Les plasmalogènes comme traitement prophylactique dans la maladie de Parkinson au niveau intestinal
|Advisor:||Soulet, Denis; Di Paolo, Thérèse|
|Abstract:||The advanced stage of Parkinson's disease (PD) is characterized by motor symptoms witch are often preceded by gastrointestinal disorders that would result from alteration of the dopaminergic neurons (DAergics) of the intestine. Studies suggested that the disease would spread to the brain by the vagus nerve. Our laboratory has demonstrated the major role of inflammation in the intestine in parkinsonian mice. Recently, decreased levels of plasmalogens, glycerophospholipids, in the brain and blood of PD patients have been reported. Ethanolamine plasmalogens (EP) play an important role in the membrane functional structure of cells through the mediation of various mechanisms including neurotransmission, membrane proteins activity and free radicals removal. In this study, we evaluated the neuroprotective and anti-inflammatory effects of the administration of a PGE precursor, PPI-1011, in the intestine of parkinsonian mice. The neurotoxin 1-mehyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to model PD in mice, and PPI-1011 (10, 50 and 200 mg / kg) was administered by gavage. Total neurons, DAergics TH-positive (TH+) neurons, macrophages, proinflammatory macrophages and G-protein coupled receptor 120 (GPR120) were labeled in the myenteric plexus by immuno-labeling. This latest is interesting, since it plays an antiinflammatory role via its link with DHA. To do this, a dose-response protocol, a pre-treatment protocol and a post-treatment protocol were performed. MPTP induces a decrease of DAergic neurons and an increase in the density of macrophages in the myenteric plexus. Treatment with PPI-1011 (50 and 200 mg / kg) protected DAergic neurons against this alteration and limited the infiltration of macrophages into the enteric nervous system. This new therapeutic approach could be used to prevent and delay initiation and progression of PD.|
|Document Type:||Mémoire de maîtrise|
|Open Access Date:||5 July 2018|
|Collection:||Thèses et mémoires|
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