(-)-Deprenyl fails to promote axonal regeneration of retinal ganglion cells in vitro and in vivo.
(-)-Deprenyl ( L-deprenyl, selegiline hydrochloride), a selective monoamine oxidase B (MAO-B) inhibitor employed in the pharmacological therapy of Parkinson's disease, increases neuronal survival in both animal models of neurodegenerative disorders and acute CNS lesions. Despite intensive investigations, the mechanisms of (-)-deprenyl-mediated neuroprotection remain poorly understood. To test the hypothesis that (-)-deprenyl might have a beneficial effect not only on neuronal survival, but also on axonal regeneration, we describe here experiments performed in vitro and in vivo which clearly demonstrate that (-)-deprenyl fails to promote axonal regeneration of severed rat retinal ganglion cells (RGCs). Furthermore, (-)-deprenyl was not able to overcome free-radical-induced RGC axon degeneration. These results challenge the notion that (-)-deprenyl might be useful as a monotherapy for acute CNS lesions and give rise to a more critical viewpoint of the trophic-like function of this widely used therapeutic agent.
Rosenstiel
Philip
P
Institute of Anatomy, Christian Albrechts University of Kiel, Olshausenstr. 40, 24098 Kiel, Germany.
Sievers
Jobst
J
Lucius
Ralph
R
D000818:Animals; D001369:Axons / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D005609:Free Radicals / Q000633:toxicity; D019922:GAP-43 Protein / Q000096:biosynthesis; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D005786:Gene Expression Regulation / Q000187:drug effects; D019254:Genes, bcl-2 / Q000235:genetics; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000517:prevention & control; D009416:Nerve Regeneration / Q000187:drug effects*; D016501:Neurites / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009900:Optic Nerve / Q000166:cytology / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020917:Receptor, trkA / Q000096:biosynthesis; D020813:Receptor, trkB / Q000096:biosynthesis; D012165:Retinal Ganglion Cells / Q000187:drug effects*; D012642:Selegiline / Q000494:pharmacology*
D019208:Brain-Derived Neurotrophic Factor; D005609:Free Radicals; D019922:GAP-43 Protein; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D012642:Selegiline; C002385:linsidomine; D008981:Molsidomine; D020917:Receptor, trkA; D020813:Receptor, trkB