期刊
TOXICOLOGICAL SCIENCES
卷 124, 期 2, 页码 414-423出版社
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfr234
关键词
manganese speciation; developmental neurotoxicity; mitochondrial dysfunction; cerebellar granule neurons; cortical neurons
类别
资金
- Spanish Ministries of Health and of Science and Innovation [PI 061212, PI 10/0453]
- Generalitat of Catalunya [2009/SGR/214]
- Brazilian Sao Paulo Research Foundation [FAPESP 06/00001-3, 09/16018-0]
- Brazilian National Council for Scientific and Technological Development [CNPq 201362/2007-4]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [09/16018-0] Funding Source: FAPESP
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 MnCl2, 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.
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