Effects of the dual orexin receptor antagonist DORA-22 on sleep in 5XFAD mice
Effects of the dual orexin receptor antagonist DORA-22 on sleep in 5XFAD mice
复制标题
DOI：
10.1016/j.trci.2019.01.003
复制
发表时间：
2019-01-01
影响因子：
4.8
通讯作者：
Bachstetter, Adam D.
中科院分区：
文献类型：
--
作者：
Duncan, Marilyn J.;Farlow, Hannah;Bachstetter, Adam D.
简介：睡眠中断是阿尔茨海默病（AD）的一个特征，可能会加剧疾病的进展。本研究测试了双重食欲素受体拮抗剂（DORA）是否会在AD相关小鼠模型5XFAD中增强睡眠并减弱神经病理学、神经炎症和认知缺陷。方法：野生型（C57 B16/SJL）和5XFAD小鼠接受用媒介物或DORA-22的长期治疗。压电记录监测睡眠和空间记忆通过自发Y-迷宫交替进行评估。A β斑块，A β水平，神经炎症标记物进行了测定，免疫组织化学，酶联免疫吸附试验，和实时聚合酶链反应，real-time polymerase chain reactions.Results：在5XFAD小鼠，DORA-22显着增加光相睡眠，而不降低A β水平，斑块密度，或神经炎症。DORA-22对认知缺陷的影响无法确定，因为5XFAD小鼠没有表现出deficits.Discussion：这些发现表明，DORA可能会改善AD患者的睡眠。进一步的研究应该优化DORA-22治疗的剂量和持续时间，并探索其他AD相关的动物模型和认知测试。(C)2019作者爱思唯尔公司出版代表老年痴呆症协会
Introduction: Sleep disruption is a characteristic of Alzheimer's disease (AD) that may exacerbate disease progression. This study tested whether a dual orexin receptor antagonist (DORA) would enhance sleep and attenuate neuropathology, neuroinflammation, and cognitive deficits in an AD-relevant mouse model, 5XFAD.Methods: Wild-type (C57Bl6/SJL) and 5XFAD mice received chronic treatment with vehicle or DORA-22. Piezoelectric recordings monitored sleep and spatial memory was assessed via spontaneous Y-maze alternations. A beta plaques, A beta levels, and neuroinflammatory markers were measured by immunohistochemistry, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction, respectively.Results: In 5XFAD mice, DORA-22 significantly increased light-phase sleep without reducing A beta levels, plaque density, or neuroinflammation. Effects of DORA-22 on cognitive deficits could not be determined because the 5XFAD mice did not exhibit deficits.Discussion: These findings suggest that DORAs may improve sleep in AD patients. Further investigations should optimize the dose and duration of DORA-22 treatment and explore additional AD-relevant animal models and cognitive tests. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.