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Yakugaku Zasshi : Journal of the... 2022Myelin is a multilamellar membrane structure formed by oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS). It... (Review)
Review
Myelin is a multilamellar membrane structure formed by oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS). It has been recognized as an insulator that is essential for the rapid and efficient propagation of action potentials by saltatory conduction. However, recently many studies have shown that myelin and myelin-forming cells interact with axons and regulate the nervous system far more actively than previously thought. For example, myelination changes axons dynamically and divides them into four distinct functional domains: node of Ranvier, paranode, juxtaparanode, and internode. Voltage-gated Na channels are clustered at the node, while K channels are at the juxtaparanode, and segregation of these channels by paranodal axoglial junction is necessary for proper axonal function. My research experience began at the neurology ward of the Niigata University Medical Hospital, where I saw a patient with peripheral neuropathy of unknown etiology more than 37 years ago. In the patient's serum, we found an autoantibody against a glycolipid enriched in the PNS. Since then, I have been interested in myelin because of its beautiful structure and unique roles in the nervous system. In this review, our recent studies related to CNS and PNS myelin are presented.
Topics: Autoantibodies; Axons; Central Nervous System; Humans; Myelin Sheath; Ranvier's Nodes; Schwann Cells
PubMed: 35908945
DOI: 10.1248/yakushi.21-00224 -
Glia Apr 2021YAP and TAZ are effectors of the Hippo pathway that controls multicellular development by integrating chemical and mechanical signals. Peripheral nervous system...
YAP and TAZ are effectors of the Hippo pathway that controls multicellular development by integrating chemical and mechanical signals. Peripheral nervous system development depends on the Hippo pathway. We previously showed that loss of YAP and TAZ impairs the development of peripheral nerve as well as Schwann cell myelination. The role of the Hippo pathway in peripheral nerve regeneration has just started to be explored. After injury, Schwann cells adopt new identities to promote regeneration by converting to a repair-promoting phenotype. While the reprogramming of Schwann cells to repair cells has been well characterized, the maintenance of such repair phenotype cannot be sustained for a very long period, which limits nerve repair in human. First, we show that short or long-term myelin maintenance is not affected by defect in YAP and TAZ expression. Using crush nerve injury and conditional mutagenesis in mice, we also show that YAP and TAZ are regulators of repair Schwann cell proliferation and differentiation. We found that YAP and TAZ are required in repair Schwann cells for their redifferentiation into myelinating Schwann cell following crush injury. In this present study, we describe how the Hippo pathway and YAP and TAZ regulate remyelination over time during peripheral nerve regeneration.
Topics: Adaptor Proteins, Signal Transducing; Animals; Cell Cycle Proteins; Cell Differentiation; Cell Proliferation; Hippo Signaling Pathway; Mice; Nerve Regeneration; Schwann Cells
PubMed: 33336855
DOI: 10.1002/glia.23949 -
Glia Aug 2015In the peripheral nervous system, Schwann cells are glial cells that are in intimate contact with axons throughout development. Schwann cells generate the insulating... (Review)
Review
In the peripheral nervous system, Schwann cells are glial cells that are in intimate contact with axons throughout development. Schwann cells generate the insulating myelin sheath and provide vital trophic support to the neurons that they ensheathe. Schwann cell precursors arise from neural crest progenitor cells, and a highly ordered developmental sequence controls the progression of these cells to become mature myelinating or nonmyelinating Schwann cells. Here, we discuss both seminal discoveries and recent advances in our understanding of the molecular mechanisms that drive Schwann cell development and myelination with a focus on cell-cell and cell-matrix signaling events.
Topics: Animals; Humans; Myelin Sheath; Neural Stem Cells; Schwann Cells
PubMed: 25921593
DOI: 10.1002/glia.22852 -
The Neuroscientist : a Review Journal... Feb 2012Myelination of axons by oligodendrocytes and Schwann cells in the central and peripheral nervous system, respectively, is essential for normal neuronal functions, and... (Review)
Review
Myelination of axons by oligodendrocytes and Schwann cells in the central and peripheral nervous system, respectively, is essential for normal neuronal functions, and its failure results in devastating demyelinating diseases. During development, both oligodendrocyte and Schwann cell precursors undergo a temporally well-defined series of molecular and structural changes, ultimately culminating in the cessation of proliferation and the elaboration of a highly complex myelin sheath. Recent studies have demonstrated a critical role of microRNAs (miRNAs) in the progression of oligodendrocyte and Schwann cell precursors to the myelinating state-depletion of miRNAs from either cell type results in an arrest in differentiation and lack of myelination. Furthermore, these studies have begun to elucidate the dynamic regulation of miRNA expression and the complexity of miRNA-mediated gene regulation during differentiation of myelinating cells. In this review, the authors highlight the recent understanding of functional links of miRNAs to regulatory networks for central and peripheral myelination, as well as perspectives on the role of miRNAs in demyelinating diseases.
