Possible role of BDNF-induced microglial intracellular Ca(2+) elevation in the pathophysiology of neuropsychiatric disorders

• Published in: Mini reviews in medicinal chemistry Vol. 11; no. 7; p. 575
• Main Authors: Mizoguchi, Y, Monji, A, Kato, T A, Horikawa, H, Seki, Y, Kasai, M, Kanba, S, Yamada, S
• Format: Journal Article
• Language: English
• Published: Netherlands 01.06.2011
• Subjects: Animals; Brain-Derived Neurotrophic Factor - pharmacology; Brain-Derived Neurotrophic Factor - therapeutic use; Calcium - chemistry; Calcium - metabolism; Cations, Divalent - chemistry; Cations, Divalent - metabolism; Humans; Inflammation - drug therapy; Inflammation - physiopathology; Microglia - cytology; Microglia - drug effects; Microglia - metabolism; Neurotic Disorders - drug therapy; Neurotic Disorders - physiopathology
• ISSN: 1875-5607
• DOI: 10.2174/138955711795906932

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 Ca(2+) concentration ([Ca(2+)]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 [Ca(2+)]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 [Ca(2+)]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 BDNF-induced increase in [Ca(2+)]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 Ca(2+) signaling in microglial cells.