Cross-Talk Between The Gut And The Brain In Rats Subjected To Lps-Induced Inflammation: Role Of Alpha-Synuclein

It is now well established that the involvement of the gastrointestinal tract is of great interest as a contributing factor to the development and progression of neurodegenerative diseases. The dysregulation of the Gut‐Brain‐Axis (GBA) may be associated with gastrointestinal manifestations preceding disorders of cognitive and/or memory and learning process, supporting the hypothesis that the pathological process is spread from the gut to the brain (Mayer et al. 2014). The extensive involvement of the gut in neurodegenerative diseases such as Parkinson's disease, even in its early stages, has led to the evaluation of enteric α‐synuclein as a possible biomarker (Forsyth et al. 2011). Therefore, the overall goal of the proposed study is to assess the time course of the compromised intestinal barrier capable of influencing brain function in rats challenged with LPS. Specifically, we hypothesize that alterations of the intestinal barrier (or leaky guts) enhances inflammation as well as the production of a unique protein α‐synuclein which has characteristic of degenerative diseases. To induce inflammation, Lipopolysaccharide (LPS) was administered intravenously (IV) in rats at a dose of 20 mg/kg (Doursout et al. 2013). A single dose LPS was elected based on previously reported results from a mouse model (Qin et al. 2007). Animals were divided into 2 groups (saline and LPS). Animals were divided into 2 sub‐groups (short term; 1 week and long term 4 weeks). Following sacrifice at each time point, tissues (gut and brain e.g. hippocampus and olfactory bulb) were harvested. We measured edema formation in the gut in rats subjected to LPS as compared to saline by wet/dry ratio. Alpha‐synuclein was determined using ELISA (R&D Systems) in small and large intestines as well as in the brain at each time point. Data are expressed as Mean ± SEM. Our data show that LPS induced edema in the gut, suggesting inflammation. Our data demonstrate that increases in α‐synuclein protein concentrations were time‐dependent in the hippocampus and in the olfactory bulb. We postulate that LPS induce an increase in α‐synuclein concentrations in the gut and spread to the brain at a later time point.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.