Possible Role of BDNF-Induced Microglial Intracellular Ca2+ Elevation in the Pathophysiology of Neuropsychiatric Disorders

Author(s): Y. Mizoguchi , A. Monji , T. A. Kato , H. Horikawa , Y. Seki , M. Kasai , S. Kanba , S. Yamada .

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 11 , Issue 7 , 2011

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Microglia are intrinsic immune cells that release factors, including proinflammatory cytokines, nitric oxide (NO) and neurotrophins, following activation after disturbance in the brain. Elevation of intracellular Ca2+ concentration ([Ca2+]i) is important for microglial functions, such as the release of cytokines and NO from activated microglia. There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to the inflammatory responses mediated by microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia as well as in pathophysiology and/or treatment of neuropsychiatric disorders. We have recently reported that BDNF induces a sustained increase in [Ca2+]i through binding with the truncated TrkB receptor, resulting in activation of the PLC pathway and store-operated calcium entry (SOCE) in rodent microglial cells. Sustained activation of SOCE, possibly mediated by TRP channels, occurred after brief BDNF application and contributed to the maintenance of sustained [Ca2+]i elevation. Pretreatment with BDNF significantly suppressed the release of NO from activated microglia. Additionally, selective serotonin reuptake inhibitors (SSRIs), including paroxetine or sertraline, potentiated the BDNFinduced increase in [Ca2+]i in rodent microglial cells This article provides a review of recent findings on the role of BDNF in the pathophysiology of neuropsychiatric disorders, especially by focusing on its effect on intracellular Ca2+ signaling in microglial cells.

Keywords: BDNF, microglia, calcium, TRP channels, inflammation, depression, schizophrenia, cytokines, neurotrophins, brain, neuropsychiatric, SSRIs, paroxetine, sertraline

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Article Details

Year: 2011
Page: [575 - 581]
Pages: 7
DOI: 10.2174/138955711795906932
Price: $58

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