Gender-specific differences in cholinergic and GABA-ergic activity in the prefrontal cortex in prenatally valproic acid exposed adult rats

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by behavioral deficits. ASD is more common in males than in females; the neurobiological basis of the male prevalence remain poorly understood. The present study was designed to investigate gender specific differences in the expression level of the cholinergic (α7 nACh, M1) and GABA-ergic (γ-aminobutyric acid) alfa1 receptors in the medial prefrontal cortex (mPFC) in a rat model of autism. Experiments were carried out on prenatally VPA-treated and control (saline treated) adult (6 months) male and female rats. Immunoblotting studies revealed that the mean level of cholinergic M1 receptors in the mPFC is significantly higher in VPA treated group as compared to control in male rats only, while α7 nACh receptors in rats of both sexes. In addition, expression level of cholinergic α7 nACh as well as M1 receptors is significantly higher in male rats as compared to females only in control rats. However, expression level of GABA-ergic receptors is significantly higher in female rats as compared to males in control or VPA treated rats. In addition, significant difference between control and VPA treated control rats was not observed, while in females difference between control and VPA treated groups is significant. Identifying problems with neurotransmitter systems in different brain regions is a key component to determining the neurobiological basis of behavioral dysfunction and understanding the high prevalence of ASD in male.Supported by the funding from the SRNSFG: Grant #-FR-22-10650