Objective First-line immunomodulatory treatments such as beta-interferons (IFN-alpha/beta) for multiple sclerosis are available to reduce the rate of relapses and disease activity. However, in addition to its therapeutic effect, systemic IFN-beta treatment causes severe neuropsychiatric complications in humans, including depression and cognitive impairments. These side effects are common and can limit the treatment utility. Our long-term goal is to elucidate the molecular mechanisms of these unwanted side effects in order to improve IFN-beta therapy. The specific hypothesis is that systemically applied IFN-beta exerts adverse side effects by activation of the respective receptor of type I interferons (IFNAR) in the central nervous system (CNS). To identify the actual cell type targeted by IFN-beta in the brain, we have generated brain-specific and glia-specific IFNAR-deficient mice. With the help of these animals we will determine which interferon-stimulated genes will be activated in the brain upon systemic IFN-beta application. We will further assess the contribution of central IFNARs to IFN-beta mediated “sickness” behavior, which includes depressive-like behavior and cognitive impairment and we will correlate these behaviors to changes in hippocampal synaptic plasticity. Together, these experiments will be crucial to identify neurobiological mechanisms responsible for the unfavorable side effects accompanying IFN-beta therapy and to evaluate interventions to ameliorate them. Fields of science natural sciencesbiological sciencesneurobiologymedical and health sciencesbasic medicineneurologymultiple sclerosis Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants" Call for proposal FP7-PEOPLE-2009-RG See other projects for this call Funding Scheme MC-IRG - International Re-integration Grants (IRG) Coordinator UNIVERSITAETSKLINIKUM FREIBURG EU contribution € 75 000,00 Address HUGSTETTER STRASSE 49 79106 Freiburg Germany See on map Region Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis Activity type Higher or Secondary Education Establishments Administrative Contact Juergen Dreyer (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
