Deletion of <i>Sod1</i> in Motor Neurons Exacerbates Age-Related Changes in Axons and Neuromuscular Junctions in Mice.



Pollock, N, Macpherson, PC, Staunton, CA ORCID: 0000-0003-0647-3063, Hemmings, K, Davis, CS, Owen, ED, Vasilaki, A, Van Remmen, H, Richardson, A, McArdle, A
et al (show 2 more authors) (2023) Deletion of <i>Sod1</i> in Motor Neurons Exacerbates Age-Related Changes in Axons and Neuromuscular Junctions in Mice. eNeuro, 10 (3). ENEURO.0086-ENEU22.2023.

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Abstract

Whole-body knock-out of Cu,Zn superoxide dismutase (Sod1KO) results in accelerated, age-related loss of muscle mass and function associated with neuromuscular junction (NMJ) breakdown similar to sarcopenia. In order to determine whether altered redox in motor neurons underlies this phenotype, an inducible neuron-specific deletion of Sod1 (i-mnSod1KO) was compared with wild-type (WT) mice of different ages (adult, mid-age, and old) and whole-body Sod1KO mice. Nerve oxidative damage, motor neuron numbers and structural changes to neurons and NMJ were examined. Tamoxifen-induced deletion of neuronal Sod1 from two months of age. No specific effect of a lack of neuronal Sod1 was seen on markers of nerve oxidation (electron paramagnetic resonance of an <i>in vivo</i> spin probe, protein carbonyl, or protein 3-nitrotyrosine contents). i-mnSod1KO mice showed increased denervated NMJ, reduced numbers of large axons and increased number of small axons compared with old WT mice. A large proportion of the innervated NMJs in old i-mnSod1KO mice displayed a simpler structure than that seen in adult or old WT mice. Thus, previous work showed that neuronal deletion of Sod1 induced exaggerated loss of muscle in old mice, and we report that this deletion leads to a specific nerve phenotype including reduced axonal area, increased proportion of denervated NMJ, and reduced acetyl choline receptor complexity. Other changes in nerve and NMJ structure seen in the old i-mnSod1KO mice reflect aging of the mice.

Item Type: Article
Uncontrolled Keywords: axon, motor unit, oxidative stress, skeletal muscle
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 15 May 2023 07:45
Last Modified: 01 Jun 2023 00:31
DOI: 10.1523/eneuro.0086-22.2023
Open Access URL: https://www.eneuro.org/content/10/3/ENEURO.0086-22...
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3170318