Manganese exposure causes movement deficit and changes in the protein profile of the external globus pallidus in Sprague Dawley rats.

Kaiqin Zhang, Kaiwu He, Jia Xu, Lulin Nie, Shupeng Li, Jianjun Liu, Dingxin Long, Zhongliang Dai, Xifei Yang

Toxicology and industrial health 2021 Dec

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Manganese (Mn) is required for normal brain development and function. Excess Mn may trigger a parkinsonian movement disorder but the underlying mechanisms are incompletely understood. We explored changes in the brain proteomic profile and movement behavior of adult Sprague Dawley (SD) rats systemically treated with or without 1.0 mg/mL MnCl2 for 3 months. Mn treatment significantly increased the concentration of protein-bound Mn in the external globus pallidus (GP), as demonstrated by inductively coupled plasma mass spectrometry. Behavioral study showed that Mn treatment induced movement deficits, especially of skilled movement. Proteome analysis by two-dimensional fluorescence difference gel electrophoresis coupled with mass spectrometry revealed 13 differentially expressed proteins in the GP of Mn-treated versus Mn-untreated SD rats. The differentially expressed proteins were mostly involved in glycolysis, metabolic pathways, and response to hypoxia. Selected pathway class analysis of differentially expressed GP proteins, which included phosphoglycerate mutase 1 (PGAM1), primarily identified enrichment in glycolytic process and innate immune response. In conclusion, perturbation of brain energy production and innate immune response, in which PGAM1 has key roles, may contribute to the movement disorder associated with Mn neurotoxicity.

Citation

Kaiqin Zhang, Kaiwu He, Jia Xu, Lulin Nie, Shupeng Li, Jianjun Liu, Dingxin Long, Zhongliang Dai, Xifei Yang. Manganese exposure causes movement deficit and changes in the protein profile of the external globus pallidus in Sprague Dawley rats. Toxicology and industrial health. 2021 Dec;37(12):715-726