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Qi G, Tang H, Hu J, Kang S, Qin S. Potential role of tanycyte-derived neurogenesis in Alzheimer's disease. Neural Regen Res 2025; 20:1599-1612. [PMID: 38934388 PMCID: PMC11688558 DOI: 10.4103/nrr.nrr-d-23-01865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 02/19/2024] [Accepted: 04/17/2024] [Indexed: 06/28/2024] Open
Abstract
Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly, metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore, the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood-brain barrier function. However, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could provide valuable insights into potential therapeutic strategies for Alzheimer's disease and related conditions.
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Affiliation(s)
- Guibo Qi
- Department of Anatomy, Histology, and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Han Tang
- Department of Anatomy, Histology, and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Jianian Hu
- Department of Anatomy, Histology, and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Siying Kang
- Department of Anatomy, Histology, and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Song Qin
- Department of Anatomy, Histology, and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai, China
- State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China
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Butruille L, Batailler M, Vaudin P, Pillon D, Migaud M. GFAP-expressing cells in the adult hypothalamus can generate multiple neural cell lineages in vitro. Neurosci Lett 2024; 824:137674. [PMID: 38355005 DOI: 10.1016/j.neulet.2024.137674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 01/05/2024] [Accepted: 02/07/2024] [Indexed: 02/16/2024]
Abstract
Adult neural stem cells (NSCs) located in the two canonical neurogenic niches, the subventricular zone (SVZ) and the subgranular zone (SGZ), express the glial fibrillary acidic protein (GFAP). Recently, proliferative activity has been described in the hypothalamus although the characterization of hypothalamic neural stem/progenitor cells (NSPCs) is still uncertain. We therefore investigated whether hypothalamic GFAP-positive cells, as in the SVZ and SGZ, also have neurogenic potential. We used a transgenic mouse line expressing green fluorescent protein (GFP) under the control of the GFAP promoter. GFAP-GFP expressing cells are localized in the ependymal layer as well as in the parenchyma of the mediobasal hypothalamus (MBH) and express Sox2, a marker for NSCs. Interestingly, no sexual dimorphism was observed in the numbers of GFP + and GFP-Sox2 + cells. After cells sorting, these cells were able to generate neurospheres in vitro and give rise to neurons, astrocytes and oligodendrocytes. Taken together, these results show that hypothalamic GFAP-expressing cells form a population of NSPCs.
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Affiliation(s)
- Lucile Butruille
- CNRS, IFCE, INRAE, Université de Tours, PRC, F-37380 Nouzilly, France
| | - Martine Batailler
- CNRS, IFCE, INRAE, Université de Tours, PRC, F-37380 Nouzilly, France
| | - Pascal Vaudin
- CNRS, IFCE, INRAE, Université de Tours, PRC, F-37380 Nouzilly, France
| | - Delphine Pillon
- CNRS, IFCE, INRAE, Université de Tours, PRC, F-37380 Nouzilly, France
| | - Martine Migaud
- CNRS, IFCE, INRAE, Université de Tours, PRC, F-37380 Nouzilly, France.
