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Developmental exposure to manganese induces lasting motor and cognitive impairment in rats

  • Exposure to high manganese (Mn) levels may damage the basal ganglia, leading to a syndrome analogous to Parkinson's disease, with motor and cognitive impairments. The molecular mechanisms underlying Mn neurotoxicity, particularly during development, still deserve further investigation. Herein, we addressed whether early-life Mn exposure affects motor coordination and cognitive function in adulthood and potential underlying mechanisms. Male Wistar rats were exposed intraperitoneally to saline (control) or MnCl2 (5, 10 or 20 mg/kg/day) from post-natal day (PND) 8-12. Behavioral tests were performed on PND 60-65 and biochemical analysis in the striatum and hippocampus were performed on PND14 or PND70. Rats exposed to Mn (10 and 20 mg/kg) performed significantly worse on the rotarod test than controls indicating motor coordination and balance impairments. The object and social recognition tasks were used to evaluate short-term memory. Rats exposed to the highest Mn dose failed to recognize a familiar object when replaced by a novel objectExposure to high manganese (Mn) levels may damage the basal ganglia, leading to a syndrome analogous to Parkinson's disease, with motor and cognitive impairments. The molecular mechanisms underlying Mn neurotoxicity, particularly during development, still deserve further investigation. Herein, we addressed whether early-life Mn exposure affects motor coordination and cognitive function in adulthood and potential underlying mechanisms. Male Wistar rats were exposed intraperitoneally to saline (control) or MnCl2 (5, 10 or 20 mg/kg/day) from post-natal day (PND) 8-12. Behavioral tests were performed on PND 60-65 and biochemical analysis in the striatum and hippocampus were performed on PND14 or PND70. Rats exposed to Mn (10 and 20 mg/kg) performed significantly worse on the rotarod test than controls indicating motor coordination and balance impairments. The object and social recognition tasks were used to evaluate short-term memory. Rats exposed to the highest Mn dose failed to recognize a familiar object when replaced by a novel object as well as to recognize a familiar juvenile rat after a short period of time. However, Mn did not alter olfactory discrimination ability. In addition, Mn-treated rats displayed decreased levels of non-protein thiols (e.g. glutathione) and increased levels of glial fibrillary acidic protein (GFAP) in the striatum. Moreover, Mn significantly increased hippocampal glutathione peroxidase (GPx) activity. These findings demonstrate that acute low-level exposure to Mn during a critical neurodevelopmental period causes cognitive and motor dysfunctions that last into adulthood, that are accompanied by alterations in antioxidant defense system in both the hippocampus and striatum. (C) 2015 Elsevier Inc. All rights reserved.show moreshow less

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Metadaten
Author:Tanara V. Peres, Helena Eyng, Samantha C. Lopes, Dirleise Colle, Filipe M. Goncalves, Debora K. R. Venske, Mark W. Lopes, Juliana Ben, Julia Bornhorst, Tanja Schwerdtle, Michael Aschner, Marcelo Farina, Rui D. Prediger, Rodrigo B. Leal
DOI:https://doi.org/10.1016/j.neuro.2015.07.005
ISSN:0161-813X (print)
ISSN:1872-9711 (online)
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=26215118
Parent Title (English):Neurotoxicology : the interdisciplinary journal of effects to toxic substances on the nervous system
Publisher:Elsevier
Place of publication:Amsterdam
Document Type:Article
Language:English
Year of first Publication:2015
Year of Completion:2015
Release Date:2017/03/27
Tag:Cognition; Development; Manganese; Motor coordination; Neurotoxicity
Volume:50
Pagenumber:10
First Page:28
Last Page:37
Funder:Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) Brazil [308459/2013-0, 481523/2013-8]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [249-14]; National Institute of Science and Technology (INCT) for Excitotoxicity and Neuroprotection; Fundacao de Amparo a Pesquisa de Santa Catarina (FAPESC)/PRONEX - Nucleo de Excelencia em Neurociencias Aplicadas de Santa Catarina (NENASC) [1262/2012-9]; CNPq; CAPES Foundation, Ministry of Education of Brazil [0407/13-5]
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft
Peer Review:Referiert