Unveiling sex-based differences in developing propionic acid-induced features in mice as a rodent model of ASD

PeerJ

article

Nasreen Kamalmaz¹  Abir Ben Bacha¹  Mona Alonazi¹  Gadah Albasher²  Arwa Ishaq A. Khayyat¹  Afaf El-Ansary³ 

[1] Biochemistry Department, Science College, King Saud University;Zoology Department, Science College, King Saud University;Central Research Laboratory, King Saud University

关键词: Autism;    Sex difference;    Propionic acid;    Behavior;   

DOI  :  10.7717/peerj.15488

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundMales are more likely to develop autism as a neurodevelopmental disorder than females are, although the mechanisms underlying male vulnerability are not fully understood. Therefore, studying the role of autism etiologies considering sex differences in the propionic acid (PPA) rodent model of autism would build greater understanding of how females are protected from autism spectrum disorder, which may be used as a treatment strategy for males with autism.ObjectivesThis study aimed to investigate the sex differences in oxidative stress, glutamate excitotoxicity, neuroinflammation, and gut microbiota impairment as etiological mechanisms for many neurological diseases, with specific reference to autism.MethodForty albino mice were divided into four groups of 10 animals each with two control and two treated groups of both sexes received only phosphate-buffered saline or a neurotoxic dose of PPA (250 mg/kg body weight) for 3 days, respectively. Biochemical markers of energy metabolism, oxidative stress, neuroinflammation, and excitotoxicity were measured in mouse brain homogenates, whereas the presence of pathogenic bacteria was assessed in mouse stool samples. Furthermore, the repetitive behavior, cognitive ability, and physical-neural coordination of the animals were examined.ResultsCollectively, selected variables related to oxidative stress, glutamate excitotoxicity, neuroinflammation, and gut bacteria were impaired concomitantly with altered behavior in PPA-induced rodent model, with males being more susceptible than females.ConclusionThis study explains the role of sex in the higher vulnerability of males to develop autistic biochemical and behavioral features compared with females. Female sex hormones and the higher detoxification capacity and higher glycolytic flux in females serve as neuroprotective contributors in a rodent model of autism.

【 授权许可】

CC BY