Striatal synaptic changes and behavior in adult mouse upon prenatal exposure to valproic acid

Abstract

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by persistent deficits in social communication and social interaction. Altered synaptogenesis and aberrant connectivity responsible for social behavior and communication have been reported in autism pathogenesis. Autism has a strong genetic and heritable component; however, environmental factors including toxins, pesticides, infection and in utero exposure to drugs such as VPA have also been implicated in ASD. Administration of VPA during pregnancy has been used as a rodent model to study pathophysiological mechanisms involved in ASD, and in this study, we used the mouse model of prenatal exposure to VPA to assess the effects on striatal and dorsal hippocampus function in adult mice.Alterations in repetitive behaviors and shift habits were observed in mice prenatally exposed to VPA. In particular, such mice presented a better performance in learned motor skills and cognitive deficits in Y-maze learning frequently associated with striatal and hippocampal function. These behavioral changes were associated with a decreased level of proteins involved in the formation and maintenance of excitatory synapses, such as Nlgn-1 and PSD-95. In conclusion, motor skill abilities, repetitive behaviors, and impaired flexibility to shift habits are associated with reduced striatal excitatory synaptic function in the adult mouse prenatally exposed to VPA.