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Erschienen in: Metabolic Brain Disease 4/2010

01.12.2010 | Original Paper

Role of inducible or neuronal nitric oxide synthase in neurogenesis of the dentate gyrus in aged mice

verfasst von: Minami Adachi, Manami Abe, Taeko Sasaki, Hiroyuki Kato, Jiro Kasahara, Tsutomu Araki

Erschienen in: Metabolic Brain Disease | Ausgabe 4/2010

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Abstract

We evaluated mainly the iNOS (inducible nitric oxide synthase) and nNOS (neuronal NOS) expression in the subgranular zone (SGZ) of the dentate gyrus of the hippocampus in young adult (8-week-old) and aged (60-week-old) mice. The present study demonstrates that the expression of nNOS was more pronounced than that of iNOS expression in the dentate gyrus of aged mice. Our study also suggests that aged mice exhibited a significant loss of motor activity as compared with young adult animals. Furthermore, our results provide that no significant change in the number of Neu N (Neuronal nuclei)-immunopositive neurons and GFAP (glial fibrillary acidic protein)—immunopositive astrocytes was observed in the dentate gyrus between young adult and aged mice. In contrast, a significant change in the number of Iba 1(ionized calcium-binding adaptor molecule 1)—immunopositive microglia in aged mice was observed in the dentate gyrus as compared to young adult animals. These results provide the novel evidence showing that the expression of nNOS may be crucial for the role of neurogenesis of the SGZ of the dentate gyrus in aged mice. Furthermore, our present findings demonstrate that the inhibition of nNOS expression in the SGZ of the dentate gyrus during aging processes may offer novel therapeutic strategies for anti-aging in humans.
Literatur
Zurück zum Zitat Alvarez-Buylla A, Garcia-Verdugo JM (2002) Neurogenesis in adult subventricular zone. J Neurosci 22:629–634PubMed Alvarez-Buylla A, Garcia-Verdugo JM (2002) Neurogenesis in adult subventricular zone. J Neurosci 22:629–634PubMed
Zurück zum Zitat Aoki E, Yokoyama H, Kimoto H, Yano R, Kato H, Araki T (2009) Chronic administration with rotenone does not enhance MPTP neurotoxicity in C57BL/6 mice. J Mol Neurosci 41:17–24CrossRefPubMed Aoki E, Yokoyama H, Kimoto H, Yano R, Kato H, Araki T (2009) Chronic administration with rotenone does not enhance MPTP neurotoxicity in C57BL/6 mice. J Mol Neurosci 41:17–24CrossRefPubMed
Zurück zum Zitat Calhoun ME, Kurth D, Phinney AL, Long JM, Hengemihle J, Mouton PR, Ingram DK, Jucker M (1998) Hippocampal neuron and synaptophysin-positive bouton number in aging C57BL/6 mice. Neurobiol Aging 19:599–606CrossRefPubMed Calhoun ME, Kurth D, Phinney AL, Long JM, Hengemihle J, Mouton PR, Ingram DK, Jucker M (1998) Hippocampal neuron and synaptophysin-positive bouton number in aging C57BL/6 mice. Neurobiol Aging 19:599–606CrossRefPubMed
Zurück zum Zitat Cheng A, Wang S, Cai J, Rao MS, Mattson MP (2003) Nitric oxide acts in a positive feedback loop with BDNF to regulate neural progenitor cell proliferation and differentiation in the mammalian brain. Dev Biol 258:319–333CrossRefPubMed Cheng A, Wang S, Cai J, Rao MS, Mattson MP (2003) Nitric oxide acts in a positive feedback loop with BDNF to regulate neural progenitor cell proliferation and differentiation in the mammalian brain. Dev Biol 258:319–333CrossRefPubMed
