Mechanisms of Manganese-Induced Neurotoxicity in Primary Neuronal Cultures: the Role of Manganese Speciation and Cell Type

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dc.contributor.author Hernandez, R. B. [UNIFESP]
dc.contributor.author Farina, M.
dc.contributor.author Esposito, B. P.
dc.contributor.author Souza-Pinto, N. C.
dc.contributor.author Barbosa, F.
dc.contributor.author Sunol, C.
dc.date.accessioned 2016-01-24T14:17:28Z
dc.date.available 2016-01-24T14:17:28Z
dc.date.issued 2011-12-01
dc.identifier http://dx.doi.org/10.1093/toxsci/kfr234
dc.identifier.citation Toxicological Sciences. Oxford: Oxford Univ Press, v. 124, n. 2, p. 414-423, 2011.
dc.identifier.issn 1096-6080
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/34250
dc.description.abstract Manganese (Mn) is an essential trace element required for the proper functioning of a variety of physiological processes. However, chronic exposures to Mn can cause neurotoxicity in humans, especially when it occurs during critical stages of the central nervous system development. the mechanisms mediating this phenomenon as well as the contribution of Mn speciation and the sensitivity of different types of neuronal cells in such toxicity are poorly understood. This study was aimed to investigate the mechanisms mediating the toxic effects of MnCl(2), Mn(II) citrate, Mn(III) citrate, and Mn(III) pyrophosphate in primary cultures of neocortical (CTX) and cerebellar granular (CGC) neurons. Cell viability, mitochondrial function, and glutathione levels were evaluated after Mn exposure. CGC were significantly more susceptible to Mn-induced toxicity when compared with CTX. Moreover, undifferentiated CGC were more vulnerable to Mn toxicity than mature neurons. Mitochondrial dysfunction was observed after the exposure to all the tested Mn species. Ascorbate protected CGC against Mn-induced neurotoxicity, and this event seemed to be related to the dual role of ascorbate in neurons, acting as antioxidant and metabolic energetic supplier. CTX were protected from Mn-induced toxicity by ascorbate only when coincubated with lactate. These findings reinforce and extend the notion of the hazardous effects of Mn toward neuronal cells. in addition, the present results indicate that Mn-induced neurotoxicity is influenced by brain cell types, their origins, and developmental stages as well as by the chemical speciation of Mn, thus providing important information about Mn-induced developmental neurotoxicity and its risk assessment. en
dc.description.sponsorship Spanish Ministries of Health and of Science and Innovation
dc.description.sponsorship Generalitat of Catalunya
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Brazilian National Council for Scientific and Technological Development
dc.format.extent 414-423
dc.language.iso eng
dc.publisher Oxford Univ Press
dc.relation.ispartof Toxicological Sciences
dc.rights Acesso aberto
dc.subject manganese speciation en
dc.subject developmental neurotoxicity en
dc.subject mitochondrial dysfunction en
dc.subject cerebellar granule neurons en
dc.subject cortical neurons en
dc.title Mechanisms of Manganese-Induced Neurotoxicity in Primary Neuronal Cultures: the Role of Manganese Speciation and Cell Type en
dc.type Artigo
dc.rights.license http://www.oxfordjournals.org/access_purchase/self-archiving_policyb.html
dc.contributor.institution IIBB CSIC IDIBAPS
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Universidade de São Paulo (USP)
dc.contributor.institution Universidade Federal de Santa Catarina (UFSC)
dc.contributor.institution CIBERESP
dc.description.affiliation IIBB CSIC IDIBAPS, Inst Invest Biomed Barcelona, Dept Neurochem & Neuropharmacol, Barcelona 08036, Spain
dc.description.affiliation Universidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Dept Ciencias Exatas & Terra, BR-09972270 São Paulo, Brazil
dc.description.affiliation Univ São Paulo, Inst Quim, Dept Quim Fundamental, BR-05508000 São Paulo, Brazil
dc.description.affiliation Univ Fed Santa Catarina, Ctr Ciencias Biol, Dept Bioquim, BR-88040900 Florianopolis, SC, Brazil
dc.description.affiliation Univ São Paulo, Fac Pharmaceut Sci Ribeirao Preto, Dept Clin Toxicol & Bromatol Anal, BR-14040903 São Paulo, Brazil
dc.description.affiliation CIBERESP, Madrid 08029, Spain
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Dept Ciencias Exatas & Terra, BR-09972270 São Paulo, Brazil
dc.description.sponsorshipID Spanish Ministries of Health and of Science and Innovation: PI 061212
dc.description.sponsorshipID Spanish Ministries of Health and of Science and Innovation: PI 10/0453
dc.description.sponsorshipID Generalitat of Catalunya: 2009/SGR/214
dc.description.sponsorshipID FAPESP: FAPESP 06/00001-3
dc.description.sponsorshipID FAPESP: 09/16018-0
dc.description.sponsorshipID Brazilian National Council for Scientific and Technological Development: CNPq 201362/2007-4
dc.identifier.doi 10.1093/toxsci/kfr234
dc.description.source Web of Science
dc.identifier.wos WOS:000297223600017



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