MitoPark Transgenic Mouse Model Recapitulates the Gastrointestinal Dysfunction and Gut-Microbiome Changes of Parkinson's Disease.

MitoPark Transgenic Mouse Model Recapitulates the Gastrointestinal Dysfunction and Gut-Microbiome Changes of Parkinson's Disease. Neurotoxicology. 2019 Sep 07;: Authors: Ghaisas S, Langley MR, Palanisamy BN, Dutta S, Narayanaswamy K, Plummer PJ, Sarkar S, Ay M, Jin H, Anantharam V, Kanthasamy A, Kanthasamy AG Abstract Gastrointestinal (GI) disturbances are one of the earliest symptoms affecting most patients with Parkinson's disease (PD). In many cases, these symptoms are observed years before motor impairments become apparent. Hence, the molecular and cellular underpinnings that contribute to this early GI dysfunction in PD using a relevant animal model has actively been explored. The MitoPark model is a chronic, progressive mouse model recapitulating several key pathophysiological aspects of PD. However, GI dysfunction and gut microbiome changes have not been categorized in this model. Herein, we show that decreased GI motility was one of the first non-motor symptoms to develop, evident as early as 8 weeks with significantly different transit times from 12 weeks onwards. These symptoms were observed well before motor symptoms developed, thereby paralleling PD progression in humans. At age 24 weeks, we observed increased colon transit time and reduced fecal water content, indicative of constipation. Intestinal inflammation was evidenced with increased expression of iNOS and TNFα in the small and large intestine. Specifically, iNOS ...
Source: Neurotoxicology - Category: Neurology Authors: Tags: Neurotoxicology Source Type: research