scholarly journals The Extracellular Matrix Glycoprotein Tenascin-C Is Beneficial for Spinal Cord Regeneration

2010 ◽  
Vol 18 (10) ◽  
pp. 1769-1777 ◽  
Author(s):  
Jian Chen ◽  
Hyun Joon Lee ◽  
Igor Jakovcevski ◽  
Ronak Shah ◽  
Neha Bhagat ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Extracellular Matrix ◽  
Spinal Cord Regeneration ◽  
Tenascin C

The extracellular matrix glycoprotein tenascin-C promotes locomotor recovery after spinal cord injury in adult zebrafish

Neuroscience ◽  
2011 ◽  
Vol 183 ◽  
pp. 238-250 ◽  
Author(s):  
Y.-M. Yu ◽  
M. Cristofanilli ◽  
A. Valiveti ◽  
L. Ma ◽  
M. Yoo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Extracellular Matrix ◽  
Adult Zebrafish ◽  
Locomotor Recovery ◽  
Tenascin C ◽  
Cord Injury

scholarly journals Cellular response to spinal cord injury in regenerative and non-regenerative stages in Xenopus laevis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Gabriela Edwards-Faret ◽  
Karina González-Pinto ◽  
Arantxa Cebrián-Silla ◽  
Johany Peñailillo ◽  
José Manuel García-Verdugo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Extracellular Matrix ◽  
Xenopus Laevis ◽  
Cellular Response ◽  
Central Canal ◽  
Spinal Cord Regeneration ◽  
Post Injury ◽  
Cord Injury ◽  
Regenerative Stage

Abstract Background The efficient regenerative abilities at larvae stages followed by a non-regenerative response after metamorphosis in froglets makes Xenopus an ideal model organism to understand the cellular responses leading to spinal cord regeneration. Methods We compared the cellular response to spinal cord injury between the regenerative and non-regenerative stages of Xenopus laevis. For this analysis, we used electron microscopy, immunofluorescence and histological staining of the extracellular matrix. We generated two transgenic lines: i) the reporter line with the zebrafish GFAP regulatory regions driving the expression of EGFP, and ii) a cell specific inducible ablation line with the same GFAP regulatory regions. In addition, we used FACS to isolate EGFP+ cells for RNAseq analysis. Results In regenerative stage animals, spinal cord regeneration triggers a rapid sealing of the injured stumps, followed by proliferation of cells lining the central canal, and formation of rosette-like structures in the ablation gap. In addition, the central canal is filled by cells with similar morphology to the cells lining the central canal, neurons, axons, and even synaptic structures. Regeneration is almost completed after 20 days post injury. In non-regenerative stage animals, mostly damaged tissue was observed, without clear closure of the stumps. The ablation gap was filled with fibroblast-like cells, and deposition of extracellular matrix components. No reconstruction of the spinal cord was observed even after 40 days post injury. Cellular markers analysis confirmed these histological differences, a transient increase of vimentin, fibronectin and collagen was detected in regenerative stages, contrary to a sustained accumulation of most of these markers, including chondroitin sulfate proteoglycans in the NR-stage. The zebrafish GFAP transgenic line was validated, and we have demonstrated that is a very reliable and new tool to study the role of neural stem progenitor cells (NSPCs). RNASeq of GFAP::EGFP cells has allowed us to clearly demonstrate that indeed these cells are NSPCs. On the contrary, the GFAP::EGFP transgene is mainly expressed in astrocytes in non-regenerative stages. During regenerative stages, spinal cord injury activates proliferation of NSPCs, and we found that are mainly differentiated into neurons and glial cells. Specific ablation of these cells abolished proper regeneration, confirming that NSPCs cells are necessary for functional regeneration of the spinal cord. Conclusions The cellular response to spinal cord injury in regenerative and non-regenerative stages is profoundly different between both stages. A key hallmark of the regenerative response is the activation of NSPCs, which massively proliferate, and are differentiated into neurons to reconstruct the spinal cord. Also very notably, no glial scar formation is observed in regenerative stages, but a transient, glial scar-like structure is formed in non-regenerative stage animals.

scholarly journals Cellular Response to Spinal Cord Injury in Regenerative and Non-Regenerative Stages in Xenopus Laevis

2020 ◽  
Author(s):  
Gabriela Edwards-Faret ◽  
Karina González-Pinto ◽  
Arantxa Cebrián-Silla ◽  
Johany Peñailillo ◽  
José Manuel García-Verdugo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Extracellular Matrix ◽  
Xenopus Laevis ◽  
Cellular Response ◽  
Central Canal ◽  
Spinal Cord Regeneration ◽  
Post Injury ◽  
Cord Injury ◽  
Regenerative Stage

