Abstract
Spinal cord injury (SCI) is generally divided into primary and secondary injuries, and apoptosis is an important event of the secondary injury. As an endogenous bile acid and recognized endoplasmic reticulum (ER) stress inhibitor, tauroursodeoxycholic acid (TUDCA) administration has been reported to have a potentially therapeutic effect on neurodegenerative diseases, but its real mechanism is still unclear. In this study, we evaluated whether TUDCA could alleviate traumatic damage of the spinal cord and improve locomotion function in a mouse model of SCI. Traumatic SCI mice were intraperitoneally injected with TUDCA, and the effects were evaluated based on motor function assessment, histopathology, apoptosis detection, qRT-PCR, and western blot at different time periods. TUDCA administration can improve motor function and reduce secondary injury and lesion area after SCI. Furthermore, the apoptotic ratios were significantly reduced; Grp78, Erdj4, and CHOP were attenuated by the treatment. Unexpectedly, the levels of CIBZ, a novel therapeutic target for SCI, were specifically up-regulated. Taken together, it is suggested that TUDCA effectively suppressed ER stress through targeted up-regulation of CIBZ. This study also provides a new strategy for relieving secondary damage by inhibiting apoptosis in the early treatment of spinal cord injury.
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Funding
This study was supported by the National Natural Science Foundation of China (NSFC, 31372207 and 81570094), the Innovation Team of Scientific Research Platform in Anhui Province, a start-up grant from Nanjing Agricultural University (804090), and the “Sanxin” Research Program of Jiangsu Province (SXGC[2016]312).
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All animal experiments complied with the ARRIVE guidelines and were carried out according to the National Institutes of Health guide for the care and use of laboratory animals. All animal experiments were approved by the Anhui Normal University Academic Ethics Committee.
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Zongmeng Zhang, Jie Chen, and Fanghui Chen are co-first authors.
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Zhang, Z., Chen, J., Chen, F. et al. Tauroursodeoxycholic acid alleviates secondary injury in the spinal cord via up-regulation of CIBZ gene. Cell Stress and Chaperones 23, 551–560 (2018). https://doi.org/10.1007/s12192-017-0862-1
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DOI: https://doi.org/10.1007/s12192-017-0862-1