Investigating the enduring effects of early-life adversity on oligodendrocyte function in the post-mortem brain: from myelination to the remodeling of the extracellular matrix, by Arnaud Tanti

Summary:  Investigating the enduring effects of early-life adversity on oligodendrocyte function in the post-mortem brain: from myelination to the remodeling of the extracellular matrix

Early-life adversity (ELA) has devastating consequences on psychological development. It is amongst the strongest predictors of psychopathologies, in particular depression, and suicide. While imaging studies suggest that ELA may lead to altered trajectories of brain structural and functional development, the cellular and molecular basis of these changes are unclear. As a protracted form of brain plasticity essential to the functional maturation of the central nervous system, myelination has emerged as an interesting candidate to support these changes. Using a combination of molecular and histological approaches in well-characterized post-mortem samples from depressed suicides, our research aims at describing the long-lasting impact of ELA on oligodendrocyte function. Our main findings suggest that in prefrontal regions of the brain, child abuse lastingly disrupts the epigenetic and transcriptional program of myelination, modifies the balance of oligodendrocyte-lineage cells, and associates with changes in myelin properties of individual fibers. Considering the essential role of myelination in normal brain development, these changes during critical periods may possibly mediate some of the negative mental health outcomes associated with child abuse, in particular increased vulnerability to psychopathology. Beyond myelination, our recent work focuses on glial-glial interactions and oligodendrocyte contribution to extracellular matrix plasticity, one of the multiple aspects of oligodendrocyte functions which may contribute to ELA-associated prefrontal circuits remodeling.

Short Bio
Throughout his career, Arnaud Tanti has studied how different forms of brain structural plasticity are impacted by stress-related disorders, in particular depression. His experiences have led him to study these processes using both animal models and post-mortem brain samples from depressed suicides. During his PhD, obtained from the University of Tours in 2012 under the supervision of Pr Catherine Belzung, his work focused on investigating the contribution of adult hippocampal neurogenesis to the pathophysiology of depression using rodent models. He then joined the McGill Group for Suicide Studies (Montreal, Canada) as a postdoctoral fellow, where he applied molecular tools to comprehensively study the post-mortem depressed brain. His work there has highlighted that early-life adversity has enduring effects on oligodendrocyte function at the cellular and molecular level, long-lastingly impacting cortical myelination. He recently joined INSERM UMR1253 (Tours, France), integrating these different aspects of his research to better characterize the neurobiological factors that mediate vulnerability to psychopathology.

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Code : 421174