Synaptic Defects in the Spinal and Neuromuscular Circuitry in a Mouse Model of Spinal Muscular Atrophy

Hdl Handle:
http://hdl.handle.net/10675.2/608
Title:
Synaptic Defects in the Spinal and Neuromuscular Circuitry in a Mouse Model of Spinal Muscular Atrophy
Authors:
Ling, Karen K. Y.; Lin, Ming-Yi; Zingg, Brian; Feng, Zhihua; Ko, Chien-Ping
Abstract:
Spinal muscular atrophy (SMA) is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNÎ 7). In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs) in hindlimb muscles of SMNÎ 7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a â ¼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3â 5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1)-positive synapses onto SMNÎ 7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNÎ 7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNÎ 7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy.
Editors:
Mei, Lin
Citation:
PLoS One. 2010 Nov 11; 5(11):e15457
Issue Date:
11-Nov-2010
URI:
http://hdl.handle.net/10675.2/608
DOI:
10.1371/journal.pone.0015457
PubMed ID:
21085654
PubMed Central ID:
PMC2978709
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Neurology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorLing, Karen K. Y.en_US
dc.contributor.authorLin, Ming-Yien_US
dc.contributor.authorZingg, Brianen_US
dc.contributor.authorFeng, Zhihuaen_US
dc.contributor.authorKo, Chien-Pingen_US
dc.contributor.editorMei, Lin-
dc.date.accessioned2012-10-26T16:26:52Z-
dc.date.available2012-10-26T16:26:52Z-
dc.date.issued2010-11-11en_US
dc.identifier.citationPLoS One. 2010 Nov 11; 5(11):e15457en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid21085654en_US
dc.identifier.doi10.1371/journal.pone.0015457en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/608-
dc.description.abstractSpinal muscular atrophy (SMA) is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNÎ 7). In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs) in hindlimb muscles of SMNÎ 7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a â ¼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3â 5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1)-positive synapses onto SMNÎ 7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNÎ 7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNÎ 7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy.en_US
dc.rightsLing et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectNeuroscienceen_US
dc.subjectCellular Neuroscienceen_US
dc.subjectNeuronal Morphologyen_US
dc.subjectNeurophysiologyen_US
dc.subjectNeuromuscular Junctionen_US
dc.subjectNeurobiology of Disease and Regenerationen_US
dc.subjectMedicineen_US
dc.subjectNeurologyen_US
dc.subjectNeuromuscular Diseasesen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAxonsen_US
dc.subject.meshDisease Models, Animalen_US
dc.subject.meshDisease Progressionen_US
dc.subject.meshElectrophysiologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshGanglia, Spinalen_US
dc.subject.meshHindlimben_US
dc.subject.meshImmunohistochemistryen_US
dc.subject.meshMaleen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Transgenicen_US
dc.subject.meshMotor Neuronsen_US
dc.subject.meshMuscle, Skeletalen_US
dc.subject.meshMuscular Atrophy, Spinalen_US
dc.subject.meshNeuromuscular Junctionen_US
dc.subject.meshProprioceptionen_US
dc.subject.meshReceptors, Cholinergicen_US
dc.subject.meshSpinal Corden_US
dc.subject.meshSpinal Nerve Rootsen_US
dc.subject.meshSynapsesen_US
dc.titleSynaptic Defects in the Spinal and Neuromuscular Circuitry in a Mouse Model of Spinal Muscular Atrophyen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC2978709en_US
dc.contributor.corporatenameDepartment of Neurology-
dc.contributor.corporatenameCollege of Graduate Studies-

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