Time Course Transcriptome Analysis of Spina Biﬁda Progression in Fetal Rats

Brain Sci, 2021 · DOI: https://doi.org/10.3390/brainsci11121593 · Published: November 30, 2021

Simple Explanation

This study looks at the molecular changes in the spinal cords of fetal rats with spina bifida at different stages of development. The research uses RNA sequencing to identify genes that are expressed differently in the spinal cords of rats with spina bifida compared to control groups. The results suggest that the timing of treatment for spina bifida during pregnancy could be important for developing new regenerative therapies.

Study Duration

Not specified

Participants

Fetal rats with retinoic acid-induced spina bifida and controls

Evidence Level

Not specified

Key Findings

1
The study found approximately 3000, 1000, and 300 genes were differentially expressed at E15, E17, and E20, respectively, compared to control groups.
2
Upregulation in p53 and sonic hedgehog signaling at E15 and E17 and downregulation in the myelin sheath at E17 and E20 were observed.
3
Skeletal muscle development at E15, downregulated glucose metabolism at E17, and upregulated inﬂammation at E20 were identified as modifications specific to gestational time points.

Research Summary

The study used RNA-sequencing to identify differentially expressed genes in fetal spinal cords from rats with retinoic acid-induced spina biﬁda at E15, E17, and E20. The results suggest common alterations in certain pathways between gestational time points, such as upregulation in p53 and sonic hedgehog signaling at E15 and E17 and downregulation in the myelin sheath at E17 and E20. This work provides evidence that gestational age during spina biﬁda repair may be a signiﬁcant variable to consider during the development of new regenerative therapeutics approaches.

Practical Implications

Therapeutic Target Identification

Identifies potential pathways as therapeutic targets to aid in spinal cord regeneration.

Timing-Specific Treatments

Suggests the tailoring of therapeutic strategies to the gestational age at the time of treatment.

Combination Therapies

Encourages an approach where a combination of pathways is targeted in treatment strategies.

Study Limitations

1
Models created from single or double mutants in mice do not always match the phenotype of human neural tube defect with the same mutation
2
Changes in gene expression observed may be due to exposure of the spinal cord to the amniotic ﬂuid
3
The speciﬁc role of amylase in spinal cord inﬂammation and spina biﬁda outcomes has not been investigated

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