title: Neuronal NOS deficiency promotes apoptotic cell death of spinal cord neurons after peripheral nerve transection.
abstract: To study the role of endogenous NO in survival and recovery of spinal cord neurons after nerve lesions, wild type mice were compared to knock-out mice lacking neuronal, endothelial or inducible NO synthase (NOS) after sciatic nerve transection. The NO-generating capacities were assessed by NOS immunohistochemistry and NADPH-diaphorase staining. The feature of affected neurons was evaluated following Nissl- and TUNEL-staining, by immunocytochemical demonstration of cytochrome c-translocation, and by ultrastructural examination. Time point of cell loss was found to be independent of the mice type and occurred only at later post-axotomy states. The extent of neuronal degeneration, however, depended on the NO supply. Whereas a lack of endothelial or inducible NOS was well tolerated, deficiency of neuronal NOS enhanced the competence-to-die and led to a substantial apoptotic cell death of spinal cord neurons. Thus, NO supply turned out to be essential for cell survival and recovery with reference to the neuronal NOS isoform.
authors.affiliation: Institute of Medical Neurobiology, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany. gerburg.keilhoff@medizin.uni-magdeburg.de
authors.forename: Gerburg
authors.initials: G
authors.lastname: Keilhoff
authors.forename: Hisham
authors.initials: H
authors.lastname: Fansa
authors.forename: Gerald
authors.initials: G
authors.lastname: Wolf
mesh_terms: D000818:Animals; D017209:Apoptosis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000166:cytology / Q000201:enzymology; D012584:Sciatic Nerve / Q000166:cytology / Q000201:enzymology / Q000601:surgery; D013116:Spinal Cord / Q000166:cytology / Q000201:enzymology*
chemical_list: D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse