Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system
Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system
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DOI：
10.1038/sj.npp.1301649
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发表时间：
2008-09-01
影响因子：
7.6
通讯作者：
Johnson, Rodney W.
中科院分区：
文献类型：
--
作者：
Godbout, Jonathan P.;Moreau, Maite;Johnson, Rodney W.
暴露于外周感染可能允许认知和行为并发症的老年人。我们已经报道了用脂多糖（LPS）外周刺激先天免疫系统导致老年BALB/c小鼠过度的神经炎症反应和延长的疾病行为。由于LPS也会导致抑郁行为，因此本研究的目的是确定衰老是否与加重的抑郁样反应相关。我们证实，LPS（0.33毫克/公斤腹腔注射）诱导了一个长期的疾病反应，在老年小鼠减少运动和喂养活动24和48小时注射后，当年轻的成年人已经完全恢复。当LPS后24小时进行强迫游泳测试时，年轻成年小鼠和老年小鼠都表现出增加的不动持续时间。然而，当提交给强迫游泳测试或尾部悬挂测试72小时后，LPS，增加的不动持续时间是明显的，只有在老年小鼠。与LPS注射后24小时的年轻成年小鼠相比，LPS处理的老年小鼠中这种延长的抑郁样行为与外周和脑吲哚胺2，3-双加氧酶的更明显诱导以及脑5-羟色胺的显著更高的周转率（通过5-羟基吲哚乙酸与5-羟基色胺的比率测量）相关。这些结果提供了第一个证据表明，年龄相关的反应，脑细胞因子系统可以发挥病理生理作用，在老年人中观察到的抑郁症的患病率增加。
Exposure to peripheral infections may be permissive to cognitive and behavioral complications in the elderly. We have reported that peripheral stimulation of the innate immune system with lipopolysaccharide (LPS) causes an exaggerated neuroinflammatory response and prolonged sickness behavior in aged BALB/c mice. Because LPS also causes depressive behavior, the purpose of this study was to determine whether aging is associated with an exacerbated depressive-like response. We confirmed that LPS (0.33 mg/kg intraperitoneal) induced a protracted sickness response in aged mice with reductions in locomotor and feeding activities 24 and 48 h postinjection, when young adults had fully recovered. When submitted to the forced swim test 24 h post-LPS, both young adult and aged mice exhibited an increased duration of immobility. However, when submitted to either the forced swim test or the tail suspension test 72 h post-LPS, an increased duration of immobility was evident only in aged mice. This prolonged depressive-like behavior in aged LPS-treated mice was associated with a more pronounced induction of peripheral and brain indoleamine 2,3-dioxygenase and a markedly higher turnover rate of brain serotonin (as measured by the ratio of 5-hydroxy-indoleacetic acid over 5-hydroxyt-tryptamine) compared to young adult mice at 24 post-LPS injection. These results provide the first evidence that age-associated reactivity of the brain cytokine system could play a pathophysiological role in the increased prevalence of depression observed in the elderly.