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Neural Stem Cell Transplantation in Experimental Contusive Model of Spinal Cord Injury
Published on: December 17, 2014
miR-378-3p alleviates contusion spinal cord injury by negatively regulating ATG12
Haocong Zhang1, Hailong Yu1, Huifeng Yang1
1Department of Orthopaedics, General Hospital of Northern Theater Command, Shenyang, China.
Abstract:
MicroRNAs (miRNAs or miRs) serve essential roles in the pathogenic process of spinal cord injury (SCI). The present study investigated the role of miR-378-3p and autophagy-related 12 (ATG12) in SCI. RT-qPCR was used to detect the mRNA expression levels of miR-378-3p and ATG12. Cell viability and membrane integrity were evaluated using CCK-8 and LDH assays. For the analysis of the interaction between miR-378-3p and ATG12, a dual-luciferase reporter assay was conducted. The hindlimb function of rats was detected with the Basso, Beattie and Bresnahan score, and the motor deficit index score was used to evaluate nerve function. Using these approaches, it was identified that miR-378-3p expression was downregulated, while that of ATG12 was upregulated in SCI tissues and in cells exposed to hypoxia. Hypoxia repressed the expression of miR-378-3p via hypoxia-inducible factor 1-α. The overexpression of miR-378-3p exerted anti-apoptotic effects on nerve cells by directly repressing ATG12. The infusion of miR-378-3p improved hindlimb motor function and the neurological functions of rats with contusion SCI, which contributed to amelioration of functional deficits and the relief of contusion SCI. Therefore, it was concluded that upregulated expression of miR-378-3p in PC12 or N2A cells repressed the apoptosis of nerve cells, and the administration of miR-378-3p in model rats with contusion SCI improved neurological and motor functions.
Insights
MicroRNA-378-3p (miR-378-3p) protects nerve cells from apoptosis and improves motor function after spinal cord injury (SCI). Upregulating miR-378-3p in SCI models reduces nerve cell death and enhances neurological recovery.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- MicroRNAs (miRNAs) are critical regulators in spinal cord injury (SCI) pathogenesis.
- The specific roles of miR-378-3p and autophagy-related 12 (ATG12) in SCI remain incompletely understood.
Purpose of the Study:
- To investigate the functional relationship between miR-378-3p and ATG12 in SCI.
- To evaluate the therapeutic potential of miR-378-3p in a rat model of contusion SCI.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) for gene expression analysis.
- Cell viability (CCK-8) and membrane integrity (LDH) assays.
- Dual-luciferase reporter assay to confirm direct interaction.
- Basso, Beattie and Bresnahan (BBB) score and motor deficit index for functional assessment in rats.
Main Results:
- miR-378-3p was downregulated, while ATG12 was upregulated in SCI tissues and hypoxic cells.
- Hypoxia-induced factor 1-α (HIF-1α) repressed miR-378-3p expression.
- Overexpression of miR-378-3p inhibited apoptosis by directly repressing ATG12.
- miR-378-3p administration improved hindlimb motor function and neurological recovery in rats with contusion SCI.
Conclusions:
- miR-378-3p acts as a neuroprotective agent by suppressing nerve cell apoptosis through ATG12 repression.
- Restoring miR-378-3p levels offers a promising therapeutic strategy for ameliorating functional deficits following spinal cord injury.

