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

Impression of degeneration of dopaminergic neurons, a key stage in the development of Parkinson's disease. Kateryna Kon/Shutterstock

In a series of experiments conducted in mice, researchers found more evidence in favor of the crucial role of the gut-brain connection in the development of Parkinson’s disease, a long-term neurodegenerative condition.

Since 2003, researchers have observed a connection between the gut of people suffering from Parkinson’s and changes in their brain. In particular, they found accumulations of misfolded proteins known as alpha-synuclein (α-syn) in regions of the brain involved in the digestive system. These proteins can damage neurons, so their presence was a potential alarm bell to researchers.

As reported in the journal Neuron, scientists from Johns Hopkins looked at how these alpha-synuclein proteins end up in the brain by exploring the possibility they travel along the vagus nerve – the connection between the stomach and the small intestine into the base of the brain.  

"The Braak hypothesis posits that α-syn pathology can spread in a stereotyped fashion from the gastrointestinal tract via the vagus nerve to the ventral midbrain, where it selectively kills dopamine neurons of the substantia nigra pars compacta [a region in the midbrain]," write the researchers.

To test this hypothesis, the team injected two groups of mice with misfolded alpha-synuclein and had a third one for a control. In one of the injected groups, researchers severed the vagus nerve. They then looked at the distribution of these proteins in the mice over a period of one, three, seven, and finally 10 months. The mice with a severed vagus nerve showed no sign of neurological damage from alpha-synuclein build-up. However, those with an intact vagus nerve saw alpha-synuclein spread in 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," senior author Professor Ted Dawson said in a statement

The team also investigated the behavior of all three rat groups to determine whether they too experience behavioral changes, specifically shifts to their nest-building activities and exploration of a new environment. These behaviors are models for motor control and anxiety, respectively.

They found that at seven months, mice with an intact vagus nerve and injected with alpha-synuclein were significantly worse at building nests than both the controls and the mice who had their vagus nerve severed. Similar results were seen in tests where mice were put in a new environment.

Overall, the research suggests alpha-synuclein proteins can climb along the vagus nerve. Perhaps if the transmission route is blocked, it might be possible to prevent the physical and cognitive symptoms of the condition, but more research is needed before drawing conclusions. Researchers next hope to investigate exactly how the proteins move across the nerve and find some mechanism to halt them.

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