Cyclooxygenase 2 inhibition protects motor neurons and prolongs survival in a transgenic mouse model of ALS

Daniel B. Drachman, Krystl Frank, Margaret Dykes-Hoberg, Peter Teismann, Gabrielle Almer, Serge Przedborski, Jeffrey D. Rothstein

Research output: Contribution to journalArticlepeer-review

Abstract

The pathogenesis of cell death in amyotrophic lateral sclerosis (ALS) may involve glutamate-mediated excitotoxicity, oxidative damage, and apoptosis. We used a transgenic mouse model of ALS to determine the effect of inhibition of cyclooxygenase-2 in treating the disease. Cyclooxygenase-2, present in spinal neurons and astrocytes, catalyzes the synthesis of prostaglandin E2. Prostaglandin E2 stimulates glutamate release from astrocytes, whereas cyclooxygenase-2 also plays a key role in the production of proinflammatory cytokines, reactive oxygen species, and free radicals. Treatment with a selective cyclooxygenase-2 inhibitor, celecoxib, markedly inhibited production of prostaglandin E2 in the spinal cords of ALS mice. Celecoxib treatment significantly delayed the onset of weakness and weight loss and prolonged survival by 25%. Spinal cords of treated ALS mice showed significant preservation of spinal neurons and diminished astrogliosis and microglial activation. Our results suggest that cyclooxygenase-2 inhibition may benefit ALS patients.

Original languageEnglish (US)
Pages (from-to)771-778
Number of pages8
JournalAnnals of neurology
Volume52
Issue number6
DOIs
StatePublished - Dec 1 2002

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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