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

Scientists studied mice that were missing a protein called HCAR1, which normally responds to lactate (a substance made during exercise and metabolism). When they tested these mice, they found they showed autism-like behaviors. The researchers also looked at which genes were affected and found autism was the most impacted condition. This suggests that lactate and this protein might play a role in autism, which could lead to new research directions.

This 2023 study investigated the role of HCAR1, a protein receptor for lactate, in autism-related behaviors. Researchers conducted transcriptomic analysis on cells lacking HCAR1 and found that autism spectrum disorder was the most significantly affected process. Behavioral testing of HCAR1 knockout mice revealed autistic-like behaviors, suggesting a potential link between lactate signaling and autism. The study also identified enrichment for immune regulation, cancer, and neurodegenerative disease processes.

These findings suggest HCAR1 and lactate metabolism may play previously unrecognized roles in autism pathophysiology, opening new research directions for understanding autism mechanisms.

This research identifies a novel potential pathway in autism involving lactate signaling. While preliminary, it suggests new directions for understanding autism biology and potential therapeutic targets. Further research needed to determine clinical relevance and translation to human autism.

Sample sizes not reported. Study type unclear from abstract. Limited behavioral characterization details provided. Transcriptomic analysis methodology not fully described. Unclear how findings in knockout mice translate to human autism.

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.