Neuroprotective effects of lithium on a chronic MPTP mouse model of Parkinson's disease via regulation of α‑synuclein methylation

Zhao,Qing; Liu,Hui; Cheng,Jiwei; Zhu,Yudan; Xiao,Qian; Bai,Yu; Tao,Jie

doi:10.3892/mmr.2019.10152

Neuroprotective effects of lithium on a chronic MPTP mouse model of Parkinson's disease via regulation of α‑synuclein methylation

Authors:
- Qing Zhao
- Hui Liu
- Jiwei Cheng
- Yudan Zhu
- Qian Xiao
- Yu Bai
- Jie Tao
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Affiliations: Department of Neurology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China, Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
Published online on: April 11, 2019 https://doi.org/10.3892/mmr.2019.10152
Pages: 4989-4997

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Abstract

The pathological process of Parkinson's disease (PD) is closely associated with the death of nigral neurons, for which an effective treatment has yet to be found. Lithium, one of the most widely certified anticonvulsant and mood‑stabilizing agents, exhibits evident neuroprotective effects in the treatment of epilepsy and bipolar disorder. In the present study, the neuroprotective mechanisms by which lithium acts on a chronic 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine (MPTP) mouse model of PD were investigated by employing animal behavioral tests, immunohistochemistry, RT‑PCR, and western blotting. The results revealed that, in open field tests, lithium treatment counteracted the reduction in movement distance as well as activity time induced by MPTP administration. The compound could also prolong the drop time of MPTP‑treated mice in rotarod tests. Moreover, lithium treatment corrected the loss of nigral neurons, the increase of α‑synuclein (SNCA) in substantia nigra as well as in the striatum of MPTP‑treated mice, and decreased the methylation of SNCA intron 1 in DNA from the same regions. Furthermore, marked changes were observed in the expression of miRNAs including miR‑148a, a potential inhibitor of DNMT1, in the MPTP‑treated mice. These results suggested that the early application of lithium was important for alleviating the behavioral deficits experienced in the PD model, and that the neuroprotective action of lithium was achieved through a lithium‑triggered miRNA regulation mechanism. Essentially, our findings indicated that lithium may be beneficial in the prevention and treatment of PD through the regulation of α‑synuclein methylation.

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