View source for Glia

{{short description|Support-cells in the nervous system}}
{{for|the scientific journal|Glia (journal)}}
{{for|the genus of plants|Glia (plant)}}
{{Redirect|Neuroglia|the nerve pain|Neuralgia}}
{{Infobox cell
| Name    = Glia
| Latin    =
| Greek    =
| Image    = Glial Cell Types.png
| Caption   = Illustration of the four different types of glial cells found in the [[central nervous system]]: [[ependymal cells]] (light pink), [[astrocyte]]s (green), [[microglial cells]] (dark red) and [[oligodendrocyte]]s (light blue)
| Width    =
| Image2   =
| Caption2  =
| Precursor  = [[Neuroectoderm]] for macroglia, and [[hematopoietic stem cell]]s for microglia
| System   = [[Nervous system]]
}}
{{wikt | glia}}

'''Glia''', also called '''glial cells''' ('''gliocytes''') or '''neuroglia''', are non-[[neuron]]al [[cell (biology)|cell]]s in the [[central nervous system]] (the [[brain]] and the [[spinal cord]]) and in the [[peripheral nervous system]] that do not produce [[Action potential|electrical impulses]]. The neuroglia make up more than one half the volume of neural [[Tissue (biology)|tissue]] in the [[human body]].<ref name="Fields-2014">{{Cite journal |last1=Fields |first1=R. Douglas |last2=Araque |first2=Alfonso |last3=Johansen-Berg |first3=Heidi |last4=Lim |first4=Soo-Siang |last5=Lynch |first5=Gary |last6=Nave |first6=Klaus-Armin |last7=Nedergaard |first7=Maiken |last8=Perez |first8=Ray |last9=Sejnowski |first9=Terrence |last10=Wake |first10=Hiroaki |date=October 2014 |title=Glial Biology in Learning and Cognition |journal=The Neuroscientist |volume=20 |issue=5 |pages=426–31 |doi=10.1177/1073858413504465|issn=1073-8584|pmc=4161624|pmid=24122821}}</ref> They contribute to the maintenance of [[homeostasis]], help form [[myelin]], while also providing support and protection for [[neuron]]s.<ref>{{cite journal |vauthors =Jessen KR, Mirsky R |title =Glial cells in the enteric nervous system contain glial fibrillary acidic protein |journal =Nature |volume =286 |issue =5774 |pages =736–37 |date =August 1980 |pmid =6997753 |doi =10.1038/286736a0 |bibcode=1980Natur.286..736J |s2cid =4247900 }}</ref> In the central nervous system, glial cells include [[oligodendrocyte]]s (that produce myelin), [[astrocyte]]s, [[ependymal cell]]s and [[microglia]], and in the peripheral nervous system they include [[Schwann cell]]s (that produce myelin), and [[Satellite glial cell|satellite cells]].

