Monday, May 23, 2022

Which Cells Produce Myelin In The Brain And Spinal Cord

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Astrocytes Provide Lipids For Myelin Sheath Production

Three ways to tackle myelin repair in MS | Meet the Researchers

Besides providing lipids for the synthesis of myelin sheaths during development, astrocytes, namely those contacting the nodes of Ranvier, were also reported to reversibly modify myelin thickness and nodal gap length thus appropriately regulating conduction velocity in individual axons. In support of this observation, the reduction of exocytosis induced in transgenic mice expressing a dominant-negative fragment of the vesicle-associated membrane protein 2 in astrocytes, exhibited detachment of adjacent paranodal loops of myelin from the axon, increased nodal gap length, thinning of myelin sheath in the optic nerve and finally decrease in visual acuity. These data led to propose that thrombin-dependent proteolysis of the cell adhesion molecule neurofascin 155 that attaches myelin to the axon, is inhibited by the vesicular release of thrombin protease inhibitors from perinodal astrocytes, which likely involves these cells in myelin remodeling necessary for optimal electrical conduction .

Reactive Astrocytes Provide Pro

IL-1 also stimulates the astroglial production of LIF promoting survival of oligodendrocytes and thus decreasing disease severity in EAE mice . In a pathological context where tumor necrosis factor is a key component of the inflammatory response, LIF can alternatively be released upon TNFR2-mediated activation of the PI3K-PKB/Akt pathway in primary astrocytes. The selective stimulation of TNFR2 on astrocytes cocultured with OPCs promoted OPC differentiation into mature oligodendrocytes while the process was blocked in the presence of LIF neutralizing antibodies . Reactive astrocytes also produce BDNF supporting oligodendrogenesis and regeneration after white matter damage. In vitro, conditioned medium from astrocytes restored the process of OPC maturation even under hypoxic stress known to block OPC differentiation unless the medium was specifically treated to remove BDNF. Similarly, in vivo, the conditional astroglial deletion of BDNF led to a highly reduced number of newly generated oligodendrocytes and thus to larger white matter damage in animals subjected to prolonged cerebral hypoperfusion .

Ohsu Research Could Lead To New Therapies To Heal Nervous System Disorders

Oregon Health & Science University
Scientists have discovered that a special type of cell is much more prolific in generating a protective sheath covering nerve fibers than previously believed.

Scientists have discovered that a special type of cell is much more prolific in generating a protective sheath covering nerve fibers than previously believed.

The revelation about Schwann cells raises the possibility of new avenues to treat nerve injuries and various forms of neuropathy. Further research could prove useful in promoting myelin repair in central nervous system disorders such as multiple sclerosis, where damage to myelin slows or blocks electric signals from the brain.

“This totally overturns the textbook definition of the way Schwann cells work,” said senior author Kelly Monk, Ph.D., professor and co-director of the Vollum Institute at Oregon Health & Science University.

The research published today in the journal Nature Communications.

Two types of cells in the body produce myelin: oligodendrocytes in the brain and spinal cord, and Schwann cells in the rest of the body. Until now, scientists thought that only oligodendrocytes generated multiple myelin sheaths around axons, the slender projection of a nerve cell that carries electrical signals between cells.

The new research reveals that Schwann cells also are capable of spreading myelin across multiple axons.

“It highlights a very plastic potential for these cells,” Monk said.

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Remyelination: How To Increase Myelin For Longevity

Slowing down mentally and physically is a normal side effect of aging. But what if someone told you that these unwanted experiences could be greatly reduced or even delayed? Enter: myelin repair. As more studies reveal the role of myelinating cells in a healthy brain and body, more people are asking how to increase myelin to boost their longevity.

So what exactly is myelin and the myelin sheath, and what do these things mean for living your best life? Here, we outline everything you need to know about myelin loss and myelin repair, including how to create new myelin for a sharper, healthier, and longer life.

Key Studies Supporting Detrimental Roles Of Astrocytes On Oligodendrocytes And Myelin

Myelin: An Overview

Several publications using astrocyte ablation have improved our knowledge about the main detrimental roles of reactive astrocytes in the context of CNS demyelination. For instance, OPC transplantation in ethidium bromide-demyelinated animals in the presence or absence of astrocytes indicated that astrocyte-free regions favor Schwann cell differentiation whereas the presence of astrocytes delayed the interaction of OPCs with the demyelinated axons . Similarly, the depletion of astrocytes via intracallosal injection of La-aminoadipate in cuprizone-treated animals revealed a notable increase in the percentage of myelinated areas, decrease in Iba-1+ microglia staining and collapse in the expression of genes related to either recruitment of microglia classically triggered by astrocytes or suppression of OPC differentiation . The considerable amount of fibronectin produced by astrocytes and the ability of astrocytic fibronectin to become aggregated after treatment with lipopolysaccharide led to conclude to the deleterious effects of such aggregates on oligodendrocyte differentiation and myelin regeneration in vivo, in agreement with the detection of a low level of fibronectin aggregates in remyelinated MS lesions . The signaling molecule endothelin-1 expressed by reactive astrocytes in MS and murine demyelinated lesions is a negative regulator of OPC differentiation and remyelination acting by promoting Notch activation in OPCs during remyelination .

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Astrocytes Control The Availability Of Cues Regulating Oligodendrocyte Production

Besides the secretion of trophic factors, astrocytes are also able to control the bioavailability of oligodendrocyte-regulating cues . The best-documented example was provided by the capacity of astrocytes to control the concentration of the morphogen Sonic Hedgehog during OPC production in the optic nerve. Shh participates in the proliferation and migration of OPCs during the colonization of this nerve . The multiligand receptor megalin, a member of the low-density lipoprotein receptor family able to bind Shh, was found to be exclusively expressed by astrocytes according to a dynamic pattern paralleling optic nerve colonization by OPCs arising from the optic chiasm and migrating to the retina. Indeed, when OPCs start their migration throughout the nerve at E14.5 in the mouse, megalin is more widely distributed in the region close to the optic chiasm whereas the distribution is reversed at E16.5 when the first OPCs reach the retina. Since, thereafter, megalin was found to be weakly and uniformly expressed all along the nerve, this receptor was proposed to control Shh internalization and its subsequent release at the suitable concentration during the various steps leading to oligodendrogenesis .

Other Types Of Macroglia

Central Nervous System

  • Ependymal cells: Ependymal cells line the spinal cord and ventricles of the brain. They are involved in creating cerebrospinal fluid .
  • Radial glia: Radial glial cells are progenitor cells that can generate neurons, astrocytes and oligodendrocytes.

Peripheral Nervous System

  • Schwann cells: Similar to oligodendrocytes in the central nervous system, Schwann cells myelinate neurons in the peripheral nervous system.
  • Satellite cells: Satellite cells surround neurons in the sensory, sympathetic and parasympathetic ganglia and help regulate the chemical environment. They may contribute to chronic pain.
  • Enteric glial cells: Enteric glial cells are found in the nerves in the digestive system.

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Iimorphologic And Structural Aspects Of Myelin Formation

Diagram of a single myelinated internode of the PNS, as it would appear if the myelin sheath, with its associated Schwann cell, were unrolled from around the axon. Note the very large myelin membrane surface area, as well as the many cytoplasm-containing structures , all continuous with the cytoplasm of the Schwann cell perikarya. This cytoplasmic continuity is presumably necessary for metabolic maintenance of compact myelin. Sites of synthesis, as well as ultrastructural locations, of the major myelin proteins are also shown. In mature compact myelin, the large trapezoidal sheet of myelin membrane is tightly spiraled around the axons, with apposing inner surfaces of the original plasma membrane fusing to give the electron-dense intraperiod lines and the outer surfaces of the original plasma membrane forming the lighter appearing intraperiod line . Abbreviations: RER, rough endoplasmic reticulum MBP, myelin basic protein MAG, myelin-associated glycoprotein PMP-22, peripheral myelin protein-22.

Electron micrograph of compact myelin from the mammalian CNS. Although there are minor ultrastructural differences, compact PNS myelin has a similar ultrastructural appearance. Note the alternating pattern of darker major dense lines and paler intraperiod lines, originally formed by fusion of apposing surfaces of the inner and outer leaflets, respectively, of the oligodendroglial plasma membrane. Cytoplasm-containing internal mesaxons can be seen on two of the myelinated axons.

