IL-1RA blocks E. coli-induced suppression of Arc and long-term memory in aged F344xBN F1 rats.
IL-1RA blocks E. coli-induced suppression of Arc and long-term memory in aged F344xBN F1 rats.
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DOI：
10.1016/j.bbi.2009.10.005
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发表时间：
2010-02
影响因子：
15.1
通讯作者：
Maier, Steven F.
中科院分区：
文献类型：
--
作者：
Frank, Matthew G.;Barrientos, Ruth M.;Hein, Amy M.;Biedenkapp, Joseph C.;Watkins, Linda R.;Maier, Steven F.
在正常衰老中，外周免疫激发诱导致敏和持久的神经炎症反应，同时伴有长期记忆（LTM）损伤。神经炎症的促炎介质损害LTM、突触可塑性和LTP。即早基因Arc被认为是调节LTM和突触可塑性的关键蛋白。本研究探讨了1）外周E. 2）中枢促炎细胞因子（IL-1β和IL-6）介导外周E. Arc和LTM上的大肠杆菌感染。在24个月的F344 × BN F1大鼠中，E.大肠杆菌感染抑制了基础Arc基因的表达以及情境恐惧条件诱导的Arc表达。E. coli处理未能改变基础或条件诱导的c-Fos表达。在感染后24 h，用抗炎细胞因子IL-1 RA处理小脑延髓池（ICM）可阻断E.大肠杆菌诱导的海马Arc的抑制和IL-6蛋白的增加。感染后4d，IL-1 RA阻断E.大肠杆菌诱导的LTM损伤和IL-6蛋白的增加。本研究结果表明，中央促炎细胞因子发挥了显着的作用，在抑制弧和损伤的LTM的外周免疫挑战老年动物。
In normal aging, a peripheral immune challenge induces a sensitized and protracted neuroinflammatory response in parallel with long-term memory (LTM) impairments. Proinflammatory mediators of neuroinflammation impair LTM, synaptic plasticity and LTP. The immediate early gene Arc is considered a critical protein regulating LTM and synaptic plasticity. The present investigation examined whether 1) a peripheral E. coli infection suppresses hippocampal Arc expression, and 2) central proinflammatory cytokines (IL-1β and IL-6) mediate the effects of peripheral E. coli infection on Arc and LTM. In 24 mo F344 × BN F1 rats, E. coli infection suppressed basal Arc gene expression as well as contextual fear conditioning-induced Arc expression. E. coli treatment failed to alter either basal or conditioning-induced c-Fos expression. At 24 h post-infection, intracisterna magna (ICM) treatment with the anti-inflammatory cytokine IL-1RA blocked the E. coli-induced suppression of hippocampal Arc and increases in IL-6 protein. At 4 d post-infection, IL-1RA blocked the E. coli-induced LTM impairments and increases in IL-6 protein. The present results suggest that central proinflammatory cytokines play a salient role in the suppression of Arc and impairments of LTM by a peripheral immune challenge in older animals.
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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：
4.7
作者：
Cumiskey, D.;Curran, B. P.;O'Connor, J. J.
通讯作者：
O'Connor, J. J.
影响因子：
3.3
作者：
Hein, A. M.;Stutzman, D. L.;Maier, S. F.
通讯作者：
Maier, S. F.
影响因子：
15.1
作者：
Abraham, Jayne;Johnson, Rodney W.
通讯作者：
Johnson, Rodney W.
影响因子：
2.5
作者：
Curran, BP;O'Connor, JJ
通讯作者：
O'Connor, JJ