Resveratrol protects dopaminergic neurons in a mouse model of Parkinson's disease by regulating the gut-brain axis via inhibiting the TLR4 signaling pathway
10.12122/j.issn.1673-4254.2024.02.09
- VernacularTitle:白藜芦醇对帕金森病模型小鼠多巴胺能神经元的保护作用:基于抑制TLR4/MyD88/NF-κB通路
- Author:
Jianjun GUI
1
,
2
,
3
,
4
;
Xiaodong SUN
;
Shu WEN
;
Xin LIU
;
Bingqing QIN
;
Ming SANG
Author Information
1. 湖北医药学院基础医学院,湖北 十堰 442000
2. 湖北医药学院附属襄阳市第一人民医院转化医学中心,湖北襄阳 441000
3. 湖北省帕金森病临床医学研究中心,湖北 襄阳 441000
4. 武当特色中药研究湖北省重点实验室,湖北 十堰 442000
- Keywords:
resveratrol;
Parkinson's disease;
microbiota-gut-brain axis;
dopaminergic neurons;
TLR4
- From:
Journal of Southern Medical University
2024;44(2):270-279
- CountryChina
- Language:Chinese
-
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.
