Parkinson’s disease is one of the most common diseases causing brain degeneration.

Most people recognize Parkinson’s disease for its effect on the entire body, such as slowness of movement, stooped posture, constant tremors, and rigidity, all of which we call motor symptoms.

Surprisingly, there are many non-motor symptoms that arise earlier and may hold the key to understanding this disease.

Parkinson’s disease is due to the accumulation of a protein called alpha-synuclein found throughout the brain. This leads to degeneration of the brain, specifically the death of nerve cells in a region of the brain known as the basal ganglia — an area essential for your body’s control of motor movement. It is thought that a certain level of nerve cell death in this region must be reached before a patient develops classic motor symptoms.

On the other hand, there are non-motor symptoms of Parkinson’s disease, including gut disorders and sleep abnormalities that occur in patients many years before developing abnormal motor symptoms. This means Parkinson’s disease may actually begin years before it is diagnosed.

Sleep disturbances are one of the most common non-motor symptoms seen in Parkinson’s disease patients. Specifically, patients move and act out their dreams during the phase of sleep known as REM sleep. Some studies suggest over 50 percent of people with this sleep disorder will eventually develop Parkinson’s or a similar brain disease.

The majority of Parkinson’s disease patients also show signs of gut disorders, most commonly constipation, years before the onset of abnormal motor symptoms. Importantly, this is one of the reasons many scientists believe Parkinson’s disease starts in the gut and only later reaches the brain.

This critical period of time where non-motor symptoms are seen years before the onset of motor symptoms represents the earliest signs of Parkinson’s disease. What if we could target Parkinson’s disease during this early timepoint to prevent the progression of disease?

The challenge to biomedical researchers is our inability to study the brains of Parkinson’s patients early in the disease course. For this reason, animal models of this disease are critical. My research project focuses on characterizing a rat model of Parkinson’s disease which will allow scientists to better understand the early stages of Parkinson’s disease and develop treatments to stop or slow the progression.

Using our rat model, we administer by mouth very small doses of an herbicide called paraquat in combination with lectins, a protein common in our diets. By using this diet, we see the hallmark accumulation of alpha-synuclein in the gut and in the brain, which we believe spreads from the gut to the brain via the vagus nerve, which is an important gut-brain connection. Our rat model therefore supports the important concept of a gut-to-brain progression of Parkinson’s disease.

My specific research project involves investigating the early non-motor symptoms of Parkinson’s disease, including sleep abnormalities and abnormal gut function. Using electronic sleep monitoring equipment, I have been able to show that sleep abnormalities are present before the onset of abnormal motor symptoms, indicating that this rat model is a very good one for studying the natural progression of Parkinson’s disease.

We are also using this rat model of Parkinson’s disease to investigate the potential of drugs to slow the progression of Parkinson’s early in its course. Specifically, we are investigating drugs which, when given by mouth, have actions that remain local to the gut. By targeting the gut, we hope to decrease alpha-synuclein accumulation in the gut and prevent the gut-to-brain progression of Parkinson’s in our rat model.

Excitingly, my results show that by targeting the gut locally with these drugs, we have been able to decrease alpha-synuclein accumulation in the brain, decrease nerve cell death in the brain, and prevent abnormal motor symptoms in our rat model. Our research shows promising results for locally targeting treatment to the gut to prevent the progression of Parkinson’s disease.

I will continue to build on my research characterizing this rat model as a relevant experimental tool to make a positive impact on the future of Parkinson’s research.

Caroline Swain is an M.D./Ph.D. candidate in the Neuroscience and Neurological Disorders Track in The University of Toledo College of Medicine and Life Sciences Biomedical Sciences Program. Caroline is conducting her research with Dr. Thyagarajan Subramanian, M.D., M.B.A. For more information, contact caroline.swain@rockets.utoledo.edu or visit https://www.utoledo.edu/med/grad/biomedical/

First Published February 3, 2025, 5:00 a.m.