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  4. The Human ApoE4 Variant Reduces Functional Recovery and Neuronal Sprouting After Incomplete Spinal Cord Injury in Male Mice

The Human ApoE4 Variant Reduces Functional Recovery and Neuronal Sprouting After Incomplete Spinal Cord Injury in Male Mice

Frontiers in Cellular Neuroscience, 2021 · DOI: 10.3389/fncel.2021.626192 · Published: February 18, 2021

Spinal Cord InjuryGeneticsNeuroplasticity

Simple Explanation

This study investigates how different versions of the ApoE gene (ApoE3 and ApoE4) affect recovery after spinal cord injury (SCI) in mice. Mice with the ApoE4 gene showed worse motor function and coordination after SCI compared to those with ApoE3. The researchers found that ApoE4 mice had more glial cell activity and less nerve fiber sprouting in the injured area. This suggests that ApoE4 may hinder the nervous system's ability to repair itself after SCI. The study also looked at gene activity in the spinal cord after SCI. They discovered that ApoE4 mice had increased activity in genes related to inflammation, while ApoE3 mice had increased activity in genes related to nerve cell development.

Study Duration
28 days
Participants
Transgenic mice expressing human ApoE3 or ApoE4
Evidence Level
Not specified

Key Findings

  • 1
    ApoE4 mice showed worse locomotor function and coordination after SCI compared to ApoE3 mice, as measured by the Basso Mouse Scale (BMS) and ladder rung walk test (LRWT).
  • 2
    Histological examination revealed greater glial staining (GFAP and IBA-1) in ApoE4 mice after SCI, indicating increased glial activation and inflammatory responses compared to ApoE3 mice.
  • 3
    RNA sequencing showed upregulation of genes related to extracellular matrix organization and inflammatory responses in ApoE4 mice at 7 days after SCI, while genes related to neuronal action potential and neuron projection development were increased in ApoE3 mice at 21 days.

Research Summary

This study examined the impact of ApoE variants on functional recovery after spinal cord injury (SCI) in transgenic mice expressing either human ApoE3 or ApoE4. The findings indicate that ApoE4 mice exhibit impaired locomotor function and reduced coordination compared to ApoE3 mice following SCI. Histological analysis revealed that ApoE4 mice had increased glial activation and reduced neuronal sprouting markers in the injured spinal cord, suggesting that ApoE4 hinders neuroplasticity and repair mechanisms after SCI. Transcriptomic profiling showed that ApoE4 mice had an initial inflammatory response characterized by extracellular matrix organization, while ApoE3 mice showed increased expression of genes related to neuronal action potential and neuron projection development at later time points.

Practical Implications

Therapeutic targets

Targeting glial activation and promoting neuronal sprouting may improve outcomes after SCI, particularly in individuals with the ApoE4 allele.

Personalized medicine

ApoE genotype could be used as a biomarker to predict recovery potential after SCI and tailor rehabilitation strategies accordingly.

Further research

Future studies should investigate the specific molecular mechanisms by which ApoE4 impairs neuronal sprouting and exacerbates glial activation after SCI.

Study Limitations

  • 1
    The study was conducted in mice, and the results may not directly translate to humans.
  • 2
    The study focused on male mice, and further research is needed to determine if the findings are similar in females.
  • 3
    The study only examined one specific type of SCI (moderate contusion), and the effects of ApoE variants may differ in other types of SCI.

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