Dopaminergic Neurotoxicity Induces Parkinsonian-Like Phenotypes in Daphnia magna

Parkinson's disease (PD) is associated with dopaminergic neurodegeneration, in which mitochondrial dysfunction and oxidative stress play central roles. However, environmentally relevant invertebrate models for studying dopaminergic neurotoxicity remain limited. Here, we developed a Parkinsonism-like model in Daphnia magna using sublethal exposures to the prototypical dopaminergic neurotoxicant MPTP [1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine] and the environmentally relevant pesticide rotenone. Both compounds induced concentration-dependent increases in reactive oxygen species, marked depletion of dopamine and related metabolites in the head, and a strong downregulation of key dopaminergic genes, indicating profound disruption of dopaminergic homeostasis and redox balance and providing evidence consistent with construct validity. These molecular alterations were accompanied by functional alterations consistent with face validity, including reduced hopping distance, increased low-locomotion states, impaired photomotor responses and habituation, altered phototaxis and colour preference, particularly after MPTP exposure, and reduced heart rate. Together, these findings support the potential utility of D. magna as a sensitive, integrative, and ecologically relevant model for investigating dopaminergic neurotoxicity and Parkinsonism-related adverse outcome pathways triggered by environmental chemicals.