期刊
CELLS
卷 10, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/cells10123368
关键词
Nogo-A; Parkinson's disease; tyrosine hydroxylase; substantia nigra pars compacta; human; immunofluorescence
类别
资金
- Swiss Parkinson Foundation
- HANELA Foundation
- Switzerland and the Research Grant of the Inselspital, University Hospital Bern, Switzerland [RGI- 84800855]
The study revealed that co-expression of Nogo-A in nigral dopaminergic neurons of patients with Parkinson's disease decreases significantly with age, contrary to observations in normal aging and the animal model of Parkinson's disease. This suggests that Nogo-A may play a substantial role in the vulnerability of dopaminergic neurons in Parkinson's disease.
Parkinson's disease is mainly characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Together with the small number, the high vulnerability of the dopaminergic neurons is a major pathogenic culprit of Parkinson's disease. Our previous findings of a higher survival of dopaminergic neurons in the substantia nigra co-expressing Nogo-A in an animal model of Parkinson's disease suggested that Nogo-A may be associated with dopaminergic neurons resilience against Parkinson's disease neurodegeneration. In the present study, we have addressed the expression of Nogo-A in the dopaminergic neurons in the substantia nigra in postmortem specimens of diseased and non-diseased subjects of different ages. For this purpose, in a collaborative effort we developed a tissue micro array (TMA) that allows for simultaneous staining of many samples in a single run. Interestingly, and in contrast to the observations gathered during normal aging and in the animal model of Parkinson's disease, increasing age was significantly associated with a lower co-expression of Nogo-A in nigral dopaminergic neurons of patients with Parkinson's disease. In sum, while Nogo-A expression in dopaminergic neurons is higher with increasing age, the opposite is the case in Parkinson's disease. These observations suggest that Nogo-A might play a substantial role in the vulnerability of dopaminergic neurons in Parkinson's disease.
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