title: Developmental exposure to manganese induces lasting motor and cognitive impairment in rats.
abstract: 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 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.
authors.affiliation: Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: tanaravp@gmail.com.
authors.forename: Tanara V
authors.initials: TV
authors.lastname: Peres
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Helena
authors.initials: H
authors.lastname: Eyng
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Samantha C
authors.initials: SC
authors.lastname: Lopes
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Dirleise
authors.initials: D
authors.lastname: Colle
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Filipe M
authors.initials: FM
authors.lastname: Gonçalves
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Débora K R
authors.initials: DK
authors.lastname: Venske
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Lopes
authors.affiliation: Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Ben
authors.affiliation: Institute of Nutritional Sciences, University of Potsdam, Nuthetal, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Bornhorst
authors.affiliation: Institute of Nutritional Sciences, University of Potsdam, Nuthetal, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schwerdtle
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
authors.affiliation: Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farina
authors.affiliation: Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Rui D
authors.initials: RD
authors.lastname: Prediger
authors.affiliation: Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: rbleal@gmail.com.
authors.forename: Rodrigo B
authors.initials: RB
authors.lastname: Leal
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced*; D002658:Developmental Disabilities / Q000139:chemically induced*; D004192:Discrimination, Psychological / Q000187:drug effects; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000633:toxicity*; D009069:Movement Disorders / Q000209:etiology*; D010468:Perceptual Disorders / Q000139:chemically induced; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects; D012903:Smell / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D013438:Sulfhydryl Compounds; D008345:Manganese; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione
keywords: Cognition; Development; Manganese; Motor coordination; Neurotoxicity