Hydroxycarboxylic Acid Receptor 1 and Neuroprotection in a Mouse Model of Cerebral Ischemia-Reperfusion.
KAUST DepartmentBioscience Program
Biological and Environmental Sciences and Engineering (BESE) Division
Office of the President
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AbstractLactate is an intriguing molecule with emerging physiological roles in the brain. It has beneficial effects in animal models of acute brain injuries and traumatic brain injury or subarachnoid hemorrhage patients. However, the mechanism by which lactate provides protection is unclear. While there is evidence of a metabolic effect of lactate providing energy to deprived neurons, it can also activate the hydroxycarboxylic acid receptor 1 (HCAR1), a Gi-coupled protein receptor that modulates neuronal firing rates. After cerebral hypoxia-ischemia, endogenously produced brain lactate is largely increased, and the exogenous administration of more lactate can decrease lesion size and ameliorate the neurological outcome. To test whether HCAR1 plays a role in lactate-induced neuroprotection, we injected the agonists 3-chloro-5-hydroxybenzoic acid and 3,5-dihydroxybenzoic acid into mice subjected to 30-min middle cerebral artery occlusion. The in vivo administration of HCAR1 agonists at reperfusion did not appear to exert any relevant protective effect as seen with lactate administration. Our results suggest that the protective effects of lactate after hypoxia-ischemia come rather from the metabolic effects of lactate than its signaling through HCAR1.
CitationBuscemi, L., Blochet, C., Magistretti, P. J., & Hirt, L. (2021). Hydroxycarboxylic Acid Receptor 1 and Neuroprotection in a Mouse Model of Cerebral Ischemia-Reperfusion. Frontiers in Physiology, 12. doi:10.3389/fphys.2021.689239
SponsorsThe authors acknowledge Melanie Price for the careful proofreading of the manuscript and her helpful comments, Mor Mishkovsky for her helpful discussion, and the Neuro-BAU behavioral platform of the Department of Fundamental Neurosciences (Lausanne University) and the Cellular Imaging Facility (CIF, Lausanne University) for their support.
The authors declare that this work was supported by funding from the Biaggi and Juchum Foundations, the Novartis Foundation for Medical Biological Research grant 18C170, the Swissheart Foundation FF 19053, and the Swiss National Science Foundation grant 31003A_163465/1. The authors further declare that the funders were not involved in the study design, collection, analysis and interpretation of data, or the writing of the article and the decision to submit it for publication.
PublisherFrontiers Media SA
JournalFrontiers in physiology
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