Effect of Copaxone® treatment on CMS induced alterations in behaviour and TH1/TH2 balance in BALB/c mice

PALUMBO ML; ZORRILLA-ZUBILETE MA; CREMASCHI GA; GENARO AM

Barcelona

Congreso; 10th International Congress of Neuroimmunology; 2010

International Society for Neuroimmunomodulation

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, IFNgamma and IL-6 have been implicated in psychiatric disorders. Glatiramer acetate (Copaxone®) 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. The aim of the present work was to study Copaxone effects in the behaviour and in the TH1/TH2 balance induced by chronic stress in BALB/c mice. We found that BALB/c mice exposed to chronic stress had a poor learning performance with 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 copaxone (100 μg per injection s.c. to four times during three weeks). These results indicate that copaxone is able to reverse both the memory impairment and the TH1/TH2 cytokine balance. These results suggest that TH1 response could constitute a protective mechanism preventing behaviour impairment. Supported by UBACyT-MO24 and PIP 00281 from CONICET. Copaxone was a generous gift from laboratory Teva-Tuteur from Argentina.