Dissociation between sickness behavior and emotionality during lipopolysaccharide challenge in lymphocyte deficient Rag2(-/-) mice.
Dissociation between sickness behavior and emotionality during lipopolysaccharide challenge in lymphocyte deficient Rag2(-/-) mice.
复制标题
DOI：
10.1016/j.bbr.2014.09.030
复制
发表时间：
2015-02-01
影响因子：
2.7
通讯作者：
Tonelli, Leonardo H.
中科院分区：
文献类型：
--
作者：
Clark, Sarah M.;Michael, Kerry C.;Klaus, Joseph;Mert, Abdullah;Romano-Verthelyi, Ari;Sand, Joseph;Tonelli, Leonardo H.
炎症性疾病与包括抑郁和焦虑在内的情感障碍高度相关。虽然先天免疫系统对情绪的作用已经得到了广泛的研究，但适应性免疫的作用却鲜为人知。考虑到慢性炎症性疾病主要是由适应不良的淋巴细胞功能介导的，这些细胞在炎症期间对脑功能和行为的作用值得研究。在本研究中，我们采用淋巴细胞功能缺陷的小鼠，研究了细菌脂多糖（LPS）攻击过程中的行为和炎症反应。缺乏成熟淋巴细胞的Rag 2 −/−小鼠在亚脓毒症（5 mg/kg）剂量的LPS下容易死亡，并且仅在中等剂量（1 mg/kg）的LPS下存活。在这些条件下，与免疫活性小鼠相比，它们显示出减弱的TNF-α反应和疾病的行为症状。然而，Rag 2 −/−小鼠在从疾病中恢复后具有长期的动机障碍，这表明淋巴细胞在先天免疫系统激活后重建动机状态方面具有特定功能。行为测试后，Rag 2 −/−小鼠的行为障碍被血浆皮质酮的升高所掩盖。这些结果提供的证据表明，缺乏适应性免疫可能与炎症期间的情绪缺陷，并表明与医学疾病相关的抑郁状态可能是介导的部分受损的淋巴细胞反应。
Inflammatory diseases are highly associated with affective disorders including depression and anxiety. While the role of the innate immune system on emotionality has been extensively studied, the role of adaptive immunity is less understood. Considering that chronic inflammatory conditions are mediated largely by maladaptive lymphocyte function, the role of these cells on brain function and behavior during inflammation warrants investigation. In the present study we employed mice deficient in lymphocyte function and studied behavioral and inflammatory responses during challenge with bacterial lipopolysaccharides (LPS). Rag2−/− mice lacking mature lymphocytes were susceptible to death under sub-septic (5 mg/kg) doses of LPS and survived only to moderate (1 mg/kg) doses of LPS. Under these conditions, they displayed attenuated TNF-alpha responses and behavioral symptoms of sickness when compared with immunocompetent mice. Nevertheless, Rag2−/− mice had protracted motivational impairments after recovery from sickness suggesting a specific function for lymphocytes on the reestablishment of motivational states after activation of the innate immune system. The behavioral impairments in Rag2−/− mice were paralleled by an elevation in plasma corticosterone after behavioral tests. These results provide evidence that the absence of adaptive immunity may be associated with emotional deficits during inflammation and suggest that depressive states associated with medical illness may be mediated in part by impaired lymphocyte responses.
登录
查看更多内容
脑膜免疫调节学习和记忆：IL-4 的关键作用。
影响因子：
15.3
作者：
Derecki, Noel C.;Cardani, Amber N.;Yang, Chun Hui;Quinnies, Kayla M.;Crihfield, Anastasia;Lynch, Kevin R.;Kipnis, Jonathan
通讯作者：
Kipnis, Jonathan
DOI：
10.1196/annals.1366.028
发表时间：
2006-01-01
期刊：
NEUROENDOCRINE AND IMMUNE CROSSTALK
影响因子：
--
作者：
Costa-Pinto, Frederico Azevedo;Basso, Alexandre Salgado;Palermo-Neto, Joao
通讯作者：
Palermo-Neto, Joao
影响因子：
3.7
作者：
Frenois, Francois;Moreau, Maite;Castanon, Nathalie
通讯作者：
Castanon, Nathalie
DOI：
10.1111/j.1749-6632.1998.tb08321.x
发表时间：
1998-01-01
期刊：
MOLECULAR MECHANISMS OF FEVER
影响因子：
--
作者：
Dantzer, R;Bluthé, RM;Kelley, KW
通讯作者：
Kelley, KW
DOI：
10.1155/2010/491928
发表时间：
2010-01-01
期刊：
Journal of allergy
影响因子：
--
作者：
Mirotti, L;Castro, J;Russo, M
通讯作者：
Russo, M