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Journal of Neural Transmission

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19.04.2019 | Neurology and Preclinical Neurological Studies - Original Article

Microglia activation induces oxidative injury and decreases SIRT3 expression in dopaminergic neuronal cells

verfasst von: De-Qi Jiang, Yan-Jiao Ma, Yong Wang, Hai-Xiao Lu, Shu-Hui Mao, Shi-Hua Zhao

Erschienen in: Journal of Neural Transmission | Ausgabe 5/2019

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Abstract

Microglia activation-mediated neuroinflammation plays an important role in the progression of Parkinson’s disease (PD). However, effects of microglia activation on dopaminergic neuronal cell (DAC) fate are still poorly understood. The objective of this study was to explore the neurotoxic effects of microglia activation-mediated oxidative injury in DACs and its possible mechanisms. In the present study, microglia-DACs co-culture systems (murine BV-2 and MN9D cells, or primary microglia and mesencephalic neurons) were used to display the crosstalk between both cell types. The cytotoxicity of lipopolysaccharide-induced microglia activation led to the accumulation of intracellular reactive oxygen species, increased cell apoptosis rate, reduced number of DACs, concomitant to cell cycle arrest at G₁ phase. Molecular mechanisms of apoptosis caused by microglia activation-induced oxidative injury included the increased opening of mitochondrial permeability transition pore and enhanced membrane potential depolarization in MN9D cells, down-regulation of Bcl-2 and up-regulation of Bax, caspase-3 expression in DACs. In addition, microglia activation made a significant reduction of SIRT3 and superoxide dismutase 2 gene expression in DACs. Taken together, these data imply that microglia activation promotes cell apoptosis through mitochondrial pathway and decreases SIRT3 expression in DACs, which may provide some support for PD progression promoted by neuroinflammation.

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Titel: Microglia activation induces oxidative injury and decreases SIRT3 expression in dopaminergic neuronal cells
verfasst von: De-Qi Jiang
Yan-Jiao Ma
Yong Wang
Hai-Xiao Lu
Shu-Hui Mao
Shi-Hua Zhao
Publikationsdatum: 19.04.2019
Verlag: Springer Vienna
Erschienen in: Journal of Neural Transmission / Ausgabe 5/2019
Print ISSN: 0300-9564
Elektronische ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-019-02005-z

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Microglia activation induces oxidative injury and decreases SIRT3 expression in dopaminergic neuronal cells

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