Microvesicles a tool for delivery of rotenone and induction of Parkinson disease

SANCHO, M.I; BRUERA, M; ARCE, M.E.; SANCHEZ, S.I.; CIUFFO, G.E.

Villa de Merlo

Congreso; XXXV Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2017

Sociedad de Biología de Cuyo

With the aim to develop an animal model for Parkinson Disease (PD), we selected microvesicles as a tool for rotenone administration. Rotenone is an herbicide, which is known to produce neurotoxic effects. Several methods of delivery have been explored, some of them with high mortality. The use of microvesicles allows a slow delivery of the drug an thus a long duration with a single dose administration. We assayed two different protocols for microvesicles preparation and evaluated the stability of microvesicles under different conditions. Under light microscope, microvesicles showed a homogenous size average 30 um. After liofilization, resuspension was assayed under different conditions. Resuspended microvesicles were administered by subcutaneous injection in a dose of 50 mg/kg. Animal´s behavior was observed by using the bar test, grid test and rearing test. Rats were weighted every day and no difference with control animals was observed during the first month of treatment. At the dose assayed with two different protocols of microvesicle preparation, no mortality of the animals was observed. Significant changes were observed on behavior tests after 5 weeks of treatment (p< 0.01). Physiological symptoms such as rigidity and immobility are expected to appear after 3 to 5 months of treatment. An accurate experimental model of PD should reproduce the slow, progressive, and selective nigrostriatal dopaminergic degeneration seen in the disease. Although these are preliminary results, the lack of mortalitity in the treated group and the behavioral changes supports a good selection in the dose of rotenone applied in the present study.