AD/PD 2021 | Chronic gut inflammation confers a sex-dependent PD vulnerability

We are going to be talking a little bit about a study that was done to try to understand what might be the connection between inflammatory bowel disorders and the risk for Parkinson’s or Parkinsonian pathology, and specifically the idea that chronic gut inflammation could give you brain inflammation, which could contribute to the loss of dopaminergic cells in the brain.

What we did is we gave these mice that have a predisposition for inflammation in the brain, we gave them chronic gut inflammation and then we asked the question, does that chronic gut inflammation affect the features of their nigrostriatal or dopaminergic pathway in the brain? And if so, what are some of the features that it affects? And then we tried to block that gut inflammation, and we pinned down a certain immune cell type to that process and by blocking the migration of that cell type to the brain, we were able to protect those dopaminergic cells in the brain.

What we think the study tells us is that there might be a relationship between having continuous insults peripherally in the gut, or maybe in the circulation, over many decades or many years, that bombard neurons that are vulnerable, like dopaminergic neurons, with too much brain inflammation, and if you’re able to mitigate that or lower that potentially with drugs that lower that inflammation, potentially drugs that treat IBD, such has been shown in epidemiological studies, that that may lower the brain inflammation at the same time as you lower the gut inflammation, and that might protect your brain.

Those are epidemiological studies that implicate anti-TNF drugs, for instance, in lowering the incidence of Parkinson’s, and we really want to take that a step further. Based on our study, we want to see if it’s true that blocking certain cell types from coming into the brain and making these inflammatory factors could really protect your brain against Parkinsonian pathology.