92NEUROPROTECTIVE EFFECT OF PPAR-γ AGONIST IN PARKINSON’S DISEASEParkinson’s disease (PD) is a progressive neurological disorder characterized by progressive loss of dopaminergic neurons in substantianigra pars compacta (SNPc) and other brain regions. The pathogenic events that occur in this disorder include mitochondrial dysfunction, oxidative stress and formation of cytoplasmic inclusions containing α-synclein and ubiquitin. Rotenone model of Parkinson’s disease involves substantiated exposure to pesticides and complex-1 inhibition in mitochondria in the neurons, a prominent event of Parkinson’s disease etiology. The present study aims to evaluate the neuroprotective effect of pioglitazone, a peroxisome proliferator activated receptor gamma (PPAR-γ) agonist, on rotenone induced neurodegeneration and biochemical alterations. Rotenone (3 mg/kg, i.p.) was used to induce neurodegeneration. Administration of rotenone for 21 days significantly increased the tremors, muscular rigidity, and reduced the grip strength, motor activity, and numbers of poking, rearing behavior in experimental rats. Treatment with pioglitazone (10, 20 and 30 mg/kg, p.o.) for 21 days decreased the tremors, muscular rigidity and significantly increased the grip strength, rearing behavior, motor activity and number of poking in rats. Rotenone significantly increased lipid peroxidation and reduced the levels of defensive antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH) in rat brain. Pioglitazone reversed these effects of rotenone on oxidative stress indices; indicating neuroprotection in rat brains. The results of the present study indicated that pioglitazone has a protective role against rotenone-induced neurodegeneration through its action on PPAR-γ-co-activator 1 alpha (PGC-1α). Thus, use of pioglitazone as a therapeutic agent for the treatment of Parkinson’s disease may be encouraged along with standard anti-parkinsons drugs.kawalevl@rediffmail.comResearch522015Peroxisome proliferator activated receptor gamma,Parkinson’s disease,RotenoneVandana S. Nade, Sourabh V. Shah,Laxman A. Kawale,Pranita P. DharmadhikariDepartment of Pharmacology, M.V.P Samaj’s College of Pharmacy, Nashik-422002, Maharashtra, India.,Department of Pharmacology, M.V.P Samaj’s College of Pharmacy, Nashik-422002, Maharashtra, India.,Department of Pharmacology, M.V.P Samaj’s College of Pharmacy, Nashik-422002, Maharashtra, India.,Department of Pharmacology, M.V.P Samaj’s College of Pharmacy, Nashik-422002, Maharashtra, India.