Zurück zum Zitat Dalkara T, Moskowitz MA (1994) The complex role of nitric oxide in the pathophysiology of focal cerebral ischemia. Brain Pathol 4:49–57CrossRefPubMed Dalkara T, Moskowitz MA (1994) The complex role of nitric oxide in the pathophysiology of focal cerebral ischemia. Brain Pathol 4:49–57CrossRefPubMed
Zurück zum Zitat David JP, Ghozali F, Fallet-Bianco C, Wattez A, Delaine S, Boniface B, Di Menza C, Delacourte A (1997) Glial reaction in the hippocampal formation is highly correlated with aging in human brain. Neurosci Lett 235:53–56CrossRefPubMed David JP, Ghozali F, Fallet-Bianco C, Wattez A, Delaine S, Boniface B, Di Menza C, Delacourte A (1997) Glial reaction in the hippocampal formation is highly correlated with aging in human brain. Neurosci Lett 235:53–56CrossRefPubMed
Zurück zum Zitat Dun NJ, Dun SL, Wong RKS, Forstermann U (1994) Colocalization of nitric oxide synthase and somatostatin immunoreactivity in rat dentate hilar neurons. Proc Natl Acad Sci USA 91:2955–2959CrossRefPubMed Dun NJ, Dun SL, Wong RKS, Forstermann U (1994) Colocalization of nitric oxide synthase and somatostatin immunoreactivity in rat dentate hilar neurons. Proc Natl Acad Sci USA 91:2955–2959CrossRefPubMed
Zurück zum Zitat Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH (1998) Neurogenesis in the adult human hippocampus. Nat Med 4:1313–1317CrossRefPubMed Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH (1998) Neurogenesis in the adult human hippocampus. Nat Med 4:1313–1317CrossRefPubMed
Zurück zum Zitat Eto R, Abe M, Hayakawa N, Kato H, Araki T (2008) Age-related changes of calcineurin and Akt1/protein kinase Bα (AKt1/PKBα) immunoreactivity in the mouse hippocampal CA1 sector: an immunohistochemical study. Metab Brain Dis 23:399–409CrossRefPubMed Eto R, Abe M, Hayakawa N, Kato H, Araki T (2008) Age-related changes of calcineurin and Akt1/protein kinase Bα (AKt1/PKBα) immunoreactivity in the mouse hippocampal CA1 sector: an immunohistochemical study. Metab Brain Dis 23:399–409CrossRefPubMed
Zurück zum Zitat Finch CE (2002) Neurons, glia, and plasticity in normal brain aging. Adv Gerontol 10:35–39PubMed Finch CE (2002) Neurons, glia, and plasticity in normal brain aging. Adv Gerontol 10:35–39PubMed
Zurück zum Zitat Gage FH (2000) Structural plasticity: cause, result, or correlate of depression. Biol Psychiatry 48:713–714CrossRefPubMed Gage FH (2000) Structural plasticity: cause, result, or correlate of depression. Biol Psychiatry 48:713–714CrossRefPubMed
Zurück zum Zitat Hayakawa N, Kato H, Araki T (2007) Age-related changes of astorocytes, oligodendrocytes and microglia in the mouse hippocampal CA1 sector. Mech Ageing Dev 128:311–316CrossRefPubMed Hayakawa N, Kato H, Araki T (2007) Age-related changes of astorocytes, oligodendrocytes and microglia in the mouse hippocampal CA1 sector. Mech Ageing Dev 128:311–316CrossRefPubMed
Zurück zum Zitat Hayakawa N, Abe M, Eto R, Kato H, Araki T (2008) Age-related changes of NGF, BDNF, parvalbumin and neuronal nitric oxide synthase immunoreactivity in the mouse hippocampal CA1 sector. Metab Brain Dis 23:199–211CrossRefPubMed Hayakawa N, Abe M, Eto R, Kato H, Araki T (2008) Age-related changes of NGF, BDNF, parvalbumin and neuronal nitric oxide synthase immunoreactivity in the mouse hippocampal CA1 sector. Metab Brain Dis 23:199–211CrossRefPubMed
