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Neurochemical Research

, Volume 34, Issue 4, pp 764–774 | Cite as

Reduction of Nuclear Peroxisome Proliferator-Activated Receptor γ Expression in Methamphetamine-Induced Neurotoxicity and Neuroprotective Effects of Ibuprofen

  • Takeshi Tsuji
  • Masato AsanumaEmail author
  • Ikuko Miyazaki
  • Ko Miyoshi
  • Norio Ogawa
Original Paper

Abstract

We examined changes in nuclear peroxisome proliferator-activated receptor γ (PPARγ) in the striatum in methamphetamine (METH)-induced dopaminergic neurotoxicity, and also examined effects of treatment with drugs possessing PPARγ agonistic properties. The marked reduction of nuclear PPARγ-expressed cells was seen in the striatum 3 days after METH injections (4 mg/kg × 4, i.p. with 2-h interval). The reduction of dopamine transporter (DAT)-positive signals and PPARγ expression, and accumulation of activated microglial cells were significantly and dose-dependently attenuated by four injections of a nonsteroidal anti-inflammatory drug and a PPARγ ligand, ibuprofen (10 or 20 mg/kg × 4, s.c.) given 30 min prior to each METH injection, but not by either a low or high dose of aspirin. Either treatment of ibuprofen or aspirin, that showed no effects on METH-induced hyperthermia, significantly blocked the METH-induced striatal cyclooxygenase (COX) expression. Furthermore, the treatment of an intrinsic PPARγ ligand 15d-PG J2 also attenuated METH injections-induced reduction of striatal DAT. Therefore, the present study suggests the involvement of reduction of PPARγ expression in METH-induced neurotoxicity. Taken together with the previous report showing protective effects of other PPARγ ligand, these results imply that the protective effects of ibuprofen against METH-induced neurotoxicity may be based, in part, on its anti-inflammatory PPARγ agonistic properties, but not on its COX-inhibiting property or hypothermic effect.

Keywords

Methamphetamine Neurotoxicity Ibuprofen Nonsteroidal anti-inflammatory drug 15d-PG J2 PPARγ 

Notes

Acknowledgments

This work was supported in part by Health and Labour Sciences Research Grants for Research on Regulatory Science of Pharmaceuticals and Medical Devices, for Research on Measures for Intractable Diseases, from the Japanese Ministry of Health, Labour and Welfare (M.A.), and by Grants-in-Aid for Scientific Research (C) (M.A.) and for Young Scientists (B) (I.M.) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology.

