PMID- 24811179 OWN - NLM STAT- MEDLINE DCOM- 20141016 LR - 20211021 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 289 IP - 26 DP - 2014 Jun 27 TI - Brain-derived neurotrophic factor (BDNF) induces sustained intracellular Ca2+ elevation through the up-regulation of surface transient receptor potential 3 (TRPC3) channels in rodent microglia. PG - 18549-55 LID - 10.1074/jbc.M114.555334 [doi] AB - Microglia are 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. In this study, we sought to examine the underlying mechanism of BDNF-induced sustained increase in [Ca(2+)]i in rodent microglial cells. We observed that canonical transient receptor potential 3 (TRPC3) channels contribute to the maintenance of BDNF-induced sustained intracellular Ca(2+) elevation. Immunocytochemical technique and flow cytometry also revealed that BDNF rapidly up-regulated the surface expression of TRPC3 channels in rodent microglial cells. In addition, pretreatment with BDNF suppressed the production of NO induced by tumor necrosis factor alpha (TNFalpha), which was prevented by co-adiministration of a selective TRPC3 inhibitor. These suggest that BDNF induces sustained intracellular Ca(2+) elevation through the up-regulation of surface TRPC3 channels and TRPC3 channels could be important for the BDNF-induced suppression of the NO production in activated microglia. We show that TRPC3 channels could also play important roles in microglial functions, which might be important for the regulation of inflammatory responses and may also be involved in the pathophysiology and/or the treatment of neuropsychiatric disorders. CI - (c) 2014 by The American Society for Biochemistry and Molecular Biology, Inc. FAU - Mizoguchi, Yoshito AU - Mizoguchi Y AD - From the Department of Psychiatry, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan, ymizo@pk2.so-net.ne.jp. FAU - Kato, Takahiro A AU - Kato TA AD - the Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan, the Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan, and. FAU - Seki, Yoshihiro AU - Seki Y AD - the Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. FAU - Ohgidani, Masahiro AU - Ohgidani M AD - the Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan, the Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan, and. FAU - Sagata, Noriaki AU - Sagata N AD - the Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan, the Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan, and. FAU - Horikawa, Hideki AU - Horikawa H AD - the Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. FAU - Yamauchi, Yusuke AU - Yamauchi Y AD - the Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. FAU - Sato-Kasai, Mina AU - Sato-Kasai M AD - the Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. FAU - Hayakawa, Kohei AU - Hayakawa K AD - the Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. FAU - Inoue, Ryuji AU - Inoue R AD - the Department of Physiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jyonan-ku, Fukuoka 812-0180, Japan. FAU - Kanba, Shigenobu AU - Kanba S AD - the Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. FAU - Monji, Akira AU - Monji A AD - From the Department of Psychiatry, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140508 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (TRPC Cation Channels) RN - 0 (TRPC3 cation channel) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Calcium/*metabolism MH - Cells, Cultured MH - Microglia/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - TRPC Cation Channels/genetics/*metabolism MH - *Up-Regulation PMC - PMC4140290 OTO - NOTNLM OT - Brain-derived Neurotrophic Factor (BDNF) OT - Calcium OT - Microglia OT - Nitric Oxide OT - Transient Receptor Potential Channels (TRP Channels) EDAT- 2014/05/09 06:00 MHDA- 2014/10/17 06:00 PMCR- 2015/06/27 CRDT- 2014/05/10 06:00 PHST- 2014/05/10 06:00 [entrez] PHST- 2014/05/09 06:00 [pubmed] PHST- 2014/10/17 06:00 [medline] PHST- 2015/06/27 00:00 [pmc-release] AID - S0021-9258(20)40560-5 [pii] AID - M114.555334 [pii] AID - 10.1074/jbc.M114.555334 [doi] PST - ppublish SO - J Biol Chem. 2014 Jun 27;289(26):18549-55. doi: 10.1074/jbc.M114.555334. Epub 2014 May 8.