Background/Objectives: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN). Because current therapeutics have limited efficacy once PD is fully developed, it is crucial to start disease-modifying interventions during the prodromal stage of PD. In the present study, we aimed to evaluate whether intranasally delivered human umbilical cord mesenchymal stem cells (hUC-MSCs) have an efficacy in the rotenone-induced prodromal PD-like phenotype mouse model. Methods: To produce the prodromal PD mouse model, C57BL/6 mice were treated with intraperitoneal (i.p.) rotenone for 1 or 2 weeks. hUC-MSCs or PBS were delivered intranasally for 1 or 2 weeks with rotenone injection. We subsequently performed behavioral assessments to evaluate motor and non-motor features, followed by pathological analyses of the mouse brains. Results: Intranasal administration of hUCMSCs restored motor performance and protected dopaminergic neurons in the SN of mice treated with rotenone for 2 weeks. In the 1-week rotenone mice, hUC-MSCs treatment ameliorated depressive-like behaviors and attenuated olfactory dysfunction. Furthermore, intranasal hUC-MSC treatment suppressed the accumulation of protein aggregates in the brains of mice, which is associated with enhanced autophagic function, as indicated by increased LC3B and normalization of LAMP2A protein expression. Conclusions: Our data demonstrate that intranasal administration of hUC-MSCs improves non-motor symptoms at early time points and attenuates progression to nigrostriatal loss and motor deficits in the rotenone-induced PD mouse model. These findings support the potential of a non-invasive, prodromal-stage intervention to modulate early pathological progression in PD.
Loading....