Prolonged elevation in hippocampal Aβ and cognitive deficits following repeated endotoxin exposure in the mouse
Prolonged elevation in hippocampal Aβ and cognitive deficits following repeated endotoxin exposure in the mouse
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DOI：
10.1016/j.bbr.2012.01.010
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发表时间：
2012-04-01
影响因子：
2.7
通讯作者：
Chumley, Michael J.
中科院分区：
文献类型：
--
作者：
Kahn, Marielle S.;Kranjac, Dinko;Chumley, Michael J.
阿尔茨海默病（AD）的特征是由于淀粉样蛋白β（A β）斑块和神经原纤维缠结的形成，成人大脑区域（包括海马和皮质）的神经元细胞死亡和萎缩。这些病理的存在可以限制正常的信号传导特性，并最终导致学习和记忆缺陷。慢性炎症与这些AD相关病理的发生和进展有关。我们的研究旨在通过使用细菌内毒素脂多糖（LPS）来评估外周炎症对AD相关病理学的影响。给C57 BL/6 J小鼠腹腔注射LPS或生理盐水，连续1、3或7天。接受LPS的动物的海马组织中A β 1-42（AD斑块的一种肽组分）的水平显著高于盐水对照动物。单次注射LPS后，中枢和外周促炎细胞因子水平升高，但在认知测试开始前恢复至基线水平。我们发现，一次注射LPS会导致病态行为，但连续7天不会，表明对内毒素的耐受性。然后进行认知测试以确定A β 1-42增加的缺陷是否明显。Morris水迷宫和情境恐惧条件反射的结果显示LPS处理的小鼠存在认知缺陷。总之，多次注射LPS导致小鼠海马中A β 1-42增加和认知缺陷。(C)2012爱思唯尔有限公司版权所有。
Alzheimer's disease (AD) is characterized by neuronal cell death and atrophy in regions of the adult brain, including the hippocampus and cortex, due to formation of amyloid beta (A beta) plaques and neurofibrillary tangles. The presence of these pathologies can limit normal signaling properties and ultimately lead to learning and memory deficits. Chronic inflammation has been implicated in the onset and progression of these AD-related pathologies. Our study was designed to assess the effects of peripheral inflammation on pathologies associated with AD by using the bacterial endotoxin lipopolysaccharide (LPS). C57BL/6J mice were given intraperitoneal injections of LPS or saline for 1, 3, or 7 consecutive days. Hippocampal tissue from animals receiving LPS contained significantly higher levels of A beta 1-42, a peptide component of AD plaques, than did those from saline control animals. Central and peripheral pro-inflammatory cytokine levels were increased following a single injection of LPS, but retuned to baseline levels before cognitive testing began. We show that one injection of LPS leads to sickness behavior, but 7 consecutive days does not, indicating tolerance to the endotoxin. Cognitive testing was then conducted to determine if whether deficits from increased A beta 1-42 was evident. Results from both Morris water maze and contextual fear conditioning revealed cognitive deficits in LPS-treated mice. In summary, multiple injections of LPS resulted in increased A beta 1-42 in the hippocampus and cognitive deficits in mice. (C) 2012 Elsevier B.V. All rights reserved.