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  4. Up-Regulation of Astrocytic Fgfr4 Expression in Adult Mice after Spinal Cord Injury

Up-Regulation of Astrocytic Fgfr4 Expression in Adult Mice after Spinal Cord Injury

Cells, 2023 · DOI: 10.3390/cells12040528 · Published: February 6, 2023

Spinal Cord InjuryNeurologyGenetics

Simple Explanation

Spinal cord injuries (SCI) can lead to long-term neurological problems, and effective treatments are lacking. Astrocytes, a type of brain cell, change after a spinal cord injury. This study explores using gene therapy to increase the amount of a protein called Fgfr4 in astrocytes after SCI in mice. The researchers found that increasing Fgfr4 in astrocytes immediately after injury improved the recovery of motor skills. However, the effect might be different in male and female mice. The improvement was linked to less damage in the spinal cord and less reactivity from glial cells. The study also found that certain cell signals, like Notch signaling, decreased, while other signals related to creating new nerve cells increased in astrocytes that were changing after the injury. The results suggest that using gene therapy to increase Fgfr4 in astrocytes could be a way to improve recovery after a spinal cord injury.

Study Duration
6 Weeks
Participants
C57BL6/6J mice
Evidence Level
Not specified

Key Findings

  • 1
    Fgfr4 over-expression in astrocytes immediately after SCI improves motor function recovery; however, it may display sexual dimorphism.
  • 2
    Improved functional recovery is associated with a decrease in spinal cord lesion volume and reduced glial reactivity.
  • 3
    Cell-specific transcriptomic profiling revealed concomitant downregulation of Notch signaling, and up-regulation of neurogenic pathways in converting astrocytes.

Research Summary

This study investigates the therapeutic potential of gene therapy targeting Fgfr4 over-expression in mature astrocytes following SCI in adult mice. The results show that Fgfr4 over-expression in astrocytes immediately after SCI improves motor function recovery, with possible sexual dimorphism. Transcriptomic profiling reveals downregulation of Notch signaling and up-regulation of neurogenic pathways in converting astrocytes, suggesting a feasible therapeutic approach to improve recovery.

Practical Implications

Therapeutic potential

Gene therapy targeting Fgfr4 over-expression in astrocytes after injury is a feasible therapeutic approach to improve recovery following traumatism of the spinal cord.

Sex-dependent response

A sex-dependent response to astrocytic modulation should be considered for the development of effective translational strategies in other neurological disorders.

Molecular mechanisms

SCI-induced astrocyte-to-neuron conversion involves a concomitant down-regulation of Notch signaling and an up-regulation of the neurogenic process.

Study Limitations

  • 1
    Possible dimorphic response with a differential functional recovery in female and in male mice
  • 2
    The lack of investigation on synaptic function and/or repartition of muscle fiber types that may explain better motor function recovery following SCI.
  • 3
    Not specified

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