Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models

Summary: Spinal 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 conse...

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Autores principales:	Jannik M. Buettner, Josiane K. Sime Longang, Florian Gerstner, Katharina S. Apel, Beatriz Blanco-Redondo, Leonie Sowoidnich, Eva Janzen, Tobias Langenhan, Brunhilde Wirth, Christian M. Simon
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Molecular biology Neuroscience Molecular neuroscience Science Q
Acceso en línea:	https://doaj.org/article/876d4240d23740fc9dadab41c2948ab4
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spelling	oai:doaj.org-article:876d4240d23740fc9dadab41c2948ab42021-11-20T05:10:52ZCentral synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models2589-004210.1016/j.isci.2021.103376https://doaj.org/article/876d4240d23740fc9dadab41c2948ab42021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S258900422101347Xhttps://doaj.org/toc/2589-0042Summary: Spinal 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 severe SMNΔ7 model exhibits vast motor circuit defects, including degeneration of motor neurons, spinal excitatory synapses, and neuromuscular junctions (NMJs). In contrast, the Taiwanese model shows very mild motor neuron pathology, but early central synaptic loss. In the intermediate Smn2B/- 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.Jannik M. BuettnerJosiane K. Sime LongangFlorian GerstnerKatharina S. ApelBeatriz Blanco-RedondoLeonie SowoidnichEva JanzenTobias LangenhanBrunhilde WirthChristian M. SimonElsevierarticleMolecular biologyNeuroscienceMolecular neuroscienceScienceQENiScience, Vol 24, Iss 11, Pp 103376- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Molecular biology Neuroscience Molecular neuroscience Science Q
spellingShingle	Molecular biology Neuroscience Molecular neuroscience Science Q Jannik M. Buettner Josiane K. Sime Longang Florian Gerstner Katharina S. Apel Beatriz Blanco-Redondo Leonie Sowoidnich Eva Janzen Tobias Langenhan Brunhilde Wirth Christian M. Simon Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models
description	Summary: Spinal 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 severe SMNΔ7 model exhibits vast motor circuit defects, including degeneration of motor neurons, spinal excitatory synapses, and neuromuscular junctions (NMJs). In contrast, the Taiwanese model shows very mild motor neuron pathology, but early central synaptic loss. In the intermediate Smn2B/- 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.
format	article
author	Jannik M. Buettner Josiane K. Sime Longang Florian Gerstner Katharina S. Apel Beatriz Blanco-Redondo Leonie Sowoidnich Eva Janzen Tobias Langenhan Brunhilde Wirth Christian M. Simon
author_facet	Jannik M. Buettner Josiane K. Sime Longang Florian Gerstner Katharina S. Apel Beatriz Blanco-Redondo Leonie Sowoidnich Eva Janzen Tobias Langenhan Brunhilde Wirth Christian M. Simon
author_sort	Jannik M. Buettner
title	Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models
title_short	Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models
title_full	Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models
title_fullStr	Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models
title_full_unstemmed	Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models
title_sort	central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/876d4240d23740fc9dadab41c2948ab4
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Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models

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