Glycine-induced NMDA receptor internalization provides neuroprotection and preserves vasculature following ischemic stroke

iScience

Pamela Khacho¹  Wafae Bakkar²  Boyang Wang²  Julian Pitney²  Junzheng Wu²  Prakash Chudalayandi²  Alexandra Sokolovski²  Nina Ahlskog²  Adrian Y.C. Wong²  Julia Cappelli²  Richard Bergeron²  Sophie Raymond³ 

[1] Corresponding author;Cellular and Molecular Medicine Department, University of Ottawa, 451 Smyth Road, Roger Guindon Building, Room 3501N, Ottawa, ON K1H 8M5, Canada;Ottawa Hospital Research Institute, 451 Smyth Road, Roger Guindon Building, Room 3501N, Ottawa, ON K1H 8M5, Canada;

关键词: Neuroscience;    Molecular neuroscience;    Cellular neuroscience;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Ischemic stroke is the second leading cause of death worldwide. Following an ischemic event, neuronal death is triggered by uncontrolled glutamate release leading to overactivation of glutamate sensitive N-methyl-d-aspartate receptor (NMDAR). For gating, NMDARs require not only the binding of glutamate, but also of glycine or a glycine-like compound as a co-agonist. Low glycine doses enhance NMDAR function, whereas high doses trigger glycine-induced NMDAR internalization (GINI) in vitro. Here, we report that following an ischemic event, in vivo, GINI also occurs and provides neuroprotection in the presence of a GlyT1 antagonist (GlyT1-A). Mice pretreated with a GlyT1-A, which increases synaptic glycine levels, exhibited smaller stroke volume, reduced cell death, and minimized behavioral deficits following stroke induction by either photothrombosis or endothelin-1. Moreover, we show evidence that in ischemic conditions, GlyT1-As preserve the vasculature in the peri-infarct area. Therefore, GlyT1 could be a new target for the treatment of ischemic stroke.

【 授权许可】

Unknown