CA2 Spine Density in an In-Vivo Model of Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by a wide range of social and behavioral symptoms. Pathophysiology of ASD in humans is highly variable, however, there are differences seen in spine morphology and density, specifically in the hippocampus, which is involved in social memory. Treatment of ASD is limited, targeting only certain symptoms, through both pharmacological and non-pharmacological methods. Prenatal exposure to valproic acid (VPA) can create an animal model of ASD that shows similarities to the pathophysiology of ASD in humans. Animal models of ASD can provide the framework for developing treatments targeted towards the underlying neurobiology of ASD and a wider range of symptoms. This study used a VPA-induced mouse model of ASD to examine dendritic spine density and morphology within the CA2 region of the hippocampus, a region implicated in social memory. Neuron reconstruction was performed using Neurolucida (MicroBrightField, Williston, VT, USA) at a magnification of 100x. Neurons within the CA2 of the hippocampus were traced, and spines were quantified as thin, mushroom, or stubby. Reconstruction was done with set criteria to ensure consistency across brain slices. There were no significant changes observed in thin and total spine density between treatments, but a significant decrease in thin spine density in females was observed. A significant increase in stubby spine density and decreased mushroom spine density were observed in the VPA treatment groups. Future studies may investigate additional brain regions and spine density after VPA exposure to further the development of viable treatment options.