title: In vitro manganese exposure disrupts MAPK signaling pathways in striatal and hippocampal slices from immature rats.
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.
authors: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, 88040-900 Florianópolis, SC, Brazil.
authors: Tanara Vieira
authors: TV
authors: Peres
authors: Daniela Zótico
authors: DZ
authors: Pedro
authors: Fabiano Mendes
authors: FM
authors: de Cordova
authors: Mark William
authors: MW
authors: Lopes
authors: Filipe Marques
authors: FM
authors: Gonçalves
authors: Cláudia Beatriz Nedel
authors: CB
authors: Mendes-de-Aguiar
authors: Roger
authors: R
authors: Walz
authors: Marcelo
authors: M
authors: Farina
authors: Michael
authors: M
authors: Aschner
authors: Rodrigo Bainy
authors: RB
authors: Leal
mesh_terms: D000818:Animals; D001931:Brain Mapping; D002490:Central Nervous System / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008345:Manganese / Q000633:toxicity*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D015398:Signal Transduction
chemical_list: D008345:Manganese; D020929:Mitogen-Activated Protein Kinase Kinases