Central inhibition of interleukin-1beta ameliorates sickness behavior in aged mice.
Central inhibition of interleukin-1beta ameliorates sickness behavior in aged mice.
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DOI：
10.1016/j.bbi.2008.12.008
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发表时间：
2009-03
影响因子：
15.1
通讯作者：
Johnson, Rodney W.
中科院分区：
文献类型：
--
作者：
Abraham, Jayne;Johnson, Rodney W.
在老年人中，大脑中高水平的白细胞介素-1β (IL-1β) 与感染相关的行为病理有关，但这尚未得到直接测试。因此，本研究调查了老年动物因外周注射脂多糖 (LPS) 引起的疾病行为是否是通过中枢 IL-1β 介导的。成年和老年小鼠在腹膜内注射盐水或 LPS (10 μg) 之前立即脑室内注射盐水或 IL-1ra (4 μg)，并评估运动和社会行为。正如预期的那样，LPS 会抑制成年小鼠和老年小鼠的运动活动和社会行为，但 24 小时后老年小鼠的行为缺陷明显更大。 IL-1ra 预处理不会影响成人 LPS 诱发的疾病行为；然而，在老年小鼠中，IL-1ra 可以减弱 LPS 诱导的疾病行为，使其恢复到年轻人的水平。注射后24小时收集海马和下丘脑组织测定IL-1β mRNA表达。 LPS 和 IL-1ra 都不影响成人的 IL-1β mRNA 水平，可能是因为 LPS 的影响在 24 小时内消失。相比之下，LPS 后 24 小时，老年小鼠的 IL-1β mRNA 显着升高，并且之前用 IL-1ra 治疗分别阻断或减弱了海马和下丘脑中的这种效应。总而言之，这些数据提供了第一个直接证据，证明中枢 IL-1β 是导致老年动物在 LPS 治疗后观察到的严重疾病行为的原因。因此，抑制 IL-1β 的中枢作用可能有助于最大限度地减少老年感染者的行为并发症。
In elderly individuals high levels of interleukin-1β (IL-1β) in the brain have been implicated in infection-related behavioral pathologies but this has not been directly tested. Therefore, the current study investigated if sickness behavior in aged animals elicited by peripheral injection of lipopolysaccharide (LPS) is mediated through central IL-1β. Adult and aged mice were injected intracerebroventricularly with either saline or IL-1ra (4 μg) immediately prior to intraperitoneal administration of saline or LPS (10 μg) and locomotor and social behaviors were assessed. As anticipated, LPS depressed locomotor activity and social behavior in both adult and aged mice but the behavioral deficits were markedly greater in the aged at 24 h. Pretreatment with IL-1ra did not affect LPS-induced sickness behavior in adults; however, in aged mice IL-1ra attenuated LPS-induced sickness behavior, restoring it to the level exhibited by young adults. Twenty-four h post injection hippocampal and hypothalamic tissues were collected to determine IL-1β mRNA expression. Neither LPS nor IL-1ra affected IL-1β mRNA levels in adults, presumably because any effect of LPS had dissipated by 24 h. In contrast, IL-1β mRNA was markedly higher in aged mice 24 h after LPS, and prior treatment with IL-1ra either blocked or attenuated this effect in the hippocampus and hypothalamus, respectively. Taken together these data provide the first direct evidence that central IL-1β is responsible for the severe sickness behavior observed in aged animals after LPS treatment. Thus, inhibiting the central actions of IL-1β may be useful for minimizing behavioral complications in older individuals with an infection.
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影响因子：
6.2
作者：
Streit, WJ;Sammons, NW;Sparks, DL
通讯作者：
Sparks, DL
影响因子：
15.1
作者：
Chen, Jing;Buchanan, Jessica B.;Johnson, Rodney W.
通讯作者：
Johnson, Rodney W.
影响因子：
13.8
作者：
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通讯作者：
DANTZER, R
影响因子：
4.2
作者：
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通讯作者：
CIVIN, WH
影响因子：
3.4
作者：
Lynch, AM;Lynch, MA
通讯作者：
Lynch, MA