Article record

儿童阻塞性睡眠呼吸暂停小鼠模型中的发育性髓鞘形成缺陷与精细运动功能受损

Developmental myelination deficits and impaired fine motor function in a mouse model of pediatric obstructive sleep apnea.

基础研究耳科IF 5.3Q1

文献信息

PMID	42710774
原文	在 PubMed 查看原文 ↗
发表日期	2026
作者	Mahyar J Hedayatpour 查看其他 11 位作者 Roshan Ailani；Michael R Williamson；Steen Erik Pedersen；Robia Pautler；Mathilda S Nicot-Cartsonis；Adam C Adler；Farrah Kheradmand；Benjamin Deneen；Akdes Serin Harmanci；Hyun Kyoung Lee；Arvind Chandrakantan
作者单位	Department of Anesthesiology, Perioperative and Pain Medicine, Texas Children's Hospital, Houston, TX, USA; Department of Anesthesiology, Baylor College of Medicine, Houston, TX, USA. 查看其他 10 条单位信息 Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA.；Neurosciences and Mental Health Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada.；Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA.；Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA; Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA; Small Animal Imaging Facility, Texas Children's Hospital, Houston, TX, USA; Department of Radiology, Baylor College of Medicine, Houston, TX, USA.；Department of Surgery, Baylor College of Medicine, Houston, TX, USA.；Translational Biology and Molecular Medicine Program, Baylor College of Medicine, Houston, TX, USA; Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA; Center for Translational Research in Inflammatory Diseases, Michael E. DeBakey VA, Houston, TX, USA; Biology of Inflammation Center, Baylor College of Medicine, Houston, TX, USA.；Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, USA; Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.；Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.；Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.；Department of Anesthesiology, Perioperative and Pain Medicine, Texas Children's Hospital, Houston, TX, USA; Department of Anesthesiology, Baylor College of Medicine, Houston, TX, USA. Electronic address: chandrak@bcm.edu.
期刊	Experimental neurology
SCI 分区	Q1
IF	5.3
研究类型	基础研究 · 基础／转化
所属专科	耳科

中文摘要

研究目的： 我们的主要目标是利用该疾病的临床前小鼠模型，阐明儿童阻塞性睡眠呼吸暂停（POSA）中精细运动缺陷的潜在机制。我们的目标是采用系统化方法，表征POSA小鼠的神经解剖学病变，并确定这一POSA临床前模型中精细运动改变的潜在分子驱动因素。
方法： 我们使用已建立的POSA小鼠模型，通过四种方法表征精细运动缺陷：a）神经行为学运动功能缺陷，重点关注精细运动与粗大运动技能；b）静息态功能磁共振成像（rs-fMRI）以及弥散张量成像（DTI）；c）使用谱系追踪小鼠对少突胶质细胞标志物进行免疫染色；d）使用单核RNA测序分析少突胶质细胞转录组。
结果： 与对照组相比，POSA小鼠表现出精细运动功能缺陷，而粗大运动功能未见改变。DTI显示两组在粗大运动纤维束成像方面无显著差异；然而，rs-fMRI揭示了POSA小鼠存在区域间连接差异。免疫染色显示，与对照组相比，POSA小鼠的少突胶质细胞祖细胞较少，而成熟少突胶质细胞未见减少。POSA小鼠的少突胶质细胞转录组鉴定出许多参与少突胶质细胞功能和分化的上调和下调基因。
结论： 与POSA的神经学发现一致，这些POSA小鼠表现出精细运动技能缺陷。神经回路破坏的分子机制涉及发育性髓鞘形成的丧失，这可能促成POSA中的精细运动损害。

英文摘要

STUDY OBJECTIVES: Our primary objective was to characterize the mechanism that underlies fine motor deficits in Pediatric obstructive sleep apnea (POSA) using a preclinical mouse model of the disease. Our goal was to use a systematic approach to characterize neuroanatomical lesions in POSA mice and identify potential molecular drivers of the fine motor changes in this preclinical model of POSA.
METHODS: We used our established mouse model of POSA to characterize fine motor deficits using four approaches: a) neurobehavioral deficiencies in motor function with a focus on fine versus gross motor skills; b) resting state functional magnetic resonance imaging (rs-fMRI) as well as diffusion tension imaging (DTI); c) immunostaining of oligodendrocyte markers using a lineage tracing mouse, and d) the oligodendrocyte transcriptome using single-nucleus RNA sequencing.
RESULTS: POSA mice showed deficits in fine motor function without changes in gross motor function when compared with controls. DTI showed no significant differences between groups in gross motor tractography; however, rs-fMRI revealed region-to-region connection differences in POSA mice. Immunostaining showed fewer oligodendrocyte progenitor cells with no reduction in mature oligodendrocytes in POSA mice as compared to controls. The oligodendrocyte transcriptome in POSA mice identified many upregulated and downregulated genes involved in oligodendrocyte function and differentiation.
CONCLUSIONS: Consistent with neurological findings in POSA, these POSA mice showed deficits in fine motor skills. The molecular mechanism for the disruption of neuronal circuits involved the loss of developmental myelination, which may contribute to fine motor impairments in POSA.