Neuron-specific expression of CuZnSOD prevents the loss of muscle mass and function that occurs in homozygous CuZnSOD-knockout mice

Giorgos K. Sakellariou; Carol S. Davis; Yun Shi; Maxim V. Ivannikov; Yiqiang Zhang; Aphrodite Vasilaki; Gregory T. Macleod; Arlan Richardson; Holly Van Remmen; Malcolm J. Jackson; Anne McArdle; Susan V. Brooks

doi:10.1096/fj.13-240390

Neuron-specific expression of CuZnSOD prevents the loss of muscle mass and function that occurs in homozygous CuZnSOD-knockout mice

Giorgos K. Sakellariou, Carol S. Davis, Yun Shi, Maxim V. Ivannikov, Yiqiang Zhang, Aphrodite Vasilaki, Gregory T. Macleod, Arlan Richardson, Holly Van Remmen, Malcolm J. Jackson, Anne McArdle, Susan V. Brooks

Research output: Contribution to journal › Article › peer-review

68 Scopus citations

Abstract

Deletion of copper-zinc superoxide dismutase (CuZnSOD) in Sod1 ^-/- mice leads to accelerated loss of muscle mass and force during aging, but the losses do not occur with muscle-specific deletion of CuZnSOD. To determine the role of motor neurons in the muscle decline, we generated transgenic Sod1^-/- mice in which CuZnSOD was expressed under control of the synapsin 1 promoter (SynTgSod1^-/- mice). Syn- TgSod1 ^-/- mice expressed CuZnSOD in brain, spinal cord, and peripheral nerve, but not in other tissues. Sciatic nerve CuZnSOD content in SynTgSod1 ^-/- mice was ̃20% that of control mice, but no reduction in muscle mass or isometric force was observed in SynTg- Sod1^-/- mice compared with control animals, whereas muscles of age-matched Sod1^-/- mice displayed 30- 40% reductions in mass and force. In addition, increased oxidative damage and adaptations in stress responses observed in muscles of Sod1^-/- mice were absent in SynTgSod1^-/- mice, and degeneration of neuromuscular junction (NMJ) structure and function occurred in Sod1^-/- mice but not in SynTgSod1^-/- mice. Our data demonstrate that specific CuZnSOD expression in neurons is sufficient to preserve NMJ and skeletal muscle structure and function in Sod1^-/- mice and suggest that redox homeostasis in motor neurons plays a key role in initiating sarcopenia during aging.

Original language	English (US)
Pages (from-to)	1666-1681
Number of pages	16
Journal	FASEB Journal
Volume	28
Issue number	4
DOIs	https://doi.org/10.1096/fj.13-240390
State	Published - Apr 2014

Keywords

Heat-shock protein
Neuromuscular junction
Oxidative stress
SOD1

ASJC Scopus subject areas

Genetics
Molecular Biology
Biochemistry
Biotechnology

Access to Document

10.1096/fj.13-240390

Cite this

Sakellariou, G. K., Davis, C. S., Shi, Y., Ivannikov, M. V., Zhang, Y., Vasilaki, A., Macleod, G. T., Richardson, A., Van Remmen, H., Jackson, M. J., McArdle, A., & Brooks, S. V. (2014). Neuron-specific expression of CuZnSOD prevents the loss of muscle mass and function that occurs in homozygous CuZnSOD-knockout mice. FASEB Journal, 28(4), 1666-1681. https://doi.org/10.1096/fj.13-240390

Sakellariou, GK, Davis, CS, Shi, Y, Ivannikov, MV, Zhang, Y, Vasilaki, A, Macleod, GT, Richardson, A, Van Remmen, H, Jackson, MJ, McArdle, A & Brooks, SV 2014, 'Neuron-specific expression of CuZnSOD prevents the loss of muscle mass and function that occurs in homozygous CuZnSOD-knockout mice', FASEB Journal, vol. 28, no. 4, pp. 1666-1681. https://doi.org/10.1096/fj.13-240390

@article{90024abb5d234abbb81169e75b0f793c,

title = "Neuron-specific expression of CuZnSOD prevents the loss of muscle mass and function that occurs in homozygous CuZnSOD-knockout mice",

abstract = "Deletion of copper-zinc superoxide dismutase (CuZnSOD) in Sod1 -/- mice leads to accelerated loss of muscle mass and force during aging, but the losses do not occur with muscle-specific deletion of CuZnSOD. To determine the role of motor neurons in the muscle decline, we generated transgenic Sod1-/- mice in which CuZnSOD was expressed under control of the synapsin 1 promoter (SynTgSod1-/- mice). Syn- TgSod1 -/- mice expressed CuZnSOD in brain, spinal cord, and peripheral nerve, but not in other tissues. Sciatic nerve CuZnSOD content in SynTgSod1 -/- mice was{\~ }20% that of control mice, but no reduction in muscle mass or isometric force was observed in SynTg- Sod1-/- mice compared with control animals, whereas muscles of age-matched Sod1-/- mice displayed 30- 40% reductions in mass and force. In addition, increased oxidative damage and adaptations in stress responses observed in muscles of Sod1-/- mice were absent in SynTgSod1-/- mice, and degeneration of neuromuscular junction (NMJ) structure and function occurred in Sod1-/- mice but not in SynTgSod1-/- mice. Our data demonstrate that specific CuZnSOD expression in neurons is sufficient to preserve NMJ and skeletal muscle structure and function in Sod1-/- mice and suggest that redox homeostasis in motor neurons plays a key role in initiating sarcopenia during aging.",