Zurück zum Zitat Homburger F, Russfield AB, Weisburger JH, Lim S, Chak SP, Weisburger EK (1975) Aging changes in CD-1 HaM/ICR mice reared under standard laboratory conditions. J Natl Cancer Inst 55:37–45PubMed Homburger F, Russfield AB, Weisburger JH, Lim S, Chak SP, Weisburger EK (1975) Aging changes in CD-1 HaM/ICR mice reared under standard laboratory conditions. J Natl Cancer Inst 55:37–45PubMed
Zurück zum Zitat Jin K, Minami M, Lan JQ, Mao XO, Batteur S, Simon RP, Greenberg DA (2001) Neurogenesis in the dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc Natl Acad Sci USA 98:4710–4715CrossRefPubMed Jin K, Minami M, Lan JQ, Mao XO, Batteur S, Simon RP, Greenberg DA (2001) Neurogenesis in the dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc Natl Acad Sci USA 98:4710–4715CrossRefPubMed
Zurück zum Zitat Jin K, Sun Y, Xie L, Peel A, Mao XO, Batteur S, Greenberg DA (2003) Directed migration of neuronal precursors into the ischemic cerebral cortex and striatum. Mol Cell Neurosci 24:171–189CrossRefPubMed Jin K, Sun Y, Xie L, Peel A, Mao XO, Batteur S, Greenberg DA (2003) Directed migration of neuronal precursors into the ischemic cerebral cortex and striatum. Mol Cell Neurosci 24:171–189CrossRefPubMed
Zurück zum Zitat Keynes RG, Garthwaite J (2004) Nitric oxide and its role in ischaemic brain injury. Curr Mol Med 4:179–191CrossRefPubMed Keynes RG, Garthwaite J (2004) Nitric oxide and its role in ischaemic brain injury. Curr Mol Med 4:179–191CrossRefPubMed
Zurück zum Zitat Kimoto H, Eto R, Abe M, Kato H, Araki T (2009) Alterations of glial cells in the mouse hippocampus during postnatal development. Cell Mol Neurobiol 29:1181–1189CrossRefPubMed Kimoto H, Eto R, Abe M, Kato H, Araki T (2009) Alterations of glial cells in the mouse hippocampus during postnatal development. Cell Mol Neurobiol 29:1181–1189CrossRefPubMed
Zurück zum Zitat Kornack DR, Rakic P (1999) Continuation of neurogenesis in the hippocampus of the adult macaque monkey. Proc Natl Acad Sci USA 96:5768–5773CrossRefPubMed Kornack DR, Rakic P (1999) Continuation of neurogenesis in the hippocampus of the adult macaque monkey. Proc Natl Acad Sci USA 96:5768–5773CrossRefPubMed
Zurück zum Zitat Leker RR, Lasri V, Chernoguz D (2009) Growth factors improve neurogenesis and outcome after focal cerebral ischemia. J Neural Transm 116:1397–1402CrossRefPubMed Leker RR, Lasri V, Chernoguz D (2009) Growth factors improve neurogenesis and outcome after focal cerebral ischemia. J Neural Transm 116:1397–1402CrossRefPubMed
Zurück zum Zitat Long JM, Kalehua AN, Muth NJ, Calhoun ME, Jucker M, Hengemihle JM, Ingram DK, Mouton PR (1998) Stereological analysis of astrocyte and microglia in aging mouse hippocampus. Neurobiol Aging 19:497–503CrossRefPubMed Long JM, Kalehua AN, Muth NJ, Calhoun ME, Jucker M, Hengemihle JM, Ingram DK, Mouton PR (1998) Stereological analysis of astrocyte and microglia in aging mouse hippocampus. Neurobiol Aging 19:497–503CrossRefPubMed
Zurück zum Zitat Matsuda S, Umeda M, Kato H, Araki T (2009) Glial damage after transient focal cerebral ischemia in rats. J Mol Neurosci 38:220–226CrossRefPubMed Matsuda S, Umeda M, Kato H, Araki T (2009) Glial damage after transient focal cerebral ischemia in rats. J Mol Neurosci 38:220–226CrossRefPubMed
