Maslinic acid ameliorates NMDA receptor blockade-induced schizophrenia-like behaviors in mice
Maslinic acid ameliorates NMDA receptor blockade-induced schizophrenia-like behaviors in mice
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DOI：
10.1016/j.neuropharm.2017.09.014
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发表时间：
2017-11-01
影响因子：
4.7
通讯作者：
Ryu, Jong Hoon
中科院分区：
文献类型：
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作者：
Jeon, Se Jin;Kim, Eunji;Ryu, Jong Hoon
精神分裂症是一种慢性精神病性障碍，其特征是阳性、阴性和认知症状。精神分裂症的初级治疗缓解了阳性症状，但对阴性和认知症状的效果较差。本研究旨在探讨丁香酸（Syzygium aromaticum，C.A.）对N-甲基-o-天冬氨酸（NMDA）受体拮抗剂MK-801诱导的小鼠精神分裂症样行为的改善作用。在MK-801模型中，经山楂酸处理后，我们检查了前额叶皮层中的行为改变和信号通路。用山楂酸（30 mg/kg）处理小鼠，并通过一系列行为测试来评价它们的行为。山楂酸的影响也在前额叶皮层的信号通路中进行了检查。单次给药山楂酸阻断MK-801诱导的过度运动，并逆转MK-801诱导的感觉运动门控缺陷的声音惊吓反应测试。在社会新奇偏好测试中，山楂酸改善MK-801诱导的社会行为缺陷。MK-801诱导的注意和识别记忆障碍也可通过单次给药山楂酸缓解。此外，山楂酸使前额叶皮层中Akt-GSK-3 β和ERK-CREB的磷酸化水平正常化。总体而言，山楂酸改善了MK-801诱导的精神分裂症样症状，这些作用可能部分通过Akt-GSK-3 β和ERK-CREB激活介导。这些研究结果表明，山楂酸可能是治疗精神分裂症的几种症状的候选药物，包括阳性症状，感觉运动门控中断，社会互动缺陷和认知障碍。(C)2017爱思唯尔有限公司版权所有
Schizophrenia is a chronic psychotic disorder characterized by positive, negative, and cognitive symptoms. Primary treatments for schizophrenia relieve the positive symptoms but are less effective against the negative and cognitive symptoms. In the present study, we investigated whether maslinic acid, isolated from Syzygium aromaticum (clove), can ameliorate schizophrenia-like behaviors in mice induced by MK-801, an N-methyl-o-aspartate (NMDA) receptor antagonist. After maslinic acid treatment in the MK-801 model, we examined the behavioral alteration and signaling pathways in the prefrontal cortex. Mice were treated with maslinic acid (30 mg/kg), and their behaviors were evaluated through an array of behavioral tests. The effects of maslinic acid were also examined in the signaling pathways in the prefrontal cortex. A single administration of maslinic acid blocked the MK-801-induced hyperlocomotion and reversed the MK-801-induced sensorimotor gating deficit in the acoustic startle response test. In the social novelty preference test, maslinic acid ameliorated the social behavior deficits induced by MK-801. The MK-801-induced attention and recognition memory impairments were also alleviated by a single administration of maslinic acid. Furthermore, maslinic acid normalized the phosphorylation levels of Akt-GSK-3 beta and ERK-CREB in the prefrontal cortex. Overall, maslinic acid ameliorated the schizophrenia like symptoms induced by MK-801, and these effects may be partly mediated through Akt-GSK-3 beta and ERK-CREB activation. These findings suggest that maslinic acid could be a candidate for the treatment of several symptoms of schizophrenia, including positive symptoms, sensorimotor gating disruption, social interaction deficits, and cognitive impairments. (C) 2017 Elsevier Ltd. All rights reserved.