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Lithium alleviated spinal cord injury (SCI)-induced apoptosis and inflammation in rats via BDNF-AS/miR-9-5p axis

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Abstract

Spinal cord injury (SCI) is a major cause of paralysis, disability and even death in severe cases. Lithium has neuroprotective effects on SCI, while the underlying mechanisms remain obscure. In the present study, we established a SCI rat model, which subsequently received lithium treatment. Results displayed that lithium treatment improved the locomotor function recovery and reduced apoptosis by increasing anti-apoptotic molecule expression and decreasing pro-apoptotic factor expression in SCI rats. Furthermore, lithium treatment alleviated the inflammatory response by inactivating the nuclear factor-kappa B (NF-κB) pathway and inhibited the expression of lncRNA brain-derived neurotrophic factor antisense (BDNF-AS) in SCI rats. Subsequent researches indicated that miR-9-5p was targeted and regulated by BDNF-AS. Lithium treatment rescued the upregulation of BDNF-AS expression and downregulation of miR-9-5p expression induced by H2O2 in SH-SY5Y cells. BDNF-AS overexpression or miR-9-5p interference attenuated the anti-apoptotic and anti-inflammatory effects of lithium chloride in SH-SY5Y cells that was damaged by H2O2 induction, revealing that lithium might act through the BDNF-AS/miR-9-5p axis. In vivo studies showed that the injection of BDNF-AS adenovirus vector or miR-9-5p inhibitor reversed the effects of lithium on the histologic morphology of spinal cord, motor function, inflammatory reaction and apoptosis in SCI rats, which was consistent with the results of in vitro studies. In conclusion, our data demonstrated that lithium reduced SCI-induced apoptosis and inflammation in rats via the BDNF-AS/miR-9-5p axis.

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Funding

This work was supported by the National Natural Science Foundation of China (No. 81701223), the Natural Science Foundation in Shaanxi Province (No. 2017JQ8019) and the Fundamental Research Funds for the Central Universities (No. 1191329737).

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Authors and Affiliations

  1. Department of Orthopaedics, the Second Affiliated Hospital, College of Medicine, Xi’an Jiaotong University, No. 157, Xiwu Road, Xi’an, 710004, China

    Fang Wang, Sue Chang, Jie Li, Dong Wang, Haopeng Li & Xijing He

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  1. Fang Wang
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  2. Sue Chang
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  3. Jie Li
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  4. Dong Wang
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  5. Haopeng Li
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  6. Xijing He
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Correspondence to Xijing He.

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All procedures performed in the studies involving animals were approved by the Animal Ethical and Welfare Committee of The Second Affiliated Hospital of Xi'an Jiaotong University (permit number IACUC-1803051).

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Wang, F., Chang, S., Li, J. et al. Lithium alleviated spinal cord injury (SCI)-induced apoptosis and inflammation in rats via BDNF-AS/miR-9-5p axis. Cell Tissue Res 384, 301–312 (2021). https://doi.org/10.1007/s00441-020-03298-3

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