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KMID : 1161520190230060371
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Animal Cells and Systems
2019 Volume.23 No. 6 p.371 ~ p.379
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Dexmedetomidine ameliorates memory impairment in sleep-deprived mice
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Hwang Lak-Kyong
Ko Il-Gyu
Jin Jun-Jang
Kim Sang-Hoon
Kim Chang-Ju
Chang Bok-Soon
Rho Jeong-Ho
Moon Eun-Jin
Yi Jae-Woo
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Abstract
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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.
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KEYWORD
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Sleep deprivation, α2-adrenoceptor agonist, dexmedetomidine, inflammation, memory impairment
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