Mouse cerebral prostaglandins, but not oxidative damage, change with age and are responsive to indomethacin treatment

Kathleen S. Montine, Thomas J. Montine, Jason D. Morrow, Balz Frei, Dejan Milatovic, Felix Eckenstein, Joseph Quinn

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Epidemiological and clinical trial data indicate that at least some non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk of developing Alzheimer's disease (AD). Advancing age is the most robust risk factor for AD. If NSAIDs mitigate the initiation of AD by affecting processes of aging, and if the target of NSAIDs are cyclooxygenases (COX), then COX activity would be hypothesized to increase with advancing age in brain regions affected by AD. We tested this hypothesis in mouse cerebrum by measuring two outcomes of increased COX activity, prostaglandin (PG) levels and markers of oxidative damage. Our results showed that frontal cortical PGE2 and 6-keto-PGF levels were significantly increased at 14 months compared to 2 months, but that frontal cortical levels of these PGs at 26 months returned to levels observed at 2 months of age. At all ages, 2-week treatment with indomethacin (14 μg/ml drinking water, or approximately 2.2 mg/kg per day) equally suppressed frontal cortical levels of both PGs. In contrast, basal levels of oxidative damage to cerebral cortex did not increase in mice aged up to 26 months, and indomethacin treatment did not significantly alter basal levels of oxidative damage as assayed by F2-isoprostanes or protein carbonyls. These results suggest that indomethacin may influence the initiation of AD by reducing cerebral PG elevation that may occur in middle age, but that it is unlikely to have a direct effect on levels of oxidative damage.

Original languageEnglish (US)
Pages (from-to)75-82
Number of pages8
JournalBrain Research
Volume930
Issue number1-2
DOIs
StatePublished - Mar 15 2002

Fingerprint

Indomethacin
Prostaglandins
Alzheimer Disease
Prostaglandin-Endoperoxide Synthases
Anti-Inflammatory Agents
F2-Isoprostanes
Pharmaceutical Preparations
Therapeutics
Cerebrum
Dinoprostone
Drinking Water
Cerebral Cortex
Clinical Trials
Brain
Proteins

Keywords

  • Brain aging
  • Isoprostane
  • Non-steroidal anti-inflammatory drug
  • Oxidative damage
  • Prostaglandin
  • Protein carbonyl

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Mouse cerebral prostaglandins, but not oxidative damage, change with age and are responsive to indomethacin treatment. / Montine, Kathleen S.; Montine, Thomas J.; Morrow, Jason D.; Frei, Balz; Milatovic, Dejan; Eckenstein, Felix; Quinn, Joseph.

In: Brain Research, Vol. 930, No. 1-2, 15.03.2002, p. 75-82.

Research output: Contribution to journalArticle

Montine, Kathleen S. ; Montine, Thomas J. ; Morrow, Jason D. ; Frei, Balz ; Milatovic, Dejan ; Eckenstein, Felix ; Quinn, Joseph. / Mouse cerebral prostaglandins, but not oxidative damage, change with age and are responsive to indomethacin treatment. In: Brain Research. 2002 ; Vol. 930, No. 1-2. pp. 75-82.
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