文章基本信息

标题：Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models
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作者：Jannik M. Buettner ; Josiane K. Sime Longang ; Florian Gerstner 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：11
页码：1-27
DOI：10.1016/j.isci.2021.103376
语种：English
出版社：Elsevier
摘要：SummarySpinal muscular atrophy (SMA) is a neurodegenerative disease caused by reduced survival motor neuron (SMN) protein. Recently, SMN dysfunction has been linked to individual aspects of motor circuit pathology in a severe SMA mouse model. To determine whether these disease mechanisms are conserved, we directly compared the motor circuit pathology of three SMA mouse models. The severeSMNΔ7model exhibits vast motor circuit defects, including degeneration of motor neurons, spinal excitatory synapses, and neuromuscular junctions (NMJs). In contrast, theTaiwanesemodel shows very mild motor neuron pathology, but early central synaptic loss. In the intermediateSmn2B/-model, strong pathology of central excitatory synapses and NMJs precedes the late onset of p53-dependent motor neuron death. These pathological events correlate with SMN-dependent splicing dysregulation of specific mRNAs. Our study provides a knowledge base for properly tailoring future studies and identifies central excitatory synaptopathy as a key feature of motor circuit pathology in SMA.Graphical abstractDisplay OmittedHighlights•Comparison of detailed motor circuit pathology across three SMA mouse models•Motor circuit pathology correlates with dysregulation of specific mRNAs•Motor neuron death in severe and intermediate SMA models is p53-dependent•Central excitatory synaptopathy is the most conserved feature of SMA pathologyMolecular biology; Neuroscience; Molecular neuroscience