Medical

Animal study presents best evidence to date that Parkinson’s begins in the gut

Animal study presents best evi...
New research revealed how toxic proteins can travel up from the gut into the brain to causes damage similar to that seen in Parkinson's disease
New research revealed how toxic proteins can travel up from the gut into the brain to causes damage similar to that seen in Parkinson's disease
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Route of Parkinson’s disease-causing protein propagation in mice
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Route of Parkinson’s disease-causing protein propagation in mice
New research revealed how toxic proteins can travel up from the gut into the brain to causes damage similar to that seen in Parkinson's disease
2/2
New research revealed how toxic proteins can travel up from the gut into the brain to causes damage similar to that seen in Parkinson's disease

An important and rigorous new animal study led by scientists at Johns Hopkins University has demonstrated how the misfolded proteins thought to cause Parkinson's disease may originate in the gut, and travel up to the brain via the vagus nerve. This research builds on a compelling body of evidence pointing to a gut-brain connection in the disease and hints at possible new treatment pathways.

Parkinson's disease is characterized by the progressive cell death of the brain's dopamine-secreting neurons that is believed to be caused by the aggregation of spherical misfolded clumps of the protein alpha-synuclein. These toxic protein aggregates are often referred to as Lewy bodies.

For several decades scientists have known these Lewy bodies could be found in the gastrointestinal tracts of Parkinson's disease patients, but it wasn't until a series of influential papers were published in the early 2000s that a strong gut-brain hypothesis was put forward. German scientist Heiko Braak and his team hypothesized the disease originated in the gut, and the damaging Lewy bodies subsequently traveled up into the brain via the vagus nerve. The Braak hypothesis, as it is now known, is still a divisive idea in the field of Parkinson's research, with as many skeptics as believers.

One of the first experimental challenges in verifying the Braak hypothesis is of course establishing whether Lewy bodies can actually spread directly from the gut to the brain. A 2014 rat study effectively demonstrated this spread is indeed possible, but this new Johns Hopkins research is the most rigorous evidence produced to date, demonstrating that not only can these misfolded proteins move from the gut to the brain, but that spread can also induce key pathological signs of Parkinson's disease.

The study began by injecting synthetic misfolded alpha-synuclein into the guts of healthy mice and tracking those animals for 10 months. Analyzing brain tissue at several points over the 10-month period revealed the alpha-synuclein first aggregated at the point the vagus nerve connected to the gut, and then eventually spread throughout the brain. Even more interesting, the spread of the alpha-synuclein proteins up into the brain was halted when the animals' vagus nerve was severed.

Route of Parkinson’s disease-causing protein propagation in mice
Route of Parkinson’s disease-causing protein propagation in mice

The next step in the research investigated whether this spread of alpha-synuclein from the gut to the brain conferred behavioral changes similar to those seen in Parkinson's disease. Across a number of different behavioral studies, commonly used to evaluate Parkinson's disease in animals, the mice seeded with the misfolded alpha-synuclein scored consistently lower than control group mice. Most importantly, however, the results of a third experimental group of mice, seeded with misfolded alpha-synuclein but with severed vagal nerves, showed scores similar to that of the control group. This suggests Parkinson's disease may originate in the gut, and blocking this transmission pathway could effectively prevent the onset of the disease.

"These findings provide further proof of the gut's role in Parkinson's disease, and give us a model to study the disease's progression from the start," says Ted Dawson, one of the authors of the new study. "This is an exciting discovery for the field and presents a target for early intervention in the disease."

This new study is nowhere near definitive or conclusive proof of the gut-brain origins of Parkinson's. A recent paper outlining the arguments for and against the gut origins of Parkinson's concluded there is a notable volume of evidence against this bold hypothesis. More work, especially in human subjects, is undeniably needed, but this work from the Johns Hopkins team is a positive step towards developing new potential treatments for this devastating disease.

The new research was published in the journal Neuron.

Source: Johns Hopkins Medicine

5 comments
amazed W1
This is fabulous if true, because it supports the theories of human health problems that are linked to an evolutionary sequence that since the first multicellulars has not altered over billions of years. The brain and all the various types of skin still develop from the same "place", in all embryos of all animals, and so to an intimate connection between what we are eating and the brain. In an octopus the link is very intimate as their brain surrounds their mouth, good for instant sensing of what is going in but potentially damaging even with their ultra fast reactions. And in most animals the brain is still closely located to the mouth for a more instant response.
Aross
To me this is just more proof that "we are what we eat". Many of the increasing health problems humanity faces is due to the altered, doctored and bastardized food products we are provided with today as good healthy fare is laced with junk that help the producers but is harming the consumer. We need to stop allowing innovations that only benefit the producers. Eliminating plastics, pesticides and artificial fertilizers as well as GMO will go a long way in reducing these issues going forward.
Gregg Eshelman
Some years ago, Michael J. Fox went on a trip to India and other places around there. I recall reading that while there he had no symptoms of Parkinson's. If I had Parkinson's and money like he does, and had an experience like that, I'd have gone back and figured out everything I'd had to eat during the trip. Then I would've experimented with one thing at a time to see what the results would be. Could be some obscure native dish that with the right combination of spices and preparation has something that's a very effective treatment.
Vincent M Tedone MD
Where did they get the protein aggregates from and did they screen the solution for bacterial [Borrelia] infection? Every PD patient who has taken the provocative antibiotics test, see winningthefight.org, has tested positive for a Borrelia infection. The protein aggregates Lewy bodies, Tau, Ubiquitin, TDP-43 and others are the remnants of dead cells.
Nik
Maybe if the gut bio could be changed, then the process of Parkinson's could be halted, and so give the body/brain a chance to start healing itself. It must e worth trying.