Brain-derived neurotrophic factor mRNA downregulation produced by social isolation is blocked by intrahippocampal interleukin-1 receptor antagonist
Brain-derived neurotrophic factor mRNA downregulation produced by social isolation is blocked by intrahippocampal interleukin-1 receptor antagonist
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DOI：
10.1016/s0306-4522(03)00564-5
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Maier, SF
中科院分区：
文献类型：
--
作者：
Barrientos, RM;Sprunger, DB;Maier, SF
如果记忆的形成需要海马，那么增加海马中促炎细胞因子白细胞介素-1 β（IL-1 β）表达的操作（例如脂多糖、i. c. v.糖蛋白120的外周给药、社会隔离）以及学习经历后海马内注射IL-1 β会显著损害对该经历的记忆。在这里，我们采用社会隔离来进一步研究这种现象，以及它与脑源性神经营养因子（BDNF）的关系。BDNF被研究是因为它在大脑记忆形成中的作用得到了充分的证明。一个6小时的社会隔离后立即上下文恐惧条件反射受损的记忆上下文恐惧测量48小时后，和减少BDNF mRNA的齿状回和海马CA 3区的评估后立即隔离。此外，海马内注射的IL-1受体拮抗剂之前，隔离期防止BDNF下调和隔离产生的记忆障碍。这些数据表明，脑IL-1 β水平升高引起的海马依赖性记忆障碍可能通过IL-1 β诱导的海马BDNF下调而发生。(C)2003年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Manipulations that increase the expression of the pro-inflammatory cytokine interleukin-1beta (IL-1beta) in the hippocampus (e.g. peripheral administration of lipopolysaccharide, i.c.v. glycoprotein 120, social isolation) as well as the intrahippocampal injection of IL-1beta following a learning experience, dramatically impair the memory of that experience if the formation of the memory requires the hippocampus. Here we employed social isolation to further study this phenomenon, as well as its relation to brain-derived neurotrophic factor (BDNF). BDNF was studied because of its well-documented role in the formation of hippocampally based memory. A 6 h period of social isolation immediately after contextual fear conditioning impaired memory for context fear measured 48 h later, and decreased BDNF mRNA in the dentate gyrus and the CA3 region of the hippocampus assessed immediately after the isolation. Moreover, an intrahippocampal injection of the IL-1 receptor antagonist prior to the isolation period prevented both the BDNF downregulation and the memory impairments produced by the isolation. These data suggest that hippocampal-dependent memory impairments induced by elevated levels of brain IL-1beta may occur via an IL-1beta-induced downregulation in hippocampal BDNF. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved.