Expression of spinal cord microRNAs in a rat model of chronic neuropathic pain

Brandenburger, Timo; Castoldi, Mirco; Brendel, M.; Grievink, Hilbert; Schlösser, Lukas; Werdehausen, Robert; Bauer, Inge; Hermanns, Henning

doi:10.1016/j.neulet.2011.11.023

Cited by 51 publications

(38 citation statements)

References 28 publications

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“…These comparisons revealed that the highly expressed miRNAs from our study were also reported in the study by Timo Brandenburger et al [20]; they showed that miR-124, the let-7 family and miR-34b-3p belonged to the group of highly expressed miRNAs in the rat spinal cord. These highly expressed miRNAs may be the result of the alteration of different cell populations.…”

Section: Discussionsupporting

confidence: 89%

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

Tang

Ling

et al. 2014

BMC Neurosci

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BackgroundSpinal 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.ResultsThe 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.ConclusionsThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2202-15-92) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 89%

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

Tang

Ling

et al. 2014

BMC Neurosci

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“…However, none of the early studies of miRNA in DRG after peripheral inflammation or nerve injury examined the above three miRNAs. 7,43,48 This suggests more comprehensive bioinformatic and experimental approaches to the analysis of miRNAs in DRG are necessary to guide experimentation and to delineate the roles of miRNAs in pain models.…”

Section: Resultsmentioning

confidence: 99%

Molecular Signatures of Mouse TRPV1-Lineage Neurons Revealed by RNA-Seq Transcriptome Analysis

Goswami

Mishra

Maric

et al. 2014

The Journal of Pain

106

129

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Disorders of pain neural systems are frequently chronic and, when recalcitrant to treatment, can severely degrade the quality of life. The pain pathway begins with sensory neurons in dorsal root or trigeminal ganglia and the neuronal subpopulations that express the TRPV1 ion channel transduce sensations of painful heat and inflammation, and play a fundamental role in clinical pain arising from cancer and arthritis. In the present study we elucidate the complete transcriptomes of neurons from the TRPV1 lineage and a non-TRPV1 neuro-glial population in sensory ganglia through the combined application of next-gen deep RNA-Seq, genetic neuronal labeling with fluorescence-activated cell sorting, or neuron-selective chemoablation. RNA-Seq accurately quantitates gene expression, a difficult parameter to determine with most other methods especially for very low and very high expressed genes. Differentially expressed genes are present at every level of cellular function from the nucleus to the plasma membrane. We identified many ligand receptor pairs in the TRPV1 population suggesting that autonomous presynaptic regulation maybe a major regulatory mechanism in nociceptive neurons. The data define, in a quantitative, cell population specific fashion, the molecular signature of a distinct and clinically important group of pain-sensing neurons and provide an overall framework for understanding the transcriptome of TRPV1 nociceptive neurons.

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“…It has been known that different members of the same miRNA families can simultaneously target several categories of genes and act together to regulate specific physiological processes 34. For example, members of the let-7 family are expressed highly in rat spinal cord after chronic constriction injury 35. A bioinformatics analysis revealed that the potential targets for these miRNAs include genes involved in many pathophysiological processes, such as inflammation, apoptosis and oxidation after SCI 16, 31.…”

Section: Introductionmentioning

confidence: 99%

microRNAs in Spinal Cord Injury: Potential Roles and Therapeutic Implications

Ning¹,

Gao²,

Liu³

et al. 2014

Int. J. Biol. Sci.

100

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microRNAs (miRNAs) are a novel class of small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. miRNAs can modulate gene expression and thus play important roles in diverse neurobiological processes, such as cell differentiation, growth, proliferation and neural activity, as well as the pathogenic processes of spinal cord injury (SCI) like inflammation, oxidation, demyelination and apoptosis. Results from animal studies have revealed the temporal alterations in the expression of a large set of miRNAs following SCI in adult rats, and the expressional changes in miRNAs following SCI is bidirectional (increase or decrease). In addition, several miRNAs have distinct roles in prognosis of SCI (protective, detrimental and varied). Taken together, the existing evidence suggests that abnormal miRNA expression following SCI contributes to the pathogenesis of SCI, and miRNAs may become potential targets for the therapy of SCI.

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Expression of spinal cord microRNAs in a rat model of chronic neuropathic pain

Cited by 51 publications

References 28 publications

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

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

Molecular Signatures of Mouse TRPV1-Lineage Neurons Revealed by RNA-Seq Transcriptome Analysis

microRNAs in Spinal Cord Injury: Potential Roles and Therapeutic Implications

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