Meloxicam ameliorates motor dysfunction and dopaminergic neurodegeneration by maintaining Akt-signaling in a mouse Parkinson's disease model

Yoshikazu Tasaki, Joe Yamamoto, Tomohiro Omura, Tomoki Sakaguchi, Norihisa Kimura, Ko ichi Ohtaki, Takashi Ono, Manabu Suno, Masaru Asari, Tomoko Ohkubo, Toshihiro Noda, Toshio Awaya, Keiko Shimizu, Kazuo Matsubara

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

A series of oxicam non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be neuroprotective against 1-methyl-4-phenyl pyridinium in human neuroblastoma SH-SY5Y cells via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway independent of cyclooxygenase (COX) inhibition. The present study endeavored to establish this novel effect of meloxicam (MLX), an oxicam NSAID, in a mouse Parkinson's disease (PD) model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Male C57BL/6 mice, which received MPTP (30. mg/kg/day; s.c.) for 5 consecutive days (chronic model) with 10-day follow-up saline administrations, showed significant motor dysfunction in the pole test due to reduced tyrosine hydroxylase (TH) protein levels in the brain on day 16 after MPTP/saline treatment. Daily coadministrations of MLX (10. mg/kg/day; i.p.) and MPTP for the first 5 days and follow-up 10 days with MLX administrations alone (MPTP/MLX treatment) significantly ameliorated MPTP-induced behavioral abnormalities in mice. Concomitant decreases of TH protein levels in the striatum and midbrain of MPTP/MLX-treated mice were not only significantly (p< 0.01 and p< 0.05, respectively) ameliorated but phosphorylated Akt (pAkt473) expression in the midbrain was also significantly (p< 0.01) increased in the midbrain when compared with MPTP/saline-treated mice. These results suggest that MLX, an oxicam NSAID, attenuated dopaminergic neuronal death in the experimental MPTP-PD model by maintenance of the Akt-signaling. Oxicam NSAIDs may serve as potential drugs for PD treatment via a novel mechanism of action.

Original languageEnglish
Pages (from-to)15-19
Number of pages5
JournalNeuroscience Letters
Volume521
Issue number1
DOIs
Publication statusPublished - Jul 11 2012

Keywords

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
  • Akt
  • Neuroprotection
  • Non-steroidal anti-inflammatory drugs (NSAIDs)
  • Oxicam
  • Parkinson's disease (PD)

ASJC Scopus subject areas

  • Neuroscience(all)

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