Intragastric Administration of Casein Leads to Nigrostriatal Disease Progressed Accompanied with Persistent Nigrostriatal-Intestinal Inflammation Activited and Intestinal Microbiota-Metabolic Disorders Induced in MPTP Mouse Model of Parkinson's Disease

作者全名："Liu, Xinrong; Liu, Shuya; Tang, Yong; Pu, Zhengjia; Xiao, Hong; Gao, Jieying; Yin, Qi; Jia, Yan; Bai, Qunhua"

作者地址："[Liu, Xinrong; Liu, Shuya; Pu, Zhengjia; Xiao, Hong; Gao, Jieying; Yin, Qi; Jia, Yan; Bai, Qunhua] Chongqing Med Univ, Sch Publ Hlth & Management, 1 Yi Xue Yuan Rd, Chongqing 400016, Peoples R China; [Tang, Yong] Chongqing Orthoped Hosp Tradit Chinese Med, Chongqing 400039, Peoples R China"

通信作者："Bai, QH (corresponding author), Chongqing Med Univ, Sch Publ Hlth & Management, 1 Yi Xue Yuan Rd, Chongqing 400016, Peoples R China."

来源：NEUROCHEMICAL RESEARCH

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000628732200001

JCR分区：Q2

影响因子：4.4

年份：2021

卷号：46

期号：6

开始页：1514

结束页：1539

文献类型：Article

关键词：Casein; MPTP; Neuroinflammation; Gut microbiota; Metabolites; Parkinson’ s disease

摘要："Gut microbial dysbiosis and alteration of gut microbiota composition in Parkinson's disease (PD) have been increasingly reported, no recognized therapies are available to halt or slow progression of PD and more evidence is still needed to illustrate its causative impact on gut microbiota and PD and mechanisms for targeted mitigation. Epidemiological evidence supported an association between milk intake and a higher incidence of Parkinson's disease (PD), questions have been raised about prospective associations between dietary factors and the incidence of PD. Here, we investigated the significance of casein in the development of PD. The mice were given casein (6.75 g/kg i.g.) for 21 days after MPTP (25 mg/kg i.p. x 5 days) treatment, the motor function, dopaminergic neurons, inflammation, gut microbiota and fecal metabolites were observed. The experimental results revealed that the mice with casein gavage after MPTP treatment showed a persisted dyskinesia, the content of dopamine in striatum and the expression of TH in midbrain and ileum were decreased, the expression of Iba-1, CD4, IL-22 in midbrain and ileum increased continuously with persisted intestinal histopathology and intestinal barrier injury. Decreased intestinal bile secretion in addition with abnormal digestion and metabolism of carbohydrate, lipids and proteins were found, whereas these pathological status for the MPTP mice without casein intake had recovered after 24 days, no significant differences were observed with regard to only treated with casein. Our study demonstrates that intestinal pathologic injury, intestinal dysbacteriosis and metabolism changes promoted by casein in MPTP mice ultimately exacerbated the lesions to dopaminergic neurons."

基金机构：Chongqing Yuzhong Nature Science Foundation [20190146]; Chongqing Natural Science FoundationNatural Science Foundation of Chongqing [2020ZY023699]

基金资助正文：This work was founded by the Chongqing Yuzhong Nature Science Foundation [Grant Number 20190146] and Chongqing Natural Science Foundation [Grant Number 2020ZY023699] of China.