ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Impaired synaptic vesicle release and immaturity of neuromuscular junctions in spinal muscular atrophy mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 248 papers, 3 of them syntheses that pooled it.
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Who cites it
248 citing papers in PubMed, 3 syntheses or guidelines pooled it, 387 citations in OpenAlex.
- Salbutamol in 5q spinal muscular atrophy: a systematic review and meta-analysis of efficacy and safety.European journal of pediatrics · 2025Pooled it
- A molecular systems architecture of neuromuscular junction in amyotrophic lateral sclerosis.NPJ systems biology and applications · 2025Pooled it
- Drug treatment for spinal muscular atrophy types II and III.The Cochrane database of systematic reviews · 2020Pooled it
- Maternal-Fetal Administration of Risdiplam Partially Rescues the SMNΔ7 Mouse Model of Spinal Muscular Atrophy.Annals of neurology · 2026Article
- Survival Motor Neuron Protein Requirement-Supply Mismatch in Spinal Muscular Atrophy: A Conceptual Framework.Advances in therapy · 2026Review
- Organ-specific redox imbalances in spinal muscular atrophy mice are partially rescued by SMN antisense oligonucleotides.FEBS letters · 2026Article
- Extracellular vesicles as biomarkers of disease progression and therapeutic response in patients with spinal muscular atrophy.Molecular therapy. Advances · 2026Article
- Junctions in Jeopardy: the neuromuscular junction is a selective pathological target in Charcot-Marie-Tooth disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Nanotube-Assisted Motor Neuron and Neuromuscular Junction Stabilization in Spinal Muscular Atrophy: A Hypothesis for Adjunctive Therapy.Neurology international · 2026Review
- Article
- Astrocyte targeted SMN1 gene therapy and forskolin application improves astrocyte filopodia actin defects and motor neuron synaptic dysfunction in human SMA disease pathology.bioRxiv : the preprint server for biology · 2026Article
- Therapeutic strategies for spinal muscular atrophy: the history and future perspective.Frontiers in human neuroscience · 2026Review
- Immaturity of the neuromuscular junction in spinal muscular atrophy mouse models.Frontiers in cellular neuroscience · 2026Review
- Spinal muscular atrophy in the disease-modifying therapy era: successes, limitations and future directions.Frontiers in molecular medicine · 2026Review
- The Ighmbp2-R604X mouse presents with the most severe SMARD1 clinical symptoms resulting in failure to thrive, respiratory and feeding deficits, aspiration and severe axon and muscle pathology.Neurobiology of disease · 2025Article
- The Neuromuscular Junction: A Shared Vulnerability in Aging and Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Epigenetic Mechanisms Shaping Spine Regulation: Unveiling the Role of Cytoskeletal Dynamics and Localized Protein Synthesis.Molecular neurobiology · 2025Review
- Cerebellar defects are a primary pathology in mouse models of spinal muscular atrophy.Brain pathology (Zurich, Switzerland) · 2025Article
- Munc13-1 restoration mitigates presynaptic pathology in spinal muscular atrophy.Nature communications · 2025Article
- Loss of synaptic Munc13-1 underlies neurotransmission abnormalities in spinal muscular atrophy.Cellular and molecular life sciences : CMLS · 2025Article
188 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The motor neuron disease spinal muscular atrophy (SMA) causes profound muscle weakness that most often leads to early death. At autopsy, SMA is characterized by loss of motor neurons and muscle atrophy, but the initial cellular events that precipitate motor unit dysfunction and loss remain poorly characterized. Here, we examined the function and corresponding structure of neuromuscular junction (NMJ) synapses in a mouse model of severe SMA (hSMN2/delta7SMN/mSmn-/-). Surprisingly, most SMA NMJs remained innervated even late in the disease course; however they showed abnormal synaptic transmission. There was a two-fold reduction in the amplitudes of the evoked endplate currents (EPCs), but normal spontaneous miniature EPC (MEPC) amplitudes. These features in combination indicate reduced quantal content. SMA NMJs also demonstrated increased facilitation suggesting a reduced probability of vesicle release. By electron microscopy, we found a decreased density of synaptic vesicles that is likely to contribute to the reduced release probability. In addition to presynaptic defects, there were postsynaptic abnormalities. EPC and MEPC decay time constants were prolonged because of a slowed switch from the fetal acetylcholine receptor (AChR) gamma-subunit to the adult epsilon-subunit. There was also reduced size of AChR clusters and small myofibers, which expressed an immature pattern of myosin heavy chains. Together these results indicate that impaired synaptic vesicle release at NMJs in severe SMA is likely to contribute to failed postnatal maturation of motor units and muscle weakness.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.