Investigating cerebellar oxidative stress, inflammation and apoptosis following sub-acute MPTP administration in Balb/c mice

Abstract

Background and aim: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administered mice is a known model of Parkinson's disease (PD) which is characterized by neurodegeneration primarily in the substantia nigra; however, increasing evidence highlights the role of the cerebellum in both motor and non-motor symptoms. This study investigates the effects of sub-acute MPTP administration on oxidative stress, inflammation, and apoptosis in the cerebellum of adult male Balb/c mice. Methods: Twenty adult male Balb/c mice, weighing 20-30 g, were acclimatized for 14 days and assigned to control (n=10, PBS) and MPTP groups (n=10, 20 mg/kg body weight of MPTP, intraperitoneally administered daily for five consecutive days). Behavioral assessments were performed using an open field test on day seven, focusing on cerebellar-related behaviors. Following this, histological, immunohistochemical, and biochemical analyses were conducted to evaluate markers of oxidative stress (nuclear factor erythroid 2-related factor 2 along with glutathione peroxidase), inflammation (tumor necrosis factor-alpha as well as nuclear factor kappa B), and apoptosis (B-cell lymphoma 2). Results: MPTP administration significantly reduced nuclear factor erythroid 2-related factor 2 along with glutathione peroxidase while increasing tumor necrosis factor-alpha as well as nuclear factor kappa B in the cerebellum, coinciding with enhanced apoptosis as indicated by a lower B-cell lymphoma 2 level. Behavioral results revealed significant reductions in the grooming frequency of MPTP-treated mice compared to controls. Conclusion: The findings indicate that MPTP induces oxidative stress, inflammation, and apoptosis in the cerebellum of adult male Balb/c mice, it might be worthwhile to observe the cerebellar changes in the diagnosis and management of PD.