase in C6-ConAR cells after treatment with succinyl ConA. However in both cell types the synthesis of S100 protein increases toward the end of the exponential phase of growth. These results suggest firstly that the induction of S100 protein in C6 cells by succinyl ConA is mediated by an interaction of the lectin with its membrane receptors and secondly that the initial steps in the induction of S100 protein by the lectin are different from the initial steps in the induction of this protein which occurs toward the end of the exponential phase of growth in monolayer culture.
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Legrand C, Ghandour MS, Clos J. Histochemical and biochemical studies of butyrylcholinesterase activity in adult and developing cerebellum. Effects of abnormal thyroid state and undernutrition. Neuropathol Appl Neurobiol 1983; 9:433-53. [PMID: 6656997 DOI: 10.1111/j.1365-2990.1983.tb00128.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
The cellular and subcellular localization of BuchE activity (EC.3.1.1.8) was studied in the developing and adult rat cerebellum at light and electron microscope levels. In the adult cerebellum, BuchE activity was exclusively localized to glial cells, myelin and endothelial cells. In the immature cerebellum, BuchE activity was additionally found transiently localized to the neuroblasts of the external germinative layer and in Purkinje cells of the nodulus. In both the immature and the adult animals, the main part of the activity seemed to be membrane-bound. The developmental pattern of cerebellar BuchE activity was assayed in developing normal, hypothyroid, thyroxine-treated and undernourished rats. In normal newborn rats, the specific activity was higher than in adults and it showed one characteristic peak at 6 days (1.8 times the adult value reached at 30 days). At the age of 5 days, the ratio of BuchE-containing astrocytes (numbered in the ganglionic layer) to Purkinje cells was the same as the ratio of Bergmann astrocytes to Purkinje cells determined at 35 days in Nissl preparations; their nucleus size already represented 80% of the adult value and their processes were well developed. The three experimental conditions modified the timing of BuchE development. During the early post-natal period, it was accelerated in the thyroxine-treated and undernourished animals, while in the hypothyroid rats it was delayed. During the same period, the number of labelled astrocytes per Purkinje cell was modified only by hypothyroidism and undernourishment. On the basis of these histochemical and biochemical results, BuchE can be considered as a good marker for the study of Bergmann glia development in the early post-natal period.
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Masuda T, Sakimura K, Yoshida Y, Kuwano R, Isobe T, Okuyama T, Takahashi Y. Developmental changes in the translatable mRNA for beta subunit of S-100 protein in rat brain. BIOCHIMICA ET BIOPHYSICA ACTA 1983; 740:249-54. [PMID: 6871223 DOI: 10.1016/0167-4781(83)90133-1] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
The presence of mRNA coding for beta subunit of S-100 protein was demonstrated in polyadenylated RNA from the rat brain in vitro translation in a reticulocyte lysate cell-free system. The products were identified with S-100 protein beta subunit using the immunoprecipitation of the reaction products with the specific antisera, comigration of the isolated, labelled peptide with the purified S-100 protein in SDS-polyacrylamide gel electrophoresis and fluorography and the same retention time of the labelled S-100 protein beta subunit with authentic S-100 beta subunit by high performance liquid chromatography. The size determination of mRNA for S-100 protein on sucrose density gradient centrifugation gave 6-8 S. The assay gave a linear response with increasing amounts of polyadenylated RNA, allowing quantitation of mRNA level for S-100 protein in polyadenylated RNA. During the prenatal period and 10 postnatal days, only minute amounts of mRNA for beta subunit of S-100 protein could be found, however a dramatic increase of mRNA for beta subunit of S-100 was observed within the period of 10 to about 30 days and the mRNA level maintained a plateau from 40 days to adult age. These date indicate that the development changes in the amount of S-100 protein in the rat brain found by other authors is strongly correlated with the changes in the level of its translatable mRNA.
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Shiga T, Ichikawa M, Hirata Y. A Golgi study of Bergmann glial cells in developing rat cerebellum. ANATOMY AND EMBRYOLOGY 1983; 167:191-201. [PMID: 6614504 DOI: 10.1007/bf00298510] [Citation(s) in RCA: 28] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
In order to examine the relationship between the Bergmann glial cells and the migrating granule cells, the postnatal development of the Bergmann glial cells in the rat cerebellum was analysed by a rapid Golgi method. In newborn rats where immature Purkinje cells occupied a rather thick zone (about 8 cells thick) between the thin molecular layer and the intermediate zone, immature Bergmann glial cells were recognized by the irregularly contoured somata situated within the deep part of the zone of Purkinje cells and by several perpendicular thin fibers (filiform fibers) which traversed the external granular layer (EGL) to terminate at the pial surface. After day 2 of the postnatal age (PD2), both somata and fibers of Bergmann glial cells showed gradual or fairly abrupt changes. The somata migrated upwards toward the molecular layer on PD2 and on PD4 were situated just beneath the Purkinje cells which had become arranged in a single layer. After PD6 the distance between the pial surface and the somata situated in the Purkinje cell layer and concomitantly the length of the Bergmann glial fibers, progressively increased in accordance with the thickening of the molecular layer. Between PD0 and PD8 the somata were irregularly contoured with short protoplasmic processes extending radially. After PD8 they gradually lost these short processes and became smooth. The Bergmann glial fibers were rather smooth with a few beady enlargements and tiny bud-like excrescences on their surface between PD0 and PD8. On PD12 the bushy expansions, characteristic of matured Bergmann glial fibers, suddenly increased in number on most fibers. After PD12 they continued to augment until PD25, when most fibers were entirely covered with the expansions. The number of fibers issuing from each Bergmann glial cell and entering the EGL increased postnatally reaching a peak on PD8, and then decreased gradually. These changes in the number of Bergmann glial fibers corresponded well with those in the number of external granule cells, suggesting the presence of developmental interactions between these two kinds of cells.