==Function==
Glia have four main functions:
* to structurally support neurons, holding them in place
* to supply [[nutrient]]s and [[oxygen]] to neurons
* to [[Myelination|insulate]] one neuron from another
* to destroy [[pathogen]]s and remove dead neurons.
They also play a role in [[neurotransmission]] and [[Synapse|synaptic connections]],<ref name="doi:10.1111/j.1742-4658.2008.06515.x">{{cite journal |vauthors=Wolosker H, Dumin E, Balan L, Foltyn VN |title=D-amino acids in the brain: D-serine in neurotransmission and neurodegeneration |journal=The FEBS Journal |volume=275 |issue=14 |pages=3514–26 |date=July 2008 |pmid=18564180 |doi=10.1111/j.1742-4658.2008.06515.x|s2cid=25735605 |doi-access=free }}</ref> and in physiological processes such as [[breathing]].<ref name="Discover2011JanFeb">{{Cite journal|last=Swaminathan|first=Nikhil|title=Glia – the other brain cells|journal=Discover|date=Jan–Feb 2011|url=http://discovermagazine.com/2011/jan-feb/62|access-date=2011-06-06|archive-date=2014-02-08|archive-url=https://web.archive.org/web/20140208071350/http://discovermagazine.com/2011/jan-feb/62|url-status=live}}</ref><ref name="doi:10.1126/science.1190721">{{cite journal |vauthors=Gourine AV, Kasymov V, Marina N, etal |title=Astrocytes control breathing through pH-dependent release of ATP |journal=Science |volume=329 |issue=5991 |pages=571–75 |date=July 2010 |pmid=20647426 |pmc=3160742 |doi=10.1126/science.1190721|bibcode=2010Sci...329..571G }}</ref><ref name="pmid29018191">{{cite journal| vauthors=Beltrán-Castillo S, Olivares MJ, Contreras RA, Zúñiga G, Llona I, von Bernhardi R et al.| title=D-serine released by astrocytes in brainstem regulates breathing response to CO2 levels. | journal=Nat Commun | year= 2017 | volume= 8 | issue= 1 | article-number= 838 | pmid=29018191 | doi=10.1038/s41467-017-00960-3 | pmc=5635109 | bibcode=2017NatCo...8..838B }}</ref> 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.<ref>{{Cite journal|last=von Bartheld|first=Christopher S.|date=November 2018|title=Myths and truths about the cellular composition of the human brain: A review of influential concepts|journal=Journal of Chemical Neuroanatomy|volume=93|pages=2–15|doi=10.1016/j.jchemneu.2017.08.004|issn=1873-6300|pmc=5834348|pmid=28873338}}</ref><ref name="pmid27187682"/>

Glial cells have far more cellular diversity and functions than neurons, and can respond to and manipulate neurotransmission in multiple ways. Additionally, they can affect both the preservation and [[Memory consolidation|consolidation of memories]].<ref name="Fields-2014"/>

Glia were discovered in 1856, by the pathologist [[Rudolf Virchow]] in his search for a "connective tissue" in the brain.<ref>{{cite web|title=Classic Papers|url=http://www.networkglia.eu/en/classicpapers|website=Network Glia|publisher=Max Delbrueck Center für Molekulare Medizin (MDC) Berlin-Buch|access-date=14 November 2015|archive-date=8 May 2020|archive-url=https://web.archive.org/web/20200508114226/https://www.networkglia.eu/en/classicpapers}}</ref> The term derives from [[Koine Greek|Greek]] γλία and γλοία "glue"<ref>{{LSJ|gloi/a|γλοία}}, {{LSJ|gli/a|γλία|ref}}.</ref> ({{IPAc-en|lang|ˈ|ɡ|l|iː|ə}} or {{IPAc-en|ˈ|ɡ|l|aɪ|ə}}), and suggests the original impression that they were the [[glue]] of the [[nervous system]].

==Types==
[[File:Neuroglia.png|thumb|250px|Neuroglia of the brain shown by [[Golgi's method]]]]
[[File:Gfapastr5.jpg|thumb|250px|[[Astrocyte]]s can be identified in culture because, unlike other mature glia, they express [[glial fibrillary acidic protein]] (GFAP)]]
[[File:2010-3-15 rGFAP 1-4000 1-200 Hip 20x(4).jpg|thumb|250px|Glial cells in a rat brain stained with an antibody against GFAP]]
[[File:Blausen 0870 TypesofNeuroglia.png|thumb|Different types of neuroglia]]

===Macroglia===
Derived from [[germ layer|ectodermal]] tissue.

{| class="wikitable"
! scope="col" | Location
! scope="col" | Name
! scope="col" | Description
|-
| [[central nervous system|CNS]] || [[Astrocyte]]s ||
''Astrocytes'' (also called ''astroglia'') have numerous projections that link neurons to their blood supply while forming the [[blood–brain barrier]]. They regulate the external [[chemical]] environment of neurons by removing excess [[potassium]] [[ion]]s and recycling [[neurotransmitter]]s released during [[synaptic transmission]]. Astrocytes may regulate vasoconstriction and vasodilation by producing substances such as [[arachidonic acid]], whose [[metabolite]]s are [[vasoactive]].

