ER stress and ER stress-mediated apoptosis are involved in manganese-induced neurotoxicity in the rat striatum in vivo

Neurotoxicology
Ting WangZongcan Zhou

Abstract

Manganese (Mn) is an essential trace element found in many enzymes, however, excessive Mn-exposure can result in manganism which is similar to Parkinson's movement disorder. The mechanisms of manganism are not well-known. The present in vivo study was carried out to determine whether endoplasmic reticulum stress (ER stress) and ER stress-mediated apoptosis are involved in manganese-induced neurotoxicity. Sixty-four SD rats were randomly divided into four groups and were administered intraperitoneally with normal saline (NS, as control) or MnCl₂ (7.5, 15 and 30 mg/kg body weight, respectively) for 4 weeks. We found that MnCl₂ dose-dependently accumulate in striatal. HE staining and TUNEL assay results indicated that MnCl₂ induced striatal neurocytes apoptosis in both male and female rats. The alterations of ultrastructures showed that MnCl₂ resulted in chromatin condensation, mitochondria and ER tumefaction in rat striatal neurocytes. Furthermore, MnCl₂ increased the expressions of p-IRE-1, ATF-6α, PERK, GRP78, Sigma-1R, CHOP, Bim, Bax, caspase-12 and caspase-3, and decreased the expression of Bcl-2 in rat striatal neurocytes. In conclusion, MnCl₂ could induce ER stress and ER stress-mediated apoptosis in rat striatal neurocytes...Continue Reading

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Citations

Sep 30, 2015·Journal of Biochemical and Molecular Toxicology·Martina RudgalvyteGarry Wong
Apr 25, 2016·Neurotoxicology·Dong-Suk KimAnumantha G Kanthasamy
Nov 7, 2016·BMC Pharmacology & Toxicology·Tanara V PeresMichael Aschner
Apr 1, 2017·Biological Trace Element Research·Kun ZhangXiaohua Teng
Nov 30, 2015·Biochemistry. Biokhimii︠a︡·M A Savitskaya, G E Onishchenko
Jun 21, 2019·International Journal of Environmental Research and Public Health·Chao-Yan OuShao-Jun Li
Oct 23, 2019·Journal of Cellular and Molecular Medicine·Chang LiuBin Xu
Aug 18, 2020·Expert Review of Neurotherapeutics·Airton C MartinsMichael Aschner
Sep 22, 2019·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Khristy J Thompson, Marianne Wessling-Resnick
Apr 20, 2018·Naunyn-Schmiedeberg's Archives of Pharmacology·Rania I NadeemBahia M El-Sayeh
May 6, 2017·American Journal of Medical Genetics. Part a·Ying QiaoEvica Rajcan-Separovic
May 1, 2021·International Journal of Molecular Sciences·Alexey A TinkovMichael Aschner

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