Histopathological Study of Metformin Effect on Parkinsonism Mice Model

Background: Parkinson’s disease is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. Oxidative stress and neuroinflammation are major contributors to its pathogenesis. Metformin, a widely used antidiabetic agent, has shown neuroprotective potential in several neurological conditions. Objective: To compare the histological changes between the groups of mice that received a prophylactic dose of metformin and those that did not, as well as to compare the effect of metformin when added to standard treatment. Methods: Thirty male albino mice were randomly divided into six groups: (Group 1) control group; (Group 2) a rotenone induction group; (Groups 3) pre-treated with metformin three days before induction (500mg/kg);(Group 4) received metformin (500 mg/kg) ; (group 5) received L-DOPA/Carbidopa (100/25 mg/kg); and (group 6) received both drugs concurrently At the end of the 47-day study period, the animals were sacrificed, and their brains were harvested and fixed in 10% neutral buffered formalin for histological examination. Results: Histopathological analysis showed that rotenone induced classical PD-related changes, including neuronal shrinkage, pyknotic nuclei, karyorrhexis, and marked activation of microglia and astrocytes. Prophylactic metformin administration significantly ameliorated these changes, while the combined treatment group demonstrated improved neuronal preservation compared to the standard therapy alone. Conclusions: These findings support the potential neuroprotective role of metformin, both as a prophylactic and adjunctive agent to conventional therapy in PD.