Astrocytes signal each other using [[Adenosine triphosphate|ATP]]. The [[gap junction]]s (also known as [[electrical synapse]]s) between astrocytes allow the messenger molecule [[Inositol triphosphate|IP3]] to diffuse from one astrocyte to another. IP3 activates [[calcium channel]]s on [[cellular organelles]], releasing [[calcium]] into the [[cytoplasm]]. This calcium may stimulate the production of more IP3 and cause release of ATP through channels in the membrane made of [[pannexin]]s. The net effect is a calcium wave that propagates from cell to cell. Extracellular release of ATP and consequent activation of [[purinergic receptor]]s 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 in [[gray matter]]. Fibrous astrocytes have long, thin, less-branched processes and are more commonly found in [[white 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 in [[fMRI]].<ref>{{cite journal |last=Swaminathan |first=N |title=Brain-scan mystery solved |journal=Scientific American Mind |volume=Oct–Nov |issue=5 |page=7 |year=2008|doi=10.1038/scientificamericanmind1008-7b }}</ref> They also have been involved in neuronal circuits playing an inhibitory role after sensing changes in extracellular calcium.<ref>{{cite journal |author=Torres A |title=Extracellular Ca2+ Acts as a Mediator of Communication from Neurons to Glia |journal=Science Signaling |volume=5 Jan 24 |issue=208 |page=208 |year=2012 |doi=10.1126/scisignal.2002160|pmid=22275221 |pmc=3548660 }}</ref>

Human astrocytes are larger and more abundant than any other animals'.<ref name="scientificamerican.com">{{Cite web |date=2009-10-27 |title=The Root of Thought: What do Glial Cells Do? |url=https://www.scientificamerican.com/article/the-root-of-thought-what |url-status=live |archive-url=https://web.archive.org/web/20230612124825/https://www.scientificamerican.com/article/the-root-of-thought-what/ |archive-date=2023-06-12 |access-date=2023-06-12 |website=[[Scientific American]]}}</ref>

