Manganese induced nervous injury by α-synuclein accumulation via ATP-sensitive K(+) channels and GABA receptors.

Autor: Sun Y; Department of Toxicology, School of Public Health, Guilin Medical University, Guilin 541004, China., He Y; Department of Toxicology, School of Public Health, Guilin Medical University, Guilin 541004, China., Yang L; Department of Toxicology, School of Public Health, Guilin Medical University, Guilin 541004, China., Liang D; Department of Toxicology, School of Public Health, Guilin Medical University, Guilin 541004, China., Shi W; Department of Toxicology, School of Public Health, Guilin Medical University, Guilin 541004, China., Zhu X; Department of Toxicology, School of Public Health, Guilin Medical University, Guilin 541004, China., Jiang Y; Department of Toxicology, School of Public Health, Guangxi Medical University, Naning 530021, China., Ou C; Department of Toxicology, School of Public Health, Guilin Medical University, Guilin 541004, China. Electronic address: oak009@163.com.
Jazyk: angličtina
Zdroj: Toxicology letters [Toxicol Lett] 2020 Oct 10; Vol. 332, pp. 164-170. Date of Electronic Publication: 2020 Jul 10.
DOI: 10.1016/j.toxlet.2020.07.008
Abstrakt: Manganese (Mn) is an environmental pollutant having a toxic effect on Parkinson's disease, with significant damage seen in the neurons of basal ganglia. Hence, Mn pollution is a public health concern. A Sprague-Dawley rat model was used to determine the damage to basal nuclei, and the effect of Mn intake was detected using the Morris water maze test and transmission electron microscopy. The SH-SY5Y cell line was exposed to Mn, and downstream signaling was assessed to determine the mechanism of toxicity. Mn exposure injured neurons, repressing GABA A R receptors and inducing GABA B R receptors. The synergistic effect of the GABA B R receptor and Kir6.1-SUR1 or Kir6.2-SUR1 was found to be one of the potential factors for the secretion of α-synuclein. The accumulation of α-synuclein regulated downstream factors calmodulin (CAM) cAMP response element-binding protein (CREB), thereby impairing learning and memory. Other genes downstream of CREB, rather than the feedback regulation of CREB, and brain-derived neurotrophic factor might also be involved.
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 © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: