title: Selegiline normalizes, while l-DOPA sustains the increased number of dopamine neurons in the olfactory bulb in a 6-OHDA mouse model of Parkinson's disease.
abstract: Olfactory dysfunction, often preceding the cardinal motor symptoms, such as bradykinesia, rigidity, tremor at rest and postural instability, is frequently reported in Parkinson's disease. This symptom appears to be related to an increased number of dopamine neurons in the periglomerular layer of the olfactory bulb. In animal models of Parkinson's disease, adult neural progenitor cells migrating from the subventricular zone of the lateral ventricle to the olfactory bulb are evidently altered in their survival and progeny. The modulation of neural progenitor cells contributing to the number of dopamine neurons in the periglomerular layer, however, is still poorly understood. In this study, we have investigated the survival and neuronal differentiation of newly generated cells in the olfactory bulb, following treatment with the dopamine precursor l-DOPA and the monoamine oxidase-B inhibitor selegiline in a unilateral, intranigral 6-hydroxydopamine lesion model in mice. Our data show that the number of neural progenitor cells in the subventricular zone is decreased after an intranigral 6-hydroxydopamine lesion, while there is no difference from control in lesioned mice with selegiline or l-DOPA treatment. Selegiline is able to normalize the number of dopamine neurons in the periglomerular layer, while l-DOPA treatment sustains the increased number observed in 6-hydroxydopamine lesioned animals. We conclude that there is a distinct modulation of newly generated dopamine neurons of the olfactory bulb after l-DOPA and selegiline treatment. The differential effects of the two drugs might also play a role in olfactory dysfunction in Parkinson's disease patients.
authors.affiliation: Department of Neurology, Experimental Neurology Unit, Philipps-University Marburg, Biomedical Research Center, Hans-Meerwein-Strasse 2, 35043 Marburg, Germany.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Chiu
authors.affiliation: Department of Neurology, Experimental Neurology Unit, Philipps-University Marburg, Biomedical Research Center, Hans-Meerwein-Strasse 2, 35043 Marburg, Germany; Institute of Neurophysiology, Neuroscience Center, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Carlsson
authors.affiliation: Department of Neurology, Experimental Neurology Unit, Philipps-University Marburg, Biomedical Research Center, Hans-Meerwein-Strasse 2, 35043 Marburg, Germany.
authors.forename: Candan
authors.initials: C
authors.lastname: Depboylu
authors.affiliation: Department of Neurology, Experimental Neurology Unit, Philipps-University Marburg, Biomedical Research Center, Hans-Meerwein-Strasse 2, 35043 Marburg, Germany; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; Department of Translational Neurodegeneration, Technical University Munich, Max-Lebsche-Platz 30, 81377 Munich, Germany.
authors.forename: Günter U
authors.initials: GU
authors.lastname: Höglinger
authors.affiliation: Department of Neurology, Experimental Neurology Unit, Philipps-University Marburg, Biomedical Research Center, Hans-Meerwein-Strasse 2, 35043 Marburg, Germany.
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Oertel
authors.affiliation: Department of Neurology, Experimental Neurology Unit, Philipps-University Marburg, Biomedical Research Center, Hans-Meerwein-Strasse 2, 35043 Marburg, Germany. Electronic address: ries@med.uni-marburg.de.
authors.forename: Vincent
authors.initials: V
authors.lastname: Ries
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D015259:Dopamine Agents / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D009830:Olfactory Bulb / Q000187:drug effects* / Q000503:physiopathology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000503:physiopathology; D012642:Selegiline / Q000494:pharmacology*
chemical_list: D000978:Antiparkinson Agents; D015259:Dopamine Agents; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D012642:Selegiline; D007980:Levodopa; D016627:Oxidopamine
keywords: 6-Hydroxydopamine; Adult neurogenesis; Dopamine; Neural progenitor cell; Olfactory bulb; Parkinson's disease; Selegiline; l-Dopa