An altered glial phenotype in the NL3R451C mouse model of autism

Abstract

Abstract Autism Spectrum Disorder (ASD; autism) is a neurodevelopmental disorder characterised by deficits in social communication, and restricted and/or repetitive behaviours. While the precise pathophysiologies are unclear, increasing evidence supports a role for dysregulated neuroinflammation in the brain with potential effects on synapse function. Here, we studied characteristics of microglia and astrocytes in the Neuroligin-3 (NL3 R451C ) mouse model of autism since these cell types are involved in regulating both immune and synapse function. We observed increased microglial density in the dentate gyrus (DG) of NL3 R451C mice without morphological differences. In contrast, WT and NL3 R451C mice had similar astrocyte density but astrocyte branch length, the number of branch points, as well as cell radius and area were reduced in the DG of NL3 R451C mice. Because retraction of astrocytic processes has been linked to altered synaptic transmission and dendrite formation, we assessed for regional changes in pre- and postsynaptic protein expression in the cortex, striatum and cerebellum in NL3 R451C mice. NL3 R451C mice showed increased striatal postsynaptic density 95 (PSD-95) protein levels and decreased cortical expression of synaptosomal-associated protein 25 (SNAP-25). These changes could contribute to dysregulated neurotransmission and cognition deficits previously reported in these mice.