Abstract
Previous investigations from this laboratory have demonstrated that hypophysectomy induces up-regulation of neuronal nitric oxide synthase (nNOS) in magnocellular neurons of the mammalian hypothalamo-neurohypophyseal system (HNS). Accompanied by this upregulation of nNOS, both neuronal regeneration and degeneration are also observed in this system following hypophysectomy. The specific aim of this study was to determine the potential role of nNOS upregulation in neuronal survival and regeneration after hypophysectomy in the adult Sprague–Dawley (SD) rat by using a competitive nitric oxide synthase blocker, N(G)-nitrol-l-arginine methyl ester (l-NAME). We found that l-NAME treatment effectively blocked the regeneration of magnocellular neurons of the rodent hypothalamus as observed in the lumen of the third cerebral ventricle following hypophysectomy. However, l-NAME had no effect on the survival of magnocellular neurons in the supraoptic (SON) and paraventricular (PVN) nuclei after hypophysectomy. These results suggest that the induced increase of nNOS expression enhance the regenerative ability of magnocellular neurons of the HNS following hypophysectomy.
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Choi BM, Pae HO, Jang SI, Kim YM, Chung HT (2002) Nitric oxide as a pro-apoptotic as well as anti-apoptotic modulator. J Biochem Mol Biol 35:116–126
Kibbe MR, Li J, Nie S, Choi BM, Kovesdi I, Lizonova A, Billiar TR, Tzeng E (2002) Potentiation of nitric oxide-induced apoptosis in p53-/- vascular smooth muscle cells. Am J Physiol Cell Physiol 282:C625–C634
Kim KM, Kim PK, Kwon YG, Bai SK, Nam WD, Kim YM (2002) Regulation of apoptosis by nitrosative stress. J Biochem Mol Biol 35:127–133
Leonelli M, Torrao AS, Britto LR (2009) Unconventional neurotransmitters, neurodegeneration and neuroprotection. Braz J Med Biol Res 42:68–75. doi:10.1590/S0100-879X2009000100011
Chang HM, Ling EA, Lue JH, Wen CY, Shieh JY (2000) Melatonin attenuates neuronal NADPH-d/NOS expression in the hypoglossal nucleus of adult rats following peripheral nerve injury. Brain Res 873:243–251. doi:10.1016/S0006-8993(00)02489-6
Chang HM, Lue JH, Wen CY, Shieh JY (2001) Axotomy along with hypoxia enhances the neuronal NADPH-d/NOS expression in lower brain stem motor neurons of adult rats. Exp Neurol 171:116–126. doi:10.1006/exnr.2001.7731
Chang HM, Huang YL, Lan CT, Wu UI, Hu ME, Youn SC (2008) Melatonin preserves superoxide dismutase activity in hypoglossal motoneurons of adult rats following peripheral nerve injury. J Pineal Res 44:172–180. doi:10.1111/j.1600-079X.2007.00505.x
Wei IH, Huang CC, Tseng CY, Chang HM, Tu HC, Tsai MH, Wen CY, Shieh JY (2008) Mild hypoxic preconditioning attenuates injury-induced NADPH-d/nNOS expression in brainstem motor neurons of adult rats. J Chem Neuroanat 35:123–132. doi:10.1016/j.jchemneu.2007.08.008
Yu WH (2002) Spatial and temporal correlation of nitric oxide synthase expression with CuZn-superoxide dismutase reduction in motor neurons following axotomy. Ann N Y Acad Sci 962:111–121
Bostanci MO, Bagirici F (2008) Nitric oxide synthesis inhibition attenuates iron-induced neurotoxicity: a stereological study. Neurotoxicology 29:130–135. doi:10.1016/j.neuro.2007.10.003
Chen J, Qin J, Liu X, Han Y, Yang Z, Chang X, Ji X (2008) Nitric oxide-mediated neuronal apoptosis in rats with recurrent febrile seizures through endoplasmic reticulum stress pathway. Neurosci Lett 443:134–139. doi:10.1016/j.neulet.2008.07.060
Kim HJ, Im W, Kim S, Kim SH, Sung JJ, Kim M, Lee KW (2007) Calcium-influx increases SOD1 aggregates via nitric oxide in cultured motor neurons. Exp Mol Med 39:574–582
