Melatonin has a neuroprotective function, which is mediated via its G-protein-coupled MT1 and MT2 receptors. When activated, various downstream pathways are triggered promoting cell protection and survival. By utilizing this function of melatonin, studies have shown positive effects in animal models of neurodegenerative disorders such as Parkinson’s disease (PD). In our previous studies, a physiological dose of melatonin was shown to have neuroprotective effects in the nigrostriatal pathway, as indicated by preservation of tyrosine hydroxylase (TH) immunoreactivity in a 6-hydroxydopamine (6-OHDA) model of PD. We also have reported that transplantation of MT1 receptor-expressing mouse neural stem cells (C17.2) along with melatonin treatment, preserved TH immunoreactivity in a similar PD model. Moreover, others have reported an increase in striatal melatonin levels in 6-OHDA-induced hemiparkinsonian rats. Based on these implications of a close relationship between the dopaminergic and melatonergic systems, we hypothesize that degeneration of dopaminergic neurons induced by 6-OHDA will affect the melatonergic system in the nigrostriatal pathway. In this study, 6-hydroxydopamine was unilaterally injected in the rat striatum or medial forebrain bundle. An apomorphine rotation test showed significant increases in net contralateral rotations (p<0.01) in lesioned animals as compared to sham. Also, a loss of TH immunoreactivity in the striatum and substantia nigra was seen in striatum lesioned groups, confirming lesion-induced degeneration of dopaminergic neurons in the nigrostriatal pathway. There were no significant differences in MT1 receptor protein expression in the striatum and substantia nigra, between all intrastriatal lesioned groups and the sham group. However, 6-OHDA lesions in the medial forebrain bundle caused a significant increase in MT1 receptor mRNA expression on the lesioned side (right) of the ventral midbrain as compared with the contralateral side. These results suggest that MT1 receptors are upregulated in the ventral midbrain following lesion-induced dopaminergic neurodegeneration, and may be involved in an endogenous neuroprotective mechanism. / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/16427 |
| Date | 11 1900 |
| Creators | Kang, Na Hyea (Rachel) |
| Contributors | Niles, Lennard, Neuroscience |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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