title: Nitric oxide-cGMP signaling regulates axonal elongation during optic nerve regeneration in the goldfish in vitro and in vivo.
abstract: Nitric oxide (NO) signaling results in both neurotoxic and neuroprotective effects in CNS and PNS neurons, respectively, after nerve lesioning. We investigated the role of NO signaling on optic nerve regeneration in the goldfish (Carassius auratus). NADPH diaphorase staining revealed that nitric oxide synthase (NOS) activity was up-regulated primarily in the retinal ganglion cells (RGCs) 5-40 days after axotomy. Levels of neuronal NOS (nNOS) mRNA and protein also increased in the RGCs alone during this period. This period (5-40 days) overlapped with the process of axonal elongation during regeneration of the goldfish optic nerve. Therefore, we evaluated the effect of NO signaling molecules upon neurite outgrowth from adult goldfish axotomized RGCs in culture. NO donors and dibutyryl cGMP increased neurite outgrowth dose-dependently. In contrast, a nNOS inhibitor and small interfering RNA, specific for the nNOS gene, suppressed neurite outgrowth from the injured RGCs. Intra-ocular dibutyryl cGMP promoted the axonal regeneration from injured RGCs in vivo. None of these molecules had an effect on cell death/survival in this culture system. This is the first report showing that NO-cGMP signaling pathway through nNOS activation is involved in neuroregeneration in fish CNS neurons after nerve lesioning.
authors.affiliation: Department of Molecular Neurobiology and Division of Laboratory Sciences, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan. koriyama@med.kanazawa-u.ac.jp
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Koriyama
authors.forename: Rie
authors.initials: R
authors.lastname: Yasuda
authors.forename: Keiko
authors.initials: K
authors.lastname: Homma
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mawatari
authors.forename: Mikiko
authors.initials: M
authors.lastname: Nagashima
authors.forename: Kayo
authors.initials: K
authors.lastname: Sugitani
authors.forename: Toru
authors.initials: T
authors.lastname: Matsukawa
authors.forename: Satoru
authors.initials: S
authors.lastname: Kato
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D006152:Cyclic GMP / Q000096:biosynthesis / Q000502:physiology*; D006054:Goldfish / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D016501:Neurites / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D009900:Optic Nerve / Q000502:physiology*; D020221:Optic Nerve Injuries / Q000378:metabolism / Q000473:pathology; D009924:Organ Culture Techniques; D015398:Signal Transduction / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D006152:Cyclic GMP