Loss of Nogo-A-expressing neurons in a rat model of Parkinson's disease

Schawkat, Khoschy; Di Santo, Stefano; Seiler, Stefanie; Ducray, Angélique; Widmer, Hans Rudolf (2015). Loss of Nogo-A-expressing neurons in a rat model of Parkinson's disease. Neuroscience, 288, pp. 59-72. Elsevier 10.1016/j.neuroscience.2014.12.035

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The myelin-associated protein Nogo-A is among the most potent neurite growth inhibitors in the adult CNS. Recently, Nogo-A expression was demonstrated in a number of neuronal subpopulations of the adult and developing CNS but at present, little is known about the expression of Nogo-A in the nigrostriatal system, a brain structure severely affected in Parkinson's disease (PD). The present study sought to characterize the expression pattern of Nogo-A immunoreactive (ir) cells in the adult ventral mesencephalon of control rats and in the 6-hydroxydopamine (6-OHDA) rat model of PD. Immunohistochemical analyses of normal adult rat brain showed a distinct expression of Nogo-A in the ventral mesencephalon, with the highest level in the substantia nigra pars compacta (SNc) where it co-localized with dopaminergic neurons. Analyses conducted 1week and 1 month after unilateral striatal injections of 6-OHDA disclosed a severe loss of the number of Nogo-A-ir cells in the SNc. Notably, at 1week after treatment, more dopaminergic neurons expressing Nogo-A were affected by the 6-OHDA toxicity than Nogo-A-negative dopaminergic neurons. However, at later time points more of the surviving dopaminergic neurons expressed Nogo-A. In the striatum, both small and large Nogo-A-positive cells were detected. The large cells were identified as cholinergic interneurons. Our results suggest yet unidentified functions of Nogo-A in the CNS beyond the inhibition of axonal regeneration and plasticity, and may indicate a role for Nogo-A in PD.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurosurgery
04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Institute of Diagnostic, Interventional and Paediatric Radiology

UniBE Contributor:

Schawkat, Khoschy; Di Santo, Stefano; Seiler, Stefanie; Ducray, Angélique and Widmer, Hans Rudolf

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0306-4522

Publisher:

Elsevier

Language:

English

Submitter:

Nicole Söll

Date Deposited:

20 Apr 2016 17:04

Last Modified:

21 Apr 2016 15:00

Publisher DOI:

10.1016/j.neuroscience.2014.12.035

PubMed ID:

25554426

Uncontrolled Keywords:

6-OHDA lesion; Nogo-A; Parkinson’s disease; midbrain

BORIS DOI:

10.7892/boris.81170

URI:

https://boris.unibe.ch/id/eprint/81170

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