Behavioral effects of infection with interferon-gamma adenovector
Behavioral effects of infection with interferon-gamma adenovector
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DOI：
10.1016/j.bbr.2003.08.008
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发表时间：
2004-05-05
影响因子：
2.7
通讯作者：
Sakic, B
中科院分区：
文献类型：
--
作者：
Kwant, A;Sakic, B
病因不明的焦虑和抑郁是系统性自身免疫性疾病红斑狼疮的常见并发症。为了阐明关键的致病因素，我们研究了狼疮易感MRL-1 pr患者的“自身免疫相关行为综合征”（AABS）。由于IFN-γ在人和鼠的SLE中均增加，本研究检测了在非自身免疫小鼠中持续的IFN-γ产生是否诱导与AABS相当的AABS，特别是在反映情绪反应和动机行为的任务中。为此，用携带鼠IFN-γ cDNA的腺病毒感染野生型IFN-γ敲除C57 BLJ 6 J小鼠（每只小鼠腹膜内2 × 10（8）pfu），此后不久在用于检测AABS的行为电池中进行测试。IFN-γ的血清水平在感染后24小时达到峰值，在5天内恢复正常。虽然所有感染动物的食物/水摄入量和身体都有所减少，但注射IFN-γ病毒的动物的恢复速度较慢。在焦虑模型中未观察到缺陷，但蔗糖偏好试验（一种假定的快感缺乏模型）中的反应性持续远远超过IFN-γ清除期。结果表明，全身IFN-γ水平的相对短暂的升高损害摄食行为并导致动机行为的延长。因此，它们与以下假设一致：促炎性物质合成的上调有助于诱导AABS，更具体地说，有助于狼疮样疾病期间的边缘系统功能障碍。(C)2003 Elsevier B. V.保留所有权利。
Anxiety and depression of unknown etiology are frequent complications of the systemic autoimmune disease lupus erythematosus To elucidate key pathogenic factors we study the "autoimmunity-associated behavioral syndrome" (AABS) in lupus-prone MRL-1pr Based on the evidence that serum levels of the neuroactive cytokine interferon-gamma (IFN-gamma) are increased both in human murine forms of SLE, the present study examines whether sustained IFN-gamma production in non-autoimmune mice induces comparable to AABS, particularly in tasks reflective of emotional reactivity and motivated behavior. For this purpose, wild-type IFN-gamma knockout C57BLJ6J mice were infected with adenovirus carrying the cDNA for murine IFN-gamma (i.p. 2 x 10(8) pfu of per mouse) and shortly thereafter tested in the behavioral battery used in the detection of AABS. Serum levels of IFN-gamma were peak 24 h after the infection, normalized within 5 days. Although all infected animals showed reduced food/water intake and body the recovery rate was slower in groups injected with IFN-gamma virus. No deficits were observed in the models of anxiety, but responsiveness in the sucrose preference test (a putative model of anhedonia) lasted well beyond the IFN-gamma clearance period. results suggest that a relatively brief elevation in systemic IFN-gamma levels impairs ingestive behavior and leads to prolonged in motivated behavior. As such, they are consistent with the hypothesis that upregulation in synthesis of pro-inflammatory contributes to induction of AABS and more specifically, to limbic system dysfunction during lupus-like disease. (C) 2003 Elsevier B.V. All rights reserved.