Mizoguchi Yoshito, Monji Akira
Department of Psychiatry, Faculty of Medicine, Saga University, Saga, Japan.
Adv Exp Med Biol. 2017;976:111-121. doi: 10.1007/978-94-024-1088-4_10.
Nonresolving low-grade inflammation is supposed to underly the basis of chronic disorders including cardiovascular diseases, cancer, diabetes, obesity, and psychiatric disorders such as depression and Alzheimer's diseases. There is increasing evidence suggesting that pathophysiology of psychiatric disorders is related to the inflammatory responses mediated by microglial cells. Elevation of intracellular Ca is important for the activation of microglial cell functions, including proliferation, release of NO, cytokines, and BDNF. It has been shown that alteration of intracellular Ca signaling underlies the pathophysiology of psychiatric disorders, including depression. BDNF induces a sustained intracellular Ca elevation through the upregulation of the surface expression of TRPC3 channels in rodent microglial cells. 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 psychiatric disorders. We also need to study the effect of proBDNF on microglial cells especially by focusing on the TRPC channels.
持续性低度炎症被认为是包括心血管疾病、癌症、糖尿病、肥胖症以及抑郁症和阿尔茨海默病等精神疾病在内的慢性疾病的基础。越来越多的证据表明,精神疾病的病理生理学与小胶质细胞介导的炎症反应有关。细胞内钙离子升高对于小胶质细胞功能的激活很重要,包括增殖、一氧化氮、细胞因子和脑源性神经营养因子(BDNF)的释放。研究表明,细胞内钙离子信号改变是包括抑郁症在内的精神疾病病理生理学的基础。BDNF通过上调啮齿动物小胶质细胞中TRPC3通道的表面表达诱导细胞内钙离子持续升高。小胶质细胞能够对BDNF作出反应,这可能对炎症反应的调节很重要,也可能参与精神疾病的病理生理学和/或治疗。我们还需要研究前体BDNF对小胶质细胞的影响,尤其是关注TRPC通道。