scholarly journals Myelinating Schwann cells and Netrin-1 control intra-nervous vascularization of the developing mouse sciatic nerve

2020 ◽  
Author(s):  
Sonia Taïb ◽  
Noël Lamandé ◽  
Sabrina Martin ◽  
Piotr Topilko ◽  
Isabelle Brunet
Keyword(s):  
Sciatic Nerve ◽  
Blood Vessels ◽  
Schwann Cells ◽  
Peripheral Nerves ◽  
Complex Function ◽  
Postnatal Period ◽  
Nerve Invasion ◽  
Axon Guidance Molecule ◽  
Guidance Molecule

AbstractPeripheral nerves are vascularized by a dense network of blood vessels to guarantee their complex function. Despite the crucial role of vascularization to ensure nerve homeostasis and regeneration, the mechanisms governing nerve invasion by blood vessels remain poorly understood. We found that the sciatic nerve invasion by blood vessels begins around embryonic day 16 and continues until birth. Interestingly, intra-nervous blood vessel density significantly decreases during post-natal period, starting from P10. We show that, while the axon guidance molecule Netrin-1 promotes nerve invasion by blood vessels during embryogenesis, myelinated Schwann cells negatively control intra-nervous vascularization during postnatal period.

scholarly journals Myelinating Schwann cells and Netrin-1 control intra-nervous vascularization of the developing mouse sciatic nerve

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Sonia Taïb ◽  
Noël Lamandé ◽  
Sabrina Martin ◽  
Fanny Coulpier ◽  
Piotr Topilko ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Blood Vessels ◽  
Schwann Cells ◽  
Complex Function ◽  
Postnatal Period ◽  
Nerve Invasion ◽  
Axon Guidance Molecule ◽  
Guidance Molecule ◽  
Endothelial Receptor

Peripheral nerves are vascularized by a dense network of blood vessels to guarantee their complex function. Despite the crucial role of vascularization to ensure nerve homeostasis and regeneration, the mechanisms governing nerve invasion by blood vessels remain poorly understood. We found, in mice, that the sciatic nerve invasion by blood vessels begins around embryonic day 16 and continues until birth. Interestingly, intra-nervous blood vessel density significantly decreases during post-natal period, starting from P10. We show that, while the axon guidance molecule Netrin-1 promotes nerve invasion by blood vessels via the endothelial receptor UNC5B during embryogenesis, myelinated Schwann cells negatively control intra-nervous vascularization during postnatal period.

scholarly journals Laminin γ1 is critical for Schwann cell differentiation, axon myelination, and regeneration in the peripheral nerve

2003 ◽  
Vol 163 (4) ◽  
pp. 889-899 ◽  
Author(s):  
Zu-Lin Chen ◽  
Sidney Strickland
Keyword(s):  
Schwann Cells ◽  
Peripheral Nerves ◽  
Matrix Proteins ◽  
Myelin Proteins ◽  
Sciatic Nerve Crush ◽  
Similar Reduction ◽  
Nerve Crush ◽  
And Function ◽  
Schwann Cell Differentiation

Laminins are heterotrimeric extracellular matrix proteins that regulate cell viability and function. Laminin-2, composed of α2, β1, and γ1 chains, is a major matrix component of the peripheral nervous system (PNS). To investigate the role of laminin in the PNS, we used the Cre–loxP system to disrupt the laminin γ1 gene in Schwann cells. These mice have dramatically reduced expression of laminin γ1 in Schwann cells, which results in a similar reduction in laminin α2 and β1 chains. These mice exhibit motor defects which lead to hind leg paralysis and tremor. During development, Schwann cells that lack laminin γ1 were present in peripheral nerves, and proliferated and underwent apoptosis similar to control mice. However, they were unable to differentiate and synthesize myelin proteins, and therefore unable to sort and myelinate axons. In mutant mice, after sciatic nerve crush, the axons showed impaired regeneration. These experiments demonstrate that laminin is an essential component for axon myelination and regeneration in the PNS.

scholarly journals S100ß and fibroblast growth factor-2 are present in cultured Schwann cells and may exert paracrine actions on the peripheral nerve injury

2008 ◽  
Vol 23 (6) ◽  
pp. 555-560 ◽  
Author(s):  
Tatiana Duobles ◽  
Thais de Sousa Lima ◽  
Beatriz de Freitas Azevedo Levy ◽  
Gerson Chadi
Keyword(s):  
Growth Factor ◽  
Sciatic Nerve ◽  
Fibroblast Growth Factor ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Satellite Cells ◽  
Peripheral Nerves ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Cultured Schwann Cells

