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Manganese induces dopaminergic neurodegeneration via microglial activation in a rat model of manganism.
Toxicol Sci. 2009 Jan; 107(1):156-64.TS

Abstract

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 MnCl(2).4H(2)O 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 alpha (TNF-alpha) gene expression, as well as iNOS, TNF-alpha, and interleukin-1beta (IL-1beta) protein levels in the SN. Furthermore, treatment with minocycline, an inhibitor of microglial activation, attenuated microglial activation and mitigated IL-1beta, TNF-alpha, 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.

Authors+Show Affiliations

Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, Xi'an, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18836210

Citation

Zhao, Fang, et al. "Manganese Induces Dopaminergic Neurodegeneration Via Microglial Activation in a Rat Model of Manganism." Toxicological Sciences : an Official Journal of the Society of Toxicology, vol. 107, no. 1, 2009, pp. 156-64.
Zhao F, Cai T, Liu M, et al. Manganese induces dopaminergic neurodegeneration via microglial activation in a rat model of manganism. Toxicol Sci. 2009;107(1):156-64.
Zhao, F., Cai, T., Liu, M., Zheng, G., Luo, W., & Chen, J. (2009). Manganese induces dopaminergic neurodegeneration via microglial activation in a rat model of manganism. Toxicological Sciences : an Official Journal of the Society of Toxicology, 107(1), 156-64. https://doi.org/10.1093/toxsci/kfn213
Zhao F, et al. Manganese Induces Dopaminergic Neurodegeneration Via Microglial Activation in a Rat Model of Manganism. Toxicol Sci. 2009;107(1):156-64. PubMed PMID: 18836210.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Manganese induces dopaminergic neurodegeneration via microglial activation in a rat model of manganism. AU - Zhao,Fang, AU - Cai,Tongjian, AU - Liu,Mingchao, AU - Zheng,Gang, AU - Luo,Wenjing, AU - Chen,Jingyuan, Y1 - 2008/10/04/ PY - 2008/10/7/entrez PY - 2008/10/7/pubmed PY - 2009/8/8/medline SP - 156 EP - 64 JF - Toxicological sciences : an official journal of the Society of Toxicology JO - Toxicol Sci VL - 107 IS - 1 N2 - 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 MnCl(2).4H(2)O 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 alpha (TNF-alpha) gene expression, as well as iNOS, TNF-alpha, and interleukin-1beta (IL-1beta) protein levels in the SN. Furthermore, treatment with minocycline, an inhibitor of microglial activation, attenuated microglial activation and mitigated IL-1beta, TNF-alpha, 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. SN - 1096-0929 UR - https://www.unboundmedicine.com/medline/citation/18836210/Manganese_induces_dopaminergic_neurodegeneration_via_microglial_activation_in_a_rat_model_of_manganism_ L2 - https://academic.oup.com/toxsci/article-lookup/doi/10.1093/toxsci/kfn213 DB - PRIME DP - Unbound Medicine ER -