title: Chronic mild stress eliminates the neuroprotective effect of Copaxone after CNS injury.
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.
authors.affiliation: Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Smirnov
authors.forename: James T
authors.initials: JT
authors.lastname: Walsh
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kipnis
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D004347:Drug Interactions; D004924:Escape Reaction / Q000187:drug effects; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D000068717:Glatiramer Acetate; D051379:Mice; D009409:Nerve Crush; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D020221:Optic Nerve Injuries / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D013312:Stress, Physiological / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology* / Q000523:psychology
chemical_list: D000928:Antidepressive Agents; D018696:Neuroprotective Agents; D010455:Peptides; D005473:Fluoxetine; D000068717:Glatiramer Acetate