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

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

Author Hernandez, R. B. Autor UNIFESP Google Scholar
Farina, M. Google Scholar
Esposito, B. P. Google Scholar
Souza-Pinto, N. C. Google Scholar
Barbosa, F. Google Scholar
Sunol, C. Google Scholar
Institution IIBB CSIC IDIBAPS
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Universidade Federal de Santa Catarina (UFSC)
CIBERESP
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.
Keywords manganese speciation
developmental neurotoxicity
mitochondrial dysfunction
cerebellar granule neurons
cortical neurons
Language English
Sponsor Spanish Ministries of Health and of Science and Innovation
Generalitat of Catalunya
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Brazilian National Council for Scientific and Technological Development
Grant number Spanish Ministries of Health and of Science and Innovation: PI 061212
Spanish Ministries of Health and of Science and Innovation: PI 10/0453
Generalitat of Catalunya: 2009/SGR/214
FAPESP: FAPESP 06/00001-3
FAPESP: 09/16018-0
Brazilian National Council for Scientific and Technological Development: CNPq 201362/2007-4
Date 2011-12-01
Published in Toxicological Sciences. Oxford: Oxford Univ Press, v. 124, n. 2, p. 414-423, 2011.
ISSN 1096-6080 (Sherpa/Romeo, impact factor)
Publisher Oxford Univ Press
Extent 414-423
Origin http://dx.doi.org/10.1093/toxsci/kfr234
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000297223600017
URI http://repositorio.unifesp.br/handle/11600/34250

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