Dataset Information

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

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.

SUBMITTER: Tang Y

PROVIDER: S-EPMC4121484 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Tang Ying Y Ling Ze-Min ZM Fu Rao R Li Ying-Qin YQ Cheng Xiao X Song Fa-Huan FH Luo Hao-Xuan HX Zhou Li-Hua LH

BMC neuroscience 20140724

<h4>Background</h4>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 conside ...[more]

PMID: 25055855

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Project description:Unilateral brachial plexus injury (BPI) impairs sensory and motor functions of the upper limb. This study aimed to map in detail brachial plexus sensory impairment both in the injured and the uninjured upper limb. Touch sensation was measured through Semmes-Weinstein monofilaments at the autonomous regions of the brachial plexus nerves, hereafter called points of exclusive innervation (PEIs). Seventeen BPI patients (31.35 years±6.9 SD) and 14 age-matched healthy controls (27.57 years±5.8 SD) were tested bilaterally at six selected PEIs (axillary, musculocutaneous, median, radial, ulnar, and medial antebrachial cutaneous [MABC]). As expected, the comparison between the control group and the brachial plexus patients' injured limb showed a robust difference for all PEIs (p ≤ 0.001). Moreover, the comparison between the control group and the brachial plexus uninjured limb revealed a difference for the median (p = 0.0074), radial (p = 0.0185), ulnar (p = 0.0404), and MABC (p = 0.0328) PEIs. After splitting the sample into two groups with respect to the dominance of the injured limb, higher threshold values were found for the uninjured side when it occurred in the right dominant limb compared to the control group at the median (p = 0.0456), radial (p = 0.0096), and MABC (p = 0.0078) PEIs. This effect was absent for the left, non-dominant arm. To assess the effect of the severity of sensory deficits observed in the injured limb upon the alterations of the uninjured limb, a K-means clustering algorithm (k = 2) was applied resulting in two groups with less or more severe sensory impairment. The less severely affected patients presented higher thresholds at the median (p = 0.0189), radial (p = 0.0081), ulnar (p = 0.0253), and MABC (p = 0.0187) PEIs in the uninjured limb in comparison with the control group, whereas higher thresholds at the uninjured limb were found only for the median PEI (p = 0.0457) in the more severely affected group. In conclusion, an expressive reduction in touch threshold was found for the injured limb allowing a precise mapping of the impairment caused by the BPI. Crucially, BPI also led to reduced tactile threshold in specific PEIs in the uninjured upper limb. These new findings suggest a superordinate model of representational plasticity occurring bilaterally in the brain after a unilateral peripheral injury.

Project description:Objective: The present study aimed to investigate the analgesic effect of electroacupuncture (EA) in neuropathic pain due to brachial plexus avulsion injury (BPAI) and related changes in the metabolic brain connectivity. Methods: Neuropathic pain model due to BPAI was established in adult female Sprague-Dawley rats. EA stimulations (2/15 Hz, 30 min/day, 5-day intervention followed by 2-day rest in each session) were applied to the fifth-seventh cervical "Jiaji" acupoints on the noninjured side from 1st to 12th weeks following BPAI (EA group, n = 8). Three control groups included sham EA (nonelectrical acupuncture applied to 3 mm lateral to the real "Jiaji" acupoints), BPAI-only, and normal rats (no particular intervention; eight rats in each group). Thermal withdrawal latency (TWL) of the noninjured forepaw was regularly tested to evaluate the threshold of thermalgesia. Small animal [fluorine-18]-fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT scans of brain were conducted at the end of 4th, 12th, and 16th weeks to explore metabolic alterations of brain. Results: In the EA group, the TWL of the noninjured forepaw significantly decreased following BPAI and then increased following EA stimulation, compared with sham EA (P < 0.001). The metabolic brain connectivity among somatosensory cortex (SC), motor cortex (MC), caudate putamen (Cpu), and dorsolateral thalamus (DLT) in bilateral hemispheres decreased throughout the 16 weeks' observation in the BPAI-only group, compared with the normal rats (P < 0.05). In the EA group, the strength of connectivity among the above regions were found to be increased at the end of 4th week following BPAI modeling, decreased at 12th week, and then increased again at 16th week (P < 0.05). The changes in metabolic connectivity were uncharacteristic and dispersed in the sham EA group. Conclusion: The study revealed long-term and extensive changes of metabolic brain connectivity in EA-treated BPAI-induced neuropathic pain rats. Bilateral sensorimotor and pain-related brain regions were mainly involved in this process. It indicated that modulation of brain metabolic connectivity might be an important mechanism of analgesic effect in EA stimulation for the treatment of neuropathic pain.

Dataset Information

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

Background

Results

Conclusions

Publications

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

Similar Datasets

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