Topics: Animals; Astrocytes; Axons; Cell Differentiation; Demyelinating Diseases; Gene Expression Regulation; Humans; Mice; Mice, Knockout; MicroRNAs; Myelin Sheath; Neurons; Oligodendroglia; Schwann Cells
PubMed: 21536841
DOI: 10.1177/1073858410392382 -
Scientific Reports Jan 2021Oral cancer is very painful and impairs a patient's ability to eat, talk, and drink. Mediators secreted from oral cancer can excite and sensitize sensory neurons...
Oral cancer is very painful and impairs a patient's ability to eat, talk, and drink. Mediators secreted from oral cancer can excite and sensitize sensory neurons inducing pain. Cancer mediators can also activate Schwann cells, the peripheral glia that regulates neuronal function and repair. The contribution of Schwann cells to oral cancer pain is unclear. We hypothesize that the oral cancer mediator TNFα activates Schwann cells, which further promotes cancer progression and pain. We demonstrate that TNFα is overexpressed in human oral cancer tissues and correlates with increased self-reported pain in patients. Antagonizing TNFα reduces oral cancer proliferation, cytokine production, and nociception in mice with oral cancer. Oral cancer or TNFα alone increases Schwann cell activation (measured by Schwann cell proliferation, migration, and activation markers), which can be inhibited by neutralizing TNFα. Cancer- or TNFα-activated Schwann cells release pro-nociceptive mediators such as TNFα and nerve growth factor (NGF). Activated Schwann cells induce nociceptive behaviors in mice, which is alleviated by blocking TNFα. Our study suggests that TNFα promotes cancer proliferation, progression, and nociception at least partially by activating Schwann cells. Inhibiting TNFα or Schwann cell activation might serve as therapeutic approaches for the treatment of oral cancer and associated pain.
Topics: Animals; Cancer Pain; Cell Proliferation; Disease Progression; Humans; Mice; Mouth Neoplasms; Nerve Growth Factor; Pain Measurement; Schwann Cells; Tumor Necrosis Factor-alpha
PubMed: 33469141
DOI: 10.1038/s41598-021-81500-4 -
Biomolecules Dec 2021Like the seasons of the year, all natural things happen in stages, going through adaptations when challenged, and Schwann cells are a great example of that. During... (Review)
Review
Like the seasons of the year, all natural things happen in stages, going through adaptations when challenged, and Schwann cells are a great example of that. During maturation, these cells regulate several steps in peripheral nervous system development. The Spring of the cell means the rise and bloom through organized stages defined by time-dependent regulation of factors and microenvironmental influences. Once matured, the Summer of the cell begins: a high energy stage focused on maintaining adult homeostasis. The Schwann cell provides many neuron-glia communications resulting in the maintenance of synapses. In the peripheral nervous system, Schwann cells are pivotal after injuries, balancing degeneration and regeneration, similarly to when Autumn comes. Their ability to acquire a repair phenotype brings the potential to reconnect axons to targets and regain function. Finally, Schwann cells age, not only by growing old, but also by imposed environmental cues, like loss of function induced by pathologies. The Winter of the cell presents as reduced activity, especially regarding their role in repair; this reflects on the regenerative potential of older/less healthy individuals. This review gathers essential information about Schwann cells in different stages, summarizing important participation of this intriguing cell in many functions throughout its lifetime.
Topics: Animals; Cellular Senescence; Homeostasis; Humans; Nerve Regeneration; Peripheral Nerve Injuries; Schwann Cells
PubMed: 34944531
DOI: 10.3390/biom11121887 -
Cells Aug 2020Functional recovery after neurotmesis, a complete transection of the nerve fiber, is often poor and requires a surgical procedure. Especially for longer gaps (>3 mm),... (Review)
Review
Functional recovery after neurotmesis, a complete transection of the nerve fiber, is often poor and requires a surgical procedure. Especially for longer gaps (>3 mm), end-to-end suturing of the proximal to the distal part is not possible, thus requiring nerve graft implantation. Artificial nerve grafts, i.e., hollow fibers, hydrogels, chitosan, collagen conduits, and decellularized scaffolds hold promise provided that these structures are populated with Schwann cells (SC) that are widely accepted to promote peripheral and spinal cord regeneration. However, these cells must be collected from the healthy peripheral nerves, resulting in significant time delay for treatment and undesired morbidities for the donors. Therefore, there is a clear need to explore the viable source of cells with a regenerative potential similar to SC. For this, we analyzed the literature for the generation of Schwann cell-like cells (SCLC) from stem cells of different origins (i.e., mesenchymal stem cells, pluripotent stem cells, and genetically programmed somatic cells) and compared their biological performance to promote axonal regeneration. Thus, the present review accounts for current developments in the field of SCLC differentiation, their applications in peripheral and central nervous system injury, and provides insights for future strategies.