Zurück zum Zitat Moreno-Lopez B, Romero-Grimaldi C, Noval JA, Murillo-Carretero M, Matarredona ER, Estrada C (2004) Nitric oxide is physiological inhibitor of neurogenesis in the adult mouse subventricular zone and olfactory bulb. J Neurosci 24:85–95CrossRefPubMed Moreno-Lopez B, Romero-Grimaldi C, Noval JA, Murillo-Carretero M, Matarredona ER, Estrada C (2004) Nitric oxide is physiological inhibitor of neurogenesis in the adult mouse subventricular zone and olfactory bulb. J Neurosci 24:85–95CrossRefPubMed
Zurück zum Zitat Mouton PR, Long JM, Lei DL, Howard V, Jucker M, Calhoun ME, Ingram DK (2002) Age and gender effects on microglia and astrocyte numbers in brains of mice. Brain Res 956:30–35CrossRefPubMed Mouton PR, Long JM, Lei DL, Howard V, Jucker M, Calhoun ME, Ingram DK (2002) Age and gender effects on microglia and astrocyte numbers in brains of mice. Brain Res 956:30–35CrossRefPubMed
Zurück zum Zitat Nithianantharajah J, Hannan AJ (2009) The neurobiology of brain and cognitive reserve: mental and physical activity as modulators of brain disorders. Prog Neurobiol 89:369–382CrossRefPubMed Nithianantharajah J, Hannan AJ (2009) The neurobiology of brain and cognitive reserve: mental and physical activity as modulators of brain disorders. Prog Neurobiol 89:369–382CrossRefPubMed
Zurück zum Zitat O’Callaghan JP, Miller DB (1991) The concentration of glial fibrillary acidic protein increases with age in the mouse and rat brain. Neurobiol Aging 12:171–174CrossRefPubMed O’Callaghan JP, Miller DB (1991) The concentration of glial fibrillary acidic protein increases with age in the mouse and rat brain. Neurobiol Aging 12:171–174CrossRefPubMed
Zurück zum Zitat Ookubo M, Yokoyama H, Kato H, Araki T (2009) Gender differences on MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) neurotoxicity in C57BL/6 mice. Mol Cell Endocrinol 311:62–68CrossRefPubMed Ookubo M, Yokoyama H, Kato H, Araki T (2009) Gender differences on MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) neurotoxicity in C57BL/6 mice. Mol Cell Endocrinol 311:62–68CrossRefPubMed
Zurück zum Zitat Packer MA, Stasiv Y, Benraiss A, Chmielnicki E, Grinberg A, Westphal H, Goldman SA, Enikolopov G (2003) Nitric oxide negatively regulates mammalian adult neurogenesis. Proc Natl Acad Sci USA 100:9566–9571CrossRefPubMed Packer MA, Stasiv Y, Benraiss A, Chmielnicki E, Grinberg A, Westphal H, Goldman SA, Enikolopov G (2003) Nitric oxide negatively regulates mammalian adult neurogenesis. Proc Natl Acad Sci USA 100:9566–9571CrossRefPubMed
Zurück zum Zitat Parent JM, Vexler ZS, Gong C, Derugin N, Ferriero DM (2002) Rat forebrain neurogenesis and striatal neuron replacement after focal stroke. Ann Neurol 52:802–813CrossRefPubMed Parent JM, Vexler ZS, Gong C, Derugin N, Ferriero DM (2002) Rat forebrain neurogenesis and striatal neuron replacement after focal stroke. Ann Neurol 52:802–813CrossRefPubMed
Zurück zum Zitat Park C, Sohn Y, Shin KS, Kim J, Ahn H, Huh Y (2003) The chronic inhibition of nitric oxide synthase enhances cell proliferation in the adult rat hippocampus. Neurosci Lett 399:9–12CrossRef Park C, Sohn Y, Shin KS, Kim J, Ahn H, Huh Y (2003) The chronic inhibition of nitric oxide synthase enhances cell proliferation in the adult rat hippocampus. Neurosci Lett 399:9–12CrossRef
Zurück zum Zitat Rietze R, Poulin P, Weiss S (2000) Mitotically active cells that generate neurons and astrocytes are present in multiple regions of the adult mouse hippocampus. J Comp Neurol 424:397–408CrossRefPubMed Rietze R, Poulin P, Weiss S (2000) Mitotically active cells that generate neurons and astrocytes are present in multiple regions of the adult mouse hippocampus. J Comp Neurol 424:397–408CrossRefPubMed
