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Sex Differences in Animal Models of Sodium-Valproate-Induced Autism in Postnatal BALB/c Mice: Whole-Brain Histoarchitecture and 5-HT2A Receptor Biomarker Evidence

Authors :
Balaji Gouda
Sukesh Narayan Sinha
Meram Chalamaiah
Validandi Vakdevi
Patangay Shashikala
Bantal Veeresh
Venkata Mullapudi Surekha
Vasudev Kasturi
Naveen Kumar Boiroju
Source :
Biology, Vol 11, Iss 1, p 79 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

Autism spectrum disorder (ASD) is characterised by problems with social interaction, verbal and nonverbal communication and repetitive behaviour. In mice, the 14th postnatal day is believed to correspond to the third trimester of human embryonic development and is considered a vital period for central nervous system development. It has been shown that ASD affects 2 to 3 times more male than female individuals. In the present study, ASD was induced in 14 postnatal day (PND) BALB/c mice using valproic acid (VPA). VPA administration brought about substantial differences in the histoarchitecture of the brain in both male and female mice, linked to behavioural deficits. We observed that both male and female mice showed similar morphological changes in the prefrontal cortex, hippocampus and Purkinje cells. We also observed hair loss from PND 17 to 25, which was again similar between male and female mice. However, there were higher rates of change in the cerebral cortex, frontal cortex and temporal lobe and hippocampus in VPA-treated male animals. With respect to the cerebellum, we did not observe any alterations by haematoxylin and eosin (H&E) staining, but detailed morphological observation using scanning electron microscopy (SEM) showed a higher rate of phenotype changes in VPA-treated male animals. Moreover, 5-HT2A receptor protein levels were upregulated in the cerebral cortex, hippocampus and Purkinje cells in VPA-treated male mice compared with control animals and VPA-treated female mice, as shown by immunohistochemical analysis. Based on all these findings, we conclude that male animals are more susceptible to VPA-induced ASD than females.

Details

Language :
English
ISSN :
20797737
Volume :
11
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.3ab56c15f6044603a96ba1933420e561
Document Type :
article
Full Text :
https://doi.org/10.3390/biology11010079