Ibuprofen effects on Alzheimer pathology and open field activity in APPsw transgenic mice

G. P. Lim, F. Yang, T. Chu, E. Gahtan, O. Ubeda, W. Beech, J. B. Overmier, K. Hsiao-Ashec, S. A. Frautschy, G. M. Cole

Research output: Contribution to journalArticlepeer-review

223 Scopus citations

Abstract

We previously showed the non-steroidal anti-inflammatory drug (NSAID) ibuprofen suppresses inflammation and amyloid in the APPsw (Tg2576) Tg2576 transgenic mouse. The mechanism for these effects and the impact on behavior are unknown. We now show ibuprofen's effects were not mediated by alterations in amyloid precursor protein (APP) expression or oxidative damage (carbonyls). Six months ibuprofen treatment in Tg+ females caused a decrease in open field behavior (p < 0.05), restoring values similar to Tg- mice. Reduced caspase activation per plaque provided further evidence for a neuroprotective action of ibuprofen. The impact of a shorter 3 month duration ibuprofen trial, beginning at a later age (from 14 to 17 months), was also investigated. Repeated measures ANOVA of Aβ levels (soluble and insoluble) demonstrated a significant ibuprofen treatment effect (p < 0.05). Post-hoc analysis showed that ibuprofen-dependent reductions of both soluble Aβ and Aβ42 were most marked in entorhinal cortex (p < 0.05). Although interleukin-1β and insoluble Aβ were more effectively reduced with longer treatment, the magnitude of the effect on soluble Aβ was not dependent on treatment duration.

Original languageEnglish (US)
Pages (from-to)983-991
Number of pages9
JournalNeurobiology of Aging
Volume22
Issue number6
DOIs
StatePublished - 2001

Bibliographical note

Funding Information:
Supported by grants from the Alzheimer’s Association, VAMerit, NIH AG13471, K.K. Siegel-UCLA Center on Aging grant and the Thomas and Elizabeth Plott Family.

Keywords

  • Alzheimer
  • Carbonyl
  • Caspase
  • Females
  • Interleukin-1β
  • NSAIDs
  • Neuroinflammation
  • Neuroprotection
  • Open-field activity
  • Oxidative damage
  • Tg2576
  • Ubiquitin

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