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Ca2+ Regulates Autophagy Through CaMKKβ/AMPK/mTOR Signaling Pathway in Mechanical Spinal cord Injury: An in vitro Study

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Abstract

Spinal cord injury (SCI), resulting in damage of the normal structure and function of the spinal cord, would do great harm to patients, physically and psychologically. The mechanism of SCI is very complex. At present, lots of studies have reported that autophagy was involved in the secondary injury process of SCI, and several researchers also found that calcium ions (Ca2+) played an important role in SCI by regulating necrosis, autophagy, or apoptosis. However, to our best of knowledge, no studies have linked the spinal cord mechanical injury, intracellular Ca2+, and autophagy in series. In this study, we have established an in vitro model of SCI using neural cells from fetal rats to explore the relationship among them, and found that mechanical injury could promote the intracellular Ca2+ concentration, and the increased Ca2+ level activated autophagy through the CaMKKβ/AMPK/mTOR pathway. Additionally, we found that apoptosis was also involved in this pathway. Thus, our study provides new insights into the specific mechanisms of SCI and may open up new avenues for the treatment of SCI.

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Funding

This work was supported by the National Natural Science Foundation of China Youth Science Fund Project (81701228 to FBL), the National Natural Science Foundation of China (81871821 to JL) and the Fundamental Research Funds for the Central Universities of Central South University (160171025 to FSL).

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Authors and Affiliations

  1. Department of Spine Surgery, The Second Xiangya Hospital, Central South University, 410011, Changsha, China

    Fu-Sheng Liu, Xiao-Bin Wang, Jing Li, Bing Wang, Guo-Hua Lv & Fu-Bing Liu

  2. Zhongshan Hospital Affiliated to Fudan University, 200032, Shanghai, China

    Chang Jiang

  3. The First Affiliated Hospital of University of Science and Technology of China, 230001, Anhui, China

    Zheng Li

  4. Department of Spine Surgery, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, 411001, Changsha, Hunan, China

    Fu-Bing Liu

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  1. Fu-Sheng Liu
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Contributions

All authors participated in data acquisition. FBL, GHL, JL and BW contributed to the conception and design of the study. FSL, CJ, ZL and XBW did the data analysis and interpretation. FSL and FBL contributed to the drafting and revision of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Fu-Bing Liu.

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Liu, FS., Jiang, C., Li, Z. et al. Ca2+ Regulates Autophagy Through CaMKKβ/AMPK/mTOR Signaling Pathway in Mechanical Spinal cord Injury: An in vitro Study. Neurochem Res 48, 447–457 (2023). https://doi.org/10.1007/s11064-022-03768-w

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