Pioglitazone improves motor function and attenuates the central and peripheral alpha-synuclein burden in a rotenone-induced model of Parkinson’s disease in rats

Purpose: To investigate the neuroprotective effect of Pioglitazone (PIO), a PPAR-γ agonist, in reducing central and peripheral α-synuclein (α-Syn) burden in rotenone-induced Parkinson disease (PD).Methods: A total of 48 adult male Wistar rats were randomly and equally divided into six groups (n = 8). Group 1 was control, groups 2, 3, 4, 5, and 6 received rotenone to induce Parkinsonism (2.5 mg/kg, intraperitoneal every 48 h for 21 days). Groups 3, 4, 5, and 6 was treated with carboxyl methylcellulose, rasagiline (1 mg/kg/day), and pioglitazone at 10 and 20 mg/kg/day respectively. Oral treatments started three days before the first rotenone injection and continued throughout the study. Body weight was recorded on days 1, 7, 14, and 21. Behavioural assessments were performed on Day 22 (24 h after the final treatment dose) using rotarod and open field tests to evaluate locomotor activity, exploratory behavior, and motor coordination. α-Syn expression was quantified using brain immunohistochemistry (IHC) and serum enzyme-linked immunosorbent assay (ELISA).Results: Rotenone administration successfully induced Parkinsonian evidenced by significant decrease in body weight, motor and behavioural impairments, higher cerebral α-syn accumulation, and lower α-syn serum levels (p < 0.05) compared to the control. Treatment with Pioglitazone significantly increased mean body weight, reduced cerebral α-syn accumulation and increased serum α-syn levels in a dose-dependent manner compared to group 2 (rotenone group; p < 0.05).Conclusion: Pioglitazone significantly reversed symptoms of Parkinsonism induced by rotenone in a dose-dependent manner.