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在睡眠剥夺期间,MLC901 可挽救大鼠的恐惧记忆障碍。

MLC901 during sleep deprivation rescues fear memory disruption in rats.

机构信息

Cognitive and Neuroscience Research Center (CNRC), Amir-Almomenin Hospital, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Department of Genetics, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2019 Jul;392(7):813-821. doi: 10.1007/s00210-018-01612-z. Epub 2019 Feb 28.

Abstract

Several lines of evidence suggest that sleep deprivation disrupts cognitive and emotional abilities and changes the expression of distinctive categories of genes in the brain. In the present study, saline- or MLC901 (a traditional Chinese medicine)-treated male Wistar rats were first submitted to a modified water box (for 24-h sleep deprivation) and then trained in contextual and tone fear conditioning tasks with the purpose to evaluate the effect of MLC901 during sleep deprivation on fear memory retention. Hippocampal mRNA measurement was performed by reverse transcription-polymerase chain reaction (RT-PCR). We found that the exposure of rats to 24 h of sleep deprivation impaired contextual and tone fear memory retention, while administration of MLC901 (0.2, 0.4, and 0.8 mg/kg, once/12 h; i.p.) during sleep deprivation abolished memory deficits. Meanwhile, different doses of MLC901 alone had no effect on performance in both tasks. We observed that MLC901 increased the expression levels of pro-apoptotic BAD, anti-apoptotic Bcl-xL, and Tfam as an index of mitochondrial biogenesis compared to sleep-deprived rats, while MLC901 during sleep deprivation increased BAX, BAD, and Bcl-xL compared to the control group. Sleep deprivation decreased BAX and Tfam, by itself. MLC901 only decreased BAX and Tfam and increased BAD level compared to the non-sleep-deprived control group. It is suggested that MLC901 might be a therapeutic option for memory impairment during sleep deprivation.

摘要

有几条证据表明,睡眠剥夺会破坏认知和情绪能力,并改变大脑中独特基因类别的表达。在本研究中,首先将生理盐水或 MLC901(一种中药)处理的雄性 Wistar 大鼠置于改良的水盒中(进行 24 小时睡眠剥夺),然后在情境和音调恐惧条件反射任务中进行训练,目的是评估 MLC901 在睡眠剥夺期间对恐惧记忆保留的影响。通过逆转录-聚合酶链反应(RT-PCR)测量海马 mRNA。我们发现,大鼠暴露于 24 小时睡眠剥夺会损害情境和音调恐惧记忆保留,而在睡眠剥夺期间给予 MLC901(0.2、0.4 和 0.8mg/kg,12 小时/次;ip)则消除了记忆缺陷。同时,单独使用不同剂量的 MLC901 对这两个任务的表现均无影响。我们观察到,与睡眠剥夺大鼠相比,MLC901 增加了促凋亡 BAD、抗凋亡 Bcl-xL 和作为线粒体生物发生指标的 Tfam 的表达水平,而在睡眠剥夺期间,MLC901 增加了 BAX、BAD 和 Bcl-xL 与对照组相比。睡眠剥夺本身会降低 BAX 和 Tfam。与非睡眠剥夺对照组相比,MLC901 仅降低 BAX 和 Tfam 并增加 BAD 水平。这表明 MLC901 可能是治疗睡眠剥夺期间记忆障碍的一种选择。

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