Co-Expression of Nogo-A in Dopaminergic Neurons of the Human Substantia Nigra Pars Compacta Is Reduced in Parkinson's Disease

• Published in: Cells (Basel, Switzerland) Switzerland), 2021-11, Vol.10 (12), p.3368
• Main Authors: Eyer, Gian-Carlo, Di Santo, Stefano, Hewer, Ekkehard, Andereggen, Lukas, Seiler, Stefanie, Widmer, Hans Rudolf
• Format: Article
• Language: English
• Subjects: Age; Age Factors; Aged; Aged, 80 and over; Aging; Aging - metabolism; Animal models; Antibodies; Cell Count; Dopamine; Dopamine receptors; Dopaminergic Neurons - metabolism; Females; human; Humans; immunofluorescence; Localization; Male; Movement disorders; Neurodegeneration; Neurodegenerative diseases; Neurons; Nogo protein; Nogo Proteins - metabolism; Nogo-A; Parkinson Disease - metabolism; Parkinson's disease; Statistical analysis; Substantia nigra; Substantia Nigra - metabolism; substantia nigra pars compacta; Tyrosine 3-Monooxygenase - metabolism; tyrosine hydroxylase
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells10123368

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.