Assessment of the Behavioral and Neurochemical Characteristics in a Mice Model of the Premotor Stage of Parkinson’s Disease Induced by Chronic Administration of a Low Dose of MPTP

Parkinson’s disease is the second most common neurodegenerative movement disorder caused by the death of dopaminergic neurons in the Substantia nigra. The motor symptoms of Parkinson’s disease only become apparent in the late stages, whereas non-motor impairments often manifest earlier. Therefore, devising adequate experimental models to study the pathogenesis of Parkinson’s disease is of fundamental scientific importance. In this study, we aimed to evaluate the behavioral and neurochemical characteristics in a model of the premotor stage of parkinsonism in mice induced by chronic administration of a low dose of methyl-4-phenyl-1,2,3,6-tetrahydropyridine MPTP. Administering 3 mg/kg of the toxin for 35 days does not cause motor deficits, except in fine motor skills, and results in impaired spatial learning. In addition, this stage is characterized by the depletion of striatum and prefrontal cortex dopamine, decreased tyrosine hydroxylase in striatum and Substantia nigra, increased cytochrome oxidase and superoxide dismutase expression, and microglia activation. Concluding, the presented model made it possible to identify a complex of physiological and neurochemical disorders characteristic of the early stage of Parkinsonism. © 2025 Elsevier B.V., All rights reserved.