"Neuroglia" redirects here. For the nerve pain, seeNeuralgia.
Glia
Illustration of the four different types of glial cells found in the central nervous system: ependymal cells (light pink), astrocytes (green), microglial cells (dark red) and oligodendrocytes (light blue)
They also play a role inneurotransmission andsynaptic connections,[3] and in physiological processes such asbreathing.[4][5][6] While glia were thought to outnumber neurons by a ratio of 10:1, studies using newer methods and reappraisal of historical quantitative evidence suggests an overall ratio of less than 1:1, with substantial variation between different brain tissues.[7][8]
Glial cells have far more cellular diversity and functions than neurons, and can respond to and manipulate neurotransmission in many ways. Additionally, they can affect both the preservation andconsolidation of memories.[1]
Glia were discovered in 1856, by the pathologistRudolf Virchow in his search for a "connective tissue" in the brain.[9] The term derives fromGreek γλία and γλοία "glue"[10] (English:/ˈɡliːə/ or/ˈɡlaɪə/), and suggests the original impression that they were theglue of thenervous system.
Neuroglia of the brain shown byGolgi's methodAstrocytes can be identified in culture because, unlike other mature glia, they expressglial fibrillary acidic protein (GFAP)Glial cells in a rat brain stained with an antibody against GFAPDifferent types of neuroglia
Astrocytes signal each other usingATP. Thegap junctions (also known aselectrical synapses) between astrocytes allow the messenger moleculeIP3 to diffuse from one astrocyte to another. IP3 activatescalcium channels oncellular organelles, releasingcalcium into thecytoplasm. This calcium may stimulate the production of more IP3 and cause release of ATP through channels in the membrane made ofpannexins. The net effect is a calcium wave that propagates from cell to cell. Extracellular release of ATP and consequent activation ofpurinergic receptors on other astrocytes may also mediate calcium waves in some cases.
In general, there are two types of astrocytes, protoplasmic and fibrous, similar in function but distinct in morphology and distribution. Protoplasmic astrocytes have short, thick, highly branched processes and are typically found ingray matter. Fibrous astrocytes have long, thin, less-branched processes and are more commonly found inwhite matter.
It has recently been shown that astrocyte activity is linked to blood flow in the brain, and that this is what is actually being measured infMRI.[11] They also have been involved in neuronal circuits playing an inhibitory role after sensing changes in extracellular calcium.[12]
Human astrocytes are larger and more abundant than any other animals'.[13]
Oligodendrocytes are cells that coat axons in the CNS with their cell membrane, forming a specialized membrane differentiation calledmyelin, producing themyelin sheath. The myelin sheath providesinsulation to the axon that allowselectrical signals to propagate more efficiently.[14]
Ependymal cells, also namedependymocytes, line the spinal cord and theventricular system of the brain. These cells are involved in the creation and secretion ofcerebrospinal fluid (CSF) and beat theircilia to help circulate the CSF and make up theblood-CSF barrier. They are also thought to act as neural stem cells.[15]
Radial glia cells arise fromneuroepithelial cells after the onset ofneurogenesis. Their differentiation abilities are more restricted than those of neuroepithelial cells. In the developing nervous system, radial glia function both as neuronal progenitors and as a scaffold upon which newborn neurons migrate. In the mature brain, thecerebellum andretina retain characteristic radial glial cells. In the cerebellum, these areBergmann glia, which regulatesynaptic plasticity. In the retina, the radialMüller cell is the glial cell that spans the thickness of the retina and, in addition to astroglial cells,[16] participates in a bidirectional communication with neurons.[17]
Similar in function to oligodendrocytes,Schwann cells provide myelination to axons in theperipheral nervous system (PNS). They also havephagocytotic activity and clear cellular debris that allows for regrowth of PNS neurons.[18]
Satellite glial cells are small cells that surround neurons in sensory,sympathetic, andparasympathetic ganglia.[19] These cells help regulate the external chemical environment. Like astrocytes, they are interconnected bygap junctions and respond to ATP by elevating the intracellular concentration of calcium ions. They are highly sensitive toinjury andinflammation and appear to contribute to pathological states, such aschronic pain.[20]
Are found in the intrinsic ganglia of thedigestive system. Glia cells are thought to have many roles in theenteric system, some related tohomeostasis and muscular digestive processes.[21]
Microglia are specializedmacrophages capable ofphagocytosis that protect neurons of thecentral nervous system.[22] They are derived from the earliest wave of mononuclear cells that originate inyolk sac blood islands early in development, and colonize the brain shortly after the neural precursors begin to differentiate.[23]
These cells are found in all regions of the brain and spinal cord. Microglial cells are small relative to macroglial cells, with changing shapes and oblong nuclei. They are mobile within the brain and multiply when the brain is damaged. In the healthy central nervous system, microglia processes constantly sample all aspects of their environment (neurons, macroglia and blood vessels). In a healthy brain, microglia direct the immune response to brain damage and play an important role in the inflammation that accompanies the damage. Many diseases and disorders are associated with deficient microglia, such asAlzheimer's disease,Parkinson's disease andALS.
