Morphological and synaptic changes in dopaminergic neurons in the autism-related model

Despite an increasing number of studies describing changes in dopamine brain regions and autism symptoms, the specific alterations in midbrain dopamine neurons projecting to the striatum remain unclear. Therefore, the aim of the present study was to examine the structural and morphological properties of primary dopaminergic neuronal cell cultures isolated from Shank3-deficient transgenic mouse, known for exhibiting autism-like symptomatology. Additionally, we evaluated the expression of selected synaptic proteins in the brain areas relevant for social behavior in wild type (WT) and Shank3-deficient mice. Our immunocytochemical data from primary dopaminergic neurons isolated from the midbrain and striatum indicate significant changes in neurite outgrowth in Shank3-deficient versus WT animals. In the striatum, we observed a decrease in the expression of synaptic proteins (synaptophysin, SVG40). We also found significantly lower immunofluorescence signal of synapsin in neurons isolated from the frontal cortex of Shank3-deficient mice compared to WT animals. These results show ultrastructural changes of dopaminergic neurons, which may explain autistic symptomatology in the used model. In a wider context, these results provide a basis for understanding the etiology of neurodevelopmental disorders. Supported by VEGA 2/0057/23 and APVV-21-0189.