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Metabolic Brain Disease

Erschienen in:

01.03.2008 | ORIGINAL PAPER

Protective action of neuronal nitric oxide synthase inhibitor in the MPTP mouse model of Parkinson’s disease

verfasst von: Yu Watanabe, Hiroyuki Kato, Tsutomu Araki

Erschienen in: Metabolic Brain Disease | Ausgabe 1/2008

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Abstract

We examined the effects of 7-nitroindazole on the dopaminergic system in mice after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. The mice received four intraperitoneal injections of MPTP (20 mg/kg) at 2 h-intervals. Administration of 7-nitroindazole showed dose-dependent neuroprotective effects against striatal dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) depletion 7 days after MPTP treatment. Behavioral testing showed that MPTP-treated mice exhibited motor deficits in the catalepsy test after 7 days, but 7-nitroindazole prevented the appearance of motor abnormalities in this test. The MPTP-treated mice exhibited the loss of tyrosine hydroxylase-containing dopaminergic neurons in mice after 1, 3 and 7 days, but 7-nitroindazole-treated mice showed a protective effect. GFAP (glial fibrillary acidic protein)-positive astrocytes were accumulated in the striatum 3 and 7 days and in the substantia nigra 1, 3 and 7 days after MPTP treatment. In contrast, 7-nitroindazole prevented a significant increase in the number of GFAP-positive astrocytes in the striatum and substantia nigra after MPTP treatment. The reactive astrocytes in the striatum and substantia nigra after MPTP treatment increased the production of S100β protein, which is thought to promote neuronal damage, but 7-nitoindazole suppressed the expression of S100 β protein. Activation of microglia, with an increase in staining intensity and morphological changes, was observed in the striatum and substantia nigra 1 and 3 days after MPTP treatment, but 7-nitroindazole prevented a significant increase in the number of isolectin B₄ positive microglia in the striatum and substantia nigra. On the other hand, nestin- immunoreactive cells were increased significantly in the striatum 3 and 7 days after MPTP treatment. 7-Nitroindazole treatment facilitated nestin expression in the striatum 7 days after MPTP treatment. Thus, nNOS inhibitor 7-nitroindazole protected dopaminergic neurons against MPTP neurotoxicity in mice and ameliorated neurological deficits. The results suggest that the neuroprotection is mediated though the modulation of glial activation, including the inhibition of S100β synthesis and the prevention of microglial activation. These results suggest the therapeutic strategy targeted to glial modulation with 7-nitoindazole offers a great potential for the development of new neuroprotective therapies for Parkinson’s disease.

Ahlemeyer B, Beier H, Semkova I, Schaper C, Krieglstein J (2000) S-100β protects cultured neurons against glutamate- and staurosporine-induced damage and is involved in the antiapoptoic action of the 5-HT1A-receptor agonist Bay x 3702. Brain Res 858:121–128PubMedCrossRef

Alvarez B, Rubbo H, Kirk M, Barnes S, Freeman BA, Raji R (1996) Peroxynitrite-dependent tryptophan nitration. Chem Res Toxicol 9:390–396PubMedCrossRef

Araki T, Mizutani H, Matsubara M, Kato H, Imai Y, Mizugaki M, Itoyama Y (2001) Nitric oxide synthase inhibitors cause deficits in mice. Eur Neuropsychopharmacol 11:125–133PubMedCrossRef

Beal MF (1995) Aging, energy and oxidative stress in neurodegenerative diseases. Ann Neurol 38:357–366PubMedCrossRef

Beal MF, Ferrantre RJ, Browme SE, Matthews RT, Kowall NW, Brown Jr RH (1997) Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis. Ann Neurol 42:646–654CrossRef

Chao CC, Hu S, Sheng WS, Bu D, Bukrinsky ML, Peterson PK (1996) Cytokine-stimulated astrocytes damage human neurons via a nitric oxide mechanism. Glia 16:276–284PubMedCrossRef

Chen LW, Hu HJ, Liu HJ, Yung KKL, Chan YS (2004) Identification of BDNF in nestin-expressing astroglial cells in the neostriatum of MPTP-treated mice. Neuroscience 126:941–953PubMedCrossRef

Chen LW, Zhang JP, Shum DKY, Chan YS (2006) Localization of nerve growth factor, neurotropin-3, and glial cell line-derived neurotrophic factor in nestin-expressing reactive astrocytes in the caudate-putaman of 1-methyl-4-phenyl-1,2,3,6-tertahydropyrideine-tetrahydropyridine-tread C57/BL mice. J Comp Neurol 497:898–909PubMedCrossRef

