title: The new P2Y-like receptor G protein-coupled receptor 17 mediates acute neuronal injury and late microgliosis after focal cerebral ischemia in rats.
abstract: G protein-coupled receptor 17 (GPR17), the new P2Y-like receptor, is phylogenetically related to the P2Y and cysteinyl leukotriene receptors, and responds to both uracil nucleotides and cysteinyl leukotrienes. GPR17 has been proposed to be a damage sensor in ischemic stroke; however, its role in brain inflammation needs further detailed investigation. Here, we extended previous studies on the spatiotemporal profiles of GPR17 expression and localization, and their implications for brain injury after focal cerebral ischemia. We found that in the ischemic core, GPR17 mRNA and protein levels were upregulated at both 12-24 h and 7-14 days, but in the boundary zone the levels increased 7-14 days after reperfusion. The spatiotemporal pattern of GPR17 expression well matched the acute and late (subacute/chronic) responses in the ischemic brain. According to previous findings, in the acute phase, after ischemia (24 h), upregulated GPR17 was localized in injured neurons in the ischemic core and in a few microglia in the ischemic core and boundary zone. In the late phase (14 days), it was localized in microglia, especially in activated (ED1-positive) microglia in the ischemic core, but weakly in most microglia in the boundary zone. No GPR17 was detectable in astrocytes. GPR17 knockdown by a small interfering RNA attenuated the neurological dysfunction, infarction, and neuron loss at 24 h, and brain atrophy, neuron loss, and microglial activation at 14 days after reperfusion. Thus, GPR17 might mediate acute neuronal injury and late microgliosis after focal cerebral ischemia.
authors.affiliation: Department of Pharmacology, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: B
authors.initials: B
authors.lastname: Zhao
authors.forename: C Z
authors.initials: CZ
authors.lastname: Zhao
authors.forename: X Y
authors.initials: XY
authors.lastname: Zhang
authors.forename: X Q
authors.initials: XQ
authors.lastname: Huang
authors.forename: W Z
authors.initials: WZ
authors.lastname: Shi
authors.forename: S H
authors.initials: SH
authors.lastname: Fang
authors.forename: Y B
authors.initials: YB
authors.lastname: Lu
authors.forename: W P
authors.initials: WP
authors.lastname: Zhang
authors.forename: Q
authors.initials: Q
authors.lastname: Xia
authors.forename: E Q
authors.initials: EQ
authors.lastname: Wei
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D007276:Injections, Intraventricular; D002546:Ischemic Attack, Transient / Q000473:pathology; D008297:Male; D017628:Microglia / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D058470:Receptors, Purinergic P2Y / Q000502:physiology*
chemical_list: D001786:Blood Glucose; C514731:GPR17 protein, rat; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D058470:Receptors, Purinergic P2Y