Lymphocytes from Chronically Stressed Mice Confer Antidepressant-Like Effects to Naive Mice
Lymphocytes from Chronically Stressed Mice Confer Antidepressant-Like Effects to Naive Mice
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DOI：
10.1523/jneurosci.2278-14.2015
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发表时间：
2015-01-28
影响因子：
5.3
通讯作者：
Herkenham, Miles
中科院分区：
文献类型：
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作者：
Brachman, Rebecca A.;Lehmann, Michael L.;Herkenham, Miles
我们研究了适应性免疫系统的细胞是否保留了心理社会压力的记忆，从而改变了宿主的情绪状态和中枢神经系统功能。分离来自经历慢性社交失败应激的小鼠或来自未应激的对照小鼠的淋巴细胞，并过继转移到幼稚淋巴细胞减少的Rag 2（-/-）小鼠中。情感行为，海马细胞增殖，小胶质细胞活化状态，和血液细胞因子水平的变化进行了检查，在重建的压力幼稚小鼠。与那些没有接受细胞或接受来自无压力供体的细胞的小鼠相比，接受来自失败供体的淋巴细胞的小鼠表现出更少的焦虑，更多的社会行为和海马细胞增殖增加。接受应激免疫细胞的小鼠血液中的促炎细胞因子水平相对于其他组降低，这与供体促炎细胞因子水平升高相反。此外，接受应激免疫细胞的小鼠的小胶质细胞倾向于抗炎、神经保护性M2样表型，这与应激供体的M1样促炎特征相反。然而，应激对供体和受体小鼠的淋巴细胞表面标志物分布没有影响。这些数据表明，慢性应激诱导的适应性免疫系统的变化，与赋予焦虑和抑郁行为相反，保护免受应激的有害影响。情感行为的改善可能是通过降低外周促炎细胞因子负荷、保护性小胶质细胞活性和增加海马细胞增殖介导的。这些数据确定了外周适应性免疫系统作为参与应激恢复机制的puerectin，并为开发新型速效抗抑郁治疗提供了潜在基础。
We examined whether cells of the adaptive immune system retain the memory of psychosocial stress and thereby alter mood states and CNS function in the host. Lymphocytes from mice undergoing chronic social defeat stress or from unstressed control mice were isolated and adoptively transferred into naive lymphopenic Rag2(-/-) mice. Changes in affective behavior, hippocampal cell proliferation, microglial activation states, and blood cytokine levels were examined in reconstituted stress-naive mice. The mice receiving lymphocytes from defeated donors showed less anxiety, more social behavior, and increased hippocampal cell proliferation compared with those receiving no cells or cells from unstressed donors. Mice receiving stressed immune cells had reduced pro-inflammatory cytokine levels in the blood relative to the other groups, an effect opposite to the elevated donor pro-inflammatory cytokine profile. Furthermore, mice receiving stressed immune cells had microglia skewed toward an anti-inflammatory, neuroprotective M2-like phenotype, an effect opposite the stressed donors' M1-like pro-inflammatory profile. However, stress had no effect on lymphocyte surface marker profiles in both donor and recipient mice. The data suggest that chronic stress-induced changes in the adaptive immune system, contrary to conferring anxiety and depressive behavior, protect against the deleterious effects of stress. Improvement in affective behavior is potentially mediated by reduced peripheral pro-inflammatory cytokine load, protective microglial activity, and increased hippocampal cell proliferation. The data identify the peripheral adaptive immune system as putatively involved in the mechanisms underlying stress resilience and a potential basis for developing novel rapid-acting antidepressant therapies.