Craft JM, Watterson DM, Marks A, Van Eldik LJ (2005) Enhanced susceptibility of S-100B transgenic mice to neuoinflammation and neuronal dysfunction induced by intracerebroventricular infusion of human beta-amyloid. Glia 51:209–216PubMedCrossRef

Dahlstrand J, Lardelli M, Lendahl U (1995) Nestin mRNA expression correlates with the central nervous system progenitor cell state in many, but not all, regions of developing central nervous system. Brain Res Dev Brain Res 84:109–129PubMedCrossRef

Dehmer T, Lindenau J, Haid S, Dichgans J, Schulz JB (2000) Deficiency of inducible nitric oxide synthase protects MPTP toxicity in vivo. J Neurochem 74:2213–2216PubMedCrossRef

Demiryurek AT, Cakici I, Kanzik I (1998) Peroxynitrite: a putative cytotoxin. Pharmacol Toxicol 82:113–117PubMed

Ferrante RJ, Hantraye P, Brouillet E, Beal MF (1997) Increased nitrotyrosine immunoreactivity in substantia nigra neurons in MPTP treated baboons is blocked by inhibition of neuronal nitric oxide synthase. Brain Res 823:177–182CrossRef

Griffin WS, Stanley LC, Ling C, White L, MacLeod V, Perrot LJ, White C, Araoz C (1989) Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci U S A 86:7611–7615PubMedCrossRef

Hantraye P, Brouillet E, Ferrante R, Palfi S, Dolan R, Matthews RT, Beal MF (1996) Inhibition of neuronal nitric oxide synthase prevents MPTP-induced parkinsonism in baboons. Nature Med 9:1017–1021

Hu J, Freira A, van Eldik L (1997) S100β induces neuronal cell death through nitric oxide release form astrocytes. J Neurochem 69:2294–2301PubMedCrossRef

Huie RE, Padmaja S (1993) The reaction of NO with superoxide. Free Radic Res Commun 18:195–199PubMedCrossRef

Hunot S, Boissiere F, Faucheux B, Brugg B, Mouatt-Prigent A, Agid Y, Hirsch EC, (1996) Nitric oxide synthase and neuronal vulnerability in Parkinson’s disease. Neurosience 72:355–363CrossRef

Ischiropoulos H, Zhu L, Chen J, Tsai M, Martin JC, Smith CD, Beckman JS (1992) Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch Biochem Biophys 298:431–437PubMedCrossRef

Itzhak Y, Martin JL, Ali SF (1999) Methamphetamine- and 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity in inducible nitric oxide synthase-deficient mice. Synapse 34:305–312PubMedCrossRef

Ishiropoulos H, al-Mehdi AB (1995) Peroxynitrite-mediated oxidative protein modifications. FEBS Lett 364:279–282CrossRef

Kato, H, Kurosaki R, Oki C, Araki T (2004) Arundic acid, an astrocyte-modulating agent, protects dopaminergic neurons against MPTP neurotoxicity in mice. Brain Res 1030:66–73PubMedCrossRef

Kelm M, Dahmann R, Wink D, Feelisch M (1997) The nitric oxide/superoxide assay. Insights into the biological chemistry of NO/O2- interaction. J Biol Chem 272:9922–9932PubMedCrossRef

Kernie SG, Erwin TM, Parada LF (2001) Brain remodeling due to neuronal and astrocytic proliferation after controlled cortical injury in mice. J Neurosci Res 166:317–326CrossRef

Kurosaki R, Muramatsu Y, Kato H, Araki T (2004) Biochemical, behavioral and immunohistochemical alterations in MPTP-treated mouse model of Parkinson’s disease. Pharmacol Biochem Behav 78:143–153PubMedCrossRef

Kurosaki R, Muramatsu Y, Michimata M, Matsubara M, Kato H, Imai Y, Itoyama Y, Araki T (2002) Role of nitric oxide synthase against MPTP neurotoxicity in mice. Neurol Res 24:655–662PubMedCrossRef

Liberatore GT, Jackson-Lewis V, Vukosavic S, Mandir AS, Vila M, McAuliffe WG, Dawson VL, Dawson TM, Przedbroski S (1999) Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease. Nat Med 5:1403–1409PubMedCrossRef