References

  1. 1.
    Ali SF, Newport GD, Holson RR, Slikker W Jr, Bowyer JF (1994) Low environmental temperatures or pharmacologic agents that produce hypothermia decrease methamphetamine neurotoxicity in mice. Brain Res 658:33–38PubMedCrossRefGoogle Scholar
  2. 2.
    Cadet JL, Brannock C (1998) Free radicals and the pathobiology of brain dopamine systems. Neurochem Int 32:117–131. doi: 10.1016/S0197-0186(97)00031-4 PubMedCrossRefGoogle Scholar
  3. 3.
    Cadet JL, Jayanthi S, Deng X (2003) Speed kills: cellular and molecular bases of methamphetamine-induced nerve terminal degeneration and neuronal apoptosis. FASEB J 17:1775–1788. doi: 10.1096/fj.03-0073rev PubMedCrossRefGoogle Scholar
  4. 4.
    Miyazaki I, Asanuma M, Diaz-Corrales FJ, Fukuda M, Kitaichi K, Miyoshi K, Ogawa N (2006) Methamphetamine-induced dopaminergic neurotoxicity is regulated by quinone formation-related molecules. FASEB J 20:571–573PubMedGoogle Scholar
  5. 5.
    Asanuma M, Cadet JL (1998) Methamphetamine-induced increase in striatal NF-κB DNA-binding activity is attenuated in superoxide dismutase transgenic mice. Brain Res Mol Brain Res 60:305–309. doi: 10.1016/S0169-328X(98)00188-0 PubMedCrossRefGoogle Scholar
  6. 6.
    Asanuma M, Miyazaki I, Higashi Y, Cadet JL, Ogawa N (2002) Methamphetamine-induced increase in striatal p53 DNA-binding activity is attenuated in Cu, Zn-superoxide dismutase transgenic mice. Neurosci Lett 325:191–194. doi: 10.1016/S0304-3940(02)00291-4 PubMedCrossRefGoogle Scholar
  7. 7.
    O’Neill LAJ, Kaltschmidt C (1997) NF-κB: a crucial transcription factor for glial and neuronal cell function. Trends Neurosci 20:252–258. doi: 10.1016/S0166-2236(96)01035-1 PubMedCrossRefGoogle Scholar
  8. 8.
    Imam SZ, Newport GD, Itzhak Y, Cadet JL, Islam F, Slikker W Jr, Ali SF (2001) Peroxynitrite plays a role in methamphetamine-induced dopaminergic neurotoxicity: evidence from mice lacking neuronal nitric oxide synthase gene or overexpressing copper-zinc superoxide dismutase. J Neurochem 76:745–749. doi: 10.1046/j.1471-4159.2001.00029.x PubMedCrossRefGoogle Scholar
  9. 9.
    Itzhak Y, Ali SF (1996) The neuronal nitric oxide synthase inhibitor, 7-nitroindazole, protects against methamphetamine-induced neurotoxicity in vivo. J Neurochem 67:1770–1773PubMedCrossRefGoogle Scholar
  10. 10.
    Kita T, Shimada K, Mastunari Y, Wagner GC, Kubo K, Nakashima T (2000) Methamphetamine-induced striatal dopamine neurotoxicity and cyclooxygenase-2 protein expression in BALB/c mice. Neuropharmacology 39:399–406. doi: 10.1016/S0028-3908(99)00175-6 PubMedCrossRefGoogle Scholar
  11. 11.
    Asanuma M, Tsuji T, Miyazaki I, Miyoshi K, Ogawa N (2003) Methamphetamine-induced neurotoxicity in mouse brain is attenuated by ketoprofen, a non-steroidal anti-inflammatory drug. Neurosci Lett 352:13–16. doi: 10.1016/j.neulet.2003.08.015 PubMedCrossRefGoogle Scholar
  12. 12.
    LaVoie MJ, Card JP, Hastings TG (2004) Microglial activation precedes dopamine terminal pathology in methamphetamine-induced neurotoxicity. Exp Neurol 187:47–57. doi: 10.1016/j.expneurol.2004.01.010 PubMedCrossRefGoogle Scholar
  13. 13.
    Thomas DM, Walker PD, Benjamins JA, Geddes TJ, Kuhn DM (2004) Methamphetamine neurotoxicity in dopamine nerve endings of the striatum is associated with microglial activation. J Pharmacol Exp Ther 311:1–7. doi: 10.1124/jpet.104.070961 PubMedCrossRefGoogle Scholar
  14. 14.
    Zhang L, Kitaichi K, Fujimoto Y, Nakayama H, Shimizu E, Iyo M, Hashimoto K (2006) Protective effects of minocycline on behavioral changes and neurotoxicity in mice after administration of methamphetamine. Prog Neuropsychopharmacol Biol Psychiatry 30:1381–1393. doi: 10.1016/j.pnpbp.2006.05.015 PubMedCrossRefGoogle Scholar
  15. 15.
    Ladenheim B, Krasnova IN, Deng X, Oyler JM, Polettini A, Moran TH, Huestis MA, Cadet JL (2000) Methamphetamine-induced neurotoxicity is attenuated in transgenic mice with a null mutation for interleukin-6. Mol Pharmacol 58:1247–1256PubMedGoogle Scholar
  16. 16.
    Aeberhard EE, Henderson SA, Arabolos NS, Griscavage JM, Castro FE, Barrett CT, Ignarro LJ (1995) Nonsteroidal anti-inflammatory drugs inhibit expression of the inducible nitric oxide synthase gene. Biochem Biophys Res Commun 208:1053–1059. doi: 10.1006/bbrc.1995.1441 PubMedCrossRefGoogle Scholar
  17. 17.
    Du ZY, Li XY (1999) Inhibitory effects of indomethacin on interleukin-1 and nitric oxide production in rat microglia in vitro. Int J Immunopharmacol 21:219–225. doi: 10.1016/S0192-0561(98)00084-8 PubMedCrossRefGoogle Scholar
  18. 18.