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3
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Sogorb MA, Candela H, Estévez J, Vilanova E. Investigation of the Effects of Metallic Nanoparticles on Fertility Outcomes and Endocrine Modification of the Hypothalamic-Pituitary-Gonadal Axis. Int J Mol Sci 2023; 24:11687. [PMID: 37511445 PMCID: PMC10380468 DOI: 10.3390/ijms241411687] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 07/11/2023] [Accepted: 07/13/2023] [Indexed: 07/30/2023] Open
Abstract
Nanotechnology is a very disruptive twenty-first-century revolution that will allow social and economic welfare to increase although it also involves a significant human exposure to nanoparticles. The aim of the present study was to contribute to the elucidation on whether metallic nanoparticles have a potential to induce fertility impairments. Regulatory studies that observed official OECD guidelines 415, 416 and 422 have failed to detect any fertility alterations caused by nanoparticle exposure. However, the scientific literature provides evidence that some nanoparticles may cause gonad impairments although the actual impact on fertility remains uncertain. This aim of the present study is to revisit the previously published RNAseq studies by analyzing the effects of several nanoparticles on the transcriptome of T98G human glioblastoma cells given that glial cells are known to play a pivotal role in the regulation of gonadotropin releasing hormone neurons. We found evidence that nanoparticles impair the gonadotropin releasing hormone receptor pathway and several related biological process like, among others, the cellular response to follicular stimulating hormone, cellular response to gonadotropin stimulus, cellular response to hormone stimulus, response to steroid hormone, ovulation cycle and response to estradiol. We propose that nanoparticles interfere with the ability of glial cells to regulate gonadotropin-releasing hormone neurons and, subsequently, the hypothalamic-pituitary-gonadal axis, potentially leading to fertility impairments. To our knowledge, this is the first proposal of a mode of action based on endocrine disruption for explaining the possible effects of nanoparticles on fertility. Whether these finding can be extended to other types of nanoparticles requires further investigation.
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Affiliation(s)
- Miguel A Sogorb
- Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Avenida de la Universidad s/n, 03202 Elche, Spain
| | - Héctor Candela
- Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Avenida de la Universidad s/n, 03202 Elche, Spain
| | - Jorge Estévez
- Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Avenida de la Universidad s/n, 03202 Elche, Spain
| | - Eugenio Vilanova
- Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Avenida de la Universidad s/n, 03202 Elche, Spain
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4
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Chevillard PM, Batailler M, Dubois JP, Estienne A, Pillon D, Vaudin P, Piégu B, Blache MC, Dupont J, Just N, Migaud M. Seasonal remodeling of the progenitor pool and its distribution in the ewe mediobasal hypothalamus. Cell Tissue Res 2023:10.1007/s00441-023-03745-x. [PMID: 36795154 DOI: 10.1007/s00441-023-03745-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 01/23/2023] [Indexed: 02/17/2023]
Abstract
Recent studies have reported the presence of adult neurogenesis in the arcuate nucleus periventricular space (pvARH) and in the median eminence (ME), two structures involved in reproductive function. In sheep, a seasonal mammal, decreasing daylight in autumn induces a higher neurogenic activity in these two structures. However, the different types of neural stem and progenitor cells (NSCs/NPCs) that populate the arcuate nucleus and median eminence, as well as their location, have not been evaluated. Here, using semi-automatic image analyzing processes, we identified and quantified the different populations of NSCs/NPCs, showing that, during short days, higher densities of [SOX2 +] cells are found in pvARH and ME. In the pvARH, higher densities of astrocytic and oligodendrocitic progenitors mainly contribute to these variations. The different populations of NSCs/NPCs were mapped according to their position relative to the third ventricle and their proximity to the vasculature. We showed that [SOX2 +] cells extended deeper into the hypothalamic parenchyma during short days. Similarly, [SOX2 +] cells were found further from the vasculature in the pvARH and the ME, at this time of year, indicating the existence of migratory signals. The expression levels of neuregulin transcripts (NRGs), whose proteins are known to stimulate proliferation and adult neurogenesis and to regulate progenitor migration, as well as the expression levels of ERBB mRNAs, cognate receptors for NRGs, were assessed. We showed that mRNA expression changed seasonally in pvARH and ME, suggesting that the ErbB-NRG system is potentially involved in the photoperiodic regulation of neurogenesis in seasonal adult mammals.
