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Increased Infarct Volume and Altered Repair Following Ischemic Stroke in Mice Lacking the Brain‐Expressed Orphan G Protein‐Coupled Receptor GPR37
Author(s) -
Owino Sharon,
Giddens Michelle,
Jiang Micheal,
Gu Xiaohuan,
Wei Ling,
Yu Shan Ping,
Hall Randy
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb620
Subject(s) - downregulation and upregulation , parkin , medicine , ischemia , receptor , neuroscience , endocrinology , pharmacology , microbiology and biotechnology , chemistry , biology , disease , biochemistry , parkinson's disease , gene
GPR37 is an orphan G protein‐coupled receptor expressed almost exclusively in the nervous system. Since its initial discovery as a substrate for parkin, the majority of studies on GPR37 have focused on its role in Parkinson's disease. Remarkably little is known about GPR37 in other models of neuronal damage/disease. We've previously shown that GPR37 mediates protection from oxidative stress in cultured astrocytes, which led us to assess the role of GPR37 in vivo in a rodent model of ischemic stroke. Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in WT and GPR37 − deficient mice. Infarct size, histochemical observations, and protein expression levels were analyzed within the brain 72 hrs. following MCAO. Following occlusion, infarct volume was markedly increased in GPR37 deficient mice compared to WT mice. Interestingly, this coincided with a decrease in the abundance of reactive astrocytes (as assessed by the upregulation of GFAP) within the stroke penumbra region of the GPR37‐deficient mice relative to WT mice. Examination of receptor expression levels within the brain also revealed that GPR37 was massively upregulated within multiple brain regions following ischemia, suggesting a critical role for this receptor in the ischemic response. Furthermore, GPR37‐deficient mice exhibited substantially decreased levels of HIF‐1α and nest in positive cells, indicative of diminished reparative processes following hypoxia. Taken together, these studies demonstrate that GPR37 plays an important role in regulating the generation of reactive astrocytes in vivo and modulating repair following ischemic insults. Support or Funding Information This study is supported by grant R01‐NS088413 from the National Institutes of Health. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .