scholarly journals Myelination: all about Rac ‘n’ roll

2007 ◽  
Vol 177 (6) ◽  
pp. 953-955 ◽  
Author(s):  
Jonah R. Chan
Keyword(s):  
Nervous System ◽  
Schwann Cells ◽  
Molecular Mechanisms ◽  
Nerve Bundle ◽  
Effector Molecule ◽  
Downstream Effector ◽  
Rho Family ◽  
Radial Sorting ◽  
Shed Light ◽  
Lamellipodia Formation

During the development of the peripheral nervous system, Schwann cells select individual axons from a nerve bundle and establish a one-to-one relationship through a process termed “radial sorting”. Recent findings identify the Rho family GTPase Rac1 as the downstream effector molecule responsible for process extension and lamellipodia formation in Schwann cells, allowing for proper radial sorting and myelination. These findings begin to shed light on our understanding of the distinct and yet essential molecular mechanisms involved in developmental processes preceding myelination.

scholarly journals Essential and distinct roles for cdc42 and rac1 in the regulation of Schwann cell biology during peripheral nervous system development

2007 ◽  
Vol 177 (6) ◽  
pp. 1051-1061 ◽  
Author(s):  
Yves Benninger ◽  
Tina Thurnherr ◽  
Jorge A. Pereira ◽  
Sven Krause ◽  
Xunwei Wu ◽  
...  
Keyword(s):  
Nervous System ◽  
Schwann Cell ◽  
Peripheral Nervous System ◽  
Schwann Cells ◽  
Rho Gtpases ◽  
Cell Biology ◽  
System Development ◽  
Nervous System Development ◽  
Conditional Gene Targeting ◽  
Radial Sorting

During peripheral nervous system (PNS) myelination, Schwann cells must interpret extracellular cues to sense their environment and regulate their intrinsic developmental program accordingly. The pathways and mechanisms involved in this process are only partially understood. We use tissue-specific conditional gene targeting to show that members of the Rho GTPases, cdc42 and rac1, have different and essential roles in axon sorting by Schwann cells. Our results indicate that although cdc42 is required for normal Schwann cell proliferation, rac1 regulates Schwann cell process extension and stabilization, allowing efficient radial sorting of axon bundles.

scholarly journals Schwann cells use TAM receptor-mediated phagocytosis in addition to autophagy to clear myelin in a mouse model of nerve injury

2017 ◽  
Vol 114 (38) ◽  
pp. E8072-E8080 ◽  
Author(s):  
Amanda Brosius Lutz ◽  
Won-Suk Chung ◽  
Steven A. Sloan ◽  
Glenn A. Carson ◽  
Lu Zhou ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mouse Model ◽  
Schwann Cells ◽  
Molecular Mechanisms ◽  
Crush Injury ◽  
Nerve Crush ◽  
Pns Myelin ◽  
Myelin Debris ◽  
Nerve Crush Injury

Ineffective myelin debris clearance is a major factor contributing to the poor regenerative ability of the central nervous system. In stark contrast, rapid clearance of myelin debris from the injured peripheral nervous system (PNS) is one of the keys to this system’s remarkable regenerative capacity, but the molecular mechanisms driving PNS myelin clearance are incompletely understood. We set out to discover new pathways of PNS myelin clearance to identify novel strategies for activating myelin clearance in the injured central nervous system, where myelin debris is not cleared efficiently. Here we show that Schwann cells, the myelinating glia of the PNS, collaborate with hematogenous macrophages to clear myelin debris using TAM (Tyro3, Axl, Mer) receptor-mediated phagocytosis as well as autophagy. In a mouse model of PNS nerve crush injury, Schwann cells up-regulate TAM phagocytic receptors Axl and Mertk following PNS injury, and Schwann cells lacking both of these phagocytic receptors exhibit significantly impaired myelin phagocytosis both in vitro and in vivo. Autophagy-deficient Schwann cells also display reductions in myelin clearance after mouse nerve crush injury, as has been recently shown following nerve transection. These findings add a mechanism, Axl/Mertk-mediated myelin clearance, to the repertoire of cellular machinery used to clear myelin in the injured PNS. Given recent evidence that astrocytes express Axl and Mertk and have previously unrecognized phagocytic potential, this pathway may be a promising avenue for activating myelin clearance after CNS injury.

Neurite Development and Repair in Worms and Flies

2019 ◽  
Vol 42 (1) ◽  
pp. 209-226 ◽  
Author(s):  
Claire E. Richardson ◽  
Kang Shen
Keyword(s):  
Nervous System ◽  
Molecular Mechanisms ◽  
Temporal Constraints ◽  
Regulate Gene Expression ◽  
Surrounding Environment ◽  
Cytoskeletal Dynamics ◽  
Recent Developments ◽  
The Many ◽  
Neurite Development ◽  
Shed Light

How the nervous system is wired has been a central question of neuroscience since the inception of the field, and many of the foundational discoveries and conceptual advances have been made through the study of invertebrate experimental organisms, including Caenorhabditis elegans and Drosophila melanogaster. Although many guidance molecules and receptors have been identified, recent experiments have shed light on the many modes of action for these pathways. Here, we summarize the recent progress in determining how the physical and temporal constraints of the surrounding environment provide instructive regulations in nervous system wiring. We use Netrin and its receptors as an example to analyze the complexity of how they guide neurite outgrowth. In neurite repair, conserved injury detection and response-signaling pathways regulate gene expression and cytoskeletal dynamics. We also describe recent developments in the research on molecular mechanisms of neurite regeneration in worms and flies.

scholarly journals GPR56/ADGRG1 regulates development and maintenance of peripheral myelin

2018 ◽  
Vol 215 (3) ◽  
pp. 941-961 ◽  
Author(s):  
Sarah D. Ackerman ◽  
Rong Luo ◽  
Yannick Poitelon ◽  
Amit Mogha ◽  
Breanne L. Harty ◽  
...  
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Schwann Cells ◽  
Myelin Sheath ◽  
Underlying Mechanism ◽  
Scaffolding Protein ◽  
Rodent Models ◽  
Myelin Thickness ◽  
Radial Sorting ◽  
Rhoa Signaling

Myelin is a multilamellar sheath generated by specialized glia called Schwann cells (SCs) in the peripheral nervous system (PNS), which serves to protect and insulate axons for rapid neuronal signaling. In zebrafish and rodent models, we identify GPR56/ADGRG1 as a conserved regulator of PNS development and health. We demonstrate that, during SC development, GPR56-dependent RhoA signaling promotes timely radial sorting of axons. In the mature PNS, GPR56 is localized to distinct SC cytoplasmic domains, is required to establish proper myelin thickness, and facilitates organization of the myelin sheath. Furthermore, we define plectin—a scaffolding protein previously linked to SC domain organization, myelin maintenance, and a series of disorders termed “plectinopathies”—as a novel interacting partner of GPR56. Finally, we show that Gpr56 mutants develop progressive neuropathy-like symptoms, suggesting an underlying mechanism for peripheral defects in some human patients with GPR56 mutations. In sum, we define Gpr56 as a new regulator in the development and maintenance of peripheral myelin.

scholarly journals SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms

2020 ◽  
Vol 21 (15) ◽  
pp. 5475 ◽  
Author(s):  
Manuela Pennisi ◽  
Giuseppe Lanza ◽  
Luca Falzone ◽  
Francesco Fisicaro ◽  
Raffaele Ferri ◽  
...  
Keyword(s):  
Nervous System ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Neurological Complications ◽  
Neurological Manifestations ◽  
Wide Range ◽  
Inflammatory State ◽  
Acute Polyneuropathy ◽  
The Central Nervous System ◽  
The Impact

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.

scholarly journals Immune Actions on the Peripheral Nervous System in Pain

2021 ◽  
Vol 22 (3) ◽  
pp. 1448
Author(s):  
Jessica Aijia Liu ◽  
Jing Yu ◽  
Chi Wai Cheung
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Process Integration ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Lipid Mediators ◽  
Cellular Changes

Pain can be induced by tissue injuries, diseases and infections. The interactions between the peripheral nervous system (PNS) and immune system are primary actions in pain sensitizations. In response to stimuli, nociceptors release various mediators from their terminals that potently activate and recruit immune cells, whereas infiltrated immune cells further promote sensitization of nociceptors and the transition from acute to chronic pain by producing cytokines, chemokines, lipid mediators and growth factors. Immune cells not only play roles in pain production but also contribute to PNS repair and pain resolution by secreting anti-inflammatory or analgesic effectors. Here, we discuss the distinct roles of four major types of immune cells (monocyte/macrophage, neutrophil, mast cell, and T cell) acting on the PNS during pain process. Integration of this current knowledge will enhance our understanding of cellular changes and molecular mechanisms underlying pain pathogenies, providing insights for developing new therapeutic strategies.

scholarly journals Aldose Reductase and the Polyol Pathway in Schwann Cells: Old and New Problems

2021 ◽  
Vol 22 (3) ◽  
pp. 1031
Author(s):  
Naoko Niimi ◽  
Hideji Yako ◽  
Shizuka Takaku ◽  
Sookja K. Chung ◽  
Kazunori Sango
Keyword(s):  
Schwann Cells ◽  
Aldose Reductase ◽  
Critical Role ◽  
Polyol Pathway ◽  
Glucose Flux ◽  
Rate Limiting ◽  
Deficient Mice ◽  
Excess Glucose ◽  
Shed Light ◽  
Immortalized Schwann Cells

Aldose reductase (AR) is a member of the reduced nicotinamide adenosine dinucleotide phosphate (NADPH)-dependent aldo-keto reductase superfamily. It is also the rate-limiting enzyme of the polyol pathway, catalyzing the conversion of glucose to sorbitol, which is subsequently converted to fructose by sorbitol dehydrogenase. AR is highly expressed by Schwann cells in the peripheral nervous system (PNS). The excess glucose flux through AR of the polyol pathway under hyperglycemic conditions has been suggested to play a critical role in the development and progression of diabetic peripheral neuropathy (DPN). Despite the intensive basic and clinical studies over the past four decades, the significance of AR over-activation as the pathogenic mechanism of DPN remains to be elucidated. Moreover, the expected efficacy of some AR inhibitors in patients with DPN has been unsatisfactory, which prompted us to further investigate and review the understanding of the physiological and pathological roles of AR in the PNS. Particularly, the investigation of AR and the polyol pathway using immortalized Schwann cells established from normal and AR-deficient mice could shed light on the causal relationship between the metabolic abnormalities of Schwann cells and discordance of axon-Schwann cell interplay in DPN, and led to the development of better therapeutic strategies against DPN.

scholarly journals The Landscape of microRNAs in βCell: Between Phenotype Maintenance and Protection

2021 ◽  
Vol 22 (2) ◽  
pp. 803
Author(s):  
Giuseppina Emanuela Grieco ◽  
Noemi Brusco ◽  
Giada Licata ◽  
Daniela Fignani ◽  
Caterina Formichi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Β Cell ◽  
Physiological Mechanisms ◽  
Effective Strategies ◽  
Chronic Hyperglycaemia ◽  
Shed Light

Diabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia mainly due to pancreatic β cell death and/or dysfunction, caused by several types of stress such as glucotoxicity, lipotoxicity and inflammation. Different patho-physiological mechanisms driving β cell response to these stresses are tightly regulated by microRNAs (miRNAs), a class of negative regulators of gene expression, involved in pathogenic mechanisms occurring in diabetes and in its complications. In this review, we aim to shed light on the most important miRNAs regulating the maintenance and the robustness of β cell identity, as well as on those miRNAs involved in the pathogenesis of the two main forms of diabetes mellitus, i.e., type 1 and type 2 diabetes. Additionally, we acknowledge that the understanding of miRNAs-regulated molecular mechanisms is fundamental in order to develop specific and effective strategies based on miRNAs as therapeutic targets, employing innovative molecules.

scholarly journals Murine Esophagus Expresses Glial-Derived Central Nervous System Antigens

2021 ◽  
Vol 22 (6) ◽  
pp. 3233
Author(s):  
Christopher Kapitza ◽  
Rittika Chunder ◽  
Anja Scheller ◽  
Katherine S. Given ◽  
Wendy B. Macklin ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Schwann Cells ◽  
Glial Cells ◽  
Proteolipid Protein ◽  
Pcr Analysis ◽  
Specific Expression ◽  
Enteric Glial Cells ◽  
Cell Type Specific Expression ◽  
Long Time

Multiple sclerosis (MS) has been considered to specifically affect the central nervous system (CNS) for a long time. As autonomic dysfunction including dysphagia can occur as accompanying phenomena in patients, the enteric nervous system has been attracting increasing attention over the past years. The aim of this study was to identify glial and myelin markers as potential target structures for autoimmune processes in the esophagus. RT-PCR analysis revealed glial fibrillary acidic protein (GFAP), proteolipid protein (PLP), and myelin basic protein (MBP) expression, but an absence of myelin oligodendrocyte glycoprotein (MOG) in the murine esophagus. Selected immunohistochemistry for GFAP, PLP, and MBP including transgenic mice with cell-type specific expression of PLP and GFAP supported these results by detection of (1) GFAP, PLP, and MBP in Schwann cells in skeletal muscle and esophagus; (2) GFAP, PLP, but no MBP in perisynaptic Schwann cells of skeletal and esophageal motor endplates; (3) GFAP and PLP, but no MBP in glial cells surrounding esophageal myenteric neurons; and (4) PLP, but no GFAP and MBP in enteric glial cells forming a network in the esophagus. Our results pave the way for further investigations regarding the involvement of esophageal glial cells in the pathogenesis of dysphagia in MS.

scholarly journals Biology of the repair of central nervous system demyelinated lesions: an appraisal

1996 ◽  
Vol 54 (2) ◽  
pp. 331-334 ◽  
Author(s):  
L. A. V Peireira ◽  
M. A. Cruz-Höfling ◽  
M. S. J. Dertkigil ◽  
D. L. Graça
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Schwann Cells ◽  
Demyelinating Disease ◽  
Experimental Models ◽  
Primitive Cell ◽  
Marked Influence ◽  
Myelin Sheaths ◽  
Human Material ◽  
The Central Nervous System

The integrity of myelin sheaths is maintained by oligodendrocytes and Schwann cells respectively in the central nervous system (CNS) and in the peripheral nervous system. The process of demyelination consisting of the withdrawal of myelin sheaths from their axons is a characteristic feature of multiple sclerosis, the most common human demyelinating disease. Many experimental models have been designed to study the biology of demyelination and remyelination (repair of the lost myelin) in the CNS, due to the difficulties in studying human material. In the ethidium bromide (an intercalating gliotoxic drug) model of demyelination, CNS remyelination may be carried out by surviving oligodendrocytes and/or by cells differentiated from the primitive cell lines or either by Schwann cells that invade the CNS. However, some factors such as the age of the experimental animals, intensity and time of exposure to the intercalating chemical and the topography of the lesions have marked influence on the repair of the tissue.

Sign in / Sign up

Export Citation Format

Share Document