Lobeglitazone Attenuates Behavioral and Histopathological Alterations in 3-Nitropropionic Acid-Induced Huntington-Like Neurodegeneration

Abstract

Huntington’s disease (HD) is a progressive neurodegenerative disorder characterized by motor dysfunction, cognitive impairment, psychiatric abnormalities, and neuronal degeneration. The present study was designed to evaluate the neuroprotective potential of Lobeglitazone, a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, in a 3-nitropropionic acid (3-NP)-induced experimental model of Huntington’s disease in rats. Healthy female Sprague–Dawley rats were divided into four groups: normal control, negative control, Lobeglitazone-treated group, and PPAR-γ antagonist-treated group. Huntington-like neurodegeneration was induced using 3-NP (20 mg/kg, i.p.), followed by treatment with Lobeglitazone (0.5 mg/kg, p.o.) for 14 days. Behavioral parameters were evaluated using Elevated Plus Maze (EPM), Morris Water Maze (MWM), and Rota-Rod apparatus. Histopathological examination of rat brain tissue was performed using hematoxylin and eosin staining. The results demonstrated that 3-NP administration produced significant behavioral impairments, reduced body weight, impaired spatial memory, and motor dysfunction associated with marked neuronal degeneration. Lobeglitazone treatment significantly improved body weight, reduced transfer latency in EPM, decreased escape latency, enhanced retention time in MWM, and improved motor coordination in the Rota-Rod test. Histopathological studies revealed restoration of neuronal architecture and reduction in neurodegenerative changes in Lobeglitazone-treated animals. However, co-administration with bisphenol A diglycidyl ether (BADGE), a PPAR-γ antagonist, attenuated the neuroprotective effects of Lobeglitazone, suggesting the involvement of PPAR-γ-mediated mechanisms.