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More evidence for the Brain-Gut connection to Parkinson’s disease

Dr Ross Walker
Wednesday, July 03, 2019

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Over the past decade, there has been increasing evidence regarding the vital importance of gut health, not only as an indication of well-being, but also as a guardian against a number of other diseases. Two months ago, I wrote an article about the vital importance of the appendix. I detailed a large study of 62 million people in the US. Of the just under 500,000 people who’d their appendix removed, just under 5,000 developed Parkinson’s disease i.e. an incidence of 1%. Of the 61.7 million people who hadn’t had their appendix removed, just under 180,000 developed Parkinson’s disease i.e. an incidence of 0.29%.

For those of us with enormous skills in mathematics, this is around a 3 times higher incidence of Parkinson’s disease in those who have had their appendix removed. It appears that the appendix harbours a protein known as alpha synuclein and when the appendix is removed, it appears the alpha synuclein is released with toxic clumps being found in parts of the gastrointestinal tract. Interestingly, the same toxic clumps appear in the brains of people with Parkinson’s disease and an associated condition known as Lewy body dementia.

This misfolded protein, alpha synuclein, clumps together within certain parts of the brain and replaces normal nerve tissue with dead clumps of cells, which are called Lewy bodies. Interestingly, one of the early symptoms of Parkinson’s disease is constipation, which is now felt to be also due to the alpha synuclein in the gut altering normal gastrointestinal function.

One of the major connections between the gut and the brain is the vagus nerve system. Researchers at the Johns Hopkins university set out to see whether the alpha synuclein can travel up the vagus nerve from the gut to the base of the brain.

They took a group of mice and injected 25 µg of synthetic, misfolded alpha synuclein into the gastrointestinal tract of healthy mice. They then sampled brain tissue at a variety of intervals over the next 10 weeks after the injection. The researchers found the alpha synuclein building up from where the vagus nerve starts in the gut and then followed the spread to-related parts of the brain.

The next step was to cut the vagus nerve in one group of mice and again inject alpha synuclein into the gastrointestinal tract. At seven months, there were no signs of alpha synuclein in the vagus nerve or the brains of these mice, compared with those who had intact nerves.

The next step was to determine whether the specific injections affected the progression of Parkinson’s disease so the mice were split into three groups. The first injected with misfolded alpha synuclein, the second had the injections but severed vagus nerves and, finally, the control mice had no injections and normal vagus nerves.

They looked at the indications of Parkinson’s disease as seen in mice, which included the mice’s ability to construct nests and also measured mice anxiety levels by seeing how often they explored new cages and general mice behaviour.

The study found that only the mice injected with misfolded alpha synuclein with intact vagus nerves developed Parkinson’s disease.

This very elegant study clearly shows a link between the gut and the brain. This information takes us much closer to developing specific treatments for conditions such as Parkinson’s disease and Lewy body dementia with research directed at blocking the ability of the vagus nerve to take up alpha synuclein. I believe this is a significant breakthrough at many levels, which hopefully will see a cure at some stage in the relatively near future for two diseases, Parkinson’s disease and Lewy body dementia, both of which have a very deleterious effect on quality of life and lifespan.

Published: Wednesday, July 03, 2019


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