Sleep Fragmentation Effects on Murine CII-Induced AR

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DESCRIPTION (provided by applicant): Patients with rheumatoid arthritis (RA) and other chronic arthritides have partial chronic sleep deprivation (PCSD) possibly related to the pain and inflammation associated with their condition. It is unknown what effect PCSD has on the immune and non-immune mediated arthritic processes of RA and related arthritides. Recent work in laboratory animals and humans indicates that sleep deprivation produces immune-related consequences. The overall goal of this study is to induce chronic, partial sleep fragmentation in DBA/1 lac mice during the evolution of the primary immune resonse to ovalbumin (OVA) in mice and during the evolution of type II collagen (CII)-induced arthritis (CIA) in this same mouse strain. We will test the hypothesis that PCSD in DBA/1 lac mice will result in alterations in the immune response to OVA and severity of arthritis. The approach will Ibe to tailor an experimental chronic sleep deprivation appartus to fit the mouse, develop and lvalidate a computerized program, implement experimental conditions of selective partial sleep Ideprivation in a consistent and reliable manner, and then assess the effects of PCSD on immune Iresponse to OVA and arthritis induced by immunization with CII. The following specific aims will address this hypothesis: Specific Aim 1: Assess sleep patterns in arthritic mice; Specific Aim 2: Conduct total sleep deprivation in mice to produce partially sleep-deprived mice; Specific Aim 3: Determine whether chronic partial sleep deprived DBA/1 lac mice immunized with OVA develop altered immunity to OVA; and Specific Aim 4: Determine whether chronic partial sleep-deprived DBA/1 lac mice immunized with CII have alterations in the incidence and/or severity of arthritis. Results of the study will provide a basis for submitting an R01 grant to explore mechanisms by which partial sleep deprivation in DBA/1 lac mice alter the immune response to antigen and arthritis development.