scholarly journals Plastin 3 Promotes Motor Neuron Axonal Growth and Extends Survival in a Mouse Model of Spinal Muscular Atrophy

2018 ◽  
Vol 9 ◽  
pp. 81-89 ◽  
Author(s):  
Aziza Alrafiah ◽  
Evangelia Karyka ◽  
Ian Coldicott ◽  
Kayleigh Iremonger ◽  
Katherin E. Lewis ◽  
...  
Keyword(s):  
Mouse Model ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Muscular Atrophy ◽  
Axonal Growth

scholarly journals Pre-symptomatic development of lower motor neuron connectivity in a mouse model of severe spinal muscular atrophy

2009 ◽  
Vol 19 (3) ◽  
pp. 420-433 ◽  
Author(s):  
Lyndsay M. Murray ◽  
Sheena Lee ◽  
Dirk Bäumer ◽  
Simon H. Parson ◽  
Kevin Talbot ◽  
...  
Keyword(s):  
Mouse Model ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Muscular Atrophy ◽  
Lower Motor Neuron

scholarly journals Ultrastructural characterization of peripheral denervation in a mouse model of Type III spinal muscular atrophy

2021 ◽  
Author(s):  
Federica Fulceri ◽  
Francesca Biagioni ◽  
Fiona Limanaqi ◽  
Carla L. Busceti ◽  
Larisa Ryskalin ◽  
...  
Keyword(s):  
Mouse Model ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Muscular Atrophy ◽  
Disease Onset ◽  
Muscle Spindles ◽  
Neuromuscular Disorder ◽  
Type Iii ◽  
Smn Protein

AbstractSpinal muscular atrophy (SMA) is a heritable, autosomal recessive neuromuscular disorder characterized by a loss of the survival of motor neurons (SMN) protein, which leads to degeneration of lower motor neurons, and muscle atrophy. Despite SMA being nosographically classified as a motor neuron disease, recent advances indicate that peripheral alterations at the level of the neuromuscular junction (NMJ), involving the muscle, and axons of the sensory-motor system, occur early, and may even precede motor neuron loss. In the present study, we used a mouse model of slow progressive (type III) SMA, whereby the absence of the mouse SMN protein is compensated by the expression of two human genes (heterozygous SMN1A2G, and SMN2). This leads to late disease onset and prolonged survival, which allows for dissecting slow degenerative steps operating early in SMA pathogenesis. In this purely morphological study carried out at transmission electron microscopy, we extend the examination of motor neurons and proximal axons towards peripheral components, including distal axons, muscle fibers, and also muscle spindles. We document remarkable ultrastructural alterations being consistent with early peripheral denervation in SMA, which may shift the ultimate anatomical target in neuromuscular disease from the spinal cord towards the muscle. This concerns mostly mitochondrial alterations within distal axons and muscle, which are quantified here through ultrastructural morphometry. The present study is expected to provide a deeper knowledge of early pathogenic mechanisms in SMA.

scholarly journals Stasimon Contributes to the Loss of Sensory Synapses and Motor Neuron Death in a Mouse Model of Spinal Muscular Atrophy

2019 ◽  
Author(s):  
Christian Simon ◽  
Meaghan Van Alstyne ◽  
Francesco Lotti ◽  
Elena Bianchetti ◽  
Sarah Tisdale ◽  
...  
Keyword(s):  
Mouse Model ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Muscular Atrophy ◽  
Neuron Death ◽  
Motor Neuron Death

scholarly journals Bone loss in survival motor neuron (Smn −/− SMN2 ) genetic mouse model of spinal muscular atrophy

2009 ◽  
Vol 219 (1) ◽  
pp. 52-60 ◽  
Author(s):  
Srinivasan Shanmugarajan ◽  
Eichi Tsuruga ◽  
Kathryn J Swoboda ◽  
Bernard L Maria ◽  
William L Ries ◽  
...  
Keyword(s):  
Bone Loss ◽  
Mouse Model ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Muscular Atrophy ◽  
Survival Motor Neuron ◽  
Genetic Mouse Model

scholarly journals IPLEX Administration Improves Motor Neuron Survival and Ameliorates Motor Functions in a Severe Mouse Model of Spinal Muscular Atrophy

2012 ◽  
Vol 18 (7) ◽  
pp. 1076-1085 ◽  
Author(s):  
Michela Murdocca ◽  
Arianna Malgieri ◽  
Andrea Luchetti ◽  
Luciano Saieva ◽  
Gabriella Dobrowolny ◽  
...  
Keyword(s):  
Mouse Model ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Muscular Atrophy ◽  
Motor Functions ◽  
Neuron Survival ◽  
Motor Neuron Survival

scholarly journals Stasimon Contributes to the Loss of Sensory Synapses and Motor Neuron Death in a Mouse Model of Spinal Muscular Atrophy

Cell Reports ◽  
2019 ◽  
Vol 29 (12) ◽  
pp. 3885-3901.e5 ◽  
Author(s):  
Christian M. Simon ◽  
Meaghan Van Alstyne ◽  
Francesco Lotti ◽  
Elena Bianchetti ◽  
Sarah Tisdale ◽  
...  
Keyword(s):  
Mouse Model ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Muscular Atrophy ◽  
Neuron Death ◽  
Motor Neuron Death

scholarly journals AAV9-Stathmin1 gene delivery improves disease phenotype in an intermediate mouse model of spinal muscular atrophy

2019 ◽  
Vol 28 (22) ◽  
pp. 3742-3754 ◽  
Author(s):  
E Villalón ◽  
R A Kline ◽  
C E Smith ◽  
Z C Lorson ◽  
E Y Osman ◽  
...  
Keyword(s):  
Mouse Model ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Muscular Atrophy ◽  
Genetic Disorder ◽  
Premature Death ◽  
Survival Motor Neuron ◽  
Motor Neuron Diseases ◽  
Smn Protein

Abstract Spinal muscular atrophy (SMA) is a devastating infantile genetic disorder caused by the loss of survival motor neuron (SMN) protein that leads to premature death due to loss of motor neurons and muscle atrophy. The approval of an antisense oligonucleotide therapy for SMA was an important milestone in SMA research; however, effective next-generation therapeutics will likely require combinatorial SMN-dependent therapeutics and SMN-independent disease modifiers. A recent cross-disease transcriptomic analysis identified Stathmin-1 (STMN1), a tubulin-depolymerizing protein, as a potential disease modifier across different motor neuron diseases, including SMA. Here, we investigated whether viral-based delivery of STMN1 decreased disease severity in a well-characterized SMA mouse model. Intracerebroventricular delivery of scAAV9-STMN1 in SMA mice at P2 significantly increased survival and weight gain compared to untreated SMA mice without elevating Smn levels. scAAV9-STMN1 improved important hallmarks of disease, including motor function, NMJ pathology and motor neuron cell preservation. Furthermore, scAAV9-STMN1 treatment restored microtubule networks and tubulin expression without affecting tubulin stability. Our results show that scAAV9-STMN1 treatment improves SMA pathology possibly by increasing microtubule turnover leading to restored levels of stable microtubules. Overall, these data demonstrate that STMN1 can significantly reduce the SMA phenotype independent of restoring SMN protein and highlight the importance of developing SMN-independent therapeutics for the treatment of SMA.

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