Synaptojanin 1 Modulates Functional Recovery After Incomplete Spinal Cord Injury in Male Apolipoprotein E Epsilon 4 Mice

Neurotrauma Reports, 2023 · DOI: 10.1089/neur.2023.0023 · Published: January 1, 2023

Simple Explanation

This study investigates the role of synaptojanin 1 (synj1) in recovery after spinal cord injury (SCI) in mice with the Apolipoprotein E epsilon 4 (ApoE4) variant. ApoE4 is a genetic risk factor for poor outcomes after SCI, and it is linked to elevated levels of synj1. The researchers found that reducing synj1 levels in ApoE4 mice improved their locomotor function recovery after SCI.

Study Duration

14 days

Participants

Male ApoE3 and ApoE4 mice with synj1+/+ or synj1+/– backgrounds

Evidence Level

Not specified

Key Findings

1
ApoE4 mice had elevated synj1 mRNA and protein levels in their spinal cords, along with lower PIP2 levels, compared to ApoE3 mice.
2
Genetic reduction of synj1 improved locomotor function recovery in ApoE4 mice 14 days after SCI, without altering spared white matter.
3
In ApoE4 mice, genetic reduction of synj1 upregulated genes involved in glutaminergic synaptic transmission near the lesion site.

Research Summary

The study aimed to investigate the role of synj1 in locomotor function recovery after SCI in ApoE4 mice. Researchers found that ApoE4 mice had higher synj1 expression and lower PIP2 levels in spinal cord tissue compared to ApoE3 mice. Genetically reducing synj1 improved locomotor function in ApoE4 mice after SCI, suggesting a link between synj1 and poor outcomes after SCI in ApoE4 mice.

Practical Implications

Potential Therapeutic Target

Synj1 could be a potential therapeutic target for improving functional recovery after SCI, particularly in individuals with the ApoE4 variant.

Personalized Medicine

Effective, personalized therapies could be developed to improve functional recovery of those who have a new SCI that involve manipulating levels of genes dysregulated by commonly occurring genetic variants.

Understanding Genetic Variability

Further study of the differential effects of ApoE variants on functional recovery after SCI is warranted to improve treatments.

Study Limitations

1
The study was conducted only on male mice, so the results may not be generalizable to females.
2
The study duration was limited to 14 days post-injury, which may not be sufficient to assess long-term functional recovery.
3
The mechanisms by which synj1 upregulation in ApoE4 mice blunts locomotor functional recovery are unclear.

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