Sleep Fragmentation Effects on Murine CII-Induced AR

描述（由申请人提供）： 类风湿性关节炎（RA）和其他慢性关节炎患者有部分慢性睡眠剥夺（PCSD），可能与疼痛和炎症有关。目前尚不清楚PCSD对RA和相关关节炎的免疫和非免疫介导的关节炎过程有何影响。最近在实验室动物和人类身上的研究表明，睡眠剥夺会产生与免疫相关的后果。本研究的总体目标是在DBA/1 lac小鼠中诱导慢性部分睡眠片段化，在小鼠中对卵清蛋白（OVA）的初级免疫应答的演变过程中以及在该相同小鼠品系中II型胶原（CII）诱导的关节炎（CIA）的演变过程中。我们将检验DBA/1 lac小鼠中PCSD将导致对OVA的免疫应答和关节炎严重程度改变的假设。本研究旨在设计一种适合小鼠的慢性睡眠剥夺实验装置，开发并验证计算机程序，以一致可靠的方式实现选择性部分睡眠剥夺的实验条件，然后评估PCSD对OVA免疫应答和CII免疫诱导的关节炎的影响。以下具体目的将解决该假设：具体目的1：评估关节炎小鼠的睡眠模式;具体目的2：在小鼠中进行完全睡眠剥夺以产生部分睡眠剥夺的小鼠;具体目的3：确定用OVA免疫的慢性部分睡眠剥夺的DBA/1 lac小鼠是否发展出对OVA的改变的免疫力;以及具体目的4：确定用CII免疫的慢性部分睡眠剥夺DBA/1 lac小鼠是否在关节炎的发病率和/或严重程度上有改变。该研究的结果将为提交R 01基金提供基础，以探索DBA/1 lac小鼠部分睡眠剥夺改变对抗原的免疫反应和关节炎发展的机制。

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.