In general, neuroglial cells are smaller than neurons. There are approximately 85 billion glia cells in the human brain,[8] about the same number as neurons.[8] Glial cells make up about half the total volume of the brain and spinal cord.[27] The glia to neuron-ratio varies from one part of the brain to another. The glia to neuron-ratio in the cerebral cortex is 3.72 (60.84 billion glia (72%); 16.34 billion neurons), while that of the cerebellum is only 0.23 (16.04 billion glia; 69.03 billion neurons). The ratio in the cerebral cortex gray matter is 1.48, with 3.76 for the gray and white matter combined.[27] The ratio of the basal ganglia, diencephalon and brainstem combined is 11.35.[27]
The total number of glia cells in the human brain is distributed into the different types witholigodendrocytes being the most frequent (45–75%), followed byastrocytes (19–40%) andmicroglia (about 10% or less).[8]
Most glia are derived fromectodermal tissue of the developingembryo, in particular theneural tube andcrest. The exception ismicroglia, which are derived fromhematopoietic stem cells. In the adult, microglia are largely a self-renewing population and are distinct from macrophages and monocytes, which infiltrate an injured and diseased CNS.
In the central nervous system, glia develop from the ventricular zone of the neural tube. These glia include the oligodendrocytes, ependymal cells, and astrocytes. In the peripheral nervous system, glia derive from the neural crest. These PNS glia include Schwann cells in nerves and satellite glial cells in ganglia.
Glia retain the ability to undergo cell divisions in adulthood, whereas most neurons cannot. The view is based on the general inability of the mature nervous system to replace neurons after an injury, such as astroke or trauma, where very often there is a substantial proliferation of glia, orgliosis, near or at the site of damage. However, detailed studies have found no evidence that 'mature' glia, such as astrocytes oroligodendrocytes, retain mitotic capacity. Only the residentoligodendrocyte precursor cells seem to keep this ability once the nervous system matures.
Glial cells are known to be capable ofmitosis. By contrast, scientific understanding of whether neurons are permanentlypost-mitotic,[28] or capable of mitosis,[29][30][31] is still developing. In the past, glia had been considered[by whom?] to lack certain features of neurons. For example, glial cells were not believed to havechemical synapses or to releasetransmitters. They were considered to be the passive bystanders of neural transmission. However, recent studies have shown this to not be entirely true.[32]
Some glial cells function primarily as the physical support for neurons. Others provide nutrients to neurons and regulate theextracellular fluid of the brain, especially surrounding neurons and theirsynapses. During earlyembryogenesis, glial cells direct the migration of neurons and produce molecules that modify the growth ofaxons anddendrites. Some glial cells display regional diversity in the CNS and their functions may vary between the CNS regions.[33]
Glia are crucial in the development of the nervous system and in processes such assynaptic plasticity andsynaptogenesis. Glia have a role in the regulation of repair of neurons after injury. In thecentral nervous system (CNS), glia suppress repair. Glial cells known asastrocytes enlarge and proliferate to form a scar and produce inhibitory molecules that inhibit regrowth of a damaged or severed axon. In theperipheral nervous system (PNS), glial cells known asSchwann cells (or also as neuri-lemmocytes) promote repair. After axonal injury, Schwann cells regress to an earlier developmental state to encourage regrowth of the axon. This difference between the CNS and the PNS, raises hopes for the regeneration of nervous tissue in the CNS. For example, a spinal cord may be able to be repaired following injury or severance.
Oligodendrocytes are found in the CNS and resemble an octopus: they have bulbous cell bodies with up to fifteen arm-like processes. Each process reaches out to an axon and spirals around it, creating a myelin sheath. The myelin sheath insulates the nerve fiber from the extracellular fluid and speeds up signal conduction along the nerve fiber.[34] In the peripheral nervous system, Schwann cells are responsible for myelin production. These cells envelop nerve fibers of the PNS by winding repeatedly around them. This process creates a myelin sheath, which not only aids in conductivity but also assists in the regeneration of damaged fibers.
