scholarly journals Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves

2015 ◽  
Vol 210 (1) ◽  
pp. 153-168 ◽  
Author(s):  
Jose A. Gomez-Sanchez ◽  
Lucy Carty ◽  
Marta Iruarrizaga-Lejarreta ◽  
Marta Palomo-Irigoyen ◽  
Marta Varela-Rey ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Peripheral Nerves ◽  
Wallerian Degeneration ◽  
Molecular Mechanisms ◽  
Demyelinating Disease ◽  
Cell Reprogramming ◽  
Selective Autophagy ◽  
Wide Range

Although Schwann cell myelin breakdown is the universal outcome of a remarkably wide range of conditions that cause disease or injury to peripheral nerves, the cellular and molecular mechanisms that make Schwann cell–mediated myelin digestion possible have not been established. We report that Schwann cells degrade myelin after injury by a novel form of selective autophagy, myelinophagy. Autophagy was up-regulated by myelinating Schwann cells after nerve injury, myelin debris was present in autophagosomes, and pharmacological and genetic inhibition of autophagy impaired myelin clearance. Myelinophagy was positively regulated by the Schwann cell JNK/c-Jun pathway, a central regulator of the Schwann cell reprogramming induced by nerve injury. We also present evidence that myelinophagy is defective in the injured central nervous system. These results reveal an important role for inductive autophagy during Wallerian degeneration, and point to potential mechanistic targets for accelerating myelin clearance and improving demyelinating disease.

scholarly journals Lessons from Injury: How Nerve Injury Studies Reveal Basic Biological Mechanisms and Therapeutic Opportunities for Peripheral Nerve Diseases

2021 ◽  
Author(s):  
Peter Arthur-Farraj ◽  
Michael P. Coleman
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Peripheral Nerves ◽  
Molecular Mechanisms ◽  
Axon Degeneration ◽  
Axon Loss ◽  
Factor C ◽  
Inherited Neuropathies

AbstractSince Waller and Cajal in the nineteenth and early twentieth centuries, laboratory traumatic peripheral nerve injury studies have provided great insight into cellular and molecular mechanisms governing axon degeneration and the responses of Schwann cells, the major glial cell type of peripheral nerves. It is now evident that pathways underlying injury-induced axon degeneration and the Schwann cell injury-specific state, the repair Schwann cell, are relevant to many inherited and acquired disorders of peripheral nerves. This review provides a timely update on the molecular understanding of axon degeneration and formation of the repair Schwann cell. We discuss how nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) and sterile alpha TIR motif containing protein 1 (SARM1) are required for axon survival and degeneration, respectively, how transcription factor c-JUN is essential for the Schwann cell response to nerve injury and what each tells us about disease mechanisms and potential therapies. Human genetic association with NMNAT2 and SARM1 strongly suggests aberrant activation of programmed axon death in polyneuropathies and motor neuron disorders, respectively, and animal studies suggest wider involvement including in chemotherapy-induced and diabetic neuropathies. In repair Schwann cells, cJUN is aberrantly expressed in a wide variety of human acquired and inherited neuropathies. Animal models suggest it limits axon loss in both genetic and traumatic neuropathies, whereas in contrast, Schwann cell secreted Neuregulin-1 type 1 drives onion bulb pathology in CMT1A. Finally, we discuss opportunities for drug-based and gene therapies to prevent axon loss or manipulate the repair Schwann cell state to treat acquired and inherited neuropathies and neuronopathies.

scholarly journals ATP Release through Lysosomal Exocytosis from Peripheral Nerves: The Effect of Lysosomal Exocytosis on Peripheral Nerve Degeneration and Regeneration after Nerve Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Junyang Jung ◽  
Hyun Woo Jo ◽  
Hyunseob Kwon ◽  
Na Young Jeong
Keyword(s):  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Peripheral Nerves ◽  
Wallerian Degeneration ◽  
Atp Release ◽  
Nerve Degeneration ◽  
Peripheral Neurons ◽  
Charcot Marie Tooth Disease ◽  
Axonal Degradation

Studies have shown that lysosomal activation increases in Schwann cells after nerve injury. Lysosomal activation is thought to promote the engulfment of myelin debris or fragments of injured axons in Schwann cells during Wallerian degeneration. However, a recent interpretation of lysosomal activation proposes a different view of the phenomenon. During Wallerian degeneration, lysosomes become secretory vesicles and are activated for lysosomal exocytosis. The lysosomal exocytosis triggers adenosine 5′-triphosphate (ATP) release from peripheral neurons and Schwann cells during Wallerian degeneration. Exocytosis is involved in demyelination and axonal degradation, which facilitate nerve regeneration following nerve degeneration. At this time, released ATP may affect the communication between cells in peripheral nerves. In this review, our description of the relationship between lysosomal exocytosis and Wallerian degeneration has implications for the understanding of peripheral nerve degenerative diseases and peripheral neuropathies, such as Charcot-Marie-Tooth disease or Guillain-Barré syndrome.

