title: Loss of Nogo-A-expressing neurons in a rat model of Parkinson's disease.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Neurocenter and Regenerative Neuroscience Cluster, University of Bern, Inselspital, CH-3010 Bern, Switzerland. Electronic address: khoschy.schawkat@insel.ch.
authors.forename: K
authors.initials: K
authors.lastname: Schawkat
authors.affiliation: Department of Neurosurgery, Neurocenter and Regenerative Neuroscience Cluster, University of Bern, Inselspital, CH-3010 Bern, Switzerland. Electronic address: stefano.disanto@insel.ch.
authors.forename: S
authors.initials: S
authors.lastname: Di Santo
authors.affiliation: Department of Neurosurgery, Neurocenter and Regenerative Neuroscience Cluster, University of Bern, Inselspital, CH-3010 Bern, Switzerland. Electronic address: stefanie.seiler@insel.ch.
authors.forename: S
authors.initials: S
authors.lastname: Seiler
authors.affiliation: Department of Neurosurgery, Neurocenter and Regenerative Neuroscience Cluster, University of Bern, Inselspital, CH-3010 Bern, Switzerland. Electronic address: angelique.ducray@vetsuisse.unibe.ch.
authors.forename: A D
authors.initials: AD
authors.lastname: Ducray
authors.affiliation: Department of Neurosurgery, Neurocenter and Regenerative Neuroscience Cluster, University of Bern, Inselspital, CH-3010 Bern, Switzerland. Electronic address: hanswi@insel.ch.
authors.forename: H R
authors.initials: HR
authors.lastname: Widmer
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D002452:Cell Count; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008636:Mesencephalon / Q000378:metabolism / Q000473:pathology*; D009185:Myelin Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D056347:Neuroanatomical Tract-Tracing Techniques; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D000070798:Nogo Proteins; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000473:pathology*; D010784:Photomicrography; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013266:Stilbamidines; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D034961:Antigens, Nuclear; D005904:Glial Fibrillary Acidic Protein; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070798:Nogo Proteins; C546339:Rbfox3 protein, rat; C000603197:Rtn4 protein, rat; D013266:Stilbamidines; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase; D004298:Dopamine
keywords: 6-OHDA lesion; Nogo-A; Parkinson’s disease; midbrain