PMID- 28642149 OWN - NLM STAT- MEDLINE DCOM- 20180417 LR - 20180417 IS - 1872-7972 (Electronic) IS - 0304-3940 (Linking) VI - 654 DP - 2017 Jul 27 TI - Activated mGluR5 protects BV2 cells against OGD/R induced cytotoxicity by modulating BDNF-TrkB pathway. PG - 70-79 LID - S0304-3940(17)30509-8 [pii] LID - 10.1016/j.neulet.2017.06.029 [doi] AB - Activated Metabotropic glutamate receptors 5(mGluR5) exhibits protective effects against ischemic brain damage, but the underlying mechanisms are not clearly known. Brain-derived neurotrophic factor (BDNF), as a valuable member of neurotrophic factor family, exerts its protection by combining with its high-affinity receptor tyrosine protein kinase B (TrkB). To investigate the role of activated mGluR5 against oxygen-glucose deprivation (OGD)/reoxygenation (R)-mediated cytotoxicity, the cell viability, apoptosis, the release of inflammatory cytokines and accumulation of reactive oxygen species (ROS) were evaluated in BV2 cells (Microglia cell line) with or without OGD/R exposure. Our data show that CHPG (the selective mGluR5 agonist) pretreatment, as an mGluR5 agonist, protected BV2 cells against OGD/R-induced cytotoxicity, apoptosis, the release of inflammatory cytokines, and the accumulation of ROS. However, these effects were significantly reversed by the mGluR5 antagonist MPEP pretreatment. Our data also show that the expressions of BDNF and TrkB were significantly decreased in BV2 cells with OGD/R exposure. CHPG pretreatment significantly enhanced the expressions of BDNF and TrkB in BV2 cells with OGD/R exposure. However, the increased expressions were significantly abrogated by MPEP pretreatment. In addition, inhibition of BDNF/TrKB pathway by K252a also attenuated the protective effects of activated mGluR5 against OGD/R-induced cytotoxicity, apoptosis and the release of inflammatory cytokines. Morever, pretreatment with exogenous BDNF protected BV2 cells against OGD/R induced apoptosis and release of inflammatory cytokines. These data suggested that BDNF/TrKB pathway may be involved in regulating activated mGluR5' protective effects against OGD/R induced cytotoxicity in BV2 cells. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Ye, Xinchun AU - Ye X AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, China. FAU - Yu, Lu AU - Yu L AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, China. FAU - Zuo, Dandan AU - Zuo D AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, China. FAU - Zhang, Liang AU - Zhang L AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, China. FAU - Zu, Jie AU - Zu J AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, China. FAU - Hu, Jinxia AU - Hu J AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, China. FAU - Tang, Jiao AU - Tang J AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, China. FAU - Bao, Lei AU - Bao L AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, China. FAU - Cui, Chengcheng AU - Cui C AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, China. FAU - Zhang, Ruixue AU - Zhang R AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, China. FAU - Jin, Guoliang AU - Jin G AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, China. FAU - Zan, Kun AU - Zan K AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, China. FAU - Zhang, Zuohui AU - Zhang Z AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, China. FAU - Yang, Xinxin AU - Yang X AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, China. FAU - Shi, Hongjuan AU - Shi H AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, China. FAU - Zhang, Zunsheng AU - Zhang Z AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, China. FAU - Xiao, Qihua AU - Xiao Q AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, China. FAU - Liu, Yonghai AU - Liu Y AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, China. FAU - Xiang, Jie AU - Xiang J AD - Department of Rehabilitation, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, China. FAU - Zhang, Xueling AU - Zhang X AD - Department of Neurology, Suqian People's Hospital, Suqian, Jiangsu Province, 223800, China. FAU - Cui, Guiyun AU - Cui G AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, China. Electronic address: guiyuncui@foxmail.com. LA - eng PT - Journal Article DEP - 20170619 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Grm5 protein, mouse) RN - 0 (Receptor, Metabotropic Glutamate 5) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cell Line MH - Hypoxia-Ischemia, Brain/*metabolism MH - Mice MH - Receptor, Metabotropic Glutamate 5/*metabolism MH - Receptor, trkB/*metabolism MH - Signal Transduction/physiology OTO - NOTNLM OT - BDNF/TrkB pathway OT - BV2 cells OT - OGD/R OT - mGluR5 EDAT- 2017/06/24 06:00 MHDA- 2018/04/18 06:00 CRDT- 2017/06/24 06:00 PHST- 2017/04/30 00:00 [received] PHST- 2017/06/12 00:00 [revised] PHST- 2017/06/16 00:00 [accepted] PHST- 2017/06/24 06:00 [pubmed] PHST- 2018/04/18 06:00 [medline] PHST- 2017/06/24 06:00 [entrez] AID - S0304-3940(17)30509-8 [pii] AID - 10.1016/j.neulet.2017.06.029 [doi] PST - ppublish SO - Neurosci Lett. 2017 Jul 27;654:70-79. doi: 10.1016/j.neulet.2017.06.029. Epub 2017 Jun 19.