Glia and Autism Spectrum Disorder: An Immunohistochemical Analysis of Microglia and Astrocytes in the Hippocampus of Cntnap2-/- and Shank3+/- Mouse Models

Abstract

Autism Spectrum Disorders (ASDs) is a group of neurodevelopmental disorders centered on three core deficits: impairments in social interaction, difficulties in communication, and repetitive/restricted patterns of interests and/or behaviors. Although the underlying neurobiological mechanism(s) of ASD remain unclear, abnormalities in neural circuitry and immune dysfunction have repeatedly been implicated in the disorder. Given the role of glia in the neuroimmune response and in modulating connectivity of neural networks during normal neurodevelopment, it has been hypothesized that glial dysfunction may be a primary contributor to the development of ASD. In light of this hypothesis, we examined glial plasticity in the hippocampus of two validated autism mouse models that are based on human genetic findings and display phenotypes reminiscent of ASD symptoms, namely Cntnap2({-/-}) and Shank3({+/-}) mice. Moreover, considering that previous research has linked reduced adult hippocampal neurogenesis with ASD-related behaviors, we also investigated possible changes in adult hippocampal neurogenesis in the two autism mouse models. Although we did not find changes in glial abnormalities that were consistent across the two models or in adult neurogenesis, we did find evidence of astrocyte atrophy in both of the models that is indicative of some glial dysfunction. This study provides the foundation for future studies investigating the precise role of glia in the pathogenesis of ASD in order to develop novel therapeutic strategies for treating the disorder.