Universität zu Köln

Buettner, Jannik M., Longang, Josiane K. Sime, Gerstner, Florian, Apel, Katharina S., Blanco-Redondo, Beatriz, Sowoidnich, Leonie, Janzen, Eva, Langenhan, Tobias ORCID: 0000-0002-9061-3809, Wirth, Brunhilde ORCID: 0000-0003-4051-5191 and Simon, Christian M. (2021). Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models. iScience, 24 (11). CAMBRIDGE: CELL PRESS. ISSN 2589-0042

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Abstract

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 SMND7 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 Smn(2B)(/-) 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Buettner, Jannik M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Longang, Josiane K. Sime UNSPECIFIED UNSPECIFIED UNSPECIFIED Gerstner, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Apel, Katharina S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Blanco-Redondo, Beatriz UNSPECIFIED UNSPECIFIED UNSPECIFIED Sowoidnich, Leonie UNSPECIFIED UNSPECIFIED UNSPECIFIED Janzen, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Langenhan, Tobias UNSPECIFIED orcid.org/0000-0002-9061-3809 UNSPECIFIED Wirth, Brunhilde UNSPECIFIED orcid.org/0000-0003-4051-5191 UNSPECIFIED Simon, Christian M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-577577
DOI:	10.1016/j.isci.2021.103376
Journal or Publication Title:	iScience
Volume:	24
Number:	11
Date:	2021
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	2589-0042
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NEUROMUSCULAR-JUNCTION; NEURON PROTEIN; SELECTIVE VULNERABILITY; SMN DEFICIENCY; MECHANISMS; PHENOTYPE; SURVIVAL; DISEASE; MICE; SEVERITY Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57757