scholarly journals mRNA and miRNA expression profile reveals the role of miR-31 overexpression in neural stem cell

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Pengfei Li ◽  
Yuantao Gao ◽  
Xiao Li ◽  
Feng Tian ◽  
Fei Wang ◽  
...  

Abstract A detailed understanding of the character and differentiation mechanism of neural stem cells (NSCs) will help us to effectively utilize their transplantation to treat spinal cord injury. In previous studies, we found that compared with motor neurons (MNs), miR-31 was significantly high-expressed in NSCs and might play an important role in the proliferation of NSCs and the differentiation into MNs. To better understand the role of miR-31, we characterized the mRNA and miRNAs expression profiles in the early stage of spinal cord-derived NSCs after miR-31 overexpression. There were 35 mRNAs and 190 miRNAs differentially expressed between the miR-31 overexpression group and the control group. Compared with the control group, both the up-regulated mRNAs and miRNAs were associated with the stemness maintenance of NSCs and inhibited their differentiation, especially to MNs, whereas the down-regulated had the opposite effect. Further analysis of the inhibition of miR-31 in NSCs showed that interfering with miR-31 could increase the expression of MNs-related genes and produce MNs-like cells. All these indicated that miR-31 is a stemness maintenance gene of NSCs and has a negative regulatory role in the differentiation of NSCs into MNs. This study deepens our understanding of the role of miR-31 in NSCs, provides an effective candidate target for effectively inducing the differentiation of NSCs into MNs, and lays a foundation for the effective application of NSCs in clinic.

2020 ◽  
Author(s):  
Xin Ye ◽  
Yilei Chen ◽  
Jiasheng Wang ◽  
Jian Chen ◽  
Ying Yao ◽  
...  

Abstract Background: Traumatic spinal cord injury (SCI) causes high rates of worldwide morbidity because of the complex secondary injury. Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNAs, which have recently been recognized as important regulators of gene expression and pathological processes. In this study, we have attempted to elucidate the expression profiles of circRNAs in a mouse model of SCI and comprehensively understand vascular endothelial proliferation, migration and angiogenesis in the early stage of secondary injury.Methods: Deep RNA sequencing (RNA-seq) and bioinformatic analysis including GO enrichment analysis, KEGG pathway analysis and circRNA-miRNA-mRNA network construction were performed to investigate the expression patterns of circRNAs in mouse spinal cord after SCI (n= 3 per group) for three days and explore the differentially expressed circRNAs related to vascular endothelial proliferation, migration and angiogenesis. Results: Total of 1288 circRNAs were altered (>2-fold change, p<0.05) in the spinal cord after SCI, including 991 were upregulated and 297 were downregulated. Meanwhile we constructed a circRNA-mRNA network to predict their functions for circRNAs can act as “miRNA sponges”,. We next analyzed the altered circRNAs related to vascular endothelial proliferation, migration and angiogenesis by GO and KEGG analyses. 121 circRNAs were found to correlating to vascular endothelial proliferation,migration and angiogenesis in spinal cord after SCI. Conclusions: Our results reveal that circRNAs locally regulate their related protein-gene expression and play key roles in the vascular endothelial proliferation, migration and angiogenesis of SCI.


2016 ◽  
Vol 10 (11) ◽  
pp. 149 ◽  
Author(s):  
Soheila Kazemi ◽  
Wendy Baltzer ◽  
Hadi Mansouri ◽  
Karl Schilke ◽  
John Mata

A cell membrane spanning peptide was used to increase the concentration of the IKVAV motif within damaged mouse spinal cord tissue. This peptide was injected directly to the lesion 24 hours after spinal cord compression injury. Because the membrane-spanning portion of the peptide adheres to tissue upon injection with a long half-life we hypothesized that the bioactive IKVAV sequence will provide a sustained regenerative signal at the sight of injury. Five different groups of mice were used and cellular morphology observations were undertaken using light and electron microscopy. Three surgical control groups: IKVAV, peptide and mannitol; one surgical treatment group: IKVAV-peptide; and one non-surgical control group: normal, were used in this experiment. In this study, treatment with IKVAV-peptide after SCI resulted in an increased number of protoplasmic astrocytes, large active motor neurons, and regeneration of muscle bundles followed by behavioral improvement. In this paper, we describe the cellular differences between all groups.


2020 ◽  
Vol 9 (11) ◽  
pp. 3395
Author(s):  
Chang-Hoon Koo ◽  
Jung-Hee Ryu ◽  
Jin-Young Hwang ◽  
Jin-Hee Kim ◽  
Hyun-Jung Shin ◽  
...  

Spinal cord ischemia is one of the most serious complications of aortic repair in patients with acute aortic syndrome. However, the effect of hypotension before aortic clamping on spinal cord injury has not been documented. A total of 48 male Sprague-Dawley rats were randomly divided into four groups: the sham group; control group (mean arterial pressure (MAP) < 90% of baseline value before aortic clamping); mild hypotension group (MAP < 80%); and profound hypotension group (MAP < 60%). Spinal cord ischemia was induced using a balloon-tipped catheter placed in the descending thoracic aorta. Neurological function of the hind limbs was evaluated for seven days after reperfusion and recorded using a motor deficit index (MDI). The spinal cord was then harvested for histopathological examination and evaluation of oxidative stress and inflammation. The profound hypotension group demonstrated a significantly higher MDI 48 h post-reperfusion and lower number of normal motor neurons than the other groups (p < 0.001). The levels of tissue malondialdehyde and tumor necrosis factor-α (TNF-α) were also significantly increased in the profound hypotension group compared with other groups. Profound hypotension before aortic clamping can aggravate neurologic outcomes after aortic surgery by exacerbating neurologic injury and reducing the number of normal motor neurons.


2020 ◽  
Vol 96 (2) ◽  
pp. 94-101
Author(s):  
I.N. Novosеlova ◽  
V.A. Machalov ◽  
I.V. Ponina ◽  
S.A. Valiullina ◽  
G.E Ivanova

Authors present a concept of early rehabilitation in children with spinal cord injury in a surgical department. The patient’s route at an early stage of rehabilitation is defined: general intensive care unit, intensive care ward in neurosurgical department and general ward in neurosurgical department. Three main stages of early comprehensive rehabilitation are also defined: perioperative, adaptation to motor deficit, motor retraining. Goals of early rehabilitation and role of multidisciplinary team involved in the care are stated as well. Article shows the role of various physical training techniques and rehabilitation tools effectiveness in patients’ care, complications prevention, motor retraining, persistent self-care skills acquisition, improvement of mobility and quality of patients' life.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lindsay Sprimont ◽  
Pauline Janssen ◽  
Kathleen De Swert ◽  
Mathias Van Bulck ◽  
Ilse Rooman ◽  
...  

AbstractxCT is the specific subunit of System xc-, an antiporter importing cystine while releasing glutamate. Although xCT expression has been found in the spinal cord, its expression and role after spinal cord injury (SCI) remain unknown. The aim of this study was to characterize the role of xCT on functional and histological outcomes following SCI induced in wild-type (xCT+/+) and in xCT-deficient mice (xCT−/−). In the normal mouse spinal cord, slc7a11/xCT mRNA was detected in meningeal fibroblasts, vascular mural cells, astrocytes, motor neurons and to a lesser extent in microglia. slc7a11/xCT gene and protein were upregulated within two weeks post-SCI. xCT−/− mice recovered muscular grip strength as well as pre-SCI weight faster than xCT+/+ mice. Histology of xCT−/− spinal cords revealed significantly more spared motor neurons and a higher number of quiescent microglia. In xCT−/− mice, inflammatory polarization shifted towards higher mRNA expression of ym1 and igf1 (anti-inflammatory) while lower levels of nox2 and tnf-a (pro-inflammatory). Although astrocyte polarization did not differ, we quantified an increased expression of lcn2 mRNA. Our results show that slc7a11/xCT is overexpressed early following SCI and is detrimental to motor neuron survival. xCT deletion modulates intraspinal glial activation by shifting towards an anti-inflammatory profile.


1995 ◽  
Vol 83 (5) ◽  
pp. 884-888 ◽  
Author(s):  
Mitsuhiro Yanase ◽  
Takashi Sakou ◽  
Takeo Fukuda

✓ To clarify the role of N-methyl-d-aspartate (NMDA) receptors in acute spinal cord injury, changes in the intraspinal microcirculation after acute spinal cord injury in rabbits were examined. Systemic administration of MK-801, an NMDA receptor antagonist, at a dose of 5 mg/kg, significantly improved motor recovery after injury and significantly reduced edema formation at the injured site without altering spinal cord blood flow or vascular permeability at the injured site. These findings indicate that excitatory amino acids contribute to secondary spinal cord damage, especially edema formation, mediated by NMDA receptors in the early stage after injury.