PURPOSE: The neurotrophic factor fibroblast growth factor-2 (FGF-2, bFGF) and Ca++ binding protein S100ß are expressed by the Schwann cells of the peripheral nerves and by the satellite cells of the dorsal root ganglia (DRG). Recent studies have pointed out the importance of the molecules in the paracrine mechanisms related to neuronal maintenance and plasticity of lesioned motor and sensory peripheral neurons. Moreover, cultured Schwann cells have been employed experimentally in the treatment of central nervous system lesions, in special the spinal cord injury, a procedure that triggers an enhanced sensorymotor function. Those cells have been proposed to repair long gap nerve injury. METHODS: Here we used double labeling immunohistochemistry and Western blot to better characterize in vitro and in vivo the presence of the proteins in the Schwann cells and in the satellite cells of the DRG as well as their regulation in those cells after a crush of the rat sciatic nerve. RESULTS: FGF-2 and S100ß are present in the Schwann cells of the sciatic nerve and in the satellite cells of the DRG. S100ß positive satellite cells showed increased size of the axotomized DRG and possessed elevated amount of FGF-2 immunoreactivity. Reactive satellite cells with increased FGF-2 labeling formed a ring-like structure surrounding DRG neuronal cell bodies.Reactive S100ß positive Schwann cells of proximal stump of axotomized sciatic nerve also expressed higher amounts of FGF-2. CONCLUSION: Reactive peripheral glial cells synthesizing FGF-2 and S100ß may be important in wound repair and restorative events in the lesioned peripheral nerves.

A Neuropathy in Goats Caused by Experimental Coyotillo (Karwinskia humboldtiana) Poisoning

1970 ◽  
Vol 7 (5) ◽  
pp. 420-434 ◽  
Author(s):  
K. M. Charlton ◽  
K. R. Pierce
Keyword(s):  
Electron Microscopy ◽  
Sciatic Nerve ◽  
Schwann Cells ◽  
Active Transport ◽  
Peripheral Nerves ◽  
Wallerian Degeneration ◽  
Light And Electron Microscopy ◽  
Segmental Demyelination ◽  
Femoral Site ◽  
Oral Doses

Lesions in peripheral nerves from 12 goats poisoned experimentally with coyotillo were studied by light and electron microscopy. The goats were poisoned with daily oral doses of the ground coyotillo fruits and killed at various times after the first day of dosing. Lesions at a mid-femoral site of the sciatic nerve included swelling of Schwann cells, degeneration of mitochondria, depletion of glycogen, splitting of myelin, segmental demyelination, and Wallerian degeneration. The results were suggestive of primary mitochondrial injury in Schwann cells with resultant impaired active transport, intracellular edema, splitting of myelin, and segmental demyelination.

scholarly journals Ndrg1-Deficient Mice Exhibit a Progressive Demyelinating Disorder of Peripheral Nerves

2004 ◽  
Vol 24 (9) ◽  
pp. 3949-3956 ◽  
Author(s):  
Tomohiko Okuda ◽  
Yujiro Higashi ◽  
Koichi Kokame ◽  
Chihiro Tanaka ◽  
Hisato Kondoh ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Schwann Cells ◽  
Peripheral Nerves ◽  
Sensory Neuropathy ◽  
Disease Type ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Hind Limbs ◽  
Deficient Mice ◽  
Tooth Disease

ABSTRACT NDRG1 is an intracellular protein that is induced under a number of stress and pathological conditions, and it is thought to be associated with cell growth and differentiation. Recently, human NDRG1 was identified as a gene responsible for hereditary motor and sensory neuropathy-Lom (classified as Charcot-Marie-Tooth disease type 4D), which is characterized by early-onset peripheral neuropathy, leading to severe disability in adulthood. In this study, we generated mice lacking Ndrg1 to analyze its function and elucidate the pathogenesis of Charcot-Marie-Tooth disease type 4D. Histological analysis showed that the sciatic nerve of Ndrg1-deficient mice degenerated with demyelination at about 5 weeks of age. However, myelination of Schwann cells in the sciatic nerve was normal for 2 weeks after birth. Ndrg1-deficient mice showed muscle weakness, especially in the hind limbs, but complicated motor skills were retained. In wild-type mice, NDRG1 was abundantly expressed in the cytoplasm of Schwann cells rather than the myelin sheath. These results indicate that NDRG1 deficiency leads to Schwann cell dysfunction, suggesting that NDRG1 is essential for maintenance of the myelin sheaths in peripheral nerves. These mice will be used for future analyses of the mechanisms of myelin maintenance.

