Parkinson Disease Initiates in the Gut, According to Animal Models

Researchers have found additional evidence that Parkinson disease (PD) initiates among cells in the gut and then travels through the body’s vagus nerve to the brain, according to a recently published study conducted in mice models.

PD is characterized by an accumulation of a misfolded protein, α-synuclein, in the brain. As more of these proteins gather together, nerve tissues begin to die off and leave behind large clumps of Lewy bodies.

This study built off of previous observations found in 2003 that showed that individuals with PD had accumulations of α-synuclein in portions of the central nervous system that also control the gut. These findings are consistent with some early symptoms of PD, including constipation.

“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,” said Ted Dawson, MD, PhD, in a statement.

Researchers postulated the connection between the α-synuclein proteins flowing from the gut to the brain through the vagus nerve, but to test it, the study authors injected 25 mcg of synthetic misfolded α-synuclein into the guts of dozens of mice. The researchers took samples of mouse brain tissue at 1, 3, 7, and 10 months after injection. Over the course of the study, the researchers found that α-synuclein began building where the vagus nerve connected to the gut and continued to spread throughout the brain.

Researchers also conducted a second experiment in which the mice were analyzed for symptoms similar to PD. Anxiety levels of mice were monitored by how they responded to new environments. Researchers placed the mice into a large open box where a camera tracked their movements. While the healthy mice were curious and spent between 20 and 30 minutes exploring the box, mice effected by cognitive decline showed more anxiety and caused them to be more likely to stay toward the sheltered edges of the box.

Overall, the study determined that the misfolded α-synuclein can be transmitted from the gut to the brain through the vagus nerve, and blocking this transmission route could be critical in preventing the physical and cognitive manifestations of PD.

In terms of next steps, the study authors wrote that they plan to further study what distinct parts of the vagus nerve allow the misfolded protein to transfer through to the brain, and to investigate potential tools to stop it.

Reference

Kim S, Kwon SH, Kam TI, et al. Transneuronal propagation of pathologic α-synuclein from the gut to the brain models Parkinson’s disease [published online June 26, 2019]. Neuron. doi.org/10.1016/j.neuron.2019.05.035