Speakers > Laetitia Davidovic
Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France
Laetitia Davidovic obtained her PhD in Canada in 2003 and has been a CNRS researcher since 2009. After working for over 12 years to unravel novel molecular and metabolic phenotypes in a genetic model of autism, she has shifted her interests towards environmental factors contributing to neurodevelopmental disorder, with a specific focus on autism. Since 2015, she has been combining preclinical studies with human cohort studies to understand whether and how the immune system and the microbiota influence behaviour.
The microbial metabolite p-Cresol induces autistic-like behaviors in mice by remodeling the gut microbiota and deregulation of central catecholamines
Autism spectrum disorders (ASD) are frequent neurodevelopmental disorders characterized by social behaviour and communication deficits, repetitive behaviours, and restricted interests. Some ASD patients also display gastro-intestinal symptoms, intestinal microbiota dysbiosis, and abnormal levels of microbial metabolites. Studies in rodents have shown that both bacteria from the microbiota and microbial metabolites regulate brain function and behaviour, including social behaviour. These findings suggest that disruption of the microbiota-gut-brain axis could contribute to the development and/or maintenance of ASD symptoms. In recent years, we have focused on the microbial metabolite p-cresol that is abnormally elevated in the feces and urine of ASD patients. We have shown that C57Bl/6 mice exposed chronically to p-cresol exhibit severe social interaction deficits driven by changes in microbiota composition. This is accompanied by a decrease in midbrain dopamine neurons excitability, suggesting that p-cresol effects on behaviour may relate to perturbations of catecholamines within the social reward circuit. Our recent data suggest that p-cresol can modulate social behaviour by directly interfering with central catecholamine biosynthesis. Our results support the notion that some microbial metabolites directly mediate the deleterious effects of microbiota dysbiosis on behaviour.
|