Schwann Cell Reactions in Acute and Chronic Segmental Demyelinating Neuropathies

1968 ◽  
Vol 26 ◽  
pp. 108-109
Author(s):  
Roy O. Weller
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Myelin Sheath ◽  
Wallerian Degeneration ◽  
Demyelinating Disease ◽  
Segmental Demyelination ◽  
Recovery Stage ◽  
Myelin Sheaths ◽  
Demyelinating Neuropathies

The length of axon that each Schwann cell myelinates in a normal peripheral nerve is approximately proportional to the diameter of the axon and the thickness of the myelin sheath produced. When segmental demyelination occurs, individual segments, represented by the length of axon covered by one Schwann cell, lose their myelin sheaths but the axons are preserved. This differs from Wallerian degeneration where myelin destruction occurs along the length of a nerve fibre following death of the axon.In experimental diphtheritic neuropathy, an acute segmental demyelinating disease, lysosomes accumulate within the Schwann cells prior to disruption of the myelin sheath; furthermore, the site of initial myelin breakdown appears to be closely related to the collections of lysosomes. The Schwann cell starts to form a new myelin sheath around the axon probably within a few hours of the destruction of the original myelin sheath, and while the latter is being catabolised within lysosomal vacuoles This stage of remyelination follows a similar course to primary myelination, so that the recovery stage is characterised by normal axons with either no myelin, or surrounded by sheaths that are very thin relative to the diameter of the axon.

scholarly journals Leukemia inhibitory factor regulates Schwann cell proliferation and migration and affects peripheral nerve regeneration

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Qianqian Chen ◽  
Qianyan Liu ◽  
Yunsong Zhang ◽  
Shiying Li ◽  
Sheng Yi
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Peripheral Nerves ◽  
Leukemia Inhibitory Factor ◽  
Peripheral Nerve Regeneration ◽  
And Migration ◽  
Proliferation And Migration

AbstractLeukemia inhibitory factor (LIF) is a pleiotropic cytokine that stimulates neuronal development and survival. Our previous study has demonstrated that LIF mRNA is dysregulated in the peripheral nerve segments after nerve injury. Here, we show that LIF protein is abundantly expressed in Schwann cells after rat sciatic nerve injury. Functionally, suppressed or elevated LIF increases or decreases the proliferation rate and migration ability of Schwann cells, respectively. Morphological observations demonstrate that in vivo application of siRNA against LIF after peripheral nerve injury promotes Schwann cell migration and proliferation, axon elongation, and myelin formation. Electrophysiological and behavior assessments disclose that knockdown of LIF benefits the function recovery of injured peripheral nerves. Differentially expressed LIF affects the metabolism of Schwann cells and negatively regulates ERFE (Erythroferrone). Collectively, our observations reveal the essential roles for LIF in regulating the proliferation and migration of Schwann cells and the regeneration of injured peripheral nerves, discover ERFE as a downstream effector of LIF, and extend our understanding of the molecular mechanisms underlying peripheral nerve regeneration.

scholarly journals Cyr61 promotes Schwann cell proliferation and migration via αvβ3 integrin

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhenghui Cheng ◽  
Yawen Zhang ◽  
Yinchao Tian ◽  
Yuhan Chen ◽  
Fei Ding ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Peripheral Nerves ◽  
Molecular Mechanisms ◽  
Αvβ3 Integrin ◽  
Promoting Effect ◽  
Ccn Family ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Schwann cells (SCs) play a crucial role in the repair of peripheral nerves. This is due to their ability to proliferate, migrate, and provide trophic support to axon regrowth. During peripheral nerve injury, SCs de-differentiate and reprogram to gain the ability to repair nerves. Cysteine-rich 61 (Cyr61/CCN1) is a member of the CCN family of matrix cell proteins and have been reported to be abundant in the secretome of repair mediating SCs. In this study we investigate the function of Cyr61 in SCs. Results We observed Cyr61 was expressed both in vivo and in vitro. The promoting effect of Cyr61 on SC proliferation and migration was through autocrine and paracrine mechanisms. SCs expressed αvβ3 integrin and the effect of Cyr61 on SC proliferation and migration could be blocked via αvβ3 integrin. Cyr61 could influence c-Jun protein expression in cultured SCs. Conclusions In this study, we found that Cyr61 promotes SC proliferation and migration via αvβ3 integrin and regulates c-Jun expression. Our study contributes to the understanding of cellular and molecular mechanisms underlying SC’s function during nerve injury, and thus, may facilitate the regeneration of peripheral nerves after injury.

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 Myelinophagy: Schwann cells dine in

2015 ◽  
Vol 210 (1) ◽  
pp. 9-10 ◽  
Author(s):  
Michael Thumm ◽  
Mikael Simons
Keyword(s):  
Schwann Cells ◽  
Nerve Injury ◽  
Injury Site ◽  
Selective Autophagy ◽  
Cell Biol

When nerve injury occurs, the axon and myelin fragments distal to the injury site have to be cleared away before repair. In this issue, Gomez-Sanchez et al. (2015; J. Cell Biol. http://dx.doi.org/10.1083/jcb.201503019) find that clearance of the damaged myelin within Schwann cells occurs not by phagocytosis but rather via selective autophagy, in a process they term “myelinophagy.”

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