|-
| CNS || [[Oligodendrocyte]]s ||
''Oligodendrocytes'' are cells that coat axons in the CNS with their cell membrane, forming a specialized membrane differentiation called [[myelin]], producing the [[myelin sheath]]. The myelin sheath provides [[Electrical insulation|insulation]] to the axon that allows [[action potential|electrical signals]] to propagate more efficiently.<ref>{{cite journal |vauthors=Baumann N, Pham-Dinh D |title=Biology of oligodendrocyte and myelin in the mammalian central nervous system |journal=Physiological Reviews |volume=81 |issue=2 |pages=871–927 |date=April 2001 |pmid=11274346 |doi=10.1152/physrev.2001.81.2.871}}</ref>
|-
| CNS || [[Ependymal cells]] ||
''Ependymal cells'', also named ''ependymocytes'', line the spinal cord and the [[ventricular system]] of the brain. These cells are involved in the creation and secretion of [[cerebrospinal fluid]] (CSF) and beat their [[cilia]] to help circulate the CSF and make up the [[blood-CSF barrier]]. They are also thought to act as neural stem cells.<ref>{{cite journal |vauthors=Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisén J |title=Identification of a neural stem cell in the adult mammalian central nervous system |journal=Cell |volume=96 |issue=1 |pages=25–34 |date=January 1999 |pmid=9989494 |doi=10.1016/S0092-8674(00)80956-3|s2cid=9658786 |doi-access=free }}</ref>
|-
| CNS || [[Radial glia]] ||
''Radial glia cells'' arise from [[neuroepithelial cell]]s after the onset of [[neurogenesis]]. 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, the [[cerebellum]] and [[retina]] retain characteristic radial glial cells. In the cerebellum, these are [[Bergmann glia]], which regulate [[synaptic plasticity]]. In the retina, the radial [[Müller cell]] is the glial cell that spans the thickness of the retina and, in addition to astroglial cells,<ref>{{cite journal |author=Newman EA |title=New roles for astrocytes: regulation of synaptic transmission |journal=Trends in Neurosciences |volume= 26|issue=10 |pages=536–42 |date=October 2003 |pmid=14522146 |doi=10.1016/S0166-2236(03)00237-6|s2cid=14105472 }}</ref> participates in a bidirectional communication with neurons.<ref>{{cite journal |vauthors=Campbell K, Götz M |title=Radial glia: multi-purpose cells for vertebrate brain development |journal=Trends in Neurosciences |volume=25 |issue=5 |pages=235–38 |date=May 2002 |pmid=11972958 |doi=10.1016/s0166-2236(02)02156-2|s2cid=41880731 }}</ref>
|-
| [[peripheral nervous system|PNS]] || [[Schwann cell]]s ||
Similar in function to oligodendrocytes, ''Schwann cells'' provide myelination to axons in the [[peripheral nervous system]] (PNS). They also have [[phagocytosis|phagocytotic]] activity and clear cellular debris that allows for regrowth of PNS neurons.<ref name="Jessen-2005">{{cite journal |vauthors=Jessen KR, Mirsky R |title=The origin and development of glial cells in peripheral nerves |journal=Nature Reviews. Neuroscience |volume=6 |issue=9 |pages=671–82 |date=September 2005 |pmid=16136171 |doi=10.1038/nrn1746|s2cid=7540462 }}</ref>
|-
| PNS || [[Satellite cells (glial)|Satellite cells]] ||
''Satellite glial cells'' are small cells that surround neurons in sensory, [[Sympathetic ganglion|sympathetic]], and [[Parasympathetic ganglion|parasympathetic]] ganglia.<ref>Hanani, M. "Satellite glial cells in sensory ganglia: from form to function". ''Brain Res. Rev.'' 48:457–76, 2005</ref> These cells help regulate the external chemical environment. Like astrocytes, they are interconnected by [[gap junction]]s and respond to ATP by elevating the intracellular concentration of calcium ions. They are highly sensitive to [[injury]] and [[inflammation]] and appear to contribute to pathological states, such as [[chronic pain]].<ref>{{cite journal |vauthors=Ohara PT, Vit JP, Bhargava A, Jasmin L |title=Evidence for a role of connexin 43 in trigeminal pain using RNA interference in vivo |journal=Journal of Neurophysiology |volume=100 |issue=6 |pages=3064–73 |date=December 2008 |pmid=18715894 |pmc=2604845 |doi=10.1152/jn.90722.2008}}</ref>
|-
| PNS || [[Enteric glia|Enteric glial cells]]||
Are found in the intrinsic ganglia of the [[Human digestive system|digestive system]]. Glia cells are thought to have a number of roles in the [[enteric]] system, some related to [[homeostasis]] and muscular digestive processes.<ref>{{cite journal |vauthors=Bassotti G, Villanacci V, Antonelli E, Morelli A, Salerni B |title=Enteric glial cells: new players in gastrointestinal motility? |journal=Laboratory Investigation |volume=87 |issue=7 |pages=628–32 |date=July 2007 |pmid=17483847 |doi=10.1038/labinvest.3700564|doi-access=free }}</ref>
|}

===Microglia===
{{Main|Microglia}}

[[Microglia]] are specialized [[macrophage]]s capable of [[phagocytosis]] that protect neurons of the [[central nervous system]].<ref>Brodal, 2010: [https://books.google.com/books?id=iJjI6yDNmr8C&pg=PA19 p. 19]</ref> They are derived from the earliest wave of mononuclear cells that originate in the [[blood islands]] of the [[yolk sac]] early in development, and colonize the brain shortly after the neural precursors begin to differentiate.<ref>"Never-resting microglia: physiological roles in the healthy brain and pathological implications". A Sierra, ME Tremblay, H Wake – 2015 – [https://books.google.com/books?id=GocSBwAAQBAJ&dq=origin+of+microglia&pg=PA6 books.google.com]</ref>

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. A number of diseases and disorders are associated with deficient microglia, such as [[Alzheimer's disease]], [[Parkinson's disease]] and [[ALS]].

