Child abuse (CA) is a strong predictor of psychopathologies and suicide, and can lastingly alter normal trajectories of brain development, in particular in areas closely linked to emotional responses such as the prefrontal cortex (PFC). Yet, the cellular underpinnings of these enduring effects are unclear. Childhood and adolescence are marked by the protracted formation of perineuronal nets (PNNs), which are essential in orchestrating the closure of developmental windows of cortical plasticity by regulating the functional integration of parvalbumin interneurons (PV) into neuronal circuits. Using well-characterized post-mortem brain samples, we explored the hypothesis that CA has lasting effects on the development of PNNs in the ventromedial PFC. We found that a history of CA was specifically associated with increased recruitment and maturation of PNNs. Through single-nucleus sequencing and fluorescent in-situ hybridization, we provide evidence for the involvement of oligodendrocyte progenitor cells (OPCs) in this phenomenon by showing that the expression of canonical components of PNNs are highly enriched and upregulated in this cell type in CA victims. These findings suggest that early-life adversity may lead to persistent patterns of maladaptive behaviours by reducing the neuroplasticity of cortical circuits through the enhancement of developmental OPC-mediated PNN formation.
bioRxiv Subject Collection: Neuroscience