Zurück zum Zitat Sasaki T, Hamada J, Shibata M, Araki N, Fukuuchi Y (2001) Inhibition of nitric oxide production during global ischemia ameliorates ischemic damage of pyramidal neurons in the hippocampus. Keio J Med 50:182–187PubMed Sasaki T, Hamada J, Shibata M, Araki N, Fukuuchi Y (2001) Inhibition of nitric oxide production during global ischemia ameliorates ischemic damage of pyramidal neurons in the hippocampus. Keio J Med 50:182–187PubMed
Zurück zum Zitat Sloane JA, Hollander W, Rosene DL, Moss MB, Kemper T, Abraham CR (2000) Astrocytic hypertrophy and altered GFAP degradation with age in subcortical white matter of the rhesus monkey. Brain Res 862:1–10CrossRefPubMed Sloane JA, Hollander W, Rosene DL, Moss MB, Kemper T, Abraham CR (2000) Astrocytic hypertrophy and altered GFAP degradation with age in subcortical white matter of the rhesus monkey. Brain Res 862:1–10CrossRefPubMed
Zurück zum Zitat Sun Y, Jin K, Childs JT, Xie L, Mao XO, Greenberg DA (2005) Neuronal nitric oxide synthase and ischemia-induced neurogenesis. J Cereb Blood Flow Metab 25:485–492CrossRefPubMed Sun Y, Jin K, Childs JT, Xie L, Mao XO, Greenberg DA (2005) Neuronal nitric oxide synthase and ischemia-induced neurogenesis. J Cereb Blood Flow Metab 25:485–492CrossRefPubMed
Zurück zum Zitat Yokoyama H, Kuroiwa H, Tsukada T, Uchida H, Kato H, Araki T (2010) Poly (ADP- ribose)polymerase inhibitor can attenuate the neuronal death after 1-methyl-4- phenyl-1, 2, 3, 6-tetrahydropyridine-induced neurotoxicity in mice. J Neurosci Res 88:1522–1536PubMed Yokoyama H, Kuroiwa H, Tsukada T, Uchida H, Kato H, Araki T (2010) Poly (ADP- ribose)polymerase inhibitor can attenuate the neuronal death after 1-methyl-4- phenyl-1, 2, 3, 6-tetrahydropyridine-induced neurotoxicity in mice. J Neurosci Res 88:1522–1536PubMed
Zurück zum Zitat Zhu DY, Liu SH, Sun HS, Lu YM (2003) Expression of inducible nitric oxide synthase after focal cerebral ischemia stimulates neurogenesis in the adult rodent dentate gyrus. J Neurosci 23:223–229PubMed Zhu DY, Liu SH, Sun HS, Lu YM (2003) Expression of inducible nitric oxide synthase after focal cerebral ischemia stimulates neurogenesis in the adult rodent dentate gyrus. J Neurosci 23:223–229PubMed
Zurück zum Zitat Zhu XJ, Hua Y, Jiang J, Zhou QG, Luo CX, Han X, Lu YM, Zhu DY (2006) Neuronal nitric oxide synthase-derived nitric oxide inhibits neurogenesis in the adult dentate gyrus by down-regulating cyclic AMP response element binding protein phosphorylation. Neuroscience 141:827–836CrossRefPubMed Zhu XJ, Hua Y, Jiang J, Zhou QG, Luo CX, Han X, Lu YM, Zhu DY (2006) Neuronal nitric oxide synthase-derived nitric oxide inhibits neurogenesis in the adult dentate gyrus by down-regulating cyclic AMP response element binding protein phosphorylation. Neuroscience 141:827–836CrossRefPubMed
Metadaten
Titel
Role of inducible or neuronal nitric oxide synthase in neurogenesis of the dentate gyrus in aged mice
verfasst von
Minami Adachi
Manami Abe
Taeko Sasaki
Hiroyuki Kato
Jiro Kasahara
Tsutomu Araki
Publikationsdatum
01.12.2010
Verlag
Springer US
Erschienen in
Metabolic Brain Disease / Ausgabe 4/2010
Print ISSN: 0885-7490
Elektronische ISSN: 1573-7365
DOI
https://doi.org/10.1007/s11011-010-9224-8

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