Simon J. Guillot, Christina Lang, Marie Simonot, Daniel Beckett, Dorothée Lulé, Luisa T. Balz, Antje Knehr, Geoffrey Stuart-Lopez, Pauline Vercruysse, Stéphane Dieterlé, Patrick Weydt, Johannes Dorst, Katharina Kandler, Jan Kassubek, Laura Wassermann, Caroline Rouaux, Sébastien Arthaud, Sandrine Da Cruz, Pierre-Hervé Luppi, Francesco Roselli, Albert C. Ludolph, Luc Dupuis, Matei Bolborea
{"title":"Early-onset sleep alterations found in patients with amyotrophic lateral sclerosis are ameliorated by orexin antagonist in mouse models","authors":"Simon J. Guillot, Christina Lang, Marie Simonot, Daniel Beckett, Dorothée Lulé, Luisa T. Balz, Antje Knehr, Geoffrey Stuart-Lopez, Pauline Vercruysse, Stéphane Dieterlé, Patrick Weydt, Johannes Dorst, Katharina Kandler, Jan Kassubek, Laura Wassermann, Caroline Rouaux, Sébastien Arthaud, Sandrine Da Cruz, Pierre-Hervé Luppi, Francesco Roselli, Albert C. Ludolph, Luc Dupuis, Matei Bolborea","doi":"10.1126/scitranslmed.adm7580","DOIUrl":null,"url":null,"abstract":"<div >Sleep alterations have been described in several neurodegenerative diseases yet are currently poorly characterized in amyotrophic lateral sclerosis (ALS). This study investigates sleep macroarchitecture and related hypothalamic signaling disruptions in ALS. Using polysomnography, we found that both patients with ALS as well as asymptomatic <i>C9ORF72</i> and <i>SOD1</i> mutation carriers exhibited increased wakefulness and reduced non–rapid eye movement sleep. Increased wakefulness correlated with diminished cognitive performance in both clinical cohorts. Similar changes in sleep macroarchitecture were observed in three ALS mouse models (<i>Sod1<sup>G86R</sup></i>, <i>Fus</i><sup>Δ<i>NLS/+</i></sup>, and <i>TDP43<sup>Q331K</sup></i>). A single oral administration of a dual-orexin receptor antagonist or intracerebroventricular delivery of melanin-concentrating hormone (MCH) through an osmotic pump over 15 days partially normalized sleep patterns in mouse models. MCH treatment did not extend the survival of <i>Sod1<sup>G86R</sup></i> mice but did decrease the loss of lumbar motor neurons. These findings suggest MCH and orexin signaling as potential targets to treat sleep alterations that arise in early stages of the disease.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 783","pages":""},"PeriodicalIF":14.6000,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/scitranslmed.adm7580","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Translational Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.science.org/doi/10.1126/scitranslmed.adm7580","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Sleep alterations have been described in several neurodegenerative diseases yet are currently poorly characterized in amyotrophic lateral sclerosis (ALS). This study investigates sleep macroarchitecture and related hypothalamic signaling disruptions in ALS. Using polysomnography, we found that both patients with ALS as well as asymptomatic C9ORF72 and SOD1 mutation carriers exhibited increased wakefulness and reduced non–rapid eye movement sleep. Increased wakefulness correlated with diminished cognitive performance in both clinical cohorts. Similar changes in sleep macroarchitecture were observed in three ALS mouse models (Sod1G86R, FusΔNLS/+, and TDP43Q331K). A single oral administration of a dual-orexin receptor antagonist or intracerebroventricular delivery of melanin-concentrating hormone (MCH) through an osmotic pump over 15 days partially normalized sleep patterns in mouse models. MCH treatment did not extend the survival of Sod1G86R mice but did decrease the loss of lumbar motor neurons. These findings suggest MCH and orexin signaling as potential targets to treat sleep alterations that arise in early stages of the disease.
期刊介绍：
Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research.
The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases.
The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine.
The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