    Asanuma M, Miyazaki I, Higashi Y, Tsuji T, Ogawa N (2004) Specific gene expression and possible involvement of inflammation in methamphetamine-induced neurotoxicity. Ann NY Acad Sci 1025:69–75. doi: 10.1196/annals.1316.009 PubMedCrossRefGoogle Scholar
  19. 19.
    Jaradat MS, Wongsud B, Phornchirasilp S, Rangwala SM, Shams G, Sutton M, Romstedt KJ, Noonan DJ, Feller DR (2001) Activation of peroxisome proliferator-activated receptor isoforms and inhibition of prostaglandin H(2) synthases by ibuprofen, naproxen, and indomethacin. Biochem Pharmacol 62:1587–1595. doi: 10.1016/S0006-2952(01)00822-X PubMedCrossRefGoogle Scholar
  20. 20.
    Lehmann JM, Lenhard JM, Oliver BB, Ringold GM, Kliewer SA (1997) Peroxisome proliferator-activated receptors α and γ are activated by indomethacin and other non-steroidal anti-inflammatory drugs. J Biol Chem 272:3406–3410. doi: 10.1074/jbc.272.6.3406 PubMedCrossRefGoogle Scholar
  21. 21.
    Lim GP, Yang F, Chu T, Chen P, Beech W, Teter B, Tran T, Ubeda O, Ashe KH, Frautschy SA, Cole GM (2000) Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer’s disease. J Neurosci 20:5709–5714PubMedGoogle Scholar
  22. 22.
    Weggen S, Eriksen JL, Das P, Sagi SA, Wang R, Pietrzik CU, Findlay KA, Smith TE, Murphy MP, Bulter T, Kang DE, Marquez-Sterling N, Golde TE, Koo EH (2001) A subset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity. Nature 414:212–216. doi: 10.1038/35102591 PubMedCrossRefGoogle Scholar
  23. 23.
    Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK (1998) The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation. Nature 391:79–82. doi: 10.1038/34178 PubMedCrossRefGoogle Scholar
  24. 24.
    Yang XY, Wang LH, Chen T, Hodge DR, Resau JH, DaSilva L, Farrar WL (2000) Activation of human T lymphocytes is inhibited by peroxisome proliferator-activated receptor γ (PPARγ) agonists. PPARγ co-association with transcription factor NFAT. J Biol Chem 275:4541–4544. doi: 10.1074/jbc.275.7.4541 PubMedCrossRefGoogle Scholar
  25. 25.
    Jiang C, Ting AT, Seed B (1998) PPAR-γ agonists inhibit production of monocyte inflammatory cytokines. Nature 391:82–86. doi: 10.1038/35154 PubMedCrossRefGoogle Scholar
  26. 26.
    Asanuma M, Hirata H, Cadet JL (1998) Attenuation of 6-hydroxydopamine-induced dopaminergic nigrostriatal lesions in superoxide dismutase transgenic mice. Neuroscience 85:907–917. doi: 10.1016/S0306-4522(97)00665-9 PubMedCrossRefGoogle Scholar
  27. 27.
    Asanuma M, Miyazaki I (2006) Nonsteroidal anti-inflammatory drugs in Parkinson’s disease: possible involvement of quinone formation. Expert Rev Neurother 6:1313–1325. doi: 10.1586/14737175.6.9.1313 PubMedCrossRefGoogle Scholar
  28. 28.
    Esposito E, Di Matteo V, Benigno A, Pierucci M, Crescimanno G, Di Giovanni G (2007) Non-steroidal anti-inflammatory drugs in Parkinson’s disease. Exp Neurol 205:295–312Google Scholar
  29. 29.
    Asanuma M, Miyazaki I (2007) Common anti-inflammatory drugs are potentially therapeutic for Parkinson’s disease? Exp Neurol 206:172–178. doi: 10.1016/j.expneurol.2007.05.006 PubMedCrossRefGoogle Scholar
  30. 30.
    Zhang X, Dong F, Mayer GE, Bruch DC, Ren J, Culver B (2007) Selective inhibition of cyclooxygenase-2 exacerbates methamphetamine-induced dopamine depletion in the striatum in rats. Neuroscience 150:950–958. doi: 10.1016/j.neuroscience.2007.09.059 PubMedCrossRefGoogle Scholar
  31. 31.
    Yamaguchi T, Kuraishi Y, Minami M, Nakai S, Hirai Y, Satoh M (1991) Methamphetamine-induced expression of interleukin-1β mRNA in the rat hypothalamus. Neurosci Lett 128:90–92. doi: 10.1016/0304-3940(91)90766-M PubMedCrossRefGoogle Scholar
  32. 32.
    Jayanthi S, Deng X, Ladenheim B, McCoy MT, Cluster A, Cai NS, Cadet JL (2005) Calcineurin/NFAT-induced up-regulation of the Fas ligand/Fas death pathway is involved in methamphetamine-induced neuronal apoptosis. Proc Natl Acad Sci USA 102:868–873. doi: 10.1073/pnas.0404990102 PubMedCrossRefGoogle Scholar
  33. 33.
    Sheng P, Ladenheim B, Moran TH, Wang X-B, Cadet JL (1996) Methamphetamine-induced neurotoxicity is associated with increased striatal AP-1 DNA-binding activity in mice. Brain Res Mol Brain Res 42:171–174. doi: 10.1016/S0169-328X(96)00192-1 PubMedCrossRefGoogle Scholar
  34. 34.
    Elsisi NS, Darling-Reed S, Lee EY, Oriaku ET, Soliman KF (2005) Ibuprofen and apigenin induce apoptosis and cell cycle arrest in activated microglia. Neurosci Lett 375:91–96. doi: 10.1016/j.neulet.2004.10.087 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Takeshi Tsuji
    • 1
  • Masato Asanuma
    • 1
    Email author
  • Ikuko Miyazaki
    • 1
  • Ko Miyoshi
    • 1
  • Norio Ogawa
    • 1
  1. 1.Department of Brain ScienceOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan

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