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

D. B. Drachman, K. Frank, M. Dykes-Hoberg, Peter Teismann, G. Almer, S. Przedborski, J. D. Rothstein

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258 Citations (Scopus)

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 AILS 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
Pages (from-to)771-778
Number of pages7
JournalAnnals of Neurology
Volume52
Issue number6
Early online date24 Sep 2002
DOIs
Publication statusPublished - Dec 2002

Keywords

  • amyotrophic-lateral-sclerosis
  • CU,ZN superoxide-dismutase
  • central-nervous-system
  • rat spinal-cord
  • Alzheimers-disease
  • prostaglandin E-2
  • up-regulation
  • brain
  • expression
  • localization

Cite this

Drachman, D. B., Frank, K., Dykes-Hoberg, M., Teismann, P., Almer, G., Przedborski, S., & Rothstein, J. D. (2002). Cyclooxygenase 2 inhibition protects motor neurones and prolongs survival in a transgenic mouse model of ALS. Annals of Neurology, 52(6), 771-778. https://doi.org/10.1002/ana.10374