Neoplastic glial cells stained with an antibody against GFAP (brown), from abrain biopsy
While glial cells in thePNS frequently assist in regeneration of lost neural functioning, loss of neurons in theCNS does not result in a similar reaction from neuroglia.[18] In the CNS, regrowth will only happen if the trauma was mild, and not severe.[40] When severe trauma presents itself, the survival of the remaining neurons becomes the optimal solution. However, some studies investigating the role of glial cells inAlzheimer's disease are beginning to contradict the usefulness of this feature, and even claim it can "exacerbate" the disease.[41] In addition to affecting the potential repair of neurons in Alzheimer's disease, scarring and inflammation from glial cells have been further implicated in the degeneration of neurons caused byamyotrophic lateral sclerosis.[42]
In addition to neurodegenerative diseases, a wide range of harmful exposure, such ashypoxia, or physical trauma, can lead to the result of physical damage to the CNS.[40] Generally, when damage occurs to the CNS, glial cells causeapoptosis among the surrounding cellular bodies.[40] Then, there is a large amount ofmicroglial activity, which results in inflammation, and, finally, there is a heavy release of growth inhibiting molecules.[40]
Although glial cells and neurons were probably first observed at the same time in the early 19th century, unlike neurons whose morphological and physiological properties were directly observable for the first investigators of the nervous system, glial cells had been considered to be merely "glue" that held neurons together until the mid-20th century.[43]
Glia were first described in 1856 by the pathologistRudolf Virchow in a comment to his 1846 publication on connective tissue. A more detailed description of glial cells was provided in the 1858 book 'Cellular Pathology' by the same author.[44]
When markers for different types of cells were analyzed,Albert Einstein's brain was discovered to contain significantly more glia than normal brains in the left angulargyrus, an area thought to be responsible for mathematical processing and language.[45] However, out of the total of 28 statistical comparisons between Einstein's brain and the control brains, finding one statistically significant result is not surprising, and the claim that Einstein's brain is different is not scientific (c.f.multiple comparisons problem).[46]
Not only does the ratio of glia to neurons increase through evolution, but so does the size of the glia. Astroglial cells in human brains have a volume 27 times greater than in mouse brains.[47]
These important scientific findings may begin to shift the neurocentric perspective into a more holistic view of the brain which encompasses the glial cells as well. For the majority of the twentieth century, scientists had disregarded glial cells as mere physical scaffolds for neurons. Recent publications have proposed that the number of glial cells in the brain is correlated with the intelligence of a species.[48] Moreover, evidences are demonstrating the active role of glia, in particular astroglia, in cognitive processes like learning and memory.[49][50]
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^abJessen KR, Mirsky R (September 2005). "The origin and development of glial cells in peripheral nerves".Nature Reviews. Neuroscience.6 (9):671–82.doi:10.1038/nrn1746.PMID16136171.S2CID7540462.
^Hanani, M. "Satellite glial cells in sensory ganglia: from form to function".Brain Res. Rev. 48:457–76, 2005
^"Never-resting microglia: physiological roles in the healthy brain and pathological implications". A Sierra, ME Tremblay, H Wake – 2015 –books.google.com
^Miyata, S; Furuya, K; Nakai, S; Bun, H; Kiyohara, T (April 1999). "Morphological plasticity and rearrangement of cytoskeletons in pituicytes cultured from adult rat neurohypophysis".Neuroscience Research.33 (4):299–306.doi:10.1016/s0168-0102(99)00021-8.PMID10401983.S2CID24687965.
^abcAzevedo FA, Carvalho LR, Grinberg LT, et al. (April 2009). "Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain".The Journal of Comparative Neurology.513 (5):532–41.doi:10.1002/cne.21974.PMID19226510.S2CID5200449.
^Herrup K, Yang Y (May 2007). "Cell cycle regulation in the postmitotic neuron: oxymoron or new biology?".Nature Reviews. Neuroscience.8 (5):368–78.doi:10.1038/nrn2124.PMID17453017.S2CID12908713.
^Halassa MM, Fellin T, Haydon PG (2007). "The tripartite synapse: roles for gliotransmission in health and disease".Trends Mol Med.13 (2):54–63.doi:10.1016/j.molmed.2006.12.005.PMID17207662.
"The Other Brain"Archived 2017-01-09 at theWayback Machine – The Leonard Lopate Show (WNYC) "Neuroscientist Douglas Field, explains how glia, which make up approximately 85 percent of the cells in the brain, work. In The Other Brain: From Dementia to Schizophrenia, How New Discoveries about the Brain Are Revolutionizing Medicine and Science, he explains recent discoveries in glia research and looks at what breakthroughs in brain science and medicine are likely to come."
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