Gender-Related Disparities in induced biochemical autistic features using propionic acid rat model

Abstract

The dramatical increase in autism spectrum disorder (ASD) prevalence as a neurodevelopmental disorder highlighted the urgent need for early detection and intervention as its symptoms vary across individuals. The question of whether females and males show ASD differently is still up for debate. Research examining the relationship between sex and symptoms of autism and other psychiatric issues typically lacks a general population comparison group, making it difficult to determine whether observed differences are unique to autism or reflect general development patterns. Methods: The present study aimed to understanding sex-related differences in vulnerability to develop autistic features in propionic acid (PPA) induced autism in the rodent model. Thirty-two Wistar albino juvenile male and female rats were divided equally into four groups. Group 1 received saline and served as a control. Group 2 received buffered PPA at 250 mg/kg b.w/day for three consecutive days. While sixteen female Wistar albino juvenile rats were divided into two groups (8 rats/group) as follows: Group 3 received saline and served as a control. While, Group 4 received buffered PPA at 250 mg/kg b.w/day for three consecutive days. Serotonin, dopamine (DA), gamma-aminobutyric acid (GABA) and glutamate were measured. Brain-derived neurotrophic factor (BDNF), caspase 9 and NF-κB were evaluated in all groups. Moreover, Expression Analysis of neurodevelopmental regulator genes (FMR1 and FOXP1) and inflammatory gene (COX-1) was detected. Results: PPA administration significantly reduced dopamine, GABA, and FMR1 gene with significant elevation in serotonin, glutamate, BDNF, caspase 9, NF-κB and Expression of FOXP1 and COX-1 genes. Conclusion: Our research highlighted different biochemical parameters that can be promising biomarkers for ASD. the study also discussed sex differences found in animal models of ASD, to provide a possible explanation of the neurological mechanisms underpinning the different presentation of autistic symptoms in males and females.