===Other===
[[Pituicyte]]s from the [[posterior pituitary]] are glial cells with characteristics in common to astrocytes.<ref>{{cite journal |last1=Miyata |first1=S |last2=Furuya |first2=K |last3=Nakai |first3=S |last4=Bun |first4=H |last5=Kiyohara |first5=T |date=April 1999 |title=Morphological plasticity and rearrangement of cytoskeletons in pituicytes cultured from adult rat neurohypophysis. |journal=Neuroscience Research |volume=33 |issue=4 |pages=299–306 |doi=10.1016/s0168-0102(99)00021-8 |pmid=10401983 |s2cid=24687965}}</ref> [[Tanycyte]]s in the [[median eminence]] of the [[hypothalamus]] are a type of [[ependymal cell]] that descend from radial glia and line the base of the [[third ventricle]].<ref>{{cite book |last1=Rodríguez |first1=EM |last2=Blázquez |first2=JL |last3=Pastor |first3=FE |last4=Peláez |first4=B |last5=Peña |first5=P |last6=Peruzzo |first6=B |last7=Amat |first7=P |year=2005 |title=Hypothalamic Tanycytes: A Key Component of Brain–Endocrine Interaction |url=https://gredos.usal.es/bitstream/10366/17544/1/DAHH_Hypothalamic%20tanycytes.pdf |series=International Review of Cytology |volume=247 |pages=89–164 |doi=10.1016/s0074-7696(05)47003-5 |pmid=16344112 |hdl-access=free |hdl=10366/17544}}</ref> ''[[Drosophila melanogaster]],'' the fruit fly, contains numerous glial types that are functionally similar to mammalian glia but are nonetheless classified differently.<ref>{{Cite journal|last=Freeman|first=Marc R.|date=2015-02-26|title=DrosophilaCentral Nervous System Glia|journal=Cold Spring Harbor Perspectives in Biology|volume=7|issue=11|article-number=a020552|doi=10.1101/cshperspect.a020552|pmid=25722465|pmc=4632667|issn=1943-0264|doi-access=free}}</ref>

===Total number===
In general, neuroglial cells are smaller than neurons. There are approximately 85&nbsp;billion glial cells in the human brain, about the same number as neurons.<ref name="pmid27187682">{{Cite journal|last1=von Bartheld|first1=Christopher S.|last2=Bahney|first2=Jami|last3=Herculano-Houzel|first3=Suzana|date=2016-12-15|title=The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting|journal=The Journal of Comparative Neurology|volume=524|issue=18|pages=3865–95|doi=10.1002/cne.24040|issn=1096-9861|pmc=5063692|pmid=27187682}}</ref> Glial cells make up about half the total volume of the brain and spinal cord.<ref name="sfn">{{cite journal |vauthors=Azevedo FA, Carvalho LR, Grinberg LT, etal |title=Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain |journal=The Journal of Comparative Neurology |volume=513 |issue=5 |pages=532–41 |date=April 2009 |pmid=19226510 |doi=10.1002/cne.21974|s2cid=5200449 }}</ref> 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.<ref name="sfn"/> The ratio of the basal ganglia, diencephalon and brainstem combined is 11.35.<ref name="sfn"/>

The total number of glial cells in the human brain is distributed into the different types with [[oligodendrocyte]]s being the most frequent (45–75%), followed by [[astrocyte]]s (19–40%) and [[microglia]] (about 10% or less).<ref name="pmid27187682"/>

==Development==
[[File:Human astrocyte.png|thumb|23-week fetal brain culture astrocyte]]
{{Main|Gliogenesis}}
Most glia are derived from [[germ layer|ectodermal]] tissue of the developing [[embryo]], in particular the [[neural tube]] and [[neural crest|crest]]. The exception is [[microglia]], which are derived from [[hematopoietic stem cell]]s. 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.

