Schwann cell
Encyclopedia
Schwann cells or neurolemmocytes are the principal glia of the peripheral nervous system
(PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ensheathing cells, enteric glia and glia that reside at sensory nerve endings, such as the Pacinian corpuscle
. Myelinating Schwann cells wrap around axons of motor and sensory neurons to form the myelin
sheath.
Schwann cells are involved in many important aspects of peripheral nerve
biology - the conduction of nervous impulses
along axon
s, nerve development and regeneration
, trophic support for neuron
s, production of the nerve extracellular matrix, modulation of neuromuscular synaptic activity, and presentation of antigen
s to T-lymphocytes. Charcot-Marie-Tooth disease
(CMT), Guillain-Barré syndrome
(GBS), schwannomatosis
and chronic inflammatory demyelinating polyneuropathy
(CIDP) are all neuropathies
involving Schwann cells.
physiologist Theodor Schwann
, Schwann cells are a variety of glial cell
that keep peripheral nerve fibres (both myelinated and unmyelinated) alive. In myelinated axons, Schwann cells form the myelin
sheath (see above). The sheath is not continuous. Individual myelinating Schwann cells cover about 100 micrometres of an axon - equating to approximately 10,000 Schwann cells along a 1 metre length of the axon - which can be up to a metre or more in length. The gaps between adjacent Schwann cells are called nodes of Ranvier
(see above).
The vertebrate
nervous system
relies on the myelin sheath for insulation and as a method of decreasing membrane capacitance
in the axon. The action potential
jumps from node to node, in a process called saltatory conduction
, which can increase conduction velocity up to ten times, without an increase in axonal diameter. In this sense, Schwann cells are the peripheral nervous system's analogues of the central nervous system
's oligodendrocyte
s. However, unlike oligodendrocytes, each myelinating Schwann cell provides insulation to only one axon (see image). This arrangement permits saltatory conduction of action potentials with repropagation at the nodes of Ranvier
. In this way, myelination greatly increases speed of conduction and saves energy.
Non-myelinating Schwann cells are involved in maintenance of axons and are crucial for neuronal survival. Some group around smaller axons (External image here) and form Remak bundles.
Myelinating Schwann cells begin to form the myelin sheath in mammals during fetal development and work by spiraling around the axon, sometimes with as many as 100 revolutions. A well-developed Schwann cell is shaped like a rolled-up sheet of paper, with layers of myelin in between each coil. The inner layers of the wrapping, which are predominantly membrane
material, form the myelin sheath while the outermost layer of nucleated cytoplasm
forms the neurolemma
. Only a small volume of residual cytoplasm communicates the inner from the outer layers. This is seen histologically
as the Schmidt-Lantermann incisure.
A number of experimental studies since 2001 have implanted Schwann cells in an attempt to induce remyelination
in multiple sclerosis
-afflicted patients. In the past two decades, many studies have demonstrated positive results and potential for Schwann cell transplantation as a therapy for spinal cord injury, both in aiding regrowth and myelination of damaged CNS axons. Indeed, Schwann cells are known for their roles in supporting nerve regeneration
. Nerves in the PNS consist of many axons myelinated by Schwann cells. If damage occurs to a nerve, the Schwann cells will aid in digestion of its axons (phagocytosis). Following this process, the Schwann cells can guide regeneration by forming a type of tunnel that leads toward the target neurons. The stump of the damaged axon is able to sprout, and those sprouts that grow through the Schwann-cell “tunnel” do so at the rate of approximately 1mm/day in good conditions. The rate of regeneration decreases with time. Successful axons can therefore reconnect with the muscles or organs they previously controlled with the help of Schwann cells, however, specificity is not maintained and errors are frequent, especially when long distances are involved.
If Schwann cells are prevented from associating with axons, the axons die. Regenerating axons will not reach any target unless Schwann cells are there to support them and guide
them. They have been shown to be in advance of the growth cone
s.
Schwann cells are essential for the maintenance of healthy axons. They produce a variety of factors, including neurotrophin
s, and also transfer essential molecules across to axons.
origin. During mouse embryonic development, neural crest cells first differentiate into Schwann cell precursors (SCPs) at around embryonic day (E) 12-13. These precursor cells subsequently differentiate into immature Schwann cells at approximately E15-16, persisting until birth. The postnatal fate of the immature Schwann cell depends on its random association with axons. In a process called radial sorting, whereby Schwann cells segregate axons by extending processes into axon bundles, the Schwann cells that happen to associate with a large diameter axon (>1 μm) will develop into myelinating Schwann cells. Small diameter axons become entrenched in the invagination
s of non-myelinating Schwann cells, also called Remak bundles. A key regulator of this process is the axonally-derived signal Neuregulin-1, which binds to cell surface receptors on the Schwann cell and promotes myelination of large diameter axons and sorting of small diameter axons in Remak bundles, dependent on the activity of the β-secretase BACE1 . A further class of non-myelinating Schwann cell, the terminal (or perisynaptic) Schwann cell, exists at the neuromuscular junction
, in close proximity to the neuron-muscle synapse
. The transition from immature Schwann cell to myelinating/non-myelinating Schwann cell is reversible. When the nerve is injured, Schwann cells can dedifferentiate to form a cell type resembling the immature Schwann cell, often referred to as a denervated or dedifferentiated Schwann cell. This allows them to re-enter the cell cycle in order to proliferate and aid nerve regeneration.
