Lack of HCAR1, the lactate GPCR, signaling promotes autistic-like behavior

Abstract The GPCR HCAR1 is known to be the sole receptor for lactate, which modulates its metabolic effects. Despite its significant role in many processes, mice deficient in HCAR1 exhibit no visible phenotype and are healthy and fertile. We performed transcriptomic analysis on HCAR1 deficient cells...

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Bibliographic Details
Main Authors: Mohammad Ali Mohammad Nezhady, Gael Cagnone, Jean-Sébastien Joyal, Sylvain Chemtob
Format: Article
Language:English
Published: BMC 2023-11-01
Series:Cell Communication and Signaling
Subjects:
Online Access:https://doi.org/10.1186/s12964-023-01188-z
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Summary:Abstract The GPCR HCAR1 is known to be the sole receptor for lactate, which modulates its metabolic effects. Despite its significant role in many processes, mice deficient in HCAR1 exhibit no visible phenotype and are healthy and fertile. We performed transcriptomic analysis on HCAR1 deficient cells, in combination with lactate, to explore pathophysiologically altered processes. Processes such as immune regulation, various cancers, and neurodegenerative diseases were significantly enriched for HCAR1 transcriptomic signature. However, the most affected process of all was autism spectrum disorder. We performed behavioral tests on HCAR1 KO mice and observed that these mice manifest autistic-like behavior. Our data opens new avenues for research on HCAR1 and lactate effect at a pathological level. Video Abstract
ISSN:1478-811X