Open AccessInhibition of G Protein‐Coupled Receptor 81 ( GPR 81) Protects Against Ischemic Brain Injury
Author(s) -
Shen Zhe,
Jiang Lei,
Yuan Yang,
Deng Tian,
Zheng YanRong,
Zhao YanYan,
Li WenLu,
Wu JiaYing,
Gao JianQing,
Hu WeiWei,
Zhang XiangNan,
Chen Zhong
Publication year - 2015
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12362
Subject(s) - pharmacology , neuroprotection , medicine , ischemia , receptor
Summary Aim Lactates accumulate in ischemic brains. G protein‐coupled receptor 81 ( GPR 81) is an endogenous receptor for lactate. We aimed to explore whether lactate is involved in ischemic injury via activating GPR 81. Methods N2A cells were transfected with GFP ‐ GPR 81 plasmids 24 h previously, and then treated with GPR 81 antagonist 3‐hydroxy‐butyrate (3‐ OBA ) alone or cotreated with agonists lactate or 3, 5‐dihydroxybenzoic acid (3, 5‐ DHBA ) during 3 h of oxygen–glucose deprivation ( OGD ). Adult male C57 BL /6J mice and primary cultured cortical neurons were treated with 3‐ OBA at the onset of middle cerebral artery occlusion ( MCAO ) or OGD , respectively. Results The GPR 81 overexpression increased the cell vulnerability to ischemic injury. And GPR 81 antagonism by 3‐ OBA significantly prevented cell death and brain injury after OGD and MCAO , respectively. Furthermore, inhibition of GPR 81 reversed ischemia‐induced apoptosis and extracellular signal‐regulated kinase ( ERK ) signaling may be involved in the neuroprotection. Conclusions G protein‐coupled receptor 81 ( GPR 81) inhibition attenuated ischemic neuronal death. Lactate may aggravate ischemic brain injury by activating GPR 81. GPR 81 antagonism might be a novel therapeutic strategy for the treatment of cerebral ischemia.