Maladaptive Nigrovagal Pathophysiology in Parkinsonism
Abstract
Recent studies have shown that Parkinson's disease (PD), the second commonest neurodegenerative disorder in America has non-motor features such as gastric dysmotility, sleep dysfunction and constipation. It has also become apparent from patient studies that such symptoms very frequently present in patients many decades prior to the diagnosis of PD. Studies suggest that a combination of insults to the lining of the stomach and intestines causes the accumulation of a misfolded protein called alpha synuclein. Examples of insults that can cause accumulation of alpha synuclein include exposure to pesticides and insecticides in combination with certain food substances that are rich in a substance called lectins. Examples of pesticides that may play a role include paraquat and rotenone. These toxic chemicals may gain entry into the stomach and intestine when raw or uncooked contaminated food are consumed. Many common food such as eggs, vegetables and fruits are rich in lectins when consumed without cooking. Our recent published studies indicate that rats fed with paraquat at very low levels in combination with lectins can cause PD like symptoms that respond to levodopa, the commonly used medication used to treat PD. Detailed examination of their nervous system and the brain indicate that the harmful protein alpha synuclein is transported from the gut via the vagus nerve to the brain and then into an area called the substantia nigra in the deep portion of the brain. Damage to the cells in the substantia nigra causes the classical symptoms of PD. Evaluation of the nerve cells of the vagus nerve that reside in the brainstem indicates that they are overactive in a futile attempt to speed up the contractions of stomach and the intestine to reduced mobility of the gut. This hyperactivity of the nerve cells of the vagus appears to be driven by the substantia nigra.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2023
- Accession Number
- AD1203265
Entities
People
- Thyagarajan Subramanian
Organizations
- University of Toledo