keywords = "Heat-shock protein, Neuromuscular junction, Oxidative stress, SOD1",

author = "Sakellariou, {Giorgos K.} and Davis, {Carol S.} and Yun Shi and Ivannikov, {Maxim V.} and Yiqiang Zhang and Aphrodite Vasilaki and Macleod, {Gregory T.} and Arlan Richardson and {Van Remmen}, Holly and Jackson, {Malcolm J.} and Anne McArdle and Brooks, {Susan V.}",

year = "2014",

month = apr,

doi = "10.1096/fj.13-240390",

language = "English (US)",

volume = "28",

pages = "1666--1681",

journal = "FASEB Journal",

issn = "0892-6638",

publisher = "FASEB",

number = "4",

}

TY - JOUR

T1 - Neuron-specific expression of CuZnSOD prevents the loss of muscle mass and function that occurs in homozygous CuZnSOD-knockout mice

AU - Sakellariou, Giorgos K.

AU - Davis, Carol S.

AU - Shi, Yun

AU - Ivannikov, Maxim V.

AU - Zhang, Yiqiang

AU - Vasilaki, Aphrodite

AU - Macleod, Gregory T.

AU - Richardson, Arlan

AU - Van Remmen, Holly

AU - Jackson, Malcolm J.

AU - McArdle, Anne

AU - Brooks, Susan V.

PY - 2014/4

Y1 - 2014/4

N2 - Deletion of copper-zinc superoxide dismutase (CuZnSOD) in Sod1 -/- mice leads to accelerated loss of muscle mass and force during aging, but the losses do not occur with muscle-specific deletion of CuZnSOD. To determine the role of motor neurons in the muscle decline, we generated transgenic Sod1-/- mice in which CuZnSOD was expressed under control of the synapsin 1 promoter (SynTgSod1-/- mice). Syn- TgSod1 -/- mice expressed CuZnSOD in brain, spinal cord, and peripheral nerve, but not in other tissues. Sciatic nerve CuZnSOD content in SynTgSod1 -/- mice was ̃20% that of control mice, but no reduction in muscle mass or isometric force was observed in SynTg- Sod1-/- mice compared with control animals, whereas muscles of age-matched Sod1-/- mice displayed 30- 40% reductions in mass and force. In addition, increased oxidative damage and adaptations in stress responses observed in muscles of Sod1-/- mice were absent in SynTgSod1-/- mice, and degeneration of neuromuscular junction (NMJ) structure and function occurred in Sod1-/- mice but not in SynTgSod1-/- mice. Our data demonstrate that specific CuZnSOD expression in neurons is sufficient to preserve NMJ and skeletal muscle structure and function in Sod1-/- mice and suggest that redox homeostasis in motor neurons plays a key role in initiating sarcopenia during aging.

AB - Deletion of copper-zinc superoxide dismutase (CuZnSOD) in Sod1 -/- mice leads to accelerated loss of muscle mass and force during aging, but the losses do not occur with muscle-specific deletion of CuZnSOD. To determine the role of motor neurons in the muscle decline, we generated transgenic Sod1-/- mice in which CuZnSOD was expressed under control of the synapsin 1 promoter (SynTgSod1-/- mice). Syn- TgSod1 -/- mice expressed CuZnSOD in brain, spinal cord, and peripheral nerve, but not in other tissues. Sciatic nerve CuZnSOD content in SynTgSod1 -/- mice was ̃20% that of control mice, but no reduction in muscle mass or isometric force was observed in SynTg- Sod1-/- mice compared with control animals, whereas muscles of age-matched Sod1-/- mice displayed 30- 40% reductions in mass and force. In addition, increased oxidative damage and adaptations in stress responses observed in muscles of Sod1-/- mice were absent in SynTgSod1-/- mice, and degeneration of neuromuscular junction (NMJ) structure and function occurred in Sod1-/- mice but not in SynTgSod1-/- mice. Our data demonstrate that specific CuZnSOD expression in neurons is sufficient to preserve NMJ and skeletal muscle structure and function in Sod1-/- mice and suggest that redox homeostasis in motor neurons plays a key role in initiating sarcopenia during aging.

KW - Heat-shock protein

KW - Neuromuscular junction

KW - Oxidative stress

KW - SOD1

UR - http://www.scopus.com/inward/record.url?scp=84899563997&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899563997&partnerID=8YFLogxK

U2 - 10.1096/fj.13-240390

DO - 10.1096/fj.13-240390

M3 - Article

C2 - 24378874

AN - SCOPUS:84899563997

SN - 0892-6638

VL - 28

SP - 1666

EP - 1681

JO - FASEB Journal

JF - FASEB Journal

IS - 4

ER -

Neuron-specific expression of CuZnSOD prevents the loss of muscle mass and function that occurs in homozygous CuZnSOD-knockout mice

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this