Neurotoxic Effects of Injected Manganese Salt

Toxicological Sciences 2009 107(1):156-164;
Manganese Induces Dopaminergic Neurodegeneration via Microglial Activation in a Rat Model of Manganism

Fang Zhao, Tongjian Cai, Mingchao Liu, Gang Zheng, Wenjing Luo1 and Jingyuan Chen1

Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, Xi'an, China

1 To whom correspondence should be addressed at Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, 17 Changlexi Street, Xi'an, China. Fax: +86-29-84774863. E-mail: jy_chen@fmmu.edu.cn

"Manganese is an essential trace element required for normal development and bodily functions. However, exposure of the brain to excessive amounts of manganese results in neurotoxicity. Although previous studies examining manganese neurotoxicity have focused on neuronal injury, especially direct injury to dopaminergic neurons, the effects of manganese-induced neurotoxicity on glial cells have not been reported. The current study was designed to examine the effect of manganese on microglial activation, and the underlying mechanism of manganese-induced dopaminergic neuronal injury in vivo. We established an animal model of manganism by intrastriatal injection of MnCl2·4H2O into male Sprague-Dawley rats. One day after administration of manganese, a few microglial cells in the substantia nigra (SN) were activated, although the number of tyrosine hydroxylase (TH)–immunoreactive neurons in the SN was unaffected. Seven days after administration of manganese, a marked reduction in the number of TH-immunoreactive neurons was observed in the SN, and the majority of microglial cells were activated. We found that manganese upregulated inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF-) gene expression, as well as iNOS, TNF-, and interleukin-1β (IL-1β) protein levels in the SN. Furthermore, treatment with minocycline, an inhibitor of microglial activation, attenuated microglial activation and mitigated IL-1β, TNF-, and iNOS production as well as dopaminergic neurotoxicity induced by manganese. These results suggested that dopaminergic neurons could be damaged by manganese neurotoxicity, and that the activated microglial cells and their associated activation products played an important role in this neurodegenerative process."

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BrooklynDodger(s) comments: This report comes from an interesting location, a sign that economic development in China is accompanied by ongoing toxicologic research. An important lesson from this paper is that the nervous system and its function include a lot more cells than just neurons. The site of action of a toxic chemical can be the glial cells - which wrap and support the neurons. Tumors arise from glial cells as well, rather than neurons.