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Open Access Highly Accessed Research article

Time-specific microRNA changes during spinal motoneuron degeneration in adult rats following unilateral brachial plexus root avulsion: ipsilateral vs. contralateral changes

Ying Tang1, Ze-Min Ling1, Rao Fu1, Ying-Qin Li12, Xiao Cheng1, Fa-Huan Song1, Hao-Xuan Luo1 and Li-Hua Zhou1*

Author Affiliations

1 Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, No. 74 Zhongshan Road 2, Guangzhou 510080, P.R. China

2 Department of Radiology, The Fifth Affiliated Hospital, Sun Yat-sen University, No. 74 Zhongshan Road 2, Guangzhou 510080, P.R. China

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BMC Neuroscience 2014, 15:92  doi:10.1186/1471-2202-15-92

Published: 24 July 2014

Abstract

Background

Spinal root avulsion induces multiple pathophysiological events consisting of altered levels of specific genes and proteins related to inflammation, apoptosis, and oxidative stress, which collectively result in the death of the affected motoneurons. Recent studies have demonstrated that the gene changes involved in spinal cord injury can be regulated by microRNAs, which are a class of short non-coding RNA molecules that repress target mRNAs post-transcriptionally. With consideration for the time course of the avulsion-induced gene expression patterns within dying motoneurons, we employed microarray analysis to determine whether and how microRNAs are involved in the changes of gene expression induced by pathophysiological events in spinal cord motoneurons.

Results

The expression of a total of 3,361 miRNAs in the spinal cord of adult rats was identified. Unilateral root-avulsion resulted in significant alterations in miRNA expression. In the ipsilateral half compared to the contralateral half of the spinal cord, on the 3rd day after the injury, 55 miRNAs were upregulated, and 24 were downregulated, and on the 14th day after the injury, 36 miRNAs were upregulated, and 23 were downregulated. The upregulation of miR-146b-5p and miR-31a-3p and the downregulation of miR-324-3p and miR-484 were observed. Eleven of the miRNAs, including miR-21-5p, demonstrated a sustained increase; however, only miR-466c-3p presented a sustained decrease 3 and 14 days after the injury. More interestingly, 4 of the miRNAs, including miR-18a, were upregulated on the 3rd day but were downregulated on the 14th day after injury.

Some of these miRNAs target inflammatory-response genes in the early stage of injury, and others target neurotransmitter transport genes in the intermediate stages of injury. The altered miRNA expression pattern suggests that the MAPK and calcium signaling pathways are consistently involved in the injury response.

Conclusions

This analysis may facilitate the understanding of the time-specific altered expression of a large set of microRNAs in the spinal cord after brachial root avulsion.

Keywords:
Brachial root avulsion; MicroRNA; Microarray; Inflammatory response; nNOS; c-jun; ATF-3; Calpain 2