Topics: Central Nervous System; Humans; Nerve Regeneration; Peripheral Nervous System; Schwann Cells
PubMed: 32872454
DOI: 10.3390/cells9091990 -
PloS One 2021Polyneuropathy is a debilitating condition characterized by distal sensory and motor deficits. Schwann cell dysfunction and axonal loss are integral factors in...
INTRODUCTION
Polyneuropathy is a debilitating condition characterized by distal sensory and motor deficits. Schwann cell dysfunction and axonal loss are integral factors in pathophysiology and disease progression of polyneuropathy.
AIMS
The aim of this study was the assessment of Schwann cell characteristics, nerve fibers and myelination parameters in polyneuropathy patients compared to controls.
METHODS
Nerve tissue was obtained from polyneuropathy patients (n = 10) undergoing diagnostic sural nerve biopsies. Biopsies of healthy peripheral nerves (n = 5) were harvested during elective sural nerve grafting for chronic peripheral nerve lesions. Exclusion criteria for the healthy control group were recent neurological trauma, diabetes, neurological and cardiovascular disease, as well as active malignancies and cytotoxic medication within the last 12 months. The over-all architecture of nerve sections and myelination parameters were histomorphometrically analyzed. Immunofluorescent imaging was used to evaluate Schwann cell phenotypes, senescence markers and myelination parameters.
RESULTS
Histomorphometric analysis of nerve biopsies showed significant axonal loss in polyneuropathy patients compared to controls, which was in accordance with the neuropathological findings. Immunofluorescent staining of Schwann cells and myelin basic protein indicated a significant impairment of myelination and lower Schwann cell counts compared to controls. Phenotypic alterations and increased numbers of non-myelinating p75-positive Schwann cells were found in polyneuropathy patients.
DISCUSSION
This study provided quantitative data of axonal loss, reduced myelination and Schwann cell dysfunction of polyneuropathy patients compared to neurologically healthy controls. Phenotypic alterations of Schwann cells were similar to those seen after peripheral nerve injury, highlighting the clinical relevance of Schwann cell dysfunction.
Topics: Adult; Axons; Female; Fluorescent Antibody Technique; Humans; Male; Middle Aged; Nerve Fibers, Myelinated; Polyneuropathies; Schwann Cells
PubMed: 34735549
DOI: 10.1371/journal.pone.0259654 -
Developmental Neurobiology Jul 2021Schwann cells play a critical role in the development of the peripheral nervous system (PNS), establishing important relationships both with the extracellular milieu and... (Review)
Review
Schwann cells play a critical role in the development of the peripheral nervous system (PNS), establishing important relationships both with the extracellular milieu and other cell types, particularly neurons. In this review, we discuss various Schwann cell interactions integral to the proper establishment, spatial arrangement, and function of the PNS. We include signals that cascade onto Schwann cells from axons and from the extracellular matrix, bidirectional signals that help to establish the axo-glial relationship and how Schwann cells in turn support the axon. Further, we speculate on how Schwann cell interactions with other components of the developing PNS ultimately promote the complete construction of the peripheral nerve.
Topics: Axons; Cell Communication; Neuroglia; Peripheral Nervous System; Schwann Cells
PubMed: 32281247
DOI: 10.1002/dneu.22744 -
Glia Apr 2023Signal propagation is the essential function of nerves. Lysophosphatidic acid 18:1 (LPA) allows the selective stimulation of calcium signaling in Schwann cells but not...
Signal propagation is the essential function of nerves. Lysophosphatidic acid 18:1 (LPA) allows the selective stimulation of calcium signaling in Schwann cells but not neurons. Here, the time course of slowing and amplitude reduction on compound action potentials due to LPA exposure was observed in myelinated and unmyelinated fibers of the mouse, indicating a clear change of axonal function. Teased nerve fiber imaging showed that Schwann cell activation is also present in axon-attached Schwann cells in freshly isolated peripheral rat nerves. The LPA receptor 1 was primarily localized at the cell extensions in isolated rat Schwann cells, suggesting a role in cell migration. Structural investigation of rat C-fibers demonstrated that LPA leads to an evagination of the axons from their Schwann cells. In A-fibers, the nodes of Ranvier appeared unchanged, but the Schmidt-Lanterman incisures were shortened and myelination reduced. The latter might increase leak current, reducing the potential spread to the next node of Ranvier and explain the changes in conduction velocity. The observed structural changes provide a plausible explanation for the functional changes in myelinated and unmyelinated axons of peripheral nerves and the reported sensory sensations such as itch and pain.
Topics: Mice; Rats; Animals; Peripheral Nerves; Schwann Cells; Myelin Sheath; Nerve Fibers, Myelinated; Axons
PubMed: 36495059
DOI: 10.1002/glia.24316