2009 ◽  
Vol 29 (4) ◽  
pp. 752-758 ◽  
Author(s):  
Masahiro Sakurai ◽  
Takae Kawamura ◽  
Hidekazu Nishimura ◽  
Hiroyoshi Suzuki ◽  
Fumiaki Tezuka ◽  
...  

The mechanism of spinal cord injury has been thought to be related to the vulnerability of spinal motor neuron cells against ischemia. However, the mechanisms of such vulnerability are not fully understood. We investigated a possible mechanism of neuronal death by immunohistochemical analysis for DJ-1, PINK1, and α-Synuclein. We used a 15-min rabbit spinal cord ischemia model, with use of a balloon catheter. Western blot analysis for DJ-1, PINK1, and α-Synuclein; temporal profiles of DJ-1, PINK1, and α-Synuclein immunoreactivity; and double-label fluorescence immunocytochemical studies were performed. Western blot analysis revealed scarce immunoreactivity for DJ-1, PINK1, and α-Synuclein in the sham-operated spinal cords. However, they became apparent at 8 h after transient ischemia, which returned to the baseline level at 1 day. Double-label fluorescence immunocytochemical study revealed that both DJ-1 and PINK1, and DJ-1 and α-Synuclein were positive at 8 h of reperfusion in the same motor neurons, which eventually die. The induction of DJ-1 and PINK1 proteins in the motor neurons at the early stage of reperfusion may indicate oxidative stress, and the induction of α-Synuclein may be implicated in the programmed cell death change after transient spinal cord ischemia.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xin Ye ◽  
Yilei Chen ◽  
Jiasheng Wang ◽  
Jian Chen ◽  
Ying Yao ◽  
...  

Background: Traumatic spinal cord injury (SCI) can result in severe disability and causes a considerable socio-economic burden worldwide. Circular RNAs (circRNAs) are important regulators of gene expression and pathological processes, and may represent therapeutic targets for SCI. To further evaluate the role of circRNAs in SCI, we elucidated circRNA expression profiles related to vascular endothelial proliferation, migration, and angiogenesis during the early stages of secondary injury in a mouse model of SCI.Methods: Microarray analysis was performed to investigate the circRNA expression patterns in the spinal cord 3 days after SCI in female mice. Bioinformatic analyses, including GO enrichment analysis, KEGG pathway analysis, and circRNA-miRNA-mRNA network construction, were conducted to explore the role of circRNA dysregulation in vascular endothelial proliferation, migration, and angiogenesis following SCI.Results: The expression of 1,288 circRNAs was altered (&gt;2-fold change, p &lt; 0.05) in the spinal cord after SCI, consisting of 991 upregulated and 297 downregulated circRNAs. We constructed a circRNA-mRNA network to predict whether these circRNAs could act as “miRNA sponges.” We next assessed the association of altered circRNAs with vascular endothelial proliferation, migration, and angiogenesis using GO and KEGG analyses. Using this analysis, we found that a total of 121 circRNAs were correlated with vascular endothelial proliferation, migration, and angiogenesis in the spinal cord after SCI.Conclusions: Our study provides circRNA expression profiles during the early stages of SCI. circRNA.7079, circRNA.7078, and circRNA.6777 were found to play key roles in the vascular endothelial proliferation, migration, and angiogenesis, and may represent therapeutic targets for SCI.


Author(s):  
Semeleva E.V. ◽  
Blinova E.V. ◽  
Zaborovsky A.V. ◽  
Vasilkina O.V. ◽  
Shukurov A.S.

In this work, we studied the pharmacological activity of zinc and magnesium salts of 2-aminoethanesulfonic acid in white non-linear male rats with amyotrophic lateral sclerosis, which was modeled by neurotoxicantsimplication into the pelvic part of spinal cord. After the reproduction of the pathology in animals, the indices of motor activity were recorded in the Rotarod test, and morphological studies of spinal cord sections stained according to Nisl in the Belshovsky modification were carried out. It was shown that the magnesium salt of 2-aminoethanesulfonic acid (compound LHT-317) to a greater extent reduces the development of motor disorders in experimental animals compared with the control group on the 4th day of observation. The course of intravenous administration of the studied compounds of 2-aminoethanesulfonic acid did not inhibit morphological changes in the spinal cord that develop in degenerative-dystrophic pathology of the central nervous system: connections. Moreover, if, against the background of treatment with zinc salt, the total area of motor zones in animals of the experimental group exceeded that of control rats, then the number of motoneurons did not differ from the control.


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