Neuroprotective potential of caffeine in a rotenone-induced Drosophila model of Parkinsonism.

Epidemiological studies have consistently reported that certain lifestyle factors, such as the habitual consumption of caffeinated beverages (notably coffee), may protect against the risk of Parkinson's disease. Thus, the current research aims to further investigate the protective effects of caffeine against rotenone-induced neurotoxicity, with a view to providing new insights into the ameliorative potential of caffeine in mitigating rotenone-induced perturbations in Drosophila melanogaster. Age-synchronised adult Drosophila melanogaster (Harwich strain; 1-3 days old) were exposed throughout their lifespan to diets containing graded doses of caffeine (0 to 500 μM) and rotenone (0 to 750 μM) in a co-treatment paradigm. Locomotor performance was assessed using negative geotaxis and Rapid Iterative Negative Geotaxis (RING) assays. Biochemical analyses were performed to determine tyrosine hydroxylase (TH) activity, indices of oxidative stress (malondialdehyde and protein carbonyls), and the status of endogenous antioxidant defence systems (GST, catalase, and total thiols). There was no significant difference in mortality between the caffeine-treated and control groups (p > 0.05). Rotenone exposure produced significant motor deficits (p < 0.05), corresponding to a 25.50% reduction in performance. Basal control performance was 83.3% while the caffeine-treated group scored 100%. Concurrent caffeine treatment prevented the rotenone-associated reduction in tyrosine hydroxylase activity and significantly attenuated oxidative stress markers (MDA, total thiols, protein carbonyls) while preserving antioxidant enzyme activities (GST, catalase) (p < 0.05). In conclusion, concurrent caffeine exposure mitigated rotenone-induced motor deficits and biochemical markers of oxidative stress and dopaminergic dysfunction in Drosophila melanogaster. These results provide experimental support for a protective effect of caffeine in this model and justify further translational molecular studies.