Muscle-restricted Nox4 knockout partially corrects muscle contractility following spinal cord injury in mice

bioRxiv preprint, 2023 · DOI: https://doi.org/10.1101/2023.08.04.551985 · Published: August 4, 2023

Simple Explanation

Spinal cord injury (SCI) leads to muscle atrophy and reduced force in paralyzed areas. This study explores the role of Nox4, an enzyme, in this muscle weakness after SCI. The researchers used mice with a conditional knockout of Nox4 in muscle to see if removing Nox4 could improve muscle function after SCI. The results showed that removing Nox4 in muscle partially restored muscle force generation after SCI, suggesting a link between Nox4 and muscle weakness.

Study Duration

56 days

Participants

Mice (Nox4 cKO and Nox4(f/f) littermates)

Evidence Level

Not specified

Key Findings

1
Peak twitch force in control mice after SCI was reduced by 42% compared to sham-operated controls.
2
Peak twitch force was increased by approximately 43% in SCI Nox4 conditional KO mice compared to SCI controls.
3
Nox4(f/f) TA had significantly more carbonylated protein than Nox4 cKO mice, regardless of whether the animals received SCI or not.

Research Summary

This study investigates the role of Nox4 in reduced muscle specific force after spinal cord injury (SCI) using a conditional knockout mouse model. The results suggest a link between Nox4 expression in muscle tissue and reduction in muscle twitch force after SCI. Conditional inactivation of Nox4 in skeletal muscle improved muscle force generation in hindlimb muscles from mice with spinal cord transection.

Practical Implications

Therapeutic Target

Nox4 may be a potential therapeutic target for improving muscle function after SCI.

Underlying Mechanisms

Further research is needed to understand the exact mechanisms by which Nox4 affects muscle contractility after SCI.

Clinical Relevance

The findings offer encouraging evidence that some defects in skeletal muscle after SCI can be prevented over the long-term.

Study Limitations

1
Mechanisms by which reducing Nox4 expression in skeletal muscle increase muscle force generating capacity after SCI cannot be ascertained from the data here presented.
2
Why our results in Nox4(f/f) mice differ from those in Sprague Dawley rats we previously reported previously is unclear.
3
The Nox4 cKO reduced though did not eliminate Nox4 in whole lysates of skeletal muscle.

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