Protective effects of prucalopride in MPTP-induced Parkinson’s disease mice: Neurochemistry, motor function and gut barrier
Yun Shi, Chen-Meng Qiao, Yu Zhou, Ji Wu, Chun Cui, Hui Hong, Xue-Bing Jia, Shu-Bing Huang, Li Yao, Wei-Jiang Zhao, Yan-Qin Shen
Journal：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
IF：3.58
DOI：10.1016/j.bbrc.2021.03.109
PMID：33836343
Published：2021-04-06
research field：药理学临床医学遗传学
Abstract
Evidence suggests constipation precedes motor dysfunction and is the most common gastrointestinal symptom in Parkinson’s disease (PD). 5-HT4 receptor (5-HT4R) agonist prucalopride has been approved to treat chronic constipation. Here, we reported intraperitoneal injection of prucalopride for 7 days increased dopamine and decreased dopamine turnover. Prucalopride administration improved motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced PD mouse models. Prucalopride treatment also ameliorated intestinal barrier impairment and increased IL-6 release in PD model mice. However, prucalopride treatment exerted no impact on JAK2/STAT3 pathway, suggesting that prucalopride may stimulate IL-6 via JAK2/STAT3-independent pathway. In conclusion, prucalopride exerted beneficial effects in MPTP-induced Parkinson’s disease mice by attenuating the loss of dopamine, improving motor dysfunction and intestinal barrier.
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