===Capacity to divide===
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 a [[stroke]] or trauma, where often there is a substantial proliferation of glia, or [[gliosis]], near or at the site of damage. However, detailed studies have found no evidence that 'mature' glia, such as astrocytes or [[oligodendrocyte]]s, retain mitotic capacity. Only the resident [[oligodendrocyte precursor cell]]s seem to keep this ability once the nervous system matures.

Glial cells are known to be capable of [[mitosis]]. By contrast, scientific understanding of whether neurons are permanently [[mitosis|post-mitotic]],<ref>{{cite journal |vauthors=Herrup K, Yang Y |title=Cell cycle regulation in the postmitotic neuron: oxymoron or new biology? |journal=Nature Reviews. Neuroscience |volume=8 |issue=5 |pages=368–78 |date=May 2007 |pmid=17453017 |doi=10.1038/nrn2124|s2cid=12908713 }}</ref> or capable of mitosis,<ref>{{cite journal |vauthors=Goldman SA, Nottebohm F |title=Neuronal production, migration, and differentiation in a vocal control nucleus of the adult female canary brain |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=80 |issue=8 |pages=2390–94 |date=April 1983 |pmid=6572982 |pmc=393826 |doi=10.1073/pnas.80.8.2390|bibcode=1983PNAS...80.2390G |doi-access=free }}</ref><ref>{{cite journal |vauthors=Eriksson PS, Perfilieva E, Björk-Eriksson T, etal |title=Neurogenesis in the adult human hippocampus |journal=Nature Medicine |volume=4 |issue=11 |pages=1313–17 |date=November 1998 |pmid=9809557 |doi=10.1038/3305|doi-access=free }}</ref><ref>{{cite journal |vauthors=Gould E, Reeves AJ, Fallah M, Tanapat P, Gross CG, Fuchs E |title=Hippocampal neurogenesis in adult Old World primates |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=96 |issue=9 |pages=5263–67 |date=April 1999 |pmid=10220454 |pmc=21852 |doi=10.1073/pnas.96.9.5263|bibcode=1999PNAS...96.5263G |doi-access=free }}</ref> is still developing. In the past, glia had been considered{{By whom|date=July 2011}} to lack certain features of neurons. For example, glial cells were not believed to have [[synapse|chemical synapses]] or to release [[neurotransmitter|transmitters]]. They were considered to be the passive bystanders of neural transmission. However, recent studies have shown this to not be entirely true.<ref>{{cite book|title=The Other Brain|first=R. Douglas|last=Fields|publisher=Simon & Schuster|year=2009|isbn=978-0-7432-9142-2}}{{page needed|date=July 2014}}</ref>

==Functions==
Some glial cells function primarily as the physical support for neurons. Others provide nutrients to neurons and regulate the [[extracellular fluid]] of the brain, especially surrounding neurons and their [[synapse]]s. During early [[embryogenesis]], glial cells direct the migration of neurons and produce molecules that modify the growth of [[axon]]s and [[dendrite]]s. Some glial cells display regional diversity in the CNS and their functions may vary between the CNS regions.<ref>{{Cite journal|last1=Werkman|first1=Inge L.|last2=Lentferink|first2=Dennis H.|last3=Baron|first3=Wia|date=2020-07-09|title=Macroglial diversity: white and grey areas and relevance to remyelination|journal=Cellular and Molecular Life Sciences|volume=78|issue=1|pages=143–71|language=en|doi=10.1007/s00018-020-03586-9|pmid=32648004|pmc=7867526|issn=1420-9071|doi-access=free}}</ref>

===Neuron repair and development===
Glia are crucial in the development of the nervous system and in processes such as [[synaptic plasticity]] and [[synaptogenesis]]. Glia have a role in the regulation of repair of neurons after injury. In the [[central nervous system]] (CNS), glia suppress repair. Glial cells known as [[astrocyte]]s enlarge and proliferate to form a scar and produce inhibitory molecules that inhibit regrowth of a damaged or severed axon. In the [[peripheral nervous system]] (PNS), glial cells known as [[Schwann cell]]s (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.