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Affiliation(s)
| | - Martine Batailler
- CNRS, IFCE, INRAE, Université de Tours, PRC, F-37380, Nouzilly, France
| | | | - Anthony Estienne
- CNRS, IFCE, INRAE, Université de Tours, PRC, F-37380, Nouzilly, France
| | - Delphine Pillon
- CNRS, IFCE, INRAE, Université de Tours, PRC, F-37380, Nouzilly, France
| | - Pascal Vaudin
- CNRS, IFCE, INRAE, Université de Tours, PRC, F-37380, Nouzilly, France
| | - Benoît Piégu
- CNRS, IFCE, INRAE, Université de Tours, PRC, F-37380, Nouzilly, France
| | | | - Joelle Dupont
- CNRS, IFCE, INRAE, Université de Tours, PRC, F-37380, Nouzilly, France
| | - Nathalie Just
- CNRS, IFCE, INRAE, Université de Tours, PRC, F-37380, Nouzilly, France
| | - Martine Migaud
- CNRS, IFCE, INRAE, Université de Tours, PRC, F-37380, Nouzilly, France.
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Ni W, Ramalingam M, Li Y, Park JH, Dashnyam K, Lee JH, Bloise N, Fassina L, Visai L, De Angelis MGC, Pedraz JL, Kim HW, Hu J. Immunomodulatory and Anti-inflammatory effect of Neural Stem/Progenitor Cells in the Central Nervous System. Stem Cell Rev Rep 2023; 19:866-885. [PMID: 36650367 DOI: 10.1007/s12015-022-10501-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2022] [Indexed: 01/19/2023]
Abstract
Neuroinflammation is a critical event that responds to disturbed homeostasis and governs various neurological diseases in the central nervous system (CNS). The excessive inflammatory microenvironment in the CNS can adversely affect endogenous neural stem cells, thereby impeding neural self-repair. Therapies with neural stem/progenitor cells (NSPCs) have shown significant inhibitory effects on inflammation, which is mainly achieved through intercellular contact and paracrine signalings. The intercellular contact between NSPCs and immune cells, the activated CNS- resident microglia, and astrocyte plays a critical role in the therapeutic NSPCs homing and immunomodulatory effects. Moreover, the paracrine effect mainly regulates infiltrating innate and adaptive immune cells, activated microglia, and astrocyte through the secretion of bioactive molecules and extracellular vesicles. However, the molecular mechanism involved in the immunomodulatory effect of NSPCs is not well discussed. This article provides a systematic analysis of the immunomodulatory mechanism of NSPCs, discusses efficient ways to enhance its immunomodulatory ability, and gives suggestions on clinical therapy.
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Affiliation(s)
- Wei Ni
- Department of Clinical Laboratory, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, 213000, Jiangsu, China.,Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China
| | - Murugan Ramalingam
- Institute of Tissue Regeneration Engineering, Dankook University, Cheonan, 31116, Republic of Korea. .,Department of Nanobiomedical Science, BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea. .,Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan, 31116, Republic of Korea. .,School of Basic Medical Sciences, Chengdu University, Chengdu, 610106, People's Republic of China.
| | - Yumeng Li
- Institute of Tissue Regeneration Engineering, Dankook University, Cheonan, 31116, Republic of Korea.,Department of Nanobiomedical Science, BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea.,Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan, 31116, Republic of Korea
| | - Jeong-Hui Park
- Institute of Tissue Regeneration Engineering, Dankook University, Cheonan, 31116, Republic of Korea.,Department of Nanobiomedical Science, BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea.,Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan, 31116, Republic of Korea
| | - Khandmaa Dashnyam
- Institute of Tissue Regeneration Engineering, Dankook University, Cheonan, 31116, Republic of Korea
| | - Jung-Hwan Lee
- Institute of Tissue Regeneration Engineering, Dankook University, Cheonan, 31116, Republic of Korea.,Department of Nanobiomedical Science, BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea.,Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan, 31116, Republic of Korea
| | - Nora Bloise
- Department of Molecular Medicine, Centre for Health Technologies (CHT), INSTM UdR of Pavia, University of Pavia, 27100, Pavia, Italy.,Medicina Clinica-Specialistica, UOR5 Laboratorio di Nanotecnologie, ICS Maugeri, IRCCS, 27100, Pavia, Italy
| | - Lorenzo Fassina
- Department of Electrical, Computer and Biomedical Engineering, University of Pavia, 27100, Pavia, Italy
| | - Livia Visai
- Department of Molecular Medicine, Centre for Health Technologies (CHT), INSTM UdR of Pavia, University of Pavia, 27100, Pavia, Italy.,Medicina Clinica-Specialistica, UOR5 Laboratorio di Nanotecnologie, ICS Maugeri, IRCCS, 27100, Pavia, Italy
| | | | - Jose Luis Pedraz
- NanoBioCel Research Group, Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), 01006, Vitoria-Gasteiz, Spain.,Networking Research Centre of Bioengineering, Biomaterials and Nanomedicine, Institute of Health Carlos III, 28029, Madrid, Spain
| | - Hae-Won Kim
- Institute of Tissue Regeneration Engineering, Dankook University, Cheonan, 31116, Republic of Korea. .,Department of Nanobiomedical Science, BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea. .,Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan, 31116, Republic of Korea.