Myelin In The Central Nervous System: Structure Function And Pathology

Healing The Myelin Sheath / Myelinating Glial Cells

Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany Institute of Neuronal Cell Biology, Technical University Munich, Munich, Germany German Center for Neurodegenerative Diseases , Munich, Germany Department of Neuropathology, University Medical Center Leipzig, Leipzig, Germany Munich Cluster of Systems Neurology , Munich, Germany and Max Planck Institute of Experimental Medicine, Göttingen, Germany

Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany Institute of Neuronal Cell Biology, Technical University Munich, Munich, Germany German Center for Neurodegenerative Diseases , Munich, Germany Department of Neuropathology, University Medical Center Leipzig, Leipzig, Germany Munich Cluster of Systems Neurology , Munich, Germany and Max Planck Institute of Experimental Medicine, Göttingen, Germany

Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany Institute of Neuronal Cell Biology, Technical University Munich, Munich, Germany German Center for Neurodegenerative Diseases , Munich, Germany Department of Neuropathology, University Medical Center Leipzig, Leipzig, Germany Munich Cluster of Systems Neurology , Munich, Germany and Max Planck Institute of Experimental Medicine, Göttingen, Germany

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Other Types Of Glial Cells

Ependymal cells are one of the four types of glial cells found in the CNS. Glial cells are one of the two major cell types that make up the nervous system and have a variety of supportive roles in neuronal function. The three other types of glial cells in the CNS are oligodendrocytes, astrocytes, and microglia.

Key Studies Supporting Detrimental Roles Of Microglia/macrophages On Oligodendrocytes And Myelin

Besides the growing number of data supporting the beneficial consequences of promoting the pro-regenerative phenotype of microglia/macrophages, several critical works support the deleterious effects of microglia activated through the classical way. First, activated microglia synthesize a multitude of cytokines, chemokines, cell adhesion glycoproteins or reactive oxygen radicals able to damage axons, myelin, oligodendrocytes and therefore involved in the initiation and propagation of the inflammatory cascade, which promotes demyelination in neural disorders . Consistently, LPS-activated microglia, polarized to pro-inflammatory status secrete tumor necrosis factor- and interleukin-1 , both known to be cytotoxic for oligodendrocytes . TNF and cuprizone supplementation to rat primary cultures of oligodendrocytes consistently decreased cell viability . Moreover, a minocycline-mediated blockade of microglial activation in cuprizone-treated mice prevented demyelination while a positive correlation was shown between the production of nitric oxide and oligodendrocyte death . Finally, LPS-induced secretion of the stress chaperone protein, heat shock protein 60 , was found to initiate OPC apoptosis .

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Vimolecular Aspects Of Myelin Synthesis And Assembly

The synthesis and assembly of myelin has been examined by measuring incorporation of radioactive precursors into myelin components both in vivo and in tissue slices, by measuring the in vitro activities of enzymes involved in synthesis of myelin components, by examining levels of expression of mRNA species for myelin-related genes, and by actual isolation and analysis of myelin . After individual myelin components have been synthesized, they must be assembled to form mature compact myelin. Some components, such as PLP, which is synthesized on bound polyribosomes in the oligodendroglial perikaryon, show a time lag of about 45 min between their synthesis and their appearance in myelin, reflecting the time required for transport from their site of synthesis to the forming myelin. Other components, such as MBP, show only a short lag, in keeping with their synthesis of free polyribosomes in oligodendroglial processes, near the actual site of myelin assembly. In keeping with this difference, studies have shown that myelinating cells spatially segregate mRNA species for myelin-specific proteins . mRNA for MBP is transported to near the sites of myelin assembly before the protein is synthesized , whereas PLP mRNA is present in a perinuclear location. Individual lipids also show different kinetics of entry into myelin following synthesis, and some of this may be due to synthesis in, or movement through, different intracellular pools .

A Neuroglia In Central Nervous System

Neurons and Glial Cells · Biology

1. Asrtocytes

  • They are the largest glial cells.
  • They are star-shaped cells with many processes.
  • The ends of the processes are called foot processes which cover the capillaries to form blood brain barrier.
  • Function: They also provide structural support to the neurons.
  • Astrocytes are of two types:
  • Protoplasmic astrocytes: They are found in gray matter.
  • Fibrous astrocytes: They are found in white matter.

2. Oligodendrocytes

  • They are smaller than astrocytes and have fewer processes.
  • Function:They form myelin around the axons in CNS.

3. Microglia

  • These are the smallest glial cells.
  • Function: They phagocytose the pathogens and cell debris within the CNS.

4. Ependymal cells

  • They line the ventricles of brain and central canal of spinal cord.
  • Function: They produce cerebrospinal fluid.

