Reduction of nuclear peroxisome proliferator-activated receptor γ expression in methamphetamine-induced neurotoxicity and neuroprotective effects of ibuprofen

Takeshi Tsuji, Masato Asanuma, Ikuko Miyazaki, Ko Miyoshi, Norio Ogawa

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)764-774
Number of pages11
JournalNeurochemical Research
Volume34
Issue number4
DOIs
Publication statusPublished - Apr 2009

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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