短期GABA拮抗剂治疗可改善唐氏综合征小鼠模型的长期睡眠质量、记忆力和决策能力。

IF 5.6 2区 医学 Q1 Medicine
Sleep Pub Date : 2025-05-12 DOI:10.1093/sleep/zsae300
Elsa C Pittaras, Jonathan M Artal, Grace Ajibola, Giancarlo Allocca, Mia Bennett, Alexandra Camargo, Angelica Carpio, Nicholas Gessner, Myles Hinton, Rebecca Pizzitola, Natalie Tan, Evelyn Zhang, Alan Zhong, Horace C Heller
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引用次数: 0

摘要

唐氏综合症(DS)是一种影响全世界人们的常见遗传病。它涉及到没有药物治疗的认知障碍。由于GABA拮抗剂治疗可恢复这些小鼠的记忆,DS小鼠Ts65Dn模型显示出由于神经元数量和连通性减少以及神经元活动过度而导致的认知障碍。我们的研究显示了GABA拮抗剂治疗对Ts65Dn小鼠睡眠和决策的影响。我们每天给Ts65Dn小鼠低剂量口服牛奶中的戊四唑(PTZ) 17天。采用PTZ治疗和不采用PTZ治疗对决策进行测试。在PTZ治疗前、治疗后和治疗后一个月分别测试短时记忆和长时记忆。在这三个时间点记录脑电图(EEG),以研究治疗对睡眠的影响。我们发现,PTZ治疗改善了长期认知,而不是短期记忆,并导致更多的Ts65Dn小鼠表现出更安全的决策行为。在Ts65Dn小鼠中,PTZ治疗通过减少整体清醒时间和增加NREM睡眠时间,显示出中度且仅整体有益的睡眠效果,这可能解释了观察到的认知改善。这些结果为GABA在退行性痴呆患者睡眠、记忆巩固和决策能力中的作用提供了新的认识。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Short-term γ-aminobutyric acid antagonist treatment improves long-term sleep quality, memory, and decision-making in a Down syndrome mouse model.

Down syndrome (DS) is a common genetic condition affecting people worldwide. It involves cognitive disabilities for which there are no drug therapies. The Ts65Dn mouse model of DS shows cognitive impairment due to a reduction in neuron number and connectivity as well as excessive neuronal activity, as γ-aminobutyric acid (GABA) antagonist treatment restores memory in these mice. Our study showed the effects of GABA antagonist treatment on sleep and decision-making in Ts65Dn mice. We administered a daily, low oral dose of pentylenetetrazol (PTZ) in milk to Ts65Dn mice for 17 days. Decision-making was tested with and without PTZ treatment. Short and long-term memories were tested before, immediately after, and 1 month following PTZ treatment. Electro-encephalography was also recorded at these three time points to study the effect of the treatment on sleep. We showed that PTZ treatment improved long-term recognition, but not short term memory and led to more Ts65Dn mice showing safer decision-making behavior. PTZ treatment showed a moderate and only global beneficial effect on sleep by decreasing the global amount of wake and increasing non-rapid eye movement sleep in the Ts65Dn mice, which may explain the observed cognitive improvements. These results bring new knowledge on the role of GABA in sleep, memory consolidation, and decision-making abilities in DS.

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来源期刊
Sleep
Sleep Medicine-Neurology (clinical)
CiteScore
8.70
自引率
10.70%
发文量
0
期刊介绍: SLEEP® publishes findings from studies conducted at any level of analysis, including: Genes Molecules Cells Physiology Neural systems and circuits Behavior and cognition Self-report SLEEP® publishes articles that use a wide variety of scientific approaches and address a broad range of topics. These may include, but are not limited to: Basic and neuroscience studies of sleep and circadian mechanisms In vitro and animal models of sleep, circadian rhythms, and human disorders Pre-clinical human investigations, including the measurement and manipulation of sleep and circadian rhythms Studies in clinical or population samples. These may address factors influencing sleep and circadian rhythms (e.g., development and aging, and social and environmental influences) and relationships between sleep, circadian rhythms, health, and disease Clinical trials, epidemiology studies, implementation, and dissemination research.
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