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新型去氢表雄酮衍生物 BNN27 可拮抗麻醉剂氯胺酮对大鼠非空间和空间识别记忆的损害作用。

The novel dehydroepiandrosterone derivative BNN27 counteracts the impairing effects of anesthetic ketamine on rats' non-spatial and spatial recognition memory.

机构信息

Department of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Thessaly, Larissa, Greece.

Department of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Thessaly, Larissa, Greece.

出版信息

Behav Brain Res. 2022 Jul 26;430:113937. doi: 10.1016/j.bbr.2022.113937. Epub 2022 May 26.

Abstract

Conspicuous experimental evidence indicates that anesthetic doses of the non-competitive NMDA receptor antagonist ketamine disrupt memory abilities in rodents. BNN27 is a synthetic analogue of dehydroepiandrosterone (DHEA) with potent antioxidant properties and its involvement in cognition has recently been shown. It is not yet clarified whether BNN27 can attenuate the cognition deficits induced by anesthetic ketamine. The present study was designed to elucidate this issue in the rat. For this purpose, the object recognition and the object location tests which are behavioral procedures evaluating non-spatial and spatial recognition memory respectively in rodents were used. The effects of compounds on motility were also tested utilizing a motor activity cage. Post-training administration of BNN27 (3 and 6 mg/kg, intraperitoneally) counteracted anesthetic ketamine (100 mg/kg, intraperitoneally)-induced non-spatial and spatial recognition memory deficits. Further, these effects cannot be attributed to changes to locomotor activity. Our findings clearly show the protective role of BNN27, on recognition memory impairment induced by anesthetic ketamine, indicating a functional interaction following co-administration of synthetic microneurotrophins and ketamine.

摘要

明显的实验证据表明,麻醉剂量的非竞争性 NMDA 受体拮抗剂氯胺酮会破坏啮齿动物的记忆能力。BNN27 是脱氢表雄酮 (DHEA) 的合成类似物,具有很强的抗氧化特性,其与认知的关系最近已经得到证实。目前尚不清楚 BNN27 是否可以减轻麻醉性氯胺酮引起的认知缺陷。本研究旨在阐明这一问题。为此,使用了评估啮齿动物非空间和空间识别记忆的物体识别和物体位置测试。还利用运动活动笼测试了化合物对运动能力的影响。BNN27(3 和 6mg/kg,腹腔内给药)在麻醉性氯胺酮(100mg/kg,腹腔内给药)诱导的非空间和空间识别记忆缺陷后给药,可拮抗其作用。此外,这些作用不能归因于运动活动的变化。我们的研究结果清楚地表明,BNN27 对麻醉性氯胺酮引起的识别记忆损伤具有保护作用,表明在给予合成微神经生长因子和氯胺酮后存在功能相互作用。

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