Administration of the inverse benzodiazepine agonist MRK-016 rescues acquisition and memory consolidation following peripheral administration of bacterial endotoxin
Administration of the inverse benzodiazepine agonist MRK-016 rescues acquisition and memory consolidation following peripheral administration of bacterial endotoxin
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DOI：
10.1016/j.bbr.2015.03.048
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发表时间：
2015-07-15
影响因子：
2.7
通讯作者：
Boehm, G. W.
中科院分区：
文献类型：
--
作者：
Eimerbrink, M. J.;White, J. D.;Boehm, G. W.
最近的证据表明，炎症引起的认知功能减退可以通过操纵兴奋性或抑制性传递来减轻。我们测试了反向苯二氮卓类激动剂MRK-016（MRK）的能力，以防止LPS诱导的记忆获得和巩固的缺陷，使用上下文恐惧条件反射（CFC）的范例。在实验一中，小鼠在CFC训练前接受脂多糖（LPS）和/或MRK注射，然后在训练后24小时进行测试。在实验二中，动物在训练后立即接受类似的治疗注射，并在24小时后进行测试。另外，在LPS注射后4 h和测试后立即收集海马样品，以评估脑源性神经营养因子（BDNF）和胰岛素样生长因子1（IGF-1）mRNA表达。结果表明，MRK可以防止LPS诱导的学习/记忆减退，在这两个范例。我们还发现，在这两个范例中，与生理盐水/生理盐水处理的动物相比，在LPS给药后4小时，LPS/生理盐水处理的动物表达显著减少的BDNF mRNA，但MRK没有恢复BDNF表达水平。此外，在任何采集时间点，给药对IGF-1 mRNA表达均无影响。总之，MRK-016可以防止LPS诱导的记忆获得和巩固的缺陷，在这种依赖于大脑皮层的范例中，尽管这种保护作用独立于BDNF表达的恢复而发生。(C)2015年由Elsevier B. V.出版
Recent evidence suggests that inflammation-induced decrements in cognitive function can be mitigated via manipulation of excitatory or inhibitory transmission. We tested the ability of the inverse benzodiazepine agonist, MRK-016 (MRK) to protect against LPS-induced deficits in memory acquisition and consolidation, using a contextual fear conditioning (CFC) paradigm. In Experiment One, mice received lipopolysaccharide (LPS) and/or MRK injections prior to CFC training, and were then tested 24 h after training. In Experiment Two, animals received similar treatment injections immediately after training, and were tested 24h later. Additionally, hippocampal samples were collected 4h after LPS injections and immediately after testing, to evaluate brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1) mRNA expression. Results indicate that MRK can protect against LPS-induced learning/memory decrements in both paradigms. We also found, in both paradigms, that animals treated with LPS/Saline expressed significantly less BDNF mRNA when compared to Saline/Saline-treated animals 4 h after LPS administration, but that MRK did not restore BDNF expression levels. Further, treatment administrations had no effect on IGF-1 mRNA expression at any collection time-point. In summary, MRK-016 can protect against LPS-induced deficits in memory acquisition and consolidation, in this hippocampus-dependent paradigm, though this protection occurs independently of recovery of BDNF expression. (C) 2015 Published by Elsevier B.V.