Mori A, Ohashi S, Nakai M, Moriizumi T, Mitsumoto Y (2005) Neuronal mechanisms underlying motor dysfunction as detected by the tail suspension test in MPTP-treated C57BL/6 mice. Neurosci Res 51:267–274CrossRef

Muramatsu Y, Kurosaki R, Mikami T, Michimata M, Matsubara M, Imai Y, Kato H, Itoyama Y, Araki T (2002) Therapeutic effect of neuronal nitric oxide synthase inhibitor (7-nitroindazole) against MPTP neurotoxicity in mice. Metab Brain Dis 17:169–182PubMedCrossRef

Murphy S (2000) Production of nitric oxide by glial cells: regulation and potential roles in the CNS. Glia 9:1–14CrossRef

Nakai M, Mori A, Watanabe A, Mitsumoto Y (2003) 1-Methyl-4-phenyl- pyridinium (MPP⁺) decreases mitochondrial oxidation-reduction (REDOX) activity and membrane potential (Deltapsi(m)) in rat striatum. Exp Neurol 179:103–110PubMedCrossRef

Przedborski S, Jackson-Lewis V, Yokoyama R, Shibata T, Dawson VL, Dawson TD (1996) Role of neuronal nitric oxide in MPTP (1-methyl-1,2,3,6-tetrahydropyridine)-induced dopaminergic neurotoxicity. Proc Natl Acad Sci U S A 93:4565–4571PubMedCrossRef

Raji R, Beckman JS, Bush KM, Freeman BA (1991) Peroxynitrite-induced membrance lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys 288:481–487CrossRef

Regner A, Kaufman M, Friedman G, Chemale I (2001) Increased serum S100β protein concentrations following severe head injury in humans: a biochemical marker of brain death? Neuroreport 12:691–694PubMedCrossRef

Ridet JL, Malhotra SK, Privat A, Gage FH (1997) Reactive astrocytes: cellular and molecular cues to biological function. Trends Neurosci 20:507–577CrossRef

Rothermund M, Peters M, Prehn JH, Arolt V (2003) S100B in brain damage and neurodegeneration. Microsc Res Tech 60:614–632CrossRef

Salgo MG, Bermudez E, Squadrito GL, Pryor WA (1995) Peroxynitrite causes DNA damage and oxidation of thiols in rat thymocytes. Arch Biochem Biophys 322:500–505PubMedCrossRef

Sanberg PR, Bunsey MD, Giordano M, Norman AB (1998) The catalepsy test: its ups and downs. Behav Neurosci 102:748–759CrossRef

Schultz JB, Matthews RT, Muqit MMK, Browne SE, Beal MF (1995) Inhibition of neuronal nitric oxide synthase 7-nitroindazole protects against MPTP- induced neurotoxicity in mice. J Neurochem 64:936–939CrossRef

Sheng JG, Mark RE, Griffin WS (1997) Glia-neuronal interactions in Alzheimer disease: progressive association of IL-1 alpha + microglia as S100beta + astrocytes with neurofibrillary tangle stage. J Neuropathol Exp Neurol 56:285–290PubMed

Tipton KF, Singer TP (1993) Advances in our understanding of the mechanisms of the neurotoxicity of MPTP and related compounds. J Neurochem 61:1191–1206PubMedCrossRef

Van Eldik LJ, Wainwrright MS (2003) The Janus face of glial-derived S100B: beneficial and detrimental functions in the brain. Restor Neurol Neurosci 21:97–108PubMed

Watanabe H, Muramatsu Y, Kurosaki R, Michimata M, Matsubara M, Imai Y, Araki T (2004) Protective effects of neuronal nitric oxide synthase inhibitor in mouse brain against MPTP neurotoxicity: an immunohistochemical study. Eur Neuropsychopharmacol 14:93–104PubMedCrossRef

Wu DC, Jackdon-Lewis V, Vila M, Tieu K, Teismann P, Vadseth C, Choi DK, Ischiropoulos H, Przedborski S (2002) Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse of Parkinson disease. J Neurosci 22:1763–1771PubMed

Titel: Protective action of neuronal nitric oxide synthase inhibitor in the MPTP mouse model of Parkinson’s disease
verfasst von: Yu Watanabe
Hiroyuki Kato
Tsutomu Araki
Publikationsdatum: 01.03.2008
Verlag: Springer US
Erschienen in: Metabolic Brain Disease / Ausgabe 1/2008
Print ISSN: 0885-7490
Elektronische ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-007-9080-3

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