VinTSA

The research project consists in the elucidation of the implications and role of the cerebral vascular unit in autistic syndrome disorders (ASD). Indeed, as has been demonstrated for neurodegenerative diseases, the cerebral vascular system can participate (vascular dementia) and even be the cause of alteration (disease of the small arteries) of cerebral functions such as memory or fine regulation of movement. Currently the association between ASD and cerebral vascular alterations is not clearly studied and mainly by the teams involved in this project. Our recent and preliminary results allow us to hypothesize that the cerebral vascular system may present alterations involved in the genesis and maintenance of ASD. Indeed, the 16p11.2 deletion includes ASD and vascular alterations, Fragile-X syndrome presents behavioral alterations of ASD and both neuronal and vascular molecular alterations, Williams-Beuren syndrome presents vascular and social behavior alterations. Large-scale resources will be needed to analyze the close pathophysiological links between the cerebral vascular system and neurodevelopmental pathology. Our goal will be to propose molecular targets targeting the alterations of vascular and neuronal functions identified to slow down the onset and severity of behavioral disorders and support patients throughout their lives. We wish to set up analyzes on animal models of these pathologies as close as possible to those set up during clinical studies in order to take in consideration the evolution of pathological traits during development and adult life, including the cellular, tissue and behavioral aspects. To do this, we would like to submit a project to the Leducq foundation, which has a call for projects for the creation of international networks of excellence ($8 million for 5 years) about pathologies w cardiovascular origin or involving the cardiovascular system. A pair of researchers from two different continents capable of uniting the forces necessary for the project can respond to this call. We have already united forces with knowledge of these pathologies and/or of the cerebral vascular systems to form the hard core of the consortium (Morel, Lacoste, Campuzano, Dabertrand) and we have identified other partners, already identified by their skills in large-scale data analysis, genetic analysis, neurodevelopment, imaging and connectomics, and pharmacological and clinical approaches (table in chapter IV). The need for an international network of excellence on this subject of the involvement of the vascular system in ASD led us to choose this call for tenders, it will allow us to create effective links between the communities of neurodevelopment, cognitive pathologies and cardiovascular pathologies which are sorely lacking today.