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Autophagy Reduces Neuronal Damage and Promotes Locomotor Recovery via Inhibition of Apoptosis After Spinal Cord Injury in Rats

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An Erratum to this article was published on 19 December 2013

Abstract

Autophagy is an intracellular catabolic mechanism that maintains the balance of proteins, lipids and aging organelles. 3-Methyladenine (3-MA) is a selective inhibitor of autophagy, whereas rapamycin, an antifungal agent, is a specific inducer of autophagy, inhibiting the protein mammalian target of rapamycin. In the present study, we examined the role of autophagy, inhibited by 3-MA and enhanced by rapamycin, in a model of acute spinal cord injury in rats. We found that rapamycin could significantly increase the expression of microtubule-associated protein 1 light chain 3 (LC3) and Beclin1 at the injury site. At the same time, the number of neurons and astrocytes with LC3 positive in the spinal cord was upregulated with time. In addition, administration of rapamycin produced an increase in the Basso, Beattie and Bresnahan scores of injured rats, indicating high recovery of locomotor function. Furthermore, expression of the proteins Bcl-2 and Bax was upregulated and downregulated, respectively. By contrast, the results for rats treated with 3-MA, which inhibits autophagy, were the opposite of those seen with the rapamycin-treated rats. These results show that induction of autophagy can produce neuroprotective effects in acute spinal cord injury in rats via inhibition of apoptosis.

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Abbreviations

3-MA:

3-Methyladenine

ANOVA:

Analysis of variance

BBB:

Basso, Beattie and Bresnahan

LC3:

Microtubule-associated protein 1 light chain 3

mTOR:

Mammalian target of rapamycin

PI3K:

Phosphatidylinositol-3-kinase

SCI:

Spinal cord injury

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Acknowledgments

This research was supported by Natural Science Foundation of China (No. 30973068) and General projects of the Twelve-Fifth Scientific Plan in Army Medical Science and Technology (No. CWS11J101).

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Orthopaedics, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China

    Peifu Tang, Hongping Hou, Licheng Zhang, Xia Lan, Zhi Mao, Daohong Liu, Chunqing He, Hailong Du & Lihai Zhang

  2. Medical College, Nankai University, No.94 Weijin Road, Tianjin, 300071, People’s Republic of China

    Hongping Hou

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  1. Peifu Tang
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Correspondence to Lihai Zhang.

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Peifu Tang and Hongping Hou contributed equally to this work.

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Tang, P., Hou, H., Zhang, L. et al. Autophagy Reduces Neuronal Damage and Promotes Locomotor Recovery via Inhibition of Apoptosis After Spinal Cord Injury in Rats. Mol Neurobiol 49, 276–287 (2014). https://doi.org/10.1007/s12035-013-8518-3

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  • DOI: https://doi.org/10.1007/s12035-013-8518-3

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