CONICET | Buscador de Institutos y Recursos Humanos

Stress has been related to cognitive deficit. The hippocampus, a limbic area involved in learning and memory, is particularly sensitive to the effects of chronic stress. Cytokines have been shown to affect some behaviour, including memory. Moreover, IL-2, IFN-gamma and IL-6 had been implicated in psychiatric disorders. Glatiramer acetate (Cop-1) is a synthetic amino acid polymer that can weakly cross-react with CNS-resident autoantigens and can safely simulate the protective and reparative effects of autoreactive T cells. In a previous work, we found that chronic stress induced a cognitive deficit that is correlated with Th1/Th2 imbalance. The aim of the present work was to study the effect of Cop-1 treatment on the deleterious effects induced by chronic stress exposure in BALB/c mice. We found that BALB/c mice exposed to chronic stress had a decrease number of BrdU positive cells, an increase of ROS production, poor learning performance respect to control mice in both, alternation behaviour in Y-maze task and habituation in open field. The lymphoid production of cytokines analysed by ELISA showed a decrease of IFN-gamma and not changes in IL-2 (TH1-cytokines) and an increase of IL-6, IL-4 and IL-10 (TH2-cytokines) in stressed BALB/c mice. These effects induced by chronic stress were reverted by administration of Cop-1 (100ug per injection s.c. to four times during three weeks). These results indicate that Cop-1 is able to reverse the neuroimmune alterations induced by chronic stress exposure. These findings indicate that immune-based therapies could be very useful for the treatment of cognitive deficits induced by stress. Supported by grants from CONICET (PIP 00281) and from University of Buenos Aires (UBACyT-MO24) to AMG, and from the National Agency for the Promotion of Science and Technology (PICT 2008) to AFS. Copaxone was a generous gift from laboratory Teva-Tuteur from Argentina.