2009 Fiscal Year Final Research Report
Elucidation of the mechanism underlying the modulation of microglial function by antidepressants and/or BDNF
| Project/Area Number |
20790847
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | Kyushu University |
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Principal Investigator |
MIZOGUCHI Yoshito Kyushu University, 医学研究院, 特別教員 (60467892)
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| Project Period (FY) |
2008 – 2009
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| Keywords | 脳由来神経栄養因子(BDNF) / ミクログリア / 気分障害 / うつ病 / カルシウム / 神経炎症 / 精神薬理 |
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| Research 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 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. In this study, we observed that BDNF induced a sustained increase in [Ca^<2+>]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-T1receptors 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 [Ca^<2+>]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 [Ca^<2+>]i, along with a rise in basal levels of [Ca^<2+>]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.
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[Journal Article] Brain-derived neurotrophic factor (BDNF) induces sustained elevation of intracellular Ca2+ in rodent microglia.2009
Author(s)
Mizoguchi Y, Monji A, Kato T, Seki Y, Gotoh L, Horikawa H, Suzuki SO, Iwaki T, Yonaha M, Hashioka S, Kanba S
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Journal Title
J. Immunol. 183
Pages: 7778-7786
Peer Reviewed
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[Journal Article] Effect of yokukansan on the behavioral and psychological symptoms of dementia in elderly patients with Alzheimer's disease. Prog.2009
Author(s)
Monji A, Takita M, Samejima T, Takaishi T, Hashimoto K, Matsunaga H, Oda M, Sumida Y, Mizoguchi Y, Kato T, Horikawa H, Kanba S
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Journal Title
Neuropsychopharamacol. Biol. Psychiatry 33
Pages: 308-311
Peer Reviewed
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