More Evidence Highlights The Role The Gut Plays In Parkinson's Disease

Research Provides New Evidence that Parkinson's Disease Originates in the Gut

Research Provides New Evidence that Parkinson's Disease Originates in the Gut

Parkinson's is a progressive nervous system disorder that affects movement, and symptoms include tremors and changes in speech and gait. Parkinson's disease treatment is used to control symptoms such as uncontrolled movement, shakiness of hands, and some others. It was discovered that the mice that were affected by the misfolded alpha-synuclein behaved contrastingly with the healthy mice and showed all symptoms of Parkinson's disease. They found that mice that received the misfolded alpha-synuclein injection scored consistently lower on nest building. The study was conducted on mice and it confirms the theory that the abnormally folded alpha-synuclein may originate in the gut and then eventually spread to the brain.

"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, M.D., Ph.D., director of the Johns Hopkins Institute for Cell Engineering and professor of neurology at the Johns Hopkins University School of Medicine.

Pathologists have observed these clumps in post-mortem brain exams of people with Parkinson's disease.

As yet, there is no cure for Parkinson's disease, and the treatments that do exist are limited in their ability to slow the disease's progress and alleviate the more advanced symptoms.

Route of Parkinson's disease-causing protein propogation in mice.

Next, the researchers say, they plan to explore what parts of the vagus nerve allow the misfolded protein to climb to the brain, and to investigate potential mechanisms to stop it.

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The team observed that it took about 1 month for the toxic protein to spread from the injection site to start of the brainstem. Another 2 months later, the toxic protein had reached not only into the part of the brain that succumbs to Parkinson's disease - the substantia nigra pars compacta - but also into other regions, such as the amygdala, the hypothalamus, and the prefrontal cortex. Transneuronal propagation of pathologic α-synuclein from the gut to the brain models Parkinson's disease [published online June 26, 2019]. Upon examination at seven months, the researchers found that mice with severed vagus nerves showed none of the signs of cell death found in mice with intact vagus nerves.

The researchers conclude that the findings support Braak's hypothesis about the development of Parkinson's disease. To do this, they evaluated the behavior of three groups: mice injected with misfolded alpha-synuclein, mice injected with misfolded alpha-synuclein with cut vagus nerves, and control mice with no injection and intact vagus nerves.

Alpha-synuclein (also α-synuclein) is a protein which is of great interest to Parkinson's researchers because it is a major constituent of Lewy bodies and Lewy neurites, protein clumps that are the pathological hallmark of synucleinopathies, such as Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA).

Although the results of mouse studies do not necessarily mean that the same is true of humans, the team points to evidence that suggests that, in this case, they might be. Researchers found that inhibiting Drp1 improves dopamine's release and reduces neurodegeneration in mouse models of Parkinson's disease. Another reason the researchers believe that the disease origins in the gut is because those who had an appendicitis surgery early in life had a reduced risk of developing Parkinson's disease later in life. Dawson highlights three implications of the study.

"We know that the environment plays a crucial role in overall health, including the brain, and that exposures to environmental toxicants, most likely in combination with an individual's genetic makeup, may lead to all sorts of diseases, including Parkinson's", Tieu, a professor at Stempel College of Public Health and Social Work in Miami, Florida, said in a press release.

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