Effects of Mesenchymal and Neural Exosome Administration on Motor Activity and Dopamine Metabolism in a Mouse Model of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Parkinson’s disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra and a profound dopamine depletion in the striatum. The long preclinical latency period and the inability to directly investigate brain processes impede the analysis of early neurodegeneration and the search for effective therapeutic strategies. In recent years, increasing attention has focused on stem cell-derived exosomes — extracellular vesicles capable of transporting bioactive molecules and penetrating the blood-brain barrier. However, their impact on functional changes in the dopaminergic system in PD remains insufficiently explored. This study evaluated how exosomes isolated from mouse neural (NSC) and mesenchymal stem cell (MSC) conditioned media affect motor activity
and striatal dopamine metabolism in a model of early-stage symptomatic PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Behavior analysis in the open field test revealed that MPTP administration induced motor changes consistent with early Parkinsonian-like impairments. Intranasal administration of exosomes partially normalized these behavioral parameters, with MSC-derived exosomes exhibiting a more pronounced effect on motor activity. Biochemical analysis revealed a depletion of dopamine and its metabolites (dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), homovanillic acid (HVA)) following MPTP administration. Both types of exosomes partially prevented these changes, with NSC-derived exosomes having a stronger effect on dopamine and DOPAC levels. These findings demonstrate that NSC- and MSC-derived exosomes can mitigate early behavioral and biochemical impairments in MPTP-induced PD, highlighting their potential as candidates for neuroprotective therapy.

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