Abstract Background The efficient regenerative abilities at larvae stages followed by a non-regenerative response after metamorphosis in froglets makes Xenopus an ideal model organism to understand the cellular responses leading to spinal cord regeneration.Methods We compared the cellular response to spinal cord injury between the regenerative and non-regenerative stages of Xenopus laevis. For this analysis, we used electron microscopy, immunofluorescence and histological staining of the extracellular matrix. We generated two transgenic lines: i) the reporter line with the zebrafish GFAP regulatory regions driving the expression of EGFP, and ii) a cell specific inducible ablation line with the same GFAP regulatory regions. In addition, we used FACS to isolate EGFP+ cells for RNAseq analysis.Results In regenerative stage animals, spinal cord regeneration triggers a rapid sealing of the injured stumps, followed by proliferation of cells lining the central canal, and formation of rosette-like structures in the ablation gap. In addition, the central canal is filled by cells with similar morphology to the cells lining the central canal, neurons, axons, and even synaptic structures. Regeneration is almost completed after 20 days post injury. In non-regenerative stage animals, mostly damaged tissue was observed, without clear closure of the stumps. The ablation gap was filled with fibroblast-like cells, and deposition of extracellular matrix components. No reconstruction of the spinal cord was observed even after 40 days post injury. Cellular markers analysis confirmed these histological differences, a transient increase of vimentin, fibronectin and collagen was detected in regenerative stages, contrary to a sustained accumulation of most of these markers, including chondroitin sulfate proteoglycans in the NR-stage. The zebrafish GFAP transgenic line was validated, and we have demonstrated that is a very reliable and new tool to study the role of neural stem progenitor cells (NSPC). RNASeq of GFAP-EGFP cells allowed a clear demonstration that indeed these cells are NSPC. On the contrary, the GFAP-EGFP transgene is mainly expressed in astrocytes in non-regenerative stages. During regenerative stages, spinal cord injury activates proliferation of NSPC, and we found that are mainly fated to form neurons and glial cells. Specific ablation of these cells abolished proper regeneration, confirming that NSPC cells are necessary for functional regeneration of the spinal cord. Conclusions The cellular response to spinal cord injury in regenerative and non-regenerative stages is profoundly different between both stages. A key hallmark of the regenerative response is the activation of NSPC, which massively proliferate to reconstitute the spinal cord, and are differentiated into neurons. Also very notably, no glial scar formation is observed in regenerative stages, but a transient, glial scar-like structure is formed in non-regenerative stage animals.

Dorsal Root Crush in Adult Mice to Study Spinal Cord Regeneration

BIO-PROTOCOL ◽  
2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Hyukmin Kim ◽  
Harun Noristani ◽  
Seung Han ◽  
Young-Jin Son
Keyword(s):  
Spinal Cord ◽  
Dorsal Root ◽  
Spinal Cord Regeneration ◽  
Adult Mice

scholarly journals Extracellular Matrix Remodeling in the Retina and Optic Nerve of a Novel Glaucoma Mouse Model

Biology ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 169
Author(s):  
Jacqueline Reinhard ◽  
Susanne Wiemann ◽  
Sebastian Hildebrandt ◽  
Andreas Faissner
Keyword(s):  
Extracellular Matrix ◽  
Optic Nerve ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Nerve Fibers ◽  
Receptor Protein ◽  
Mrna Levels ◽  
Protein Tyrosine ◽  
Tenascin C ◽  
Iop Elevation

Glaucoma is a neurodegenerative disease that is characterized by the loss of retinal ganglion cells (RGC) and optic nerve fibers. Increased age and intraocular pressure (IOP) elevation are the main risk factors for developing glaucoma. Mice that are heterozygous (HET) for the mega-karyocyte protein tyrosine phosphatase 2 (PTP-Meg2) show chronic and progressive IOP elevation, severe RGCs loss, and optic nerve damage, and represent a valuable model for IOP-dependent primary open-angle glaucoma (POAG). Previously, evidence accumulated suggesting that glaucomatous neurodegeneration is associated with the extensive remodeling of extracellular matrix (ECM) molecules. Unfortunately, little is known about the exact ECM changes in the glaucomatous retina and optic nerve. Hence, the goal of the present study was to comparatively explore ECM alterations in glaucomatous PTP-Meg2 HET and control wild type (WT) mice. Due to their potential relevance in glaucomatous neurodegeneration, we specifically analyzed the expression pattern of the ECM glycoproteins fibronectin, laminin, tenascin-C, and tenascin-R as well as the proteoglycans aggrecan, brevican, and members of the receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) family. The analyses were carried out in the retina and optic nerve of glaucomatous PTP-Meg2 HET and WT mice using quantitative real-time PCR (RT-qPCR), immunohistochemistry, and Western blot. Interestingly, we observed increased fibronectin and laminin levels in the glaucomatous HET retina and optic nerve compared to the WT group. RT-qPCR analyses of the laminins α4, β2 and γ3 showed an altered isoform-specific regulation in the HET retina and optic nerve. In addition, an upregulation of tenascin-C and its interaction partner RPTPβ/ζ/phosphacan was found in glaucomatous tissue. However, comparable protein and mRNA levels for tenascin-R as well as aggrecan and brevican were observed in both groups. Overall, our study showed a remodeling of various ECM components in the glaucomatous retina and optic nerve of PTP-Meg2 HET mice. This dysregulation could be responsible for pathological processes such as neovascularization, inflammation, and reactive gliosis in glaucomatous neurodegeneration.

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