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暴露于空气污染和丙戊酸诱导雄性大鼠出现类似自闭症症状。

Autism-like symptoms by exposure to air pollution and valproic acid-induced in male rats.

机构信息

Department of Environmental Health Engineering, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Student Research Committee, Department of Environmental Health Engineering, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Environ Sci Pollut Res Int. 2022 Aug;29(39):59263-59286. doi: 10.1007/s11356-022-19865-w. Epub 2022 Apr 6.

Abstract

Exposure to air pollution during prenatal or neonatal periods is associated with autism spectrum disorder (ASD) according to epidemiology studies. Furthermore, prenatal exposure to valproic acid (VPA) has also been found to be associated with an increased prevalence of ASD. To assess the association between simultaneous exposure to VPA and air pollutants, seven exposure groups of rats were included in current study (PM and gaseous pollutants exposed - high dose of VPA (PGE-high); PM and gaseous pollutants exposed - low dose of VPA (PGE-low); gaseous pollutants only exposed - high dose of VPA (GE-high); gaseous pollutants only exposed - low dose of VPA (GE-low); clean air exposed - high dose of VPA (CAE-high); clean air exposed - low dose of VPA (CAE-low) and clean air exposed (CAE)). The pollution-exposed rats were exposed to air pollutants from embryonic day (E0) to postnatal day 42 (PND42). In all the induced groups, decreased oxidative stress biomarkers, decreased oxytocin receptor (OXTR) levels, and increased the expression of interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor alpha (TNF-α) were found. The volumes of the cerebellum, hippocampus, striatum, and prefrontal decreased in all induced groups in comparison to CAE. Additionally, increased numerical density of glial cells and decreased of numerical density of neurons were found in all induced groups. Results show that simultaneous exposure to air pollution and VPA can cause ASD-related behavioral deficits and air pollution reinforced the mechanism of inducing ASD ̉s in VPA-induced rat model of autism.

摘要

根据流行病学研究,产前或新生儿期暴露于空气污染与自闭症谱系障碍(ASD)有关。此外,产前暴露于丙戊酸(VPA)也与 ASD 患病率增加有关。为了评估 VPA 与空气污染物同时暴露的相关性,本研究纳入了 7 个暴露组的大鼠(PM 和气态污染物暴露-高剂量 VPA(PGE-high);PM 和气态污染物暴露-低剂量 VPA(PGE-low);仅气态污染物暴露-高剂量 VPA(GE-high);仅气态污染物暴露-低剂量 VPA(GE-low);清洁空气暴露-高剂量 VPA(CAE-high);清洁空气暴露-低剂量 VPA(CAE-low)和清洁空气暴露(CAE))。污染暴露大鼠从胚胎期(E0)到出生后第 42 天(PND42)暴露于空气污染物。在所有诱导组中,均发现氧化应激生物标志物减少、催产素受体(OXTR)水平降低,以及白细胞介素 6(IL-6)、白细胞介素 1β(IL-1β)和肿瘤坏死因子-α(TNF-α)表达增加。与 CAE 相比,所有诱导组的小脑、海马体、纹状体和前额叶体积均减小。此外,在所有诱导组中均发现神经胶质细胞数量密度增加和神经元数量密度减少。结果表明,同时暴露于空气污染和 VPA 可导致与 ASD 相关的行为缺陷,并且空气污染增强了 VPA 诱导的自闭症大鼠模型中诱导 ASD 的机制。

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