using antibodies against the proteins S-100
, Myelin protein zero
(P-Zero) and Myelin basic protein
(MBP). Non-myelinating Schwann cells such as those that form Remak bundles and terminal Schwann cells are positive for S-100 and Glial fibrillary acidic protein
(GFAP).
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...
(PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ensheathing cells, enteric glia and glia that reside at sensory nerve endings, such as the Pacinian corpuscle
Pacinian corpuscle
Lamellar corpuscles or Pacinian corpuscles are one of the four major types of mechanoreceptor. They are nerve endings in the skin, responsible for sensitivity to vibration and pressure. Vibrational role may be used to detect surface, e.g., rough vs...
. Myelinating Schwann cells wrap around axons of motor and sensory neurons to form the myelin
Myelin
Myelin is a dielectric material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination...
sheath.
Schwann cells are involved in many important aspects of peripheral nerve
Nerve
A peripheral nerve, or simply nerve, is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system...
biology - the conduction of nervous impulses
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
along axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
s, nerve development and regeneration
Nerve regeneration
Neuroregeneration refers to the regrowth or repair of nervous tissues, cells or cell products. Such mechanisms may include generation of new neurons, glia, axons, myelin, or synapses. Neuroregeneration differs between the peripheral nervous system and the central nervous system by the functional...
, trophic support for neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s, production of the nerve extracellular matrix, modulation of neuromuscular synaptic activity, and presentation of antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s to T-lymphocytes. Charcot-Marie-Tooth disease
Charcot-Marie-Tooth disease
Charcot–Marie–Tooth disease- , known also as Morbus Charcot-Marie-Tooth, Charcot-Marie-Tooth neuropathy, hereditary motor and sensory neuropathy , hereditary sensorimotor neuropathy , or peroneal muscular atrophy, is an inherited disorder of nerves that takes different forms...
(CMT), Guillain-Barré syndrome
Guillain-Barré syndrome
Guillain–Barré syndrome , sometimes called Landry's paralysis, is an acute inflammatory demyelinating polyneuropathy , a disorder affecting the peripheral nervous system. Ascending paralysis, weakness beginning in the feet and hands and migrating towards the trunk, is the most typical symptom...
(GBS), schwannomatosis
Schwannomatosis
Schwannomatosis is one form of a genetic disorder called neurofibromatosis that has only recently been recognized. Originally described in Japanese patients, it consists of multiple cutaneous schwannomas, central nervous system tumors, and other neurological complications, excluding hallmark signs...
and chronic inflammatory demyelinating polyneuropathy
Chronic inflammatory demyelinating polyneuropathy
Chronic inflammatory demyelinating polyneuropathy is an acquired immune-mediated inflammatory disorder of the peripheral nervous system. The disorder is sometimes called chronic relapsing polyneuropathy. CIDP is closely related to Guillain-Barré syndrome and it is considered the chronic...
(CIDP) are all neuropathies
Peripheral neuropathy
Peripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of or trauma to the nerve or the side-effects of systemic illness....
involving Schwann cells.
Description
Named after the GermanGermany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
physiologist Theodor Schwann
Theodor Schwann
Theodor Schwann was a German physiologist. His many contributions to biology include the development of cell theory, the discovery of Schwann cells in the peripheral nervous system, the discovery and study of pepsin, the discovery of the organic nature of yeast, and the invention of the term...
, Schwann cells are a variety of glial cell
Glial cell
Glial cells, sometimes called neuroglia or simply glia , are non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for neurons in the brain, and for neurons in other parts of the nervous system such as in the autonomous nervous system...
that keep peripheral nerve fibres (both myelinated and unmyelinated) alive. In myelinated axons, Schwann cells form the myelin
Myelin
Myelin is a dielectric material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination...
sheath (see above). The sheath is not continuous. Individual myelinating Schwann cells cover about 100 micrometres of an axon - equating to approximately 10,000 Schwann cells along a 1 metre length of the axon - which can be up to a metre or more in length. The gaps between adjacent Schwann cells are called nodes of Ranvier
Nodes of Ranvier
Myelin sheath gaps or nodes of Ranvier are the gaps formed between the myelin sheaths generated by different cells. A myelin sheath is a many-layered coating, largely composed of a fatty substance called myelin, that wraps around the axon of a neuron and very efficiently insulates it...
