Caffeine Modulates Oxidative Stress and Neuroinflammation in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Model of Parkinson’s Disease in Female Mice

Background: Parkinson's disease (PD) is a neurodegenerative disorder marked by dopaminergic neuron loss, oxidative stress, and neuroinflammation, leading to progressive motor dysfunction.Current treatments provide symptomatic relief but do not halt disease progression.Caffeine, a widely consumed neurostimulant, has been linked to a reduced risk of PD and possesses antioxidant and anti-inflammatory properties.Objectives: We investigated the effects of caffeine on motor performance, biochemical markers, and immunohistochemical changes in an MPTP (1-methyl-4-phenyl-1,2,3,6tetrahydropyridine)-induced model of PD in female Swiss mice.Methods: Twenty-five female mice were used, with 20 injected intraperitoneally (ip) with MPTP to induce PD.The mice were divided into five groups (n=5): Healthy controls, MPTPinduced PD, L-Dopa, 10 mg/kg caffeine, and 5 mg/kg caffeine for three weeks.Behavioral tests, including the pole test, beam test, and open field maze assessed motor activity and anxiety.Brain, liver, and heart tissues were analyzed for antioxidant, inflammatory, and oxidative stress markers.Brain tissues were also examined for immunohistochemistry, assessing microglial activation, TH, and -synuclein to measure dopamine loss.Results: Caffeine administration significantly (P<0.05)improved motor performance and decreased anxiety compared to MPTP-induced mice.Biochemical analyses of brain tissue showed that caffeine enhanced antioxidant activity by increasing the levels of catalase and glutathione while decreasing malondialdehyde (MDA), a marker of oxidative stress.Caffeine also significantly reduced the levels of pro-inflammatory cytokines, TNF-, and IL-1 in the brain tissue, indicating an anti-inflammatory effect.Serum biochemical analyses indicated increased superoxide dismutase (SOD) levels, elevated catalase activity, and reduced MDA levels in caffeine-treated groups.Immunohistochemical analysis revealed a significant reduction in the expression of -synuclein and microglial activation and preservation of THpositive dopaminergic neurons in the substantia nigra following caffeine treatment. Conclusion:Caffeine exerts protective effects against motor dysfunction, oxidative stress, and neuroinflammation in an MPTP-induced model of PD, highlighting its potential as a therapeutic agent for managing PD.