Chronic mild stress eliminates the neuroprotective effect of Copaxone after CNS injury

Igor Smirnov, James T. Walsh, Jonathan Kipnis

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Copolymer (Cop)-1, also known as glatiramer acetate, is an active compound of Copaxone, a drug widely used by patients with multiple sclerosis (MS). Copaxone functions in MS through two mechanisms of action, namely immunomodulation and neuroprotection. Because the immune system is suppressed or altered in depressed individuals, and since depression is often associated with neurological conditions, we were interested in examining whether the neuroprotective effect of Copaxone persists under conditions of stress-induced depressive behavior. We exposed mice to unpredictable chronic mild stress for 4. weeks and then treated them with three doses of Copaxone at 3-day intervals, with the last dose given immediately before the mice underwent a crush injury to the optic nerve. Whereas nonstressed mice exhibited a strong neuroprotective response after Copaxone treatment, this effect was completely absent in mice that underwent chronic mild stress. Interestingly, when Copaxone was combined with Prozac, the neuroprotective effect of Copaxone was regained, suggesting that chronic mild stress interferes with the neuroprotective effect of Copaxone. These results may shed a light on mechanism of action of Copaxone and lead to new combined therapies for neurodegenerative and neuroinflammatory disorders.

Original languageEnglish
Pages (from-to)177-182
Number of pages6
JournalBrain, Behavior, and Immunity
Volume31
DOIs
StatePublished - Jul 2013
Externally publishedYes

Keywords

  • CNS injury
  • Copaxone
  • Copolymer-1
  • Fluoxetine (Prozac)
  • Glatiramer acetate
  • Neuronal survival
  • Neuroprotection
  • Stress

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