Does Parkinson's disease develop in the stomach?
June 26, 2019
It has long been known that Parkinson's disease is closely related to the death of nerve cells in the midbrain.
The more nerve cells die, the more difficult it is for patients to control their body motor skills: They lose their balance, find it difficult to walk, grasp, swallow or speak.
Over time, the disease becomes increasingly severe. In the end, patients are usually bedridden and often die because the autonomic nervous system no longer functions properly.
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Defective proteins destroy nerve cells
The death of nerve cells in the brain is probably triggered by misfolded, mutated proteins, so-called alpha-synuclein proteins. These proteins occur in healthy nerve cells in all humans and serve as transport proteins.
However, if they are damaged, they destroy nerve cells of the substantia nigra pars compacta (SNc) - a core area of the midbrain. Among other things, SNc is responsible for the production of the hormone dopamine, which performs many vital tasks in the body - such as controlling blood flow.
Now researchers at Johns Hopkins University School of Medicine have been able to prove that such defective proteins can find their way from the stomach to the brain of mice. They published their study on June 26 in the journal Neuron.
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Months to migrate from the gut to the brain
The researchers injected the pathogenic forms of the proteins in high concentrations directly into the nerves between the stomach mucosa and the muscle tissue surrounding the stomach of the mice.
After several months, the physicians were able to detect the pathogenic proteins and the damage to the SNc nerve cells in different brain regions of the mice.
After one month, the alpha-synuclein proteins arrived at the brain stem - in the areas known as medulla oblongata and pons. From there, they migrated further into the midbrain and striatum. After 10 months, the disease-causing proteins reached the olfactory bulb, which makes up the foremost part of the brain.
Everything indicates that the proteins were transported by the vagus nerve. This is a central nerve of the vegetative nervous system that extends from the stomach to the brainstem. If the doctors cut this nerve, the alpha-synuclein proteins could no longer reach the brain in the mouse experiment.
No therapy yet
The discovery does not yet provide an answer to the question of how Parkinson's disease can be stopped. Nevertheless, Ted Dawson, professor of neurology and co-author of the study, considers the discovery an important breakthrough for research.
"Since the model starts in the gut, one can use it [to] study the full spectrum and time course of the pathogenesis of Parkinson's disease," he said. "For instance, one could test preventive therapies at early pre-symptomatic stages of Parkinson's disease all the way to full blown Parkinson's disease in one animal model."
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Where does Parkinson's originate?
Neuropathologist Walter Schulz-Schaeffer from Saarland University Hospital, who was not involved in the study, points out that Parkinson's disease usually spreads in the body of patients for several decades before the symptoms become clearly visible. This makes prevention more difficult.
In addition, the study did not make it clear whether the origin of the disease was actually in the stomach. The disease-causing proteins could also migrate in the other direction along the nerve tracts: "The recognition that the disease process can spread via the nerves controlling the stomach and intestines does not therefore mean that the disease must develop in the gastrointestinal tract".
However, he hopes that the new findings may open up new ways to develop early detection of Parkinson's disease. This, according to the professor, "could considerably improve the treatment options".
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