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Title: In vitro manganese exposure disrupts MAPK signaling pathways in striatal and hippocampal slices from immature rats.

Authors: Peres, Tanara Vieira; Pedro, Daniela Zótico; de Cordova, Fabiano Mendes; Lopes, Mark William; Gonçalves, Filipe Marques; Mendes-de-Aguiar, Cláudia Beatriz Nedel; Walz, Roger; Farina, Marcelo; Aschner, Michael; Leal, Rodrigo Bainy

Published In Biomed Res Int, (2013)

Abstract: The molecular mechanisms mediating manganese (Mn)-induced neurotoxicity, particularly in the immature central nervous system, have yet to be completely understood. In this study, we investigated whether mitogen-activated protein kinases (MAPKs) and tyrosine hydroxylase (TH) could represent potential targets of Mn in striatal and hippocampal slices obtained from immature rats (14 days old). The aim of this study was to evaluate if the MAPK pathways are modulated after subtoxic Mn exposure, which do not significantly affect cell viability. The concentrations of manganese chloride (MnCl₂; 10-1,000  μM) caused no change in cell viability in slices exposed for 3 or 6 hours. However, Mn exposure significantly increased extracellular signal-regulated kinase (ERK) 1/2, as well as c-Jun N-terminal kinase (JNK) 1/2/3 phosphorylation at both 3 and 6 hours incubations, in both brain structures. Furthermore, Mn exposure did not change the total content or phosphorylation of TH at the serine 40 site in striatal slices. Thus, Mn at concentrations that do not disrupt cell viability causes activation of MAPKs (ERK1/2 and JNK1/2/3) in immature hippocampal and striatal slices. These findings suggest that altered intracellular MAPKs signaling pathways may represent an early event concerning the effects of Mn in the immature brain.

PubMed ID: 24324973 Exiting the NIEHS site

MeSH Terms: Animals; Brain Mapping; Central Nervous System/drug effects*; Corpus Striatum/drug effects; Corpus Striatum/metabolism; Hippocampus/drug effects; Hippocampus/metabolism; Manganese/toxicity*; Mitogen-Activated Protein Kinase Kinases/biosynthesis*; Mitogen-Activated Protein Kinase Kinases/genetics; Rats; Signal Transduction*

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Last Reviewed: October 07, 2024