Perineuronal Nets in the Hippocampus of Autism Spectrum Disorder Mouse Models

Abstract

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by three central behavioral symptoms: impaired verbal and nonverbal social communication, impaired social interactions, and the presence of restricted/repetitive behaviors. In addition to these core symptoms, some degree of cognitive impairment has been shown in a majority of individuals diagnosed with ASD. Imaging studies have shown that the hippocampus, a brain region involved in social behavior and certain types of learning and memory, is abnormal in patients with ASD. Although the underlying cellular and molecular mechanism(s) of ASD remain unclear, abnormalities in neural circuitry and extracellular matrices (ECM) have been implicated in the disorder. Perineuronal nets (PNNs), a type of ECM, have been shown to play key roles in neural development and inhibiting synaptic plasticity. Since PNNs prevent the proper formation of synaptic connections, we hypothesized that PNN dysfunction may contribute to the neural and behavioral abnormalities seen in ASD. Here, we examined for PNN abnormalities in the hippocampus across three validated autism mouse models: one idiopathic model, BTBR T+tf/J mice, and two transgenic models, Cntnap2-/- and Shank3ΔC+/- mice. Therefore, we investigated the CA2 and dorsal CA3 (dCA3) regions for PNN abnormalities because of their roles in social behavior and cognition. We found evidence of PNN abnormalities in both the CA2 and dCA3 of BTBR T+tf/J mice, and some evidence of abnormalities in the dCA3 of transgenic mice, indicating possible PNN dysfunction. This study lays the groundwork for future studies investigating the precise role of PNNs in the pathogenesis of autism in order to develop novel treatments for the disorder.