University of Poitiers, France
Motor and gait disorders as early and biological diagnosis criteria in autism: prove of concept in animal models
Our basic research activity and project are intimately linked to human health. They are placed in the context of providing a fresh perspective in the field of autism spectrum disorder (ASD) and aim to provide potential new avenues for its diagnosis and in managing its core symptoms.
Qualitative and quantitative analysis in ASD clearly indicate impairments in visuo-motor and manual dexterity tasks, limb coordination, balance, as well as in gait. These motor impairments may be amongst the earliest ASD Symptoms but are not included in the diagnosis criteria. With this perspective, the cerebellum has attracted renewed interest as a brain area at the crossroads of cognitive and motor symptoms characteristic of ASD.
The etiology of ASD is still elusive. Evidence has strongly linked genetic and environmental factors to ASD. More than 1200 susceptibility genes are involved in ASD, most are implicating either chromatin modeling or synapse function. Maternal exposure to pharmacological agents such as valproic acid (VPA), an antiepileptic drug, significantly increases the risk of ASD in offspring. These genetic and environmental factors have led to the generation of corresponding animal models, with some showing strong construct and face validity.
In this line, we have recently published a series of 3 studies on ASD environmental and genetic animal models. In all these models, we reported behavioral, cellular and molecular alterations related to the cerebellum. We also documented motor and gait deficits in all animal models, which were correlated with the severity of social deficits as well as with the extent of Purkinje cell (PC) loss within the cerebellum. Studies were performed in both males and females and we also show that males are more affected than females, whatever the phenotype that is being analyzed.
Our studies recapitulate the spectrum of the disease and its sexual dimorphism. They further point to the cerebellum as a target area for future interventions to manage ASD core symptoms and related motor disorders.
We are pursuing currently several lines of research that combine various interventional approaches that may be translated into clinical settings following appropriate adaptations, offering a new and unique view of a pathology that has currently no cure.
He obtained his thesis from the University of Bordeaux (1993) working the expression of neuroactive molecules in the brain with a focus on dopamine neurotransmission. During his PhD, he spent 3 months at the Karolinska Institute-Sweden where he participated to the cloning and characterization of a novel neurotrophic factor receptor (TrkC). He underwent his 3 years post-doc at Duke University-USA (Marc G. Caron and Robert J. Lefkowitz) during which he participated to the characterization of transgenic mice lacking the DAT or the beta-adrenergic receptor kinase-1 gene (1993-1995). He was recruited as a CNRS researcher (1995) at Bordeaux before becoming a Professor at the University of Poitiers (2002). From 2006-2010, he was the leader of a CNRS research team working on the physiopathology of disorders associated with the malfunctioning of the dopaminergic system such as Parkinson disease and addiction. Throughout his career, he has published more than 100 papers on the topic dopamine neurotransmission in journals such as Nature, Science, Nature Neuroscience, PNAS and Neuron. His H factor is 34, several of his papers were commented in faculty 1000 Medicine and faculty 1000 Biology. He is currently thereunder and the head of an INSERM Neuroscience Unit composed of 3 research teams : “Laboratoire de Neurosciences Expérimentales et Cliniques” (LNEC) (Experimental and Clinical Neurosciences Laboratory). He was a member of the national committee of the CNRS, Physiology section 25, a member of the Neurosciences INSERM committee, was for the last 6 years member of the French Neurosciences Society board and member of the election committee; president and member of HCERES committee in Neurosciences. At the local level, he is the Inserm regional scientific correspondant.