===Myelin sheath creation===
[[Oligodendrocyte]]s are found in the CNS and resemble an octopus: they have a bulbous cell body with up to fifteen arm-like [[Cytoplasmic process|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.<ref name="Saladin">{{cite book |last=Saladin |first=K |title=Human anatomy |page=357 |date=2011 |publisher=McGraw-Hill |isbn=978-0-07-122207-5 |edition=3rd}}</ref> 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 [[Endogenous regeneration|regeneration]] of damaged fibers.

===Neurotransmission===
[[Astrocyte]]s are crucial participants in the [[tripartite synapse]].<ref>{{cite journal|last1=Newman|first1=Eric A.|title=New roles for astrocytes: Regulation of synaptic transmission|journal=Trends in Neurosciences|date=2003|volume=26|issue=10|pages=536–42|doi=10.1016/S0166-2236(03)00237-6|pmid=14522146|s2cid=14105472}}</ref><ref name="pmid17207662">{{cite journal|vauthors=Halassa MM, Fellin T, Haydon PG| title=The tripartite synapse: roles for gliotransmission in health and disease. | journal=Trends Mol Med | year= 2007 | volume= 13 | issue= 2 | pages= 54–63 | pmid=17207662 | doi=10.1016/j.molmed.2006.12.005 }}</ref><ref name="pmid19615761">{{cite journal|vauthors=Perea G, Navarrete M, Araque A| title=Tripartite synapses: astrocytes process and control synaptic information. | journal=Trends Neurosci | year= 2009 | volume= 32 | issue= 8 | pages= 421–31 | pmid=19615761 | doi=10.1016/j.tins.2009.05.001 | hdl=10261/62092 | s2cid=16355401 }}</ref><ref name="pmid22351062">{{cite book|vauthors=Santello M, Calì C, Bezzi P| chapter=Gliotransmission and the Tripartite Synapse | title=Synaptic Plasticity | year= 2012 | volume= 970 | pages= 307–31 | pmid=22351062 | doi=10.1007/978-3-7091-0932-8_14 | series=Advances in Experimental Medicine and Biology | isbn=978-3-7091-0931-1 }}</ref> They have several crucial functions, including clearance of [[neurotransmitter]]s from within the [[synaptic cleft]], which aids in distinguishing between separate action potentials and prevents toxic build-up of certain neurotransmitters such as [[glutamate]], which would otherwise lead to [[excitotoxicity]]. Furthermore, [[astrocyte]]s release [[gliotransmitter]]s such as glutamate, ATP, and D-serine in response to stimulation.<ref name="pmid24910611">{{cite journal|vauthors=Martineau M, Parpura V, Mothet JP| title=Cell-type specific mechanisms of D-serine uptake and release in the brain. | journal=Front Synaptic Neurosci | year= 2014 | volume= 6 | page= 12 | pmid=24910611 | doi=10.3389/fnsyn.2014.00012 | pmc=4039169 | doi-access=free }}</ref>

