Electronic Poster | Session 2

056 – Impact of aging on enteric and central nervous systems in a rodent model of Parkinson’s disease

Solène Pradeloux (1, 2) – Mélissa Côté (1) – Catherine Fontaine-Lavallée (1) – Katherine Coulombe (2) – Frédéric Calon (1) – Denis Soulet (2)
Faculty of Pharmacy, Laval University (1) – CHU de Québec – Laval University research centre (2)

Patients with Parkinson’s disease have motor symptoms, which are often preceded by gastrointestinal disorders associated with the alteration of dopaminergic neurons located in the myenteric plexus. Our laboratory has previously demonstrated the importance of the inflammatory response in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced toxicity on dopaminergic neurons of the enteric nervous system. MPTP is a neurotoxin used to mimic the loss of dopaminergic neurons observed in Parkinson’s disease. In this study, we aim to evaluate the impact of aging on enteric and central nervous systems neuroprotection and immunomodulation in a murine model of Parkinson’s disease, in order to determine whether aging affects the myenteric neurons sensitivity to MPTP. NF-kappa B-EGFP mice ranging from two months to one year old received four intraperitoneal injections of saline or MPTP (at 8mg/kg) at two-hour intervals. Mice were euthanised 5 or 10 days later, and the brain and gut were removed. Immunofluorescence and immunohistochemistry markings with anti-tyrosine hydroxylase (TH) and anti-ionised calcium binding adapter molecule 1 antibodies (Iba1) were performed on the substantia nigra, the striatum and the myenteric plexus for a stereological count of dopaminergic neurons (TH+) and macrophages/microglia (Iba+). Our preliminary results reveal that density in dopaminergic neurons and macrophages are respectively decreased and increased in young mice (about 100 days old) treated with MPTP. In contrast, MPTP injection in aged mice (approximately 300 days old) did not alter the number of dopaminergic neurons and macrophages compared to saline mice. The older the saline mice are, the lower the density of TH+ neurons and the higher the inflammation are. These results suggest that only young dopaminergic neurons are sensitive to MPTP.