EFFICACY OF RASAGILINE ON PROGRESSIVE DOPAMINE NEURON DEGENERATION AND NEUROINFLAMMATION IN A CHRONIC MPTPP MODEL OF PARKINSON'S DISEASE

Aims: Parkinson?s Disease (PD) is characterized by a chronic progressive loss of nigrostriatal dopaminergic neurons, associated to chronic neuroinflammation. The MAO-B inhibitors have neuroprotective activity in cellular and animal models of neurodegenerative disorders, as PD. In particular, rasagiline has a neurorestorative activity in degeneration of nigrostriatal dopamine neurons induced by acute MPTP treatment. In the present study we have evaluated the efficacy of rasagiline on neurodegeneration and neuroinflammation in a chronic mice model of MPTP administration which induce a progressive loss of nigrostriatal dopaminergic neurons and astroglia and microglia activation. Methods: Mice were treated with vehicle, or MPTP plus probenecid administered twice a week for 5 weeks, alone or in the presence of rasagiline administered 18 hrs before each MPTP administration. After treatment, the motor performance of mice was evaluated by the beam-walking test. Dopamine neuron degeneration and glial reactivity were measured by immunohistochemical evaluation of tyrosine hydroxylase (TH)-positive neurons and by CD11b (microglia) and GFAP (astroglia) in striatum and in substantia nigra pars-compacta (SNc). Results: Chronic MPTP induced an impairment of motor performance, a decrease in dopamine neurons in striatum and SNc, and an increase of astroglia and microglia. Previous administration of rasagiline decreased MPTP-induced motor deficits, as well as dopamine neuron degeneration and CD11b and GFAP activation. Conclusions: The inhibition of MAO-B with rasagiline showed neuroprotective efficacy in a model that more closely reproduce neurodegeneration in PD in which the dopamine neuron degeneration takes place over time.;