Intrathecal application of short interfering RNA knocks down c-jun expression and augments spinal motoneuron death after root avulsion in adult rats

Cheng, Xiuyuan; Fu, Rao; Gao, Mingyong; Liu, S.; Li, Y.-Q.; Song, Fahuan; Bruce, Iain C.; Zhou, Lihua; Wu, Wei

doi:10.1016/j.neuroscience.2013.03.006

Cited by 23 publications

(21 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Under the surgical microscope, the cervical spinal cords were exposed, and the ipsilateral half of the spinal cord segments were confirmed with a complete ventral and dorsal root avulsion. Then, the C5 to T1 spinal segments were removed and dissected into ipsilateral and contralateral halves as quickly as possible [3]. Total RNA was isolated using TRIzol (Invitrogen, China) and a miRNeasy mini kit (QIAGEN, China) according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

“…The images were captured using a digital camera attached to the microscope (Olympus BX50, Japan) [3]. …”

Section: Methodsmentioning

confidence: 99%

“…Previous studies have shown that avulsion-induced motoneuron damage is propagated by a cascade of molecular and cellular events including changes in the expression of genes and the phosphorylation of signaling molecules in cell death-related pathways [1–3]. Based on the microarray analysis of the affected spinal cord after root avulsion in previous studies, the downregulation of genes required for promoting neuronal survival and axonal regeneration and the upregulation of genes involved in apoptosis and DNA damage were observed.…”

Section: Introductionmentioning

confidence: 99%

“…Based on the microarray analysis of the affected spinal cord after root avulsion in previous studies, the downregulation of genes required for promoting neuronal survival and axonal regeneration and the upregulation of genes involved in apoptosis and DNA damage were observed. Furthermore, our recent studies showed that some avulsion-induced genes, such as neuronal nitric oxide synthase (nNOS), showed changes at the mRNA level that were different from the changes at the protein levels [4, 5], whereas other changes, such as those in c-jun, were similar at the protein and mRNA levels [1, 3]. However, the upstream and downstream molecular mechanisms of avulsion-induced abnormal gene expression during motoneuron degeneration are still unclear and need to be studied further.…”

Section: Introductionmentioning

confidence: 99%

“…An increasing number of studies have demonstrated that miRNAs in the spinal cord are altered in a variety of motor neuron degenerative diseases and after spinal cord injury [8, 10–12]. There is also emerging evidence that alterations in RNA metabolism in the spinal cord are time-specific and may be critical in the progression of avulsion-induced motoneuron degeneration [3, 13]. However, little is known regarding the miRNA expression profile in the spinal cord during avulsion-induced motoneuron degeneration.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

View full text Add to dashboard Cite

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.

show abstract

Section: Methodsmentioning

confidence: 99%

“…The images were captured using a digital camera attached to the microscope (Olympus BX50, Japan) [3]. …”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

View full text Add to dashboard Cite

show abstract

MicroRNA-137-3p Protects PC12 Cells Against Oxidative Stress by Downregulation of Calpain-2 and nNOS

Tang

et al. 2020

Cell Mol Neurobiol

View full text Add to dashboard Cite

Enhanced Autophagy Contributes to Protective Effects of GM1 Ganglioside Against Aβ1-42-Induced Neurotoxicity and Cognitive Deficits

et al. 2017

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. The aggregation of Aβ peptides, Aβ1-42 in particular, is thought to be a fundamental pathogenic mechanism leading to the neuronal damage in AD. Recently, monosialoganglioside GM1 is reported to possess pivotal neuroprotection in neurodegenerative diseases. Previous studies have focused on the conformational dynamics and the biochemical interaction of the amyloid-peptide with the GM1 ganglioside, as well as the protective effect of GM1 on cognition. However, the phenomenon of autophagy with regard to neuronal dysfunction in AD is less investigated. In the present study, GM1 treatment were investigated in an AD mouse model and cultured PC12 dells to examine cognition-protective and neuroprotective effects of GM1. Furthermore, GM1 was found to induce autophagy via testing light chain 3 (LC3), Beclin1, neighbor of BRCA1 gene 1 protein and p62 (a substrate of LC3). Chloroquine, an inhibitor of lysosomal, was used to exclude the interference of lysosome, which could fuse with autophagosome and then clear it. In the presence of the inhibitor of autophagy (3-methyladenine; 3-MA), the protective effect of GM1 on PC12 cells in Aβ (1-42) induced toxic conditions was diminished. Interestingly, the expression of histone deacetylase 1 was increased in PC12 cells when treated with GM1, indicating that autophagy might be activated by GM1 through a pathway integrates protein acetylation. This study provides a novel insight into the protective role of GM1 against Aβ (1-42)-induced neurotoxicity via enhancing autophagy.

show abstract

Intrathecal application of short interfering RNA knocks down c-jun expression and augments spinal motoneuron death after root avulsion in adult rats

Cited by 23 publications

References 45 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

MicroRNA-137-3p Protects PC12 Cells Against Oxidative Stress by Downregulation of Calpain-2 and nNOS

Enhanced Autophagy Contributes to Protective Effects of GM1 Ganglioside Against Aβ1-42-Induced Neurotoxicity and Cognitive Deficits

Contact Info

Product

Resources

About