DIFFERENTIAL LIPOPOLYSACCHARIDE-INDUCED IMMUNE ALTERATIONS IN THE HIPPOCAMPUS OF TWO MOUSE STRAINS: EFFECTS OF STRESS
DIFFERENTIAL LIPOPOLYSACCHARIDE-INDUCED IMMUNE ALTERATIONS IN THE HIPPOCAMPUS OF TWO MOUSE STRAINS: EFFECTS OF STRESS
复制标题
DOI：
10.1016/j.neuroscience.2012.08.031
复制
发表时间：
2012-12-06
期刊：
影响因子：
3.3
通讯作者：
Cryan, J. F.
中科院分区：
文献类型：
--
作者：
Browne, C. A.;O'Brien, F. E.;Cryan, J. F.
免疫激活可能导致大部分接受细胞因子疗法治疗的患者出现抑郁样症状。目前尚不清楚细胞因子引起的抑郁症易感性的机制。然而，色氨酸分解代谢酶吲哚胺 2,3-双加氧酶 (IDO) 的激活与细胞因子诱导的抑郁症的诱导有关。脂多糖（LPS）的外周给药是细胞因子诱导的抑郁症动物模型中最常用的免疫挑战之一。近交系小鼠品系是研究精神疾病神经生物学的有用工具。在本研究中，我们假设应激敏感性不同的两个品系，即 BALB/c 和 C57BL/6J 小鼠，在细胞因子谱、皮质酮浓度和色氨酸代谢酶 1001、1002、Tph1 和 Tph2 编码基因的 mRNA 表达方面对 LPS 和游泳应激的反应不同。应激敏感的 BALB/c 菌株对 LPS 表现出抑郁样行为增加和皮质酮浓度增加。此外，游泳应激仅减弱 BALB/c 小鼠中 LPS 诱导的皮质酮反应。 LPS 显着增加 BALB/c 小鼠血浆白细胞介素 (IL)-1 β 和肿瘤坏死因子 α (TNF α) 浓度。 C57BL/6J 小鼠海马区 LPS 诱导的 IL-1 β mRNA 表达增加因游泳应激而显着减弱，但 BALB/c 小鼠海马体中则不然。仅在 BALB/c 小鼠中 TNF α mRNA 表达显着增加；这种增加因游泳压力而减弱。 LPS 后以及 BALB/c 小鼠游泳应激和 LPS 相结合后，C57BL/6J 小鼠脑干中 Tph1 mRNA 表达上调。在应对 LPS 攻击和游泳应激时，C57BL/6J 小鼠的海马 Tph1 和 Tph2 mRNA 表达增加，但 BALB/c 小鼠则没有增加。相反，在游泳应激和 LPS 后，1002 但不是 1001 mRNA 表达显着改变，特别是在 BALB/c 小鼠的海马中。这些数据表明，与正常敏感的 C57BL/6J 品系相比，BALB/c 小鼠色氨酸代谢酶的中心 mRNA 表达和免疫激活发生了改变。 (C) 2012 年国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Immunological activation may result in the development of depressive-like symptoms in a large percentage of patients treated with cytokine-based therapies. The mechanisms underlying susceptibility to cytokine-induced depression are currently unknown; however activation of the tryptophan catabolising enzyme indoleamine 2,3-dioxygenase (IDO) is associated with the induction of cytokine-induced depression. Peripheral administration of lipopolysaccharide (LPS) is one of the most commonly used immunological challenges in animal models of cytokine-induced depression. Inbred mouse strains are useful tools in the investigation of the neurobiology of psychiatric illnesses. In this study we hypothesised that two strains which differ in stress susceptibility, namely the BALB/c and C57BL/6J mice, would respond differentially to LPS and swim-stress in cytokine profile, corticosterone concentrations and mRNA expression of genes coding for the tryptophan metabolising enzymes, 1001,1002, Tph1 and Tph2. The stress-sensitive BALB/c strain exhibited increased depressive-like behaviour and enhanced corticosterone concentrations in response to LPS. Furthermore, swim-stress attenuated the LPS-induced corticosterone response in BALB/c mice only. LPS significantly increased plasma interleukin (IL)-1 beta and tumour necrosis factor alpha (TNF alpha) concentrations to a greater extent in BALB/c mice. The LPS-induced increase in IL-1 beta mRNA expression was significantly attenuated by swim-stress in the hippocampus of C57BL/6J but not in BALB/c mice. TNF alpha mRNA expression was significantly increased in BALB/c mice only; this increase was attenuated by swim-stress. Tph1 mRNA expression was upregulated in the brainstem of C57BL/6J mice post-LPS and following the combination of swim-stress and LPS in BALB/c mice. In the hippocampus Tph1 and Tph2 mRNA expression was increased in C57BL/6J but not BALB/c mice in response to LPS challenge and swim-stress. Conversely, 1002 but not 1001 mRNA expression was significantly altered following swim-stress and LPS, particularly in the hippocampus of BALB/c mice. These data indicate altered central mRNA expression of tryptophan metabolising enzymes and immune activation in BALB/c mice compared to the normo-sensitive C57BL/6J strain. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.