Contusion spinal cord injury upregulates p53 protein expression in rat soleus muscle at multiple timepoints but not key senescence cytokines

Physiological Reports, 2020 · DOI: 10.14814/phy2.14357 · Published: January 1, 2020

Spinal Cord Injury Aging Musculoskeletal Medicine

Simple Explanation

This study investigates the impact of spinal cord injury (SCI) on muscle health, specifically looking at cellular senescence. Cellular senescence is a process where cells stop dividing and signal for immune clearance. The researchers examined whether muscle disuse after SCI leads to elevated markers of senescence in paralyzed skeletal muscle. The research focused on the soleus muscle of rats with SCI, analyzing the expression of senescence markers like p53, p27, and p16, as well as inflammatory cytokines. The goal was to determine if muscle disuse leads to changes in the time course of pro-inflammatory cytokine expression associated with SASP across the acute, subacute, and early chronic phases of SCI in rats The findings revealed a sustained elevation in p53 protein expression but no corresponding increase in inflammatory cytokine gene expression. This suggests that paralyzed skeletal muscle may not undergo accelerated cellular senescence in the early stages of paralysis.

Study Duration

2 weeks, 1 month, 2 months, or 3 months

Participants

48 male Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
SCI soleus muscle displayed 2- to 3-fold higher total p53 protein expression at 2 weeks, and at 1 and 2 months when compared with Sham.
2
p16 protein expression was lower at 3 months in SCI versus Sham, but not earlier timepoints.
3
There were no main effects for time or surgery for IL-1α, IL-1β, or CXCL1, but targeted t tests showed reductions in IL-1α and CXCL1 in SCI animals compared to Sham at 3 months and IL-1β was reduced in SCI animals compared to Sham animals at the 2-month timepoint.

Research Summary

The study investigated whether muscle disuse following spinal cord injury (SCI) induces cellular senescence and markers of senescence-associated secretory phenotypes (SASPs) in paralyzed skeletal muscle of rats. The researchers monitored protein and gene expression of senescence markers and cytokines in the soleus muscle of rats with contusion SCI over a period of 3 months. The results showed that SCI led to a sustained elevation in total p53 protein expression during the acute and subacute phases, but this was not accompanied by increased levels of inflammatory cytokine gene expression. In fact, some cytokines were downregulated in the early chronic phase of SCI. The findings suggest that paralyzed skeletal muscle does not exhibit a senescent phenotype in the early stages of paralysis, despite the elevation in p53. This indicates that the mechanisms driving muscle atrophy after SCI may not be directly linked to SASP induction.

Practical Implications

Muscle Atrophy Mechanisms

The study suggests that muscle atrophy after SCI may not be primarily driven by cellular senescence and SASP, prompting further investigation into alternative mechanisms.

Therapeutic Targets

The sustained elevation of p53 protein expression without increased SASP suggests that targeting p53 directly might be a more effective strategy for mitigating muscle atrophy after SCI.

Further Research

Future studies should investigate the specific role of p53 in muscle atrophy after SCI, as well as explore the involvement of other cell types and signaling pathways.

Study Limitations

1
The use of whole muscle homogenates limits the ability to identify the specific cell types contributing to cytokine expression.
2
The study focuses on a specific time frame (up to 3 months) and may not capture later changes in senescence markers and cytokine expression.
3
The rodent model may not fully reflect the complexities of muscle atrophy and senescence in humans with SCI.

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