Vitamin E protects dopaminergic neurons against manganese-induced neurotoxicity through stimulation of CHRM1 and KCNJ4.

Autor: Song R; Department of Epidemiology and Health Statistics, Medical School of Qingdao University, Qingdao, Shandong, China., Chen H; Qingdao Municipal Center for Disease Control and Prevention/Qingdao Institute of Preventive Medicine, Qingdao, Shandong, China., Zhan R; Qingdao University Affiliated Hiser Hospital, Qingdao, Shandong, China., Han M; Department of Epidemiology and Health Statistics, Medical School of Qingdao University, Qingdao, Shandong, China., Zhao L; Department of Epidemiology and Health Statistics, Medical School of Qingdao University, Qingdao, Shandong, China., Shen X; Department of Epidemiology and Health Statistics, Medical School of Qingdao University, Qingdao, Shandong, China. Electronic address: shenxiaoli@qdu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) [J Trace Elem Med Biol] 2024 Jan; Vol. 81, pp. 127326. Date of Electronic Publication: 2023 Oct 26.
DOI: 10.1016/j.jtemb.2023.127326
Abstrakt: Background: Manganese (Mn) overexposure can induce neurotoxicity and lead to manganism. Vitamin E (Vit E) has neuroprotective effects by acting as an ROS scavenger, preventing mitochondrial dysfunction and neuronal apoptosis. However, the effects of Vit E on Mn-induced nigrostriatal system lesions remains unknown.
Objectives: We aim to investigate whether Vit E has protective effects on Mn-induced nigrostriatal system lesions and mRNA expression profiles in the SN of mice.
Methods: Sixty 8-week-old C57BL/6 male mice were randomly divided into the Control, MnCl 2 , MnCl 2 +Vit E, and Vit E group. Twenty-four hours after the last injection, the behaviour test was performed. The numbers of dopaminergic neurons in Substantia nigra (SN), the contents of dopamine and its metabolite levels in striatium, and the morphology of mitochondria and nuclei in the dopaminergic neurons in SN were detected by immunofluorescence staining, high-performance liquid chromatography, and transmission electron microscopy. Transcriptome analysis was used to analyze the signaling pathways and RT-PCR was used to verify the mRNA levels.
Results: Vit E ameliorates behavioral disorders and attenuates the loss of nigral dopaminergic neurons in the Mn-induced mouse model. In addition, Vit E antagonized Mn-induced toxicity by restoring mitochondrial function. The results of transcriptome sequencing and RTPCR show that the protective effect of Vit E was related to the upregulation of CHRM1 and KCNJ4 mRNA in the SN.
Conclusions: Vit E has neuroprotective effects on Mn-induced neurodegeneration in the nigrostriatal system. This effect may be related to the upregulation of CHRM1 and KCNJ4 mRNA stimulated by Vit E in the SN.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
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