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Unique Phenotype Of Neonatal Microglia Implicated In Developmental Myelination

As soon as the end of the 1970s, the existence of a specific subpopulation of microglial cells had been proposed in the early postnatal corpus callosum . Unexpectedly, the pharmacological suppression of microglia activation by using the anti-inflammatory drug minocycline was reported to significantly inhibit oligodendrogenesis both in vitro in neurosphere culture and in vivo in the subventricular zone of the dorsal forebrain. This inhibition was mediated by the blockade of several proinflammatory cytokines including IL-1, IL-6, TNF-, and IFN-. Also, the observation that activated microglia significantly increased O4+ cells but decreased PDGFRa+ OPCs again confirmed microglia activity on oligodendrocyte maturation .

Why Is Myelin Important

Neurons carry messages using a chemical version of electricity. The outer surface of all types of cells is called the membrane. The axons of neurons have special membranes that maintain a difference in the balance of positive and negative charges across the membrane, like a battery. The charge of a neuron’s battery is based on the number of sodium and potassium ions inside and outside the membrane. Messages are carried, or conducted, along axons and dendrites by the change in electrical charge across the membrane.

An ‘action potential’ is the name for an electrical message carried along the axon or dendrite of a neuron, like an electrical impulse carried along a wire. These tiny electrical signals would not be able to travel very far if the axons were not insulated. Once this electrical charge or ‘action potential’ reaches the synapse, it triggers neurotransmitter release to enable the signal to reach the next neuron in the chain.

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Polysialylated Neural Cell Adhesion Molecule

SC myelination in a compression injury model was improved using a strategy to promote SC migration by changing implanted SC surface adhesivity . The polysialylated form of the neural cell adhesion molecule, NCAM, is present on SCs acutely after spinal cord demyelination but disappears as myelin repair is accomplished . Thinking that PSA would be beneficial, early postnatal GFP-SCs were engineered to express on their surface the PSA form of NCAM by introducing a retroviral vector encoding sialyl-transferase X which catalyzes transfer of PSA to NCAM . In vitro, 11X more STX-GFP-SCs entered astrocyte domains than did control SCs. In vivo, STX-GFP-SCs injected just rostral to a mouse thoracic compression injury promoted faster and significantly greater functional recovery Basso et al., 2006) compared to control engineered SCs or no cells. The earlier improvement in locomotor recovery in the STX-GFP-SC group was perhaps related to the earlier enhanced myelination by the implanted STX-GFP-SCs, increased myelination by host SCs, and enhanced recruitment/myelination by oligodendrocyte precursors. In addition, more serotonergic axons were observed to exit the caudal lesion site in the STX-GFP-SC group than in the control-GFP-SC group. Overall, STX-GFP-SC grafting appeared to lead to a more permissive CNS milieu for axonal growth and myelination, resulting in locomotor improvement .

K.R. Jessen, R. Mirsky, in, 2013

Which Cells Produce Myelin In The Brain And Spinal Cord

What is Myelin? – National MS Society

Asked by wiki @ 29/10/2021 in Medicine viewed by 28 People

Oligodendrocytes produce myelin within the central nervous system . The cells that do this in the peripheral

nervous system are.the neuronal axons themselves,O specialized fibroblasts of the surrounding connective tissue.o oligodentrocytes that follow the nerve cell axon out of the CNS and do the same job in the peripheral nervous system.Schwann cells



The nervous system is made up of neurons, specialized cells that can receive and … Glia can be compared to the workers at the electric company who make sure wires go … Along the axon there are periodic gaps in the myelin sheath. … Multipolar neurons can be found in the central nervous system .

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Exercise And Myelin Repair

Exercise is one of the best ways to ignite remyelination and keep your neurons firing quickly and efficiently. In addition to improving functions of the central nervous system, exercise has been shown to mitigate the negative impact of diet on the central nervous system, according to the Mayo Clinic.

This was revealed in a myelin study by Isobel A. Scarisbrick, which showed that a high-fat diet combined with a sedentary lifestyle can reduce myelin-forming cells, contributing to demyelination and associated cognitive decline.

Adding exercise to this high-fat intake, however, has been proven to increase myelin production. Specifically, the seven-week study on mice showed that frequent exercise training has the ability to boost myelin protein expression, even alongside a high-fat diet.

Our results suggest that consuming high levels of saturated fat in conjunction with a sedentary lifestyle can lead to a reduction in myelin-forming cells. But exercise training can help reverse this process and promote the myelinogenesis necessary to meet increased energy demands, says Dr. Scarisbrick.

Similar findings were displayed in a study on patients with multiple sclerosis. Published in the Multiple Sclerosis Journal, this study found that measures of overall functioning improved in patients after exercising with free weights, elastic bands, and exercise machines over the course of 24 weeks.

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