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
{"title":"Short-term γ-aminobutyric acid antagonist treatment improves long-term sleep quality, memory, and decision-making in a Down syndrome mouse model.","authors":"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","doi":"10.1093/sleep/zsae300","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":22018,"journal":{"name":"Sleep","volume":" ","pages":""},"PeriodicalIF":5.6000,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Sleep","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/sleep/zsae300","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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.