ETAZOLATE ABROGATES THE LIPOPOLYSACCHARIDE (LPS)-INDUCED DOWNREGULATION OF THE cAMP/pCREB/BDNF SIGNALING, NEUROINFLAMMATORY RESPONSE AND DEPRESSIVE-LIKE BEHAVIOR IN MICE
ETAZOLATE ABROGATES THE LIPOPOLYSACCHARIDE (LPS)-INDUCED DOWNREGULATION OF THE cAMP/pCREB/BDNF SIGNALING, NEUROINFLAMMATORY RESPONSE AND DEPRESSIVE-LIKE BEHAVIOR IN MICE
复制标题
Etazolate 消除脂多糖 (LPS) 诱导的小鼠 cAMP/pCREB/BDNF 信号传导、神经炎症反应和抑郁样行为的下调
DOI：
10.1016/j.neuroscience.2014.01.008
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发表时间：
2014-03-28
期刊：
影响因子：
3.3
通讯作者：
Wang, C.
中科院分区：
文献类型：
--
作者：
Guo, J.;Lin, P.;Wang, C.
越来越多的证据表明，细菌脂多糖（LPS）的免疫攻击诱导抑郁样行为，神经炎症反应和上调磷酸二酯酶-4（PDE 4），一种特异性水解环磷酸腺苷（cAMP）的酶。然而，潜在的PDE 4抑制剂etazolate是否能阻止LPS诱导的抑郁样行为仍不清楚。采用LPS诱导小鼠抑郁模型，通过强迫游泳、新奇抑制摄食、蔗糖偏好和旷场实验，研究LPS对小鼠PDE 4、IL-1 β表达的影响及依他唑酯的抗抑郁作用。我们的研究结果表明，依他唑酯预处理促进体重减轻的恢复，并防止重复给予LPS诱导的抑郁样行为。此外，依他唑酯的抗抑郁作用通过显著降低小鼠海马和前额皮质中PDE 4A、PDE 4 B、PDE 4D和IL-1 β的表达水平以及上调cAMP/磷酸化cAMP反应元件结合蛋白（pCREB）/脑源性神经营养因子（BDNF）信号传导而被证实。以上结果提示，依他唑酯对LPS诱导的抑郁样行为的影响可能部分依赖于抑制PDE 4亚型、激活海马和前额皮质cAMP/pCREB/BDNF信号通路以及抗炎反应。皇冠版权所有（C）2014由爱思唯尔有限公司代表IBRO发布。All rights reserved.
Increasing evidence has indicated that immune challenge by bacterial lipopolysaccharide (LPS) induces depressive-like behavior, neuroinflammatory response and upregulates phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes cyclic adenosine monophosphate (cAMP). However, whether the potential PDE4 inhibitor etazolate prevents the LPS-induced depressive-like behavior remains unclear. Here using a model of depression induced by the repeated administration of LPS during 16 days, and then investigated the influence of LPS on the expression of PDE4, interleukin-1 beta (IL-1 beta) and antidepressant action of etazolate in mice through forced swimming, novelty suppressed feeding, sucrose preference and open-field tests. Our results showed that etazolate pretreatment facilitated the recovery from weight loss and prevented the depressive-like behavior induced by repeated LPS administration. Moreover, the antidepressant action of etazolate was paralleled by significantly reducing the expression levels of PDE4A, PDE4B, PDE4D and IL-1 beta and up-regulating the cAMP/phosphorylated cAMP response-element binding protein (pCREB)/brain-derived neurotrophic factor (BDNF) signaling in the hippocampus and prefrontal cortex of mice. These results indicate that the effects of etazolate on the depressive-like behavior induced by repeated LPS treatment may partially depend on the inhibition of PDE4 subtypes, the activation of the cAMP/pCREB/BDNF signaling and the anti-inflammatory responses in the hippocampus and prefrontal cortex. Crown Copyright (C) 2014 Published by Elsevier Ltd. on behalf of IBRO. All rights reserved.