Abstract: Objective To investigate the protective effect of resveratrol on intestinal barrier in 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse models and its mechanism for regulating TLR4/MyD88/NF-κB signaling to protect dopaminergic neurons. Methods Fifty-two C57BL/6J mice were randomized into control group (n=12), MPTP group (n=14), MPTP + resveratrol (30 mg/kg) group (n=13), and MPTP + resveratrol (90 mg/kg) group (n=13), and mouse models were established by intraperitoneal MPTP (30 mg/kg) injection for 7 days in the latter 3 groups. Behavioral tests were conducted to evaluate the effect of resveratrol on motor symptoms of the mice. Western blotting was used to detect the expression of TH, α-syn, ZO-1, Claudin-1, TLR4, MyD88, and NF-κB in the brain tissues of the mice. Immunohistochemistry, immunofluorescence, ELISA and transmission electron microscopy were used to verify the effect of resveratrol for suppressing inflammation and protecting the intestinal barrier. Results Compared with those in the normal control group, the mice in MPTP group showed significant changes in motor function, number of dopaminergic neurons, neuroinflammation, levels of LPS and LBP, and expressions of tight junction proteins in the intestinal barrier. Resveratrol treatment significantly improved motor function of the PD mice (P<0.01), increased the number of neurons and TH protein expression (P<0.05), down-regulated the expressions of GFAP, Iba-1, and TLR4, lowered fecal and plasma levels of LPS and LBP (P<0.05), restored the expression levels of ZO-1 and Claudin-1 (P<0.01), and down-regulated the expressions of TLR4, MyD88, and NF-κB in the colon tissue (P<0.05). The mice with resveratrol treatment at 30 mg/kg showed normal morphology of the tight junction complex with neatly and tightly arranged intestinal villi. Conclusion Resveratrol repairs the intestinal barrier by inhibiting TLR4/MyD88/NF-κB signaling pathway-mediated inflammatory response, thereby improving motor function and neuropathy in mouse models of MPTP-induced PD.

Key words: resveratrol; Parkinson's disease; microbiota-gut-brain axis; dopaminergic neurons; TLR4