Biochemistry Department, Science College, King Saud University, Riyadh, Saudi Arabia.
Zoology Department, Science College, King Saud University, Riyadh, Saudi Arabia.
PeerJ. 2023 Jun 13;11:e15488. doi: 10.7717/peerj.15488. eCollection 2023.
Males 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.
This 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.
Forty 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.
Collectively, 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.
This 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.
男性比女性更易患自闭症等神经发育障碍，但男性易感性的机制尚不完全清楚。因此，在丙酸（PPA）自闭症啮齿动物模型中研究自闭症病因学时考虑性别差异，将有助于更好地了解女性为何不易患自闭症谱系障碍，这可能成为自闭症男性的一种治疗策略。
本研究旨在探讨氧化应激、谷氨酸兴奋性毒性、神经炎症和肠道微生物群损伤等作为许多神经疾病病因学机制的性别差异，特别参考自闭症。
将 40 只白化病小鼠分为 4 组，每组 10 只，每组包括 2 只对照组和 2 只实验组，雌雄各半。两组雌雄小鼠分别连续 3 天给予磷酸盐缓冲液或神经毒性剂量的 PPA（250mg/kg 体重）。测量小鼠脑匀浆中的能量代谢、氧化应激、神经炎症和兴奋性毒性的生化标志物，同时评估小鼠粪便样本中致病菌的存在。此外，还检查了动物的重复行为、认知能力和身体神经协调性。
总的来说，与 PPA 诱导的啮齿动物模型中的行为改变相关的选定变量与氧化应激、谷氨酸兴奋性毒性、神经炎症和肠道细菌有关，雄性比雌性更易受影响。
本研究解释了为什么与女性相比，男性在自闭症的生物化学和行为特征方面更容易受到影响。雌性性激素以及雌性更高的解毒能力和更高的糖酵解通量，是自闭症啮齿动物模型中神经保护的贡献因素。