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Abstract
Primitive neuroectodermal tumors are morphologically similar malignant tumors arising in intracranial and peripheral sites of the nervous system, showing varying degrees of cellular differentiation with a tendency to disseminate along cerebrospinal fluid pathways. They occur primarily in children and young adults. Under the designation primitive neuroectodermal tumors are included medulloblastomas and tumors that may differentiate in other directions, such as medulloepithelioma, neuroblastoma, polar spongioblastoma, pineoblastoma, ependymoblastoma, retinoblastoma, and olfactory neuroblastoma. From a practical, histologic point of view, these tumors are often indistinguishable from one another and are best thought of as primitive neuroectodermal tumors with or without differentiating features.
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Shiga T, Ichikawa M, Hirata Y. Spatial and temporal pattern of postnatal proliferation of Bergmann glial cells in rat cerebellum: an autoradiographic study. ANATOMY AND EMBRYOLOGY 1983; 167:203-11. [PMID: 6614505 DOI: 10.1007/bf00298511] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
In order to examine the relationship between the Bergmann glial cells and the migrating granule cells, the development of the Bergmann glial cells in the rat cerebellum was studied with 3H-thymidine autoradiography. 3H-thymidine was injected intraperitoneally into rats on two days successively between days 2 and 21 of the postnatal age (PD2 and PD21). All animals were sacrificed on PD25 and the vermis of the cerebellum was embedded in epoxy resin. Semithin sections were cut sagittally for autoradiography. The labeling index of the Bergmann glial cells in lobules I, II, III, IV, V, VIa, VIII, IX, and X reached the peak on PD6-7, and in lobules VIb and VII on PD8-9. Moreover, the lobules could be divided into three groups according to the day when cumulative labeling indices reached 50% of the total ones (LI50): The early-developing group (LI50; PD4.4-5.2) contained lobules I, II, III, IV, and V, the intermediate group (LI50; PD5.3-6.1) lobules VIa, VIII, IX, and X, and the late-developing group (LI50; PD6.6-7.8) lobules VIb and VII. The regional gradient of LI50 in the Bergmann glial cells corresponded approximately to the regional gradient in the ratio of late-forming granule cells; that is, the later the LI50 of the Bergmann glial cells, the higher is the ratio of the late-forming granule cells. This suggests that an intimate relationship exists between these two kinds of cells.
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Patel A, Hunt A, Tahourdin C. Regional development of glutamine synthetase activity in the rat brain and its association with the differentiation of astrocytes. ACTA ACUST UNITED AC 1983. [DOI: 10.1016/0165-3806(83)90154-2] [Citation(s) in RCA: 87] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Langley OK, Ghandour MS, Gombos G, Hirn M, Goridis C. Monoclonal antibodies as neural cell surface markers. Neurochem Res 1982; 7:349-62. [PMID: 7050755 DOI: 10.1007/bf00965646] [Citation(s) in RCA: 33] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
A comparison is made of the immunohistochemistry at the ultrastructural level of three monoclonal antibodies directed against surface components of DNS cells. Hybridomas secreting these antibodies were obtained from two cell fusions of a rat myeloma cell line and immune splenocytes derived from rats immunized either with primary mouse brain cultured cells or membrane components. In cultures one antibody, anti-BSP2 (Brain Surface Protein-2), was preferentially directed against neurons while another, anti-BSP-3 (Brain Surface Protein-3), preferentially labeled astrocytes. In mouse cerebellar sections, both labeled the surface of Purkinje cells, granule cells and astrocytes. In addition a cytoplasm localization was apparent in granule cells and astrocytes. Another antibody anti-MESA-1 (Mouse Endothelial Surface Antigen-1) reacted exclusively with the surface of endothelial cells lining blood vessels. These data are discussed with reference to the biochemical nature of the corresponding antigens and to known glycoproteins of neural cell membranes.
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