PUBLICATION
Activating Transcription Factor 6 Contributes to Functional Recovery After Spinal Cord Injury in Adult Zebrafish
- Authors
- Ji, Z., Zhou, Z.L., Hao, Q., Zhao, L., Cui, C., Huang, S.B., Yang, Y.L., Shen, Y.Q.
- ID
- ZDB-PUB-200909-4
- Date
- 2020
- Source
- Journal of molecular neuroscience : MN 71(4): 734-745 (Journal)
- Registered Authors
- Keywords
- Activating transcription factor 6, Endoplasmic reticulum stress, Locomotor recovery, Spinal cord injury, Zebrafish
- MeSH Terms
-
- Activating Transcription Factor 6/genetics
- Activating Transcription Factor 6/metabolism*
- Animals
- Axons/metabolism
- Axons/physiology
- CCAAT-Enhancer-Binding Proteins/metabolism
- Neuronal Outgrowth
- Spinal Cord Injuries/metabolism*
- Spinal Cord Regeneration*
- Transcription Factor CHOP/metabolism
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 32895880 Full text @ J. Mol. Neurosci.
Citation
Ji, Z., Zhou, Z.L., Hao, Q., Zhao, L., Cui, C., Huang, S.B., Yang, Y.L., Shen, Y.Q. (2020) Activating Transcription Factor 6 Contributes to Functional Recovery After Spinal Cord Injury in Adult Zebrafish. Journal of molecular neuroscience : MN. 71(4):734-745.
Abstract
Spinal cord injury (SCI) is one of the most common devastating injuries, with little possibility of recovery in humans. However, zebrafish efficiently regenerate functional nervous system tissue after SCI. Therefore, the spinal cord transection model of adult zebrafish was applied to explore the role of ATF6 in neuro-recovery. Activating transcription factor 6 (ATF6) is a type-II transmembrane protein in the endoplasmic reticulum (ER). ATF6 target genes could improve ER homeostasis, which contributes to cytoprotection. Herein, we found that the ATF6 level increased at 12 h and 3 days post SCI, and returned to sham levels at 7 days post SCI. ATF6-expressing motor neurons were present in the central canal of the spinal cord and increased at 12 h post SCI. ATF6 morpholino treatment showed that inhibition of ATF6 delayed locomotor recovery and hindered neuron axon regrowth in SCI zebrafish. Furthermore, we investigated the role of both binding immunoglobulin protein (Bip) and C/EBP homologous transcription factor protein (CHOP), the two target genes of ATF6. We found that Bip expression significantly increased in the spinal cord at 7 days after SCI, which served as a pro-survival chaperone. Our results also showed that CHOP expression significantly decreased in the spinal cord at 7 days after SCI, which was identified as a protein involved in apoptosis. Taken together, our data demonstrate that ATF6 may contribute to the functional recovery after SCI in adult zebrafish, via up-regulation of Bip and down-regulation of CHOP to restore the homeostasis of ER.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping