Effects of probiotic supplementation on intestinal tight junctions in a mouse model of Parkinson’s disease

Parkinson’s disease (PD) is a neurological disease impacting over six million people in the world. In addition to the motor symptoms of the disease, the disorder is accompanied with gastrointestinal problems. These include delayed transit time, disturbances in the microbial composition of the gut, inflammation in the intestine, structural changes in the epithelial lining and increased intestinal permeability. Paracellular permeability is regulated by tight junctions (TJ) which are complexes formed by proteins such as claudins, occludin and zonula occludens proteins. Probiotics are live microorganisms which when administered have beneficial effects on the host. Probiotic bacteria can modulate intestinal permeability and the expression of TJ proteins. These microbes are also able to improve the gastrointestinal symptoms, such as constipation, in PD patients. As a part of a larger study, the aim was to examine whether the expression of TJ proteins is altered in the lactacystin-induced mouse model of PD and to investigate whether probiotic supplementation elicits changes in their expression. The study was conducted in eight- to nine-week-old C57Bl/6JRccHsd mice, to which PD symptoms had been induced by lactacystin injection to the substantia nigra. Starting at one to two weeks after the injection, four groups of mice were treated with one out of four specific probiotic strains (A, B, C and D) for two weeks. At the end of the experiment, jejunal and colonic samples were collected from the mice. These samples were analyzed using Western Blot to determine the expression of TJ proteins claudin-1, claudin-4 and occludin. Based on the WB results, the jejunal gene level expression of these proteins in one probiotic group (D) was compared to the untreated group with reverse transcription quantitative polymerase chain reaction. The expression of TJ proteins was not altered as a result of the lactacystin injection in jejunum or colon, suggesting that lactacystin model is not optimal for investigating PD-related alterations in TJ proteins. Supplementation with microbe D increased the jejunal expression of claudin-1 on both protein and gene level, whereas in the colonic protein expression there was no change. Clear effects were not detected on claudin-4 or occludin nor when treated with microbes A, B or C. Therefore, microbe D might influence intestinal TJ function and permeability through regulating the expression of claudin-1. CLICK TO REVIEW