Brain-derived neurotrophic factor induces sustained elevation of intracellular Ca2+ in rodent microglia

Yoshito Mizoguchi, Akira Monji, Takahiro Kato, Yoshihiro Seki, Leo Gotoh, Hideki Horikawa, Satoshi O. Suzuki, Toru Iwaki, Miyuki Yonaha, Sadayuki Hashioka, Shigenobu Kanba

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Abstract

Microglia are intrinsic immune cells that release factors, including proinflammatory cytokines, 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. In this study, we observed that BDNF induced a sustained increase in [Ca2+]i through binding with the truncated tropomyosin-related kinase B receptor, resulting in activation of the PLC pathway and store-operated calcium entry in rodent microglial cells. RT-PCR and immunocytochemical techniques revealed that truncated tropomyosinrelated kinase B-T1 receptors were highly expressed in rodent microglial cells. Sustained activation of store-operated calcium entry 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, pretreatment of BDNF suppressed the IFN-γ-induced increase in [Ca2+]i, along with a rise in basal levels of [Ca2+]i in rodent microglial cells. We show direct evidence that rodent microglial cells are able to respond to BDNF, which may be important for the regulation of inflammatory responses, and may also be involved in the pathophysiology and/or the treatment of neuropsychiatric disorders.

Original languageEnglish
Pages (from-to)7778-7786
Number of pages9
JournalJournal of Immunology
Volume183
Issue number12
DOIs
Publication statusPublished - Dec 15 2009

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Mizoguchi, Y., Monji, A., Kato, T., Seki, Y., Gotoh, L., Horikawa, H., Suzuki, S. O., Iwaki, T., Yonaha, M., Hashioka, S., & Kanba, S. (2009). Brain-derived neurotrophic factor induces sustained elevation of intracellular Ca2+ in rodent microglia. Journal of Immunology, 183(12), 7778-7786. https://doi.org/10.4049/jimmunol.0901326