scholarly journals Clearance of peripheral nerve misfolded mutant protein by infiltrated macrophages correlates with motor neuron disease progression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wataru Shiraishi ◽  
Ryo Yamasaki ◽  
Yu Hashimoto ◽  
Senri Ko ◽  
Yuko Kobayakawa ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerves ◽  
Disease Onset ◽  
Green Fluorescence Protein ◽  
Macrophage Infiltration ◽  
Fluorescence Protein ◽  
End Stage ◽  
Als Patients

AbstractMacrophages expressing C–C chemokine receptor type 2 (CCR2) infiltrate the central and peripheral neural tissues of amyotrophic lateral sclerosis (ALS) patients. To identify the functional role of CCR2+ macrophages in the pathomechanisms of ALS, we used an ALS animal model, mutant Cu/Zn superoxide dismutase 1G93A (mSOD1)-transgenic (Tg) mice. To clarify the CCR2 function in the model, we generated SOD1G93A/CCR2Red fluorescence protein (RFP)/Wild type (WT)/CX3CR1Green fluorescence protein (GFP)/WT-Tg mice, which heterozygously express CCR2-RFP and CX3CR1-GFP, and SOD1G93A/CCR2RFP/RFP-Tg mice, which lack CCR2 protein expression and present with a CCR2-deficient phenotype. In mSOD1-Tg mice, mSOD1 accumulated in the sciatic nerve earlier than in the spinal cord. Furthermore, spinal cords of SOD1G93A/CCR2RFP/WT/CX3CR1GFP/WT mice showed peripheral macrophage infiltration that emerged at the end-stage, whereas in peripheral nerves, macrophage infiltration started from the pre-symptomatic stage. Before disease onset, CCR2+ macrophages harboring mSOD1 infiltrated sciatic nerves earlier than the lumbar cord. CCR2-deficient mSOD1-Tg mice showed an earlier onset and axonal derangement in the sciatic nerve than CCR2-positive mSOD1-Tg mice. CCR2-deficient mSOD1-Tg mice showed an increase in deposited mSOD1 in the sciatic nerve compared with CCR2-positive mice. These findings suggest that CCR2+ and CX3CR1+ macrophages exert neuroprotective functions in mSOD1 ALS via mSOD1 clearance from the peripheral nerves.

scholarly journals Netrin-1 as a Multitarget Barrier Stabilizer in the Peripheral Nerve after Injury

2021 ◽  
Vol 22 (18) ◽  
pp. 10090
Author(s):  
Jeremy Tsung-Chieh Chen ◽  
Lea Schmidt ◽  
Christina Schürger ◽  
Mohammed K. Hankir ◽  
Susanne M. Krug ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Injury ◽  
Peripheral Nerves ◽  
Chronic Constriction Injury ◽  
Neuronal Damage ◽  
Pain Processing ◽  
Central Nervous Systems ◽  
Neuronal Guidance ◽  
Junction Proteins

The blood–nerve barrier and myelin barrier normally shield peripheral nerves from potentially harmful insults. They are broken down during nerve injury, which contributes to neuronal damage. Netrin-1 is a neuronal guidance protein with various established functions in the peripheral and central nervous systems; however, its role in regulating barrier integrity and pain processing after nerve injury is poorly understood. Here, we show that chronic constriction injury (CCI) in Wistar rats reduced netrin-1 protein and the netrin-1 receptor neogenin-1 (Neo1) in the sciatic nerve. Replacement of netrin-1 via systemic or local administration of the recombinant protein rescued injury-induced nociceptive hypersensitivity. This was prevented by siRNA-mediated knockdown of Neo1 in the sciatic nerve. Mechanistically, netrin-1 restored endothelial and myelin, but not perineural, barrier function as measured by fluorescent dye or fibrinogen penetration. Netrin-1 also reversed the decline in the tight junction proteins claudin-5 and claudin-19 in the sciatic nerve caused by CCI. Our findings emphasize the role of the endothelial and myelin barriers in pain processing after nerve damage and reveal that exogenous netrin-1 restores their function to mitigate CCI-induced hypersensitivity via Neo1. The netrin-1-neogenin-1 signaling pathway may thus represent a multi-target barrier protector for the treatment of neuropathic pain.

scholarly journals Role of Schwann Cells in the Regeneration of Penile and Peripheral Nerves

2015 ◽  
Vol 0 (0) ◽  
pp. 0 ◽  
Author(s):  
Guiting Lin ◽  
TomF Lue ◽  
MelissaT Sanford ◽  
Lin Wang ◽  
Zhongcheng Xin
Keyword(s):  
Schwann Cells ◽  
Peripheral Nerves
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