(see above).
The vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
relies on the myelin sheath for insulation and as a method of decreasing membrane capacitance
Capacitance
In electromagnetism and electronics, capacitance is the ability of a capacitor to store energy in an electric field. Capacitance is also a measure of the amount of electric potential energy stored for a given electric potential. A common form of energy storage device is a parallel-plate capacitor...
in the axon. The action potential
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
jumps from node to node, in a process called saltatory conduction
Saltatory conduction
Saltatory conduction is the propagation of action potentials along myelinated axons from one node of Ranvier to the next node, increasing the conduction velocity of action potentials without needing to increase the diameter of an axon.-Mechanism:Because the cytoplasm of the axon is electrically...
, which can increase conduction velocity up to ten times, without an increase in axonal diameter. In this sense, Schwann cells are the peripheral nervous system's analogues of the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
's oligodendrocyte
Oligodendrocyte
Oligodendrocytes , or oligodendroglia , are a type of brain cell. They are a variety of neuroglia. Their main function is the insulation of axons in the central nervous system of some vertebrates...
s. However, unlike oligodendrocytes, each myelinating Schwann cell provides insulation to only one axon (see image). This arrangement permits saltatory conduction of action potentials with repropagation at the nodes of Ranvier
Nodes of Ranvier
Myelin sheath gaps or nodes of Ranvier are the gaps formed between the myelin sheaths generated by different cells. A myelin sheath is a many-layered coating, largely composed of a fatty substance called myelin, that wraps around the axon of a neuron and very efficiently insulates it...
. In this way, myelination greatly increases speed of conduction and saves energy.
Non-myelinating Schwann cells are involved in maintenance of axons and are crucial for neuronal survival. Some group around smaller axons (External image here) and form Remak bundles.
Myelinating Schwann cells begin to form the myelin sheath in mammals during fetal development and work by spiraling around the axon, sometimes with as many as 100 revolutions. A well-developed Schwann cell is shaped like a rolled-up sheet of paper, with layers of myelin in between each coil. The inner layers of the wrapping, which are predominantly membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
material, form the myelin sheath while the outermost layer of nucleated cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
forms the neurolemma
Neurolemma
Neurolemma is the outermost nucleated cytoplasmic layer of Schwann cells that surrounds the axon of the neuron. It forms the outermost layer of the nerve fiber in the peripheral nervous system....
. Only a small volume of residual cytoplasm communicates the inner from the outer layers. This is seen histologically
Histology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...
as the Schmidt-Lantermann incisure.
A number of experimental studies since 2001 have implanted Schwann cells in an attempt to induce remyelination
Remyelination
Remyelination is a term for the re-generation of the nerve's myelin sheath, damaged in many diseases such as multiple sclerosis and the leukodystrophies. Remyelination is a subject of active medical research.-External links:**...
in multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
-afflicted patients. In the past two decades, many studies have demonstrated positive results and potential for Schwann cell transplantation as a therapy for spinal cord injury, both in aiding regrowth and myelination of damaged CNS axons. Indeed, Schwann cells are known for their roles in supporting nerve regeneration
Nerve regeneration
Neuroregeneration refers to the regrowth or repair of nervous tissues, cells or cell products. Such mechanisms may include generation of new neurons, glia, axons, myelin, or synapses. Neuroregeneration differs between the peripheral nervous system and the central nervous system by the functional...
. Nerves in the PNS consist of many axons myelinated by Schwann cells. If damage occurs to a nerve, the Schwann cells will aid in digestion of its axons (phagocytosis). Following this process, the Schwann cells can guide regeneration by forming a type of tunnel that leads toward the target neurons. The stump of the damaged axon is able to sprout, and those sprouts that grow through the Schwann-cell “tunnel” do so at the rate of approximately 1mm/day in good conditions. The rate of regeneration decreases with time. Successful axons can therefore reconnect with the muscles or organs they previously controlled with the help of Schwann cells, however, specificity is not maintained and errors are frequent, especially when long distances are involved.
If Schwann cells are prevented from associating with axons, the axons die. Regenerating axons will not reach any target unless Schwann cells are there to support them and guide
Axon guidance
Axon guidance is a subfield of neural development concerning the process by which neurons send out axons to reach the correct targets...
them. They have been shown to be in advance of the growth cone
Growth cone
A growth cone is a dynamic, actin-supported extension of a developing axon seeking its synaptic target. Their existence was originally proposed by Spanish histologist Santiago Ramón y Cajal based upon stationary images he observed under the microscope...
s.
