Protective effects of prucalopride in MPTP-induced Parkinson's disease mice: Neurochemistry, motor function and gut barrier

  • Biochem Biophys Res Commun. 2021 Jun 4;556:16-22. doi: 10.1016/j.bbrc.2021.03.109.
Yun Shi  1 ,  Chen-Meng Qiao  1 ,  Yu Zhou  1 ,  Ji Wu  1 ,  Chun Cui  1 ,  Hui Hong  1 ,  Xue-Bing Jia  1 ,  Shu-Bing Huang  1 ,  Li Yao  1 ,  Wei-Jiang Zhao  1 ,  Yan-Qin Shen  2
Affiliations
  • 1. Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China; Department of Neurodegeneration and Injury, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.
  • 2. Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China; Department of Neurodegeneration and Injury, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China. Electronic address: [email protected].
PMID: 33836343 DOI: 10.1016/j.bbrc.2021.03.109
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.

Keywords
5-HT4R; IL-6; Intestinal barrier; Parkinson’s disease; Prucalopride.
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