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.

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. × 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.

Exercise training has a protective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice model with improved neural and intestinal pathology and modified intestinal flora.

Parkinson's disease (PD) is a common neurodegenerative disease with the exact etiology still unclear, but gut microbial disorders are thought to be related to the initiation and progression of it. Exercise training has a significant effect on the intestinal flora, so to investigate the promotion effect of exercise training on Parkinson's disease, we performed a rotarod walking training (5 times a week at 25 rpm for 20 min for 8 weeks) on a chronic mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and observed the locomotor function of mice, function of dopaminergic neurons, intestinal mucosal barrier condition, intestinal inflammation and the structure and composition of intestinal flora. The results showed in these PD mice, exercise training improved their motility, increased the dopamine (DA) content in the striatum, along with promoted the gene expression of tyrosine hydroxylase and brain-derived neurotrophic factor in the striatum, which suggests this exercise training might protect striatal dopaminergic neurons from MPTP damage; the results also showed exercise training promoted recovery from ileal pathology, reduced the gene expression of intestinal inflammatory factors, and significantly altered the composition and structure of the intestinal flora in these mice.

Casein Reactivates Dopaminergic Nerve Injury and Intestinal Inflammation with Disturbing Intestinal Microflora and Fecal Metabolites in a Convalescent Parkinson's Disease Mouse Model.

Parkinson's disease (PD) is the fastest-growing neurodegenerative disease, with pathogenic causes elusive and short of effective treatment options. Investigations have found that dairy products positively correlate with the onset of PD, but the mechanisms remain unexplored. As casein is an antigenic component in dairy products, this study assessed if casein could exacerbate PD-related symptoms by stimulating intestinal inflammation and unbalanced intestinal flora and be a risk factor for PD. Using a convalescent PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the results showed casein reduced motor coordination, caused gastrointestinal dysfunction, reduced dopamine content, and induced intestinal inflammation. Meanwhile, casein disturbed gut microbiota homeostasis by increasing the Firmicutes/Bacteroidetes ratio, decreasing α-diversity, and caused abnormal alterations in fecal metabolites. However, these adverse effects of casein attenuated much when it had hydrolyzed by acid or when antibiotics inhibited the intestinal microbiota of the mice. Therefore, our results suggested that casein could reactivate dopaminergic nerve injury and intestinal inflammation and exacerbate intestinal flora disorder and its metabolites in convalescent PD mice. These damaging effects might be related to disordered protein digestion and gut microbiota in these mice. These findings will provide new insights into the impact of milk/dairy products on PD progression and supply information on dietary options for PD patients.

Effects of Information Overload, Communication Overload, and Inequality on Digital Distrust: A Cyber-Violence Behavior Mechanism.

In recent years, there has been an escalation in cases of cyber violence, which has had a chilling effect on users' behavior toward social media sites. This article explores the causes behind cyber violence and provides empirical data for developing means for effective prevention. Using elements of the stimulus-organism-response theory, we constructed a model of cyber-violence behavior. A closed-ended questionnaire was administered to collect data through an online survey, which results in 531 valid responses. A proposed model was tested using partial least squares structural equation modeling using SmartPLS 3.0, v (3.2.8). Research findings show that information inequality is a strong external stimulus with a significant positive impact on digital distrust and negative emotion. However, the effects of information overload on digital distrust and the adverse effects of communication overload on negative emotions should not be ignored. Both digital distrust and negative emotions have significant positive impacts on cyber violence and cumulatively represent 11.5% changes in cyber violence. Furthermore, information overload, communication overload, information inequality, and digital distrust show a 27.1% change in negative emotions. This study also presents evidence for competitive mediation of digital distrust by information overload, information inequality, and cyber violence. The results of this study have implications for individual practitioners and scholars, for organizations, and at the governmental level regarding cyber-violence behavior. To test our hypotheses, we have constructed an empirical, multidimensional model, including the role of specific mediators in creating relationships.