Recently, in mouse studies the peroxisome proliferator-activated receptor-g (PPARg) agonist pioglitazone was shown to be effective in blocking the substantia nigra (SN) cell loss induced by MPTP in a pre-clinical model of Parkinson's disease. This antidiabetic drug had been previously reported to reduce inflammatory processes in the brain associated with microglial and astroglial activation. It is critical to determine whether such anti-inflammatory effects can affect SN cell loss in a non-human primate model of Parkinson's disease.
For the proposed study, we will model unilateral PD symptoms by administering MPTP through an internal carotid artery injection to animals that have received either pioglitazone or saline. Post-mortem evaluation will determine SN cell counts and basal ganglia immunohistochemical reactivities for tyrosine hydroxylase, inducible nitric oxide synthase, dopamine and serotonin fiber densities, cytochrome oxidase and glial responses. These studies will provide further evidence of neuroprotection in a non-human primate brain based on anti-inflammatory activity of a "glitazone" group antidiabetic drug that has direct applicability to the therapy of early Parkinson's disease in humans.