Colonic inflammation affects myenteric alpha-synuclein in nonhuman primates.

Area of Science:

• Neuroscience
• Gastroenterology
• Pathology

Background:

• Parkinson's disease (PD) is associated with gastrointestinal (GI) dysfunction and alpha-synuclein (α-syn) pathology in the enteric nervous system (ENS).
• GI inflammation, seen in conditions like inflammatory bowel disease, is linked to increased PD risk.
• Common marmosets with colitis provide a model to study the interplay between GI inflammation and α-syn pathology.

Purpose of the Study:

• To investigate the relationship between colonic inflammation and α-syn pathology in the ENS of common marmosets.
• To assess changes in inflammatory markers, oxidative stress, and α-syn phosphorylation in the myenteric plexus during colitis.

Main Methods:

• Sections of the proximal colon from marmosets with colitis and healthy controls were analyzed.
• Immunohistochemistry was used to detect markers for inflammation (HLA-DR, CD3), oxidative stress (8-OHdG), and α-syn (α-syn, p-α-syn).
• Quantification of immunoreactivity in the myenteric plexus was performed using NIH ImageJ software.

Main Results:

• Marmosets with colitis exhibited significantly increased expression of inflammatory markers (HLA-DR, CD3) and oxidative stress (8-OHdG) in the colonic myenteric ganglia.
• Colitis was associated with increased phosphorylation of α-syn (p-α-syn) and decreased expression of total α-syn in the myenteric plexus.
• These changes were statistically significant when compared to healthy controls.

Conclusions:

• Colonic inflammation in common marmosets is associated with alterations in α-syn expression and phosphorylation within the myenteric plexus.
• These findings suggest a potential link between GI inflammation and the development of ENS α-syn pathology relevant to Parkinson's disease.
• Further research involving the vagus nerve and brain is warranted to explore the contribution of colitis-induced ENS α-syn pathology to PD-like brain pathology.