ABSTRACT The selective α2-adrenergic receptor agonist dexmedetomidine acts as an analgesic, sedative, and anesthetic adjuvant. The most common consequence of sleep deprivation is memory impairment. We investigated whether dexmedetomidine can counteract memory impairment caused by sleep deprivation and suppress the production of inflammatory factors. For inducing sleep deprivation, adult male mice were placed inside a water cage containing 15 platforms immersed in water up to 1 cm for 7 days. One day after sleep deprivation, dexmedetomidine at the respective dosage (5, 10, and 20 μg/kg) and α2-adrenoceptor antagonist atipamezole (250 μg/kg) were intraperitoneally injected into the mice, once per day for six days. The step-down avoidance task and the Morris water maze test were performed. Western blot analysis was performed to determine the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB), nuclear transcription factor-κB (NF-κB), inhibitor of κBα (IκBα), and ionized calcium binding adapter molecule I (Iba-1) in the hippocampus. Immunohistochemistry was performed for the determination of Ki-67 and glial fibrillary acidic protein (GFAP) expression in the hippocampal dentate gyrus. Dexmedetomidine ameliorated sleep deprivation-induced deterioration of short-term memory and spatial learning ability. Dexmedetomidine inhibited production of inflammatory mediators caused by sleep deprivation. Dexmedetomidine also prevented the decrease in BDNF, TrkB expression, and cell proliferation induced by sleep deprivation. Dexmedetomidine could be used to counteract the neuropathological effects of sleep deprivation.

中文翻译：

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右美托咪定改善睡眠剥夺小鼠的记忆障碍

摘要 选择性 α2-肾上腺素能受体激动剂右美托咪定可作为镇痛、镇静和麻醉佐剂。睡眠剥夺最常见的后果是记忆障碍。我们研究了右美托咪定是否可以抵消睡眠剥夺引起的记忆障碍并抑制炎症因子的产生。为了诱导睡眠剥夺，成年雄性小鼠被放置在含有 15 个平台的水笼中，浸入水中 1 厘米，持续 7 天。睡眠剥夺一天后，将各自剂量（5、10和20 μg/kg）的右美托咪定和α2-肾上腺素受体拮抗剂阿替美唑（250 μg/kg）腹腔注射到小鼠体内，每天一次，共六天。进行了降压回避任务和莫里斯水迷宫测试。进行蛋白质印迹分析以确定肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-6、脑源性神经营养因子（BDNF）、酪氨酸激酶B（TrkB）、核转录因子-κB的水平。 NF-κB)、κBα (IκBα) 抑制剂和海马中的离子钙结合接头分子 I (Iba-1)。进行免疫组织化学以确定海马齿状回中的 Ki-67 和神经胶质纤维酸性蛋白 (GFAP) 的表达。右美托咪定改善睡眠剥夺引起的短期记忆和空间学习能力的恶化。右美托咪定抑制由睡眠剥夺引起的炎症介质的产生。右美托咪定还可以防止睡眠剥夺引起的 BDNF、TrkB 表达和细胞增殖的减少。