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Exercise protects against spinal cord injury through miR-21-mediated suppression of PDCD4.

ABSTRACT: Spinal cord injury (SCI) can lead to different levels of paraplegia. Studies have shown that exercise exerts wide protective effects against various diseases, and microRNAs (miRNAs) are involved in its beneficial effects. However, the specific role of miRNAs in the protective effects of exercise against SCI remains unclear. Here, we showed that exercise exerted protective effects against SCI as evidenced by increased locomotor activity and spinal cord cell survival in rats with SCI. Exercise upregulated circulating miR-21, detected by miRNA microarray, in rats with SCI. Treating SCI rats with agomiR-21 upregulated circulating miR-21 and exerted protective effects against SCI. Additionally, downregulating miR-21 using antagomir-21 abolished the protective effects of exercise on SCI. Programmed cell death protein 4 (PDCD4) was found to be the target of miR-21. These results suggested that exercise protects against SCI, at least partly, through miR-21-mediated suppression of PDCD4.

SUBMITTER: Li M

PROVIDER: S-EPMC7540147 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Exercise protects against spinal cord injury through miR-21-mediated suppression of PDCD4.

Li Meng M Jiang Wan-Ting WT Li Jia J Ji Wen-Chen WC

American journal of translational research 20200915 9

Spinal cord injury (SCI) can lead to different levels of paraplegia. Studies have shown that exercise exerts wide protective effects against various diseases, and microRNAs (miRNAs) are involved in its beneficial effects. However, the specific role of miRNAs in the protective effects of exercise against SCI remains unclear. Here, we showed that exercise exerted protective effects against SCI as evidenced by increased locomotor activity and spinal cord cell survival in rats with SCI. Exercise upr ...[more]

PMID: 33042450

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Project description:Gypenoside XVII (GP‑17), one of the dominant active components of Gynostemma pentaphyllum, has been studied extensively and found to have a variety of pharmacological effects, including neuroprotective properties. However, the neuroprotective effects of GP‑17 against spinal cord injury (SCI), as well as its underlying mechanisms of action remain unknown. The present study aimed to investigate the effects of GP‑17 on motor recovery and histopathological changes following SCI and to elucidate the mechanisms underlying its neuroprotective effects in a mouse model of SCI. Motor recovery was evaluated using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. Spinal cord edema was detected by the wet/dry weight method. H&E staining was performed to examine the effect of GP‑17 on spinal cord damage. Inflammatory response production was assessed by ELISA. Candidate miRNAs were identified following the integrated analysis of the Gene Expression Omnibus (GEO) dataset GSE67515. Western blot analysis was also performed to detect the expression levels of associated proteins. The results revealed that GP‑17 treatment improved functional recovery, and suppressed neuronal apoptosis and the inflammatory response in the mouse model of SCI. Moreover, it was observed that miR‑21 expression was downregulated following SCI, whereas it was upregulated following the administration of GP‑17. The inhibition of miR‑21 eliminated the protective effects of GP‑17 on SCI‑induced neuronal apoptosis and the inflammatory response. In addition, phosphatase and tensin homologue (PTEN), a key molecule in the activation of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, was identified as a target of miR‑21, and PTEN expression was downregulated by GP‑17 through miR‑21. Furthermore, the PTEN/AKT/mTOR pathway was inactivated by SCI, whereas it was re‑activated by GP‑17 through the regulation of miR‑21 in mice with SCI. On the whole, the findings of the present study suggest that GP‑17 plays a protective role in SCI via regulating the miR‑21/PTEN/AKT/mTOR pathway.

Project description:BackgroundThere is emerging evidence that astaxanthin plays a significant role in protecting neuro-cells from apoptosis after central nervous system injury. Our study examined the effects of astaxanthin on neuro-cell apoptosis after spinal cord injury.MethodsOne hundred and forty-four healthy adult Sprague-Dawley rats were randomly divided into the experimental group, control group, and sham operation group (n=48). Spinal cord injury was induced using the modified Allen method in the control group and the experimental group; while in the sham operation group, the lamina was removed without spinal cord injury. The rats in the experimental group were given astaxanthin (75 mg/kg) by gavage immediately after the operation, and in the other groups were given the same amount of olive oil. Motor function was assessed by blood-brain barrier (BBB) scores. The malondialdehyde (MDA) content and the activity of superoxide dismutase (SOD) at 24 h was determined after the operation. The apoptosis index (AI) was determined at 6, 24, and 48 h after the operation. At 48 h after the operation, we calculated the water content of the spinal cord, the lesion ratio of the spinal cord, the ultrastructure of the spinal cord, and the ultrastructure score.ResultsThe BBB scores of the control and experimental groups were significantly lower than the sham operation group at each postoperative time (P<0.05), and the BBB score of the experimental group was significantly higher than the control group at 1-4 weeks postoperatively (P<0.05). At 24 hours postoperatively, MDA content was highest in the control group and lowest in the sham operation group, while SOD activity was highest in the sham operation group and lowest in the control group (P<0.05). At each time point postoperatively, the sham operation group had the lowest AI and the control group had the highest AI (P<0.05). At 48 h after the operation, the water content and the lesion ratio of the spinal cord, and the ultrastructure score were the lowest in the sham operation group and the highest in the control group (P<0.05).ConclusionsAstaxanthin significantly improved the motor function of rats with spinal cord injury.

Dataset Information

Exercise protects against spinal cord injury through miR-21-mediated suppression of PDCD4.

Publications

Exercise protects against spinal cord injury through miR-21-mediated suppression of PDCD4.

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