PUBLICATION
Chemical modulation of Akt signaling enhances spinal cord regeneration in zebrafish
- Authors
- Shen, Y.J., Chen, H.Y., Chang, C.W., Huang, Y.C., Cheng, Y.C.
- ID
- ZDB-PUB-240924-5
- Date
- 2024
- Source
- Brain research 1846: 149248 (Journal)
- Registered Authors
- Keywords
- Akt signaling, Spinal cord regeneration, Zebrafish
- MeSH Terms
-
- Animals
- Disease Models, Animal
- Nerve Regeneration/drug effects
- Nerve Regeneration/physiology
- Neuroglia/drug effects
- Neuroglia/metabolism
- Neurons/drug effects
- Neurons/metabolism
- Proto-Oncogene Proteins c-akt*/metabolism
- Recovery of Function/drug effects
- Recovery of Function/physiology
- Signal Transduction*/drug effects
- Signal Transduction*/physiology
- Spinal Cord/drug effects
- Spinal Cord/metabolism
- Spinal Cord Injuries*/drug therapy
- Spinal Cord Injuries*/metabolism
- Spinal Cord Injuries*/physiopathology
- Spinal Cord Regeneration*/drug effects
- Spinal Cord Regeneration*/physiology
- Zebrafish*
- PubMed
- 39313168 Full text @ Brain Res.
Citation
Shen, Y.J., Chen, H.Y., Chang, C.W., Huang, Y.C., Cheng, Y.C. (2024) Chemical modulation of Akt signaling enhances spinal cord regeneration in zebrafish. Brain research. 1846:149248.
Abstract
Central nervous system lesions often cause permanent motility defects in mammals since the injured neurons cannot regenerate. In contrast, lower vertebrates like zebrafish can regenerate lost neurons and restore motor function. This study investigates the efficacy of SC79, a pan-Akt activator, and A674563, a selective Akt1 inhibitor, as potential therapeutic agents for promoting spinal cord recovery post-injury. Spinal cord injury was induced in zebrafish larvae, and the effects of SC79 and A674563 on neuronal and glial regeneration were examined. SC79 promoted neuronal regeneration without affecting glial bridging, while A674563 induced glial bridging but reduced neuronal regeneration. The combination of SC79 and A674563 induced both glial bridging and neuronal regeneration. Optomotor response tests revealed improved motor function recovery with the combined treatment compared to individual treatments. Additionally, these chemical treatments altered the expression of 12 Akt downstream transcriptional target genes, affirming that the combination treatment preferentially regulates spinal cord regeneration through its action on Akt signaling. These findings highlight the complex interplay of Akt signaling pathways in spinal cord regeneration and suggest potential therapeutic strategies for enhancing functional recovery in spinal cord injury patients.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping