Neural stem cell transplantation and melatonin treatment in a 6‐hydroxydopamine model of Parkinson’s disease

Abstract

Melatonin has multiple roles including neuroprotection. Melatonin signaling involves diverse targets including two G-protein-coupled receptors, MT(1) and MT(2), which have both been localized to the nigrostriatal pathway. Previous studies in our laboratory demonstrated preservation of tyrosine hydroxylase immunoreactivity, following chronic treatment with a physiological dose of melatonin, in the 6-hydroxydopamine rat model of Parkinson's disease. Additionally, we reported the presence of the melatonin MT(1) receptor subtype in cultured C17.2 neural stem cells (NSCs). In the present study, we examined the effects of C17.2 NSC transplantation on dopaminergic denervation following 6-hydroxydopamine lesioning in the rat striatum. Moreover, based on our detection of the MT(1) in these cells, we examined the effects of combined C17.2 NSC transplantation and melatonin treatment, following striatal lesioning. Behavioral studies indicated a marked inhibition of apomorphine-induced rotations in lesioned animals that received C17.2 NSC transplantation, melatonin, or the combined regimen. In addition, these treatments resulted in a significant protection of tyrosine hydroxylase immunoreactivity in the striatum and substantia nigra of lesioned animals, when compared with untreated controls. Lesioned animals treated with C17.2 NSCs, melatonin or a combination of both agents exhibited no significant differences in the number of tyrosine hydroxylase-positive cells in the substantia nigra or ventral tegmental area ipsilateral or contralateral to the lesioned striatum. These findings suggest that stem cell therapy and concomitant use of neuroprotective agents such as melatonin could be a viable approach in Parkinson's disease.