Ketamine-mediated alleviation of electroconvulsive shock-induced memory impairment is associated with the regulation of neuroinflammation and soluble amyloid-beta peptide in depressive-like rats
Ketamine-mediated alleviation of electroconvulsive shock-induced memory impairment is associated with the regulation of neuroinflammation and soluble amyloid-beta peptide in depressive-like rats
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DOI：
10.1016/j.neulet.2015.05.022
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发表时间：
2015-07
影响因子：
2.5
通讯作者：
Xianlin Zhu;Ping Li;Xuechao Hao;K. Wei;S. Min;Jie Luo;Fei Xie;Ju-ying Jin
中科院分区：
文献类型：
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作者：
Xianlin Zhu;Ping Li;Xuechao Hao;K. Wei;S. Min;Jie Luo;Fei Xie;Ju-ying Jin
电休克疗法 (ECT) 是治疗抑郁症的有效方法，但会导致记忆缺陷。本研究旨在确定氯胺酮是否可以减轻电休克（ECS，动物中ECT的类似物）引起的记忆障碍及其潜在的分子机制。慢性不可预测的温和应激被用来产生抑郁样症状的动物模型。 60只成年雄性Sprague-Dawley大鼠随机分为以下5组：对照组（C组）；抑郁样模型组（D组）； ECS组（DE组）；氯胺酮 + ECS 组（DKE 组）；和氯胺酮组（DK组）。使用蔗糖偏好测试和莫里斯水迷宫来评估行为变化。采用免疫组化和实时荧光定量PCR检测Iba-1、IL-1β和TNF-α的表达水平。采用酶联免疫吸附测定法检测可溶性 Aβ 的水平。我们发现ECS上调Iba-1的表达，促进IL-1β和TNF-α的释放，增加海马Aβ1-40和Aβ1-42的水平，加重抑郁样大鼠的记忆障碍。然而，氯胺酮逆转了这些 ECS 引起的分子变化，并有效减轻了 ECS 引起的记忆障碍。氯胺酮的这种认知保护作用可能归因于它对 ECS 诱导的神经炎症的抑制和可溶性 Aβ 水平的降低。
Electroconvulsive therapy (ECT) is an effective treatment for depression, but can result in memory deficits. This study aimed to determine whether ketamine could alleviate electroconvulsive shock (ECS, an analog of ECT in animals)-induced memory impairment and the potential molecular mechanism. Chronic unpredictable mild stress was used to generate animal models of depressive-like symptoms. Sixty adult male Sprague–Dawley rats were randomly divided into the following five groups: control group (group C); depressive-like model group (group D); ECS group (group DE); ketamine + ECS group (group DKE); and ketamine group (group DK). The sucrose preference test and Morris water maze were used to assess behavioral changes. The expression levels of Iba-1, IL-1β and TNF-α were measured by immunohistochemistry and real-time PCR. Enzyme-linked immunosorbent assays were used to detect the levels of soluble Aβ. We found that ECS up-regulated the expression of Iba-1, promoted the release of IL-1β and TNF-α, increased the levels of Aβ1-40 and Aβ1-42 in the hippocampus, and aggravated memory impairment of the depressive-like rats. However, ketamine reversed these ECS-induced molecular changes and effectively attenuated ECS-induced memory impairment. This cognitive protective effect of ketamine may be attributed to its suppression of ECS-induced neuroinflammation and reduction of the levels of soluble Aβ.