PROJECT: JTC2021: InflASD

Physiological and molecular effects of inflammation episode on the severity of Shank3-based ASD phenotype on mouse and hPSC model.

Abstract

Autism spectrum disorder (ASD) is a genetically heterogeneous neurodevelopmental disorder with an estimated prevalence of 1% in the childhood population. ASD is characterized by impairments of social interaction and communication accompanied by a pattern of repetitive and restrictive behavior, typically diagnosed in the first 3 years of life. Interestingly, the severity of phenotype even for similar mutations is highly variable and clinically it has been widely reported that fever or other inflammatory insults precipitates in certain subjects ASD-related symptoms. These data suggest that the heterogeneity in the phenotypes could be the consequence of the interplay between genetic and environmental factors (double-hits). Here, InflASD, will question the effect of inflammation on physiological and synaptic phenotypes observed in Shank3 models of ASD. Experiments will be performed on human pluripotent cells derived into both neurons and microglia, and on mouse models to transfer human findings into a system allowing behavioral studies. The consortium combines specialists in inflammation, human stem cell, and brain and synaptic physiology. The goal of inflASD is to understand the effect of inflammation on the severity of Shank3-induced phenotypes and to explore possible therapeutic intervention to rescue Shank3-induced phenotypes.

Keywords

Imaging techniques, Electrophisiological approaches, Behavioural methodologies, inflammation, Animal studies, Shank3

Call topic

Neurodevelopmental Disorders

Proposed runtime

n/a - n/a

Project team

Camilla Bellone (Coordinator)
Switzerland (SNSF)
Oliver Brustle
Germany (BMBF)
Michela Matteoli
Italy (MOH)
Eric Hosy
France (ANR)