Evidence map›Paper›PMID 24971750›Full record

ArticlePloS one2014

The lack of CuZnSOD leads to impaired neurotransmitter release, neuromuscular junction destabilization and reduced muscle strength in mice.

Yun Shi, Maxim V Ivannikov, Michael E Walsh, Yuhong Liu, Yiqiang Zhang, Carlos A Jaramillo, Gregory T Macleod, Holly Van Remmen

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.

  1. Pooled it
  2. Trial
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  7. Review
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  10. Article
  11. Article
  12. Saffron (Nutrients · 2022
    Review
  13. Article
  14. Mouse models of sarcopenia: classification and evaluation.Journal of cachexia, sarcopenia and muscle · 2021
    Review
  15. Review
  16. Cancer cachexia in a mouse model of oxidative stress.Journal of cachexia, sarcopenia and muscle · 2020
    Article
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Yun ShiBarshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America; Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America; Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas, United States of America.
Maxim V IvannikovBarshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America; Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
Michael E WalshBarshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America; Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
Yuhong LiuBarshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America; Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America; Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas, United States of America.
Yiqiang ZhangBarshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America; Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
Carlos A JaramilloGeriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas, United States of America; Department of Rehabilitation Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
Gregory T MacleodDepartment of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
Holly Van RemmenBarshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America; Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America; Oklahoma City VA Medical Center, Oklahoma City, Oklahoma, United States of America.
The University of Texas Health Science Center at San Antonio · USOklahoma City VA Medical Center · USSouth Texas Veterans Health Care System · US

Funding

TRAINING GRANT ON THE BIOLOGY OF AGINGT32AG021890 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Erzsebet Kokovay, JAMES FLOYD NELSON · 2003 to 2026
$11.4M
TRANSGENIC ANIMAL CORE SUBCONTRACT WITH UTHSC AT SAN ANTONIOP01AG020591 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · PI BROOKS, SUSAN V · 2002 to 2014
$10.7M
The multiple roles of mitochondria in synaptic transmissionR01NS061914 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI MACLEOD, GREGORY TALISKER · 2008 to 2016
$2.6M
Testing the mechanisms by which NMJ disruption contributes to sarcopeniaI01BX002595 · VA · SOUTH TEXAS VETERANS HEALTH CARE SYSTEM · PI VAN REMMEN, HOLLY · 2015 to 2017
–
BLRD VA I01 BX002595NIA NIH HHS AG020591NIA NIH HHS P01 AG020591NIA NIH HHS T32 AG021890NIA NIH HHS T32-AG021890NINDS NIH HHS NS061914NINDS NIH HHS R01 NS061914
6 · The paper itself

Abstract

Elevated reactive oxygen species (ROS) production and ROS-dependent protein damage is a common observation in the pathogenesis of many muscle wasting disorders, including sarcopenia. However, the contribution of elevated ROS levels to -a breakdown in neuromuscular communication and muscle atrophy remains unknown. In this study, we examined a copper zinc superoxide dismutase [CuZnSOD (Sod1)] knockout mouse (Sod1-/-), a mouse model of elevated oxidative stress that exhibits accelerated loss of muscle mass, which recapitulates many phenotypes of sarcopenia as early as 5 months of age. We found that young adult Sod1-/- mice display a considerable reduction in hind limb skeletal muscle mass and strength when compared to age-matched wild-type mice. These changes are accompanied by gross alterations in neuromuscular junction (NMJ) morphology, including reduced occupancy of the motor endplates by axons, terminal sprouting and axon thinning and irregular swelling. Surprisingly however, the average density of acetylcholine receptors in endplates is preserved. Using in vivo electromyography and ex vivo electrophysiological studies of hind limb muscles in Sod1-/- mice, we found that motor axons innervating the extensor digitorum longus (EDL) and gastrocnemius muscles release fewer synaptic vesicles upon nerve stimulation. Recordings from individually identified EDL NMJs show that reductions in neurotransmitter release are apparent in the Sod1-/- mice even when endplates are close to fully innervated. However, electrophysiological properties, such as input resistance, resting membrane potential and spontaneous neurotransmitter release kinetics (but not frequency) are similar between EDL muscles of Sod1-/- and wild-type mice. Administration of the potassium channel blocker 3,4-diaminopyridine, which broadens the presynaptic action potential, improves both neurotransmitter release and muscle strength. Together, these results suggest that ROS-associated motor nerve terminal dysfunction is a contributor to the observed muscle changes in Sod1-/- mice.

Indexed as

Muscle StrengthAcetylcholineAnimalsMiceMuscle, SkeletalNeuromuscular JunctionReceptors, CholinergicSuperoxide DismutaseSuperoxide Dismutase-1Synaptic VesiclesAcetylcholineReceptors, CholinergicSod1 protein, mouseSuperoxide DismutaseSuperoxide Dismutase-1

Identifiers

PMID24971750
PMCPMC4074103
OpenAlexW2093474376

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.