Numakawa T, Yokomaku D, Richards M, Hori H, Adachi N, Kunugi H. Functional interactions between steroid hormones and neurotrophin BDNF. World J Biol Chem 2010; 1(5): 133-143 [PMID: 21540998 DOI: 10.4331/wjbc.v1.i5.133]
Corresponding Author of This Article
Tadahiro Numakawa, PhD, Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan. numakawa@ncnp.go.jp
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Tadahiro Numakawa, Misty Richards, Hiroaki Hori, Naoki Adachi, Hiroshi Kunugi, Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, 187-8502, Japan
Tadahiro Numakawa, Naoki Adachi, Hiroshi Kunugi, Core Research for Evolutional Science and Technology Program, Japan Science and Technology Agency, Saitama, 332-0012, Japan
Daisaku Yokomaku, Brain Research Centre and Department of Psychiatry, University of British Columbia, Vancouver, BC, V6T 2B5, Canada
Misty Richards, The Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY 12208, United States
Author contributions: Numakawa T performed the research; Numakawa T, Yokomaku D, Hori H and Adachi N wrote the paper; Numakawa T, Richards M and Kunugi H edited the paper.
Supported by Research Grants for Nervous and Mental Disorders from the Ministry of Health, Labor and Welfare; Health and Labor Sciences Research Grants (Research on Psychiatric and Neurological Diseases and Mental Health); Health and Labor Sciences Research Grants, a grant from the Japan Foundation for Neuroscience and Mental Health; the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (Kunugi H), and a Grant-in-Aid for Young Scientists (A) (21680034) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Numakawa T)
Correspondence to: Tadahiro Numakawa, PhD, Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan. numakawa@ncnp.go.jp
Telephone: +81-42-3412711 Fax: +81-42-3461744
Received: April 23, 2010 Revised: May 20, 2010 Accepted: May 24, 2010 Published online: May 26, 2010
Abstract
Brain-derived neurotrophic factor (BDNF), a critical neurotrophin, regulates many neuronal aspects including cell differentiation, cell survival, neurotransmission, and synaptic plasticity in the central nervous system (CNS). Though BDNF has two types of receptors, high affinity tropomyosin-related kinase (Trk)B and low affinity p75 receptors, BDNF positively exerts its biological effects on neurons via activation of TrkB and of resultant intracellular signaling cascades including mitogen-activated protein kinase/extracellular signal-regulated protein kinase, phospholipase Cγ, and phosphoinositide 3-kinase pathways. Notably, it is possible that alteration in the expression and/or function of BDNF in the CNS is involved in the pathophysiology of various brain diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, and mental disorders. On the other hand, glucocorticoids, stress-induced steroid hormones, also putatively contribute to the pathophysiology of depression. Interestingly, in addition to the reduction in BDNF levels due to increased glucocorticoid exposure, current reports demonstrate possible interactions between glucocorticoids and BDNF-mediated neuronal functions. Other steroid hormones, such as estrogen, are involved in not only sexual differentiation in the brain, but also numerous neuronal events including cell survival and synaptic plasticity. Furthermore, it is well known that estrogen plays a role in the pathophysiology of Parkinson’s disease, Alzheimer’s disease, and mental illness, while serving to regulate BDNF expression and/or function. Here, we present a broad overview of the current knowledge concerning the association between BDNF expression/function and steroid hormones (glucocorticoids and estrogen).
