Background: Neurofilament light chain (NEFL) has been identified as a biomarker for spinal cord injury (SCI), but its effect and underlying mechanism in SCI remain unclear.
Methods: SCI rat models were established for in vivo studies. Lipopolysaccharide (LPS)-induced cell models were used for in vitro studies. The protein and mRNA expression levels of genes were evaluated by western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The pathological changes in rats after SCI were subjected to histological examinations. The interaction of NEFL and upstream miRNAs was explored using dual-luciferase reporter gene assays.
Results: NEFL was highly expressed in SCI rat spinal cord tissues and LPS-stimulated PC12 cells. NEFL silencing showed an inhibitory effect on the morphological changes of SCI rats and the secretion of inflammatory factors and facilitated functional recovery of SCI rats. MiR-30b-5p was demonstrated to target NEFL and negatively regulate NEFL mRNA and protein levels. Downregulation of miR-30b-5p in SCI cell and rat models was demonstrated. MiR-30b-5p alleviated the inflammatory response in SCI rat models and LPS-stimulated PC12 cells and promoted functional recovery in rats by targeting NEFL. NEFL activated mTOR signaling. MiR-30b-5p inactivated mTOR signaling by negatively regulating NEFL.
Conclusion: MiR-30b-5p alleviated the inflammatory response and facilitated the functional recovery of SCI rats by targeting NEFL to inactivate the mTOR pathway.
Keywords: inflammation; mTOR; miR-30b-5p; neurofilament light chain (NEFL); spinal cord injury (SCI).
© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.