Perineuronal nets in the developing brain: implications for neurodevelopmental disorders

Here, we review recent findings on the development, functions, and alterations of perineuronal nets (PNNs) in relation to neurodevelopmental pathologies. PNNs are dense extracellular matrix structures primarily found in the central nervous system, comprising a heterogeneous array of components surrounding neurons. They play a crucial role in neuronal maturation and function, particularly in synapse formation and stabilization, which impacts higher-order brain connectivity. Emerging evidence underscores the dynamic changes in PNN composition and distribution during neuronal plasticity, with PNN remodeling shown to influence social and cognitive behaviors such as learning and memory. Conversely, disruptions in PNN dynamics have been implicated in developmental brain disorders. This review aims to present recent advancements in PNN neurobiology and to integrate these findings into our understanding of the mechanisms underlying neurodevelopmental pathogenesis.