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.
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The materials used during the present study are available from the corresponding author on reasonable request.
Abbreviations
- SCI:
-
Spinal cord injury
- ATF6:
-
Activating transcription factor 6
- ER:
-
Endoplasmic reticulum
- Bip:
-
Binding immunoglobulin protein
- CHOP:
-
C/EBP homologous transcription factor protein
- UPR:
-
Unfolded protein response
- MO:
-
Morpholino
- hpi:
-
Hours post injury
- dpi:
-
Days post injury
- wpi:
-
Weeks post injury
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Acknowledgements
We sincerely thank Professor Stanley Li Lin for his careful revision of the manuscript, both language and science issues.
Funding
This study was funded by the National Natural Science Foundation of China (81771384, 81760235), and the National First-class Discipline Program of Food Science and Technology (JUFSTR20180101).
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Zhe Ji performed major experiments, Zhi-Lan Zhou contributed to manuscript preparation and surgeries for the spinal cord injury model, Qin Hao performed in situ hybridization analysis, Lin Zhao performed real-time quantitative PCR analysis. Chun Cui helped to process data, Shu-Bing Huang performed swim tracking, Yan-Ling Yang and Yan-Qin Shen conceived the study.
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Ji, Z., Zhou, ZL., Hao, Q. et al. Activating Transcription Factor 6 Contributes to Functional Recovery After Spinal Cord Injury in Adult Zebrafish. J Mol Neurosci 71, 734–745 (2021). https://doi.org/10.1007/s12031-020-01691-9
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DOI: https://doi.org/10.1007/s12031-020-01691-9