Di MV, Benigno A, Pierucci M, Giuliano DA, Crescimanno G, Esposito E, Di Giovanni G (2006) 7-Nitroindazole protects striatal dopaminergic neurons against MPP + -induced degeneration: an in vivo microdialysis study. Ann N Y Acad Sci 1089:462–471
Wu W, Li L (1993) Inhibition of nitric oxide synthase reduces motoneuron death due to spinal root avulsion. Neurosci Lett 153:121–124. doi:10.1016/0304-3940(93)90303-3
Gulturk S, Kozan R, Bostanci MO, Sefil F, Bagirici F (2008) Inhibition of neuronal nitric oxide synthase prevents iron-induced cerebellar Purkinje cell loss in the rat. Acta Neurobiol Exp (Wars) 68:26–31
Calabrese V, Mancuso C, Calvani M, Rizzarelli E, Butterfield DA, Stella AM (2007) Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nat Rev Neurosci 8:766–775. doi:10.1038/nrn2214
Zhou L, Wu W (2006) Antisense oligos to neuronal nitric oxide synthase aggravate motoneuron death induced by spinal root avulsion in adult rat. Exp Neurol 197:84–92. doi:10.1016/j.expneurol.2005.08.019
Renteria RC, Constantine-Paton M (1999) Nitric oxide in the retinotectal system: a signal but not a retrograde messenger during map refinement and segregation. J Neurosci 19:7066–7076
Van Wagenen S, Rehder V (1999) Regulation of neuronal growth cone filopodia by nitric oxide. J Neurobiol 39:168–185. doi:10.1002/(SICI)1097-4695(199905)39:2<168::AID-NEU2>3.0.CO;2-F
Chu TH, Wu WT (2006) Nitric oxide synthase inhibitor attenuates number of regenerating spinal motoneurons in adult rats. NeuroReport 17:969–973. doi:10.1097/01.wnr.0000221839.05008.85
Cristino L, Pica A, Della CF, Bentivoglio M (2000) Co-induction of nitric oxide synthase, bcl-2 and growth-associated protein-43 in spinal motoneurons during axon regeneration in the lizard tail. Neuroscience 101:451–458. doi:10.1016/S0306-4522(00)00393-6
Gonzalez-Hernandez T, Rustioni A (1999) Expression of three forms of nitric oxide synthase in peripheral nerve regeneration. J Neurosci Res 55:198–207. doi:10.1002/(SICI)1097-4547(19990115)55:2<198::AID-JNR7>3.0.CO;2-M
Stern M, Bicker G (2008) Nitric oxide regulates axonal regeneration in an insect embryonic CNS. Dev Neurobiol 68:295–308. doi:10.1002/dneu.20585
Gonzalez-Hernandez T, Rustioni A (1999) Nitric oxide synthase and growth-associated protein are coexpressed in primary sensory neurons after peripheral injury. J Comp Neurol 404:64–74. doi:10.1002/(SICI)1096-9861(19990201)404:1<64::AID-CNE5>3.0.CO;2-M
Keilhoff G, Fansa H, Wolf G (2002) Differences in peripheral nerve degeneration/regeneration between wild-type and neuronal nitric oxide synthase knockout mice. J Neurosci Res 68:432–441. doi:10.1002/jnr.10229
Zochodne DW, Levy D (2005) Nitric oxide in damage, disease and repair of the peripheral nervous system. Cell Mol Biol (Noisy-le-grand) 51:255–267
Sunico CR, Portillo F, Gonzalez-Forero D, Kasparov S, Moreno-Lopez B (2008) Evidence for a detrimental role of nitric oxide synthesized by endothelial nitric oxide synthase after peripheral nerve injury. Neuroscience 157:40–51. doi:10.1016/j.neuroscience.2008.09.001
Zochodne DW, Misra M, Cheng C, Sun H (1997) Inhibition of nitric oxide synthase enhances peripheral nerve regeneration in mice. Neurosci Lett 228:71–74. doi:10.1016/S0304-3940(97)00359-5
Scott DE, Wu W, Slusser J, Depto A, Hansen S (1995) Neural regeneration and neuronal migration following injury. I. The endocrine hypothalamus and neurohypophyseal system. Exp Neurol 131:23–38. doi:10.1016/0014-4886(95)90004-7
Yuan Q, Scott DE, So KF, Wu W (2006) The response of magnocellular neurons of the hypothalamo-neurohyphyseal system to hypophysectomy, nitric oxide synthase expression as well as survival and regeneration in developing vs. adult rats. Brain Res 1113:45–53. doi:10.1016/j.brainres.2006.07.052
