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  2. Phenanthrene induces autism-like behavior by promoting oxidative stress and mTOR pathway activation

Phenanthrene induces autism-like behavior by promoting oxidative stress and mTOR pathway activation

  • Toxicology. 2021 Sep;461:152910. doi: 10.1016/j.tox.2021.152910.
Jing Xie 1 Qi Han 1 Zhaolan Wei 1 Yunyi Wang 1 Shuwei Wang 1 Mingqing Chen 2
Affiliations

Affiliations

  • 1 Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, 430079, Hubei, China.
  • 2 Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, 430079, Hubei, China. Electronic address: chenmq@mail.ccnu.edu.cn.
Abstract

Autism is thought to be associated with both environmental and genetic factors. Phenanthrene (Phe) makes up a relatively high proportion of the low-ring polycyclic aromatic hydrocarbons. However, the association between exposure to Phe and Autism remain unclear. In this study, the effect and mechanisms of phenanthrene exposure on autistic behavior were investigated. Three-week-old male Kunming mice were exposed to doses of 5, 50, or 500 μg/kg/d Phe for 22 days. Exposure to phenanthrene induced a marked decrease in the activity of the mice in the central area in the open field test, and caused a significant decrease in communication with unfamiliar mice in the three-chambered social test. The hippocampus of the mice exposed to high concentrations of Phe showed pathological changes. Exposure to phenanthrene induced an increase in the levels of ROS and a decrease in levels of glutathione, and caused a significant decrease in the expression of Shank3 and Beclin1. This also led to an increase in the phosphorylation levels of Akt and mTOR. However, administering Rapamycin or vitamin E, inhibited the oxidative stress and activation of the mTOR pathway induced by Phe exposure, effectively alleviating the above-mentioned autistic-like anxious social behaviors. These results indicate that exposure to phenanthrene will lead to autism-like behavior. The underlying mechanism involves oxidative stress and the mTOR pathway.

Keywords

ASD; Oxidative stress; Phenanthrene; Vitamin E; mTOR.

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