RESUMEN
BACKGROUND: In recent years, dental pulp stromal cells (DPSCs) have emerged as a promising therapeutic approach for Parkinson's disease (PD), owing to their inherent neurogenic potential and the lack of neuroprotective treatments for this condition. However, uncertainties persist regarding the efficacy of these cells in an undifferentiated state versus a neuronally-induced state. This study aims to delineate the distinct therapeutic potential of uninduced and neuronally-induced DPSCs in a rodent model of PD induced by 6-Hydroxydopamine (6-OHDA). METHODS: DPSCs were isolated from human teeth, characterized as mesenchymal stromal cells, and induced to neuronal differentiation. Neuronal markers were assessed before and after induction. DPSCs were transplanted into the substantia nigra pars compacta (SNpc) of rats 7 days following the 6-OHDA lesion. In vivo tracking of the cells, evaluation of locomotor behavior, dopaminergic neuron survival, and the expression of essential proteins within the dopaminergic system were conducted 7 days postgrafting. RESULTS: Isolated DPSCs exhibited typical characteristics of mesenchymal stromal cells and maintained a normal karyotype. DPSCs consistently expressed neuronal markers, exhibiting elevated expression of ßIII-tubulin following neuronal induction. Results from the animal model showed that both DPSC types promoted substantial recovery in dopaminergic neurons, correlating with enhanced locomotion. Additionally, neuronally-induced DPSCs prevented GFAP elevation, while altering DARPP-32 phosphorylation states. Conversely, uninduced DPSCs reduced JUN levels. Both DPSC types mitigated the elevation of glycosylated DAT. CONCLUSIONS: Our results suggested that uninduced DPSCs and neuronally-induced DPSCs exhibit potential in reducing dopaminergic neuron loss and improving locomotor behavior, but their underlying mechanisms differ.
RESUMEN
Sleep disturbances are highly prevalent among patients with Parkinson's disease (PD) and often appear from the early-phase disease or prodromal stages. In this chapter, we will discuss the current evidence addressing the links between sleep dysfunctions in PD, focusing most closely on those data from animal and mathematical/computational models, as well as in human-based studies that explore the electrophysiological and molecular mechanisms by which PD and sleep may be intertwined, whether as predictors or consequences of the disease. It is possible to clearly state that leucine-rich repeat kinase 2 gene (LRRK2) is significantly related to alterations in sleep architecture, particularly affecting rapid eye movement (REM) sleep and non-REM sleep, thus impacting sleep quality. Also, decreases in gamma power, observed after dopaminergic lesions, correlates negatively with the degree of injury, which brings other levels of understanding the impacts of the disease. Besides, abnormal synchronized oscillations among basal ganglia nuclei can be detrimental for information processing considering both motor and sleep-related processes. Altogether, despite clear advances in the field, it is still difficult to definitely establish a comprehensive understanding of causality among all the sleep dysfunctions with the disease itself. Although, certainly, the search for biomarkers is helping in shortening this road towards a better and faster diagnosis, as well as looking for more efficient treatments.