• Neuroscience · Mar 2015

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

    • K Schawkat, S Di Santo, S Seiler, A D Ducray, and H R Widmer.
    • Department of Neurosurgery, Neurocenter and Regenerative Neuroscience Cluster, University of Bern, Inselspital, CH-3010 Bern, Switzerland. Electronic address: khoschy.schawkat@insel.ch.
    • Neuroscience. 2015 Mar 12; 288: 59-72.

    AbstractThe 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.Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

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