| | - Jiabo Hu
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China.
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Sahota JS, Sharma B, Guleria K, Sambyal V. Candidate genes for infertility: an in-silico study based on cytogenetic analysis. BMC Med Genomics 2022; 15:170. [PMID: 35918717 PMCID: PMC9347124 DOI: 10.1186/s12920-022-01320-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 07/22/2022] [Indexed: 11/26/2022] Open
Abstract
Background The cause of infertility remains unclear in a significant proportion of reproductive-age couples who fail to conceive naturally. Chromosomal aberrations have been identified as one of the main genetic causes of male and female infertility. Structural chromosomal aberrations may disrupt the functioning of various genes, some of which may be important for fertility. The present study aims to identify candidate genes and putative functional interaction networks involved in male and female infertility using cytogenetic data from cultured peripheral blood lymphocytes of infertile patients. Methods Karyotypic analyses was done in 201 infertile patients (100 males and 101 females) and 201 age and gender matched healthy controls (100 males and 101 females) after 72 h peripheral lymphocyte culturing and GTG banding, followed by bioinformatic analysis using Cytoscape v3.8.2 and Metascape. Results Several chromosomal regions with a significantly higher frequency of structural aberrations were identified in the infertile males (5q2, 10q2, and 17q2) and females (6q2, 16q2, and Xq2). Segregation of the patients based on type of infertility (primary v/s secondary infertility) led to the identification of chromosomal regions with a significantly higher frequency of structural aberrations exclusively within the infertile males (5q2, 17q2) and females (16q2) with primary infertility. Cytoscape identified two networks specific to these regions: a male specific network with 99 genes and a female specific network with 109 genes. The top enriched GO terms within the male and female infertility networks were “skeletal system morphogenesis” and “mRNA transport” respectively. PSME3, PSMD3, and CDC27 were the top 3 hub genes identified within the male infertility network. Similarly, UPF3B, IRF8, and PSMB1 were the top 3 hub genes identified with the female infertility network. Among the hub genes identified in the male- and female-specific networks, PSMB1, PSMD3, and PSME3 are functional components of the proteasome complex. These hub genes have a limited number of reports related to their respective roles in maintenance of fertility in mice model and humans and require validation in further studies. Conclusion The candidate genes predicted in the present study can serve as targets for future research on infertility. Supplementary Information The online version contains supplementary material available at 10.1186/s12920-022-01320-x.
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Affiliation(s)
- Jatinder Singh Sahota
- Department of Human Genetics, Cytogenetics Laboratory, Guru Nanak Dev University (GNDU), Amritsar, Punjab, 143005, India
| | - Bhavna Sharma
- Department of Human Genetics, Cytogenetics Laboratory, Guru Nanak Dev University (GNDU), Amritsar, Punjab, 143005, India
| | - Kamlesh Guleria
- Department of Human Genetics, Cytogenetics Laboratory, Guru Nanak Dev University (GNDU), Amritsar, Punjab, 143005, India
| | - Vasudha Sambyal
- Department of Human Genetics, Cytogenetics Laboratory, Guru Nanak Dev University (GNDU), Amritsar, Punjab, 143005, India.
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