Kawamoto K, Kawashima S (1987) Regeneration of neurohypophyseal hormone-producing neurons in hypophysectomized immature rats. Brain Res 422:106–117. doi:10.1016/0006-8993(87)90545-2
Wang Y, Zhao C, Wang Z, Wang C, Feng W, Huang L, Zhang J, Qi S (2008) Apoptosis of supraoptic AVP neurons is involved in the development of central diabetes insipidus after hypophysectomy in rats. BMC Neurosci 9:54. doi:10.1186/1471-2202-9-54
Thorngren KG, Hansson LI, Menander-Sellman K, Stenstrom A (1973) Effect of hypophysectomy on longitudinal bone growth in the rat. Calcif Tissue Res 11:281–300. doi:10.1007/BF02547228
Zimmerman EA, Nilaver G, Hou-Yu A, Silverman AJ (1984) Vasopressinergic and oxytocinergic pathways in the central nervous system. Fed Proc 43:91–96
Wu W, Han K, Li L, Schinco FP (1994) Implantation of PNS graft inhibits the induction of neuronal nitric oxide synthase and enhances the survival of spinal motoneurons following root avulsion. Exp Neurol 129:335–339. doi:10.1006/exnr.1994.1176
Ceccatelli S, Eriksson M (1993) The effect of lactation on nitric oxide synthase gene expression. Brain Res 625:177–179. doi:10.1016/0006-8993(93)90153-E
Popeski N, Amir S, Woodside B (1999) Changes in NADPH-d staining in the paraventricular and supraoptic nuclei during pregnancy and lactation in rats: role of ovarian steroids and oxytocin. J Neuroendocrinol 11:53–61. doi:10.1046/j.1365-2826.1999.00291.x
Lipton SA, Choi YB, Pan ZH, Lei SZ, Chen HS, Sucher NJ, Loscalzo J, Singel DJ, Stamler JS (1993) A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature 364:626–632. doi:10.1038/364626a0
Ding M, St Pierre BA, Parkinson JF, Medberry P, Wong JL, Rogers NE, Ignarro LJ, Merrill JE (1997) Inducible nitric-oxide synthase and nitric oxide production in human fetal astrocytes and microglia. A kinetic analysis. J Biol Chem 272:11327–11335. doi:10.1074/jbc.272.44.28142
Pahan K, Sheikh FG, Liu X, Hilger S, McKinney M, Petro TM (2001) Induction of nitric-oxide synthase and activation of NF-kappaB by interleukin-12 p40 in microglial cells. J Biol Chem 276:7899–7905. doi:10.1074/jbc.M008262200
Possel H, Noack H, Putzke J, Wolf G, Sies H (2000) Selective upregulation of inducible nitric oxide synthase (iNOS) by lipopolysaccharide (LPS) and cytokines in microglia: in vitro and in vivo studies. Glia 32:51–59. doi:10.1002/1098-1136(200010)32:1<51::AID-GLIA50>3.0.CO;2-4
Bains JS, Ferguson AV (1997) Nitric oxide regulates NMDA-driven GABAergic inputs to type I neurones of the rat paraventricular nucleus. J Physiol 499(Pt 3):733–746
Yang QZ, Hatton GI (1999) Nitric oxide via cGMP-dependent mechanisms increases dye coupling and excitability of rat supraoptic nucleus neurons. J Neurosci 19:4270–4279
Scott DE (1999) Post-traumatic migration and emergence of a novel cell line upon the ependymal surface of the third cerebral ventricle in the adult mammalian brain. Anat Rec 256:233–241. doi:10.1002/(SICI)1097-0185(19991101)256:3<233::AID-AR3>3.0.CO;2-H
Wu WT, Scott DE, Gilman AM (1989) Correlative scanning-immunoelectromicroscopic analysis of neuropeptide localization and neuronal plasticity in the endocrine hypothalamus. Brain Res Bull 22:399–410. doi:10.1016/0361-9230(89)90067-1
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Yuan, Q., Scott, D.E., So, KF. et al. The Potential Role of Nitric Oxide Synthase in Survival and Regeneration of Magnocellular Neurons of Hypothalamo-Neurohypophyseal System. Neurochem Res 34, 1907–1913 (2009). https://doi.org/10.1007/s11064-009-9965-0
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DOI: https://doi.org/10.1007/s11064-009-9965-0