Schwann cells are essential for the maintenance of healthy axons. They produce a variety of factors, including neurotrophin
Neurotrophin
Neurotrophins are a family of proteins that induce the survival, development, and function of neurons.They belong to a class of growth factors, secreted proteins that are capable of signaling particular cells to survive, differentiate, or grow. Growth factors such as neurotrophins that promote the...
s, and also transfer essential molecules across to axons.
Schwann cell lineage
Schwann cells are of neural crestNeural crest
Neural crest cells are a transient, multipotent, migratory cell population unique to vertebrates that gives rise to a diverse cell lineage including melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons and glia....
origin. During mouse embryonic development, neural crest cells first differentiate into Schwann cell precursors (SCPs) at around embryonic day (E) 12-13. These precursor cells subsequently differentiate into immature Schwann cells at approximately E15-16, persisting until birth. The postnatal fate of the immature Schwann cell depends on its random association with axons. In a process called radial sorting, whereby Schwann cells segregate axons by extending processes into axon bundles, the Schwann cells that happen to associate with a large diameter axon (>1 μm) will develop into myelinating Schwann cells. Small diameter axons become entrenched in the invagination
Invagination
Invagination means to fold inward or to sheath. In biology, this can refer to a number of processes.* Invagination is the morphogenetic processes by which an embryo takes form, and is the initial step of gastrulation, the massive reorganization of the embryo from a simple spherical ball of cells,...
s of non-myelinating Schwann cells, also called Remak bundles. A key regulator of this process is the axonally-derived signal Neuregulin-1, which binds to cell surface receptors on the Schwann cell and promotes myelination of large diameter axons and sorting of small diameter axons in Remak bundles, dependent on the activity of the β-secretase BACE1 . A further class of non-myelinating Schwann cell, the terminal (or perisynaptic) Schwann cell, exists at the neuromuscular junction
Neuromuscular junction
A neuromuscular junction is the synapse or junction of the axon terminal of a motor neuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscle's surface, ultimately causing the muscle to contract...
, in close proximity to the neuron-muscle synapse
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
. The transition from immature Schwann cell to myelinating/non-myelinating Schwann cell is reversible. When the nerve is injured, Schwann cells can dedifferentiate to form a cell type resembling the immature Schwann cell, often referred to as a denervated or dedifferentiated Schwann cell. This allows them to re-enter the cell cycle in order to proliferate and aid nerve regeneration.
Immunoreactivity
The different classes of Schwann cells express characteristic antigenic markers that can be targeted with antibodies. Myelinating Schwann cells can be visualised by immunohistochemistryImmunohistochemistry
Immunohistochemistry or IHC refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...
using antibodies against the proteins S-100
S-100 protein
S-100 protein is a family of low molecular weight protein found in vertebrates characterized by two calcium binding sites of the helix-loop-helix conformation. There are at least 21 different types of S100 proteins...
, Myelin protein zero
Myelin protein zero
Myelin protein zero is a glycoprotein associated with Charcot-Marie-Tooth disease and Dejerine-Sottas disease.-Interactions:Myelin protein zero has been shown to interact with Peripheral myelin protein 22.-Further reading:...
(P-Zero) and Myelin basic protein
Myelin basic protein
Myelin basic protein is a protein believed to be important in the process of myelination of nerves in the central nervous system .MBP was initially sequenced in 1971 after isolation from myelin membranes...
(MBP). Non-myelinating Schwann cells such as those that form Remak bundles and terminal Schwann cells are positive for S-100 and Glial fibrillary acidic protein
Glial fibrillary acidic protein
Glial fibrillary acidic protein is an intermediate filament protein that was thought to be specific for astrocytes in the central nervous system . Later, it was shown that GFAP is also expressed by other cell types in CNS, including ependymal cells...
(GFAP).
See also
- ElectrophysiologyElectrophysiologyElectrophysiology is the study of the electrical properties of biological cells and tissues. It involves measurements of voltage change or electric current on a wide variety of scales from single ion channel proteins to whole organs like the heart...
- Hodgkin-Huxley ModelHodgkin-Huxley modelThe Hodgkin–Huxley model is a mathematical model that describes how action potentials in neurons are initiated and propagated....
- NeurotransmissionNeurotransmissionNeurotransmission , also called synaptic transmission, is the process by which signaling molecules called neurotransmitters are released by a neuron , and bind to and activate the receptors of another neuron...
- SchwannomaSchwannomaA schwannoma is a benign nerve sheath tumor composed of Schwann cells, which normally produce the insulating myelin sheath covering peripheral nerves....
External links
- Diagram at clc.uc.edu - "Ultrastructure of the Cell: myelinated axon and Schwann cell"
- Cell Centered Database - Schwann cell