Chronic stress-induced gut dysfunction exacerbates Parkinson's disease phenotype and pathology in a rotenone-induced mouse model of Parkinson's disease.

Chronic stress-induced gut dysfunction exacerbates Parkinson's disease phenotype and pathology in a rotenone-induced mouse model of Parkinson's disease. Neurobiol Dis. 2018 Dec 20;: Authors: Dodiya HB, Forsyth CB, Voigt RM, Engen PA, Patel J, Shaikh M, Green SJ, Naqib A, Roy A, Kordower JH, Pahan K, Shannon KM, Keshavarzian A Abstract Recent evidence provides support for involvement of the microbiota-gut-brain axis in Parkinson's disease (PD) pathogenesis. We propose that a pro-inflammatory intestinal milieu, due to intestinal hyper-permeability and/or microbial dysbiosis, initiates or exacerbates PD pathogenesis. One factor that can cause intestinal hyper-permeability and dysbiosis is chronic stress which has been shown to accelerate neuronal degeneration and motor deficits in Parkinsonism rodent models. We hypothesized that stress-induced intestinal barrier dysfunction and microbial dysbiosis lead to a pro-inflammatory milieu that exacerbates the PD phenotype in the low-dose oral rotenone PD mice model. To test this hypothesis, mice received unpredictable restraint stress (RS) for 12 weeks, and during the last six weeks mice also received a daily administration of low-dose rotenone (10 mg/kg/day) orally. The initial six weeks of RS caused significantly higher urinary cortisol, intestinal hyperpermeability, and decreased abundance of putative "anti-inflammatory" bacteria (Lactobacillus) compared to non-stressed mice. Rotenone al...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research