1. Academic Validation
  2. PM2.5 exposure exacerbates seizure symptoms and cognitive dysfunction by disrupting iron metabolism and the Nrf2-mediated ferroptosis pathway

PM2.5 exposure exacerbates seizure symptoms and cognitive dysfunction by disrupting iron metabolism and the Nrf2-mediated ferroptosis pathway

  • Sci Total Environ. 2023 Nov 17:168578. doi: 10.1016/j.scitotenv.2023.168578.
Huiya Mei 1 Dongqin Wu 1 Zenghua Yong 2 Yinsi Cao 1 Yuanjing Chang 1 Junjie Liang 1 Xiaofan Jiang 1 Hua Xu 3 Jiatao Yang 4 Xian Shi 4 Ruijin Xie 1 Wenjing Zhao 5 Yu Wu 6 Yueying Liu 7
Affiliations

Affiliations

  • 1 Department of Pediatrics, Affiliated Hospital of Jiangnan University, Wuxi, China; Lab of Modern Environmental Toxicology, Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, China.
  • 2 Department of Pediatrics, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
  • 3 Department of Pediatrics, Affiliated Hospital of Jiangnan University, Wuxi, China.
  • 4 Lab of Modern Environmental Toxicology, Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, China; Environment and Health Research Division, Public Health Research Center, Wuxi School of Medicine, Jiangnan University, Wuxi, China.
  • 5 Yangzhou Key Laboratory of Anesthesiology, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
  • 6 Lab of Modern Environmental Toxicology, Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, China; Environment and Health Research Division, Public Health Research Center, Wuxi School of Medicine, Jiangnan University, Wuxi, China; The Key Laboratory of Modern Toxicology of Ministry of Education, Nanjing Medical University, Nanjing, Jiangsu, China.
  • 7 Department of Pediatrics, Affiliated Hospital of Jiangnan University, Wuxi, China. Electronic address: shadow7671@163.com.
Abstract

In recent years, air pollution has garnered global attention due to its ability to traverse borders and regions, thereby impacting areas far removed from the emission sources. While prior studies predominantly focused on the deleterious effects of PM2.5 on the respiratory and cardiovascular systems, emerging evidence has highlighted the potential risks of PM2.5 exposure to the central nervous system. Nonetheless, research elucidating the potential influences of PM2.5 exposure on seizures, specifically in relation to neuronal Ferroptosis, remains limited. In this study, we investigated the potential effects of PM2.5 exposure on seizure symptoms and seizures-induced hippocampal neuronal Ferroptosis. Our findings suggest that seizure patients residing in regions with high PM2.5 levels are more likely to disturb iron homeostasis and the Nrf-2 dependent Ferroptosis pathway compared to those living in areas with lower PM2.5 levels. The Morris Water Maze test, Racine scores, and EEG recordings in epileptic mice suggest that PM2.5 exposure can exacerbate seizure symptoms and cognitive dysfunction. Neurotoxic effects of PM2.5 exposure were demonstrated via Nissl staining and CCK-8 assays. Direct evidence of PM2.5-induced hippocampal neuronal Ferroptosis was provided through TEM images. Additionally, increased Fe2+ and lipid ROS levels indirectly supported the notion of PM2.5-induced hippocampal Ferroptosis. Therefore, our study underscores the necessity of preventing and controlling PM2.5 levels, particularly for patients with seizures.

Keywords

Epilepsy; Ferroptosis; Iron metabolism; Neuroinflammation; Nrf2; PM(2.5).

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