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Pretreatment with GPR88 Agonist Attenuates Postischemic Brain Injury in a Stroke Mouse Model

Journal of Life Science 2020년 30권 11호 p.939 ~ 946
이서연, 박정화, 김민재, 최병태, 신화경,
소속 상세정보
이서연 ( Lee Seo-Yeon ) - Wonkwang University School of Medicine Department of Pharmacology
박정화 ( Park Jung-Hwa ) - Pusan National University School of Korean Medicine Department of Korean Medical Science
김민재 ( Kim Min-Jae ) - Pusan National University School of Korean Medicine Department of Korean Medical Science
최병태 ( Choi Byung-Tae ) - Pusan National University School of Korean Medicine Department of Korean Medical Science
신화경 ( Shin Hwa-Kyoung ) - Pusan National University School of Korean Medicine Department of Korean Medical Science

Abstract


Stroke is one of the leading causes of neurological disability worldwide and stroke patients exhibit a range of motor, cognitive, and psychiatric impairments. GPR88 is an orphan G protein-coupled receptor (GPCR) that is highly expressed in striatal medium spiny neurons; its deletion results in poor motor coordination and motor learning. There are currently no studies on the involvement of GPR88 in stroke or in post-stroke brain function recovery. In this study, we found a decrease in GPR88 protein and mRNA expression levels in an ischemic mouse model using Western blot and real-time PCR, respectively. In addition, we observed that, among the three types of cells derived from the brain (brain microvascular endothelial cells, BV2 microglial cells, and HT22 hippocampal neuronal cells), the expression of GPR88 was highest in HT22 neuronal cells, and that GPR88 expression was downregulated in HT22 cells under oxygen-glucose deprivation (OGD) conditions. Moreover, pretreatment with RTI- 13951-33 (10 mg/kg), a brain-penetrant GPR88 agonist, ameliorated brain injury following ischemia, as evidenced by improvements in infarct volume, vestibular-motor function, and neurological score. Collectively, our results suggest that GPR88 could be a potential drug target for the treatment of central nervous system (CNS) diseases, including ischemic stroke.

키워드

Cerebral ischemia; GPCR; oxygen glucose deprivation; stroke

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