== Clinical significance ==
{{see also|Glioma}}
[[File:Anaplastic astrocytoma - gfap - very high mag.jpg|thumb|250px|[[Neoplastic]] glial cells stained with an antibody against GFAP (brown), from a [[brain biopsy]]]]
While glial cells in the [[Peripheral nervous system|PNS]] frequently assist in regeneration of lost neural functioning, loss of neurons in the [[Central nervous system|CNS]] does not result in a similar reaction from neuroglia.<ref name="Jessen-2005"/> In the CNS, regrowth will only happen if the trauma was mild, and not severe.<ref name="Puves-2012"/> When severe trauma presents itself, the survival of the remaining neurons becomes the optimal solution. However, some studies investigating the role of glial cells in [[Alzheimer's disease]] are beginning to contradict the usefulness of this feature, and even claim it can "exacerbate" the disease.<ref>{{Cite journal|last1=Lopategui Cabezas|first1=I.|last2=Batista|first2=A. Herrera|last3=Rol|first3=G. Pentón|title=Papel de la glía en la enfermedad de Alzheimer. Futuras implicaciones terapéuticas|journal=Neurología|volume=29|issue=5|pages=305–09|doi=10.1016/j.nrl.2012.10.006|pmid=23246214|year=2014|doi-access=free}}</ref> 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 by [[amyotrophic lateral sclerosis]].<ref>{{Cite journal|last1=Valori|first1=Chiara F.|last2=Brambilla|first2=Liliana|last3=Martorana|first3=Francesca|last4=Rossi|first4=Daniela|date=2013-08-03|title=The multifaceted role of glial cells in amyotrophic lateral sclerosis|journal=Cellular and Molecular Life Sciences|volume=71|issue=2|pages=287–97|doi=10.1007/s00018-013-1429-7|pmid=23912896|s2cid=14388918|issn=1420-682X|pmc=11113174}}</ref>

In addition to neurodegenerative diseases, a wide range of harmful exposure, such as [[Hypoxia (medical)|hypoxia]], or physical trauma, can lead to the result of physical damage to the CNS.<ref name="Puves-2012"/> Generally, when damage occurs to the CNS, glial cells cause [[apoptosis]] among the surrounding cellular bodies.<ref name="Puves-2012"/> Then, there is a large amount of [[microglia]]l activity, which results in inflammation, and, finally, there is a heavy release of growth inhibiting molecules.<ref name="Puves-2012">{{Cite book|title=Neuroscience |edition=5th |last=Puves|first=Dale|publisher=Sinauer Associates|year=2012|isbn=978-0-87893-646-5|pages=560–80}}</ref>

==History==
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.<ref>{{Cite journal|last1=Fan|first1=Xue|last2=Agid|first2=Yves|date=August 2018|title=At the Origin of the History of Glia|journal=Neuroscience|volume=385|pages=255–71|doi=10.1016/j.neuroscience.2018.05.050|pmid=29890289|s2cid=48360939}}</ref>

Glia were first described in 1856 by the pathologist [[Rudolf 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.<ref>{{cite journal |vauthors=Kettenmann H, Verkhratsky A |title=Neuroglia: the 150 years after |journal=Trends in Neurosciences |volume=31 |issue=12 |pages=653–59 |date=December 2008 |pmid=18945498 |doi=10.1016/j.tins.2008.09.003|s2cid=7135630 }}</ref>

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 angular [[gyrus]], an area thought to be responsible for mathematical processing and language.<ref>Diamond MC, Scheibel AB, Murphy GM Jr, Harvey T, [https://www.ncbi.nlm.nih.gov/pubmed/3979509/ "On the Brain of a Scientist: Albert Einstein"] {{Webarchive|url=https://web.archive.org/web/20190926002649/https://www.ncbi.nlm.nih.gov/pubmed/3979509/ |date=2019-09-26 }}, ''Experimental Neurology'' 1985; 198–204", Retrieved February 18, 2017</ref> 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 (cf. [[multiple comparisons problem]]).<ref>{{Cite journal|last=Hines|first=Terence|date=2014-07-01|title=Neuromythology of Einstein's brain|journal=Brain and Cognition|language=en|volume=88|pages=21–25|doi=10.1016/j.bandc.2014.04.004|pmid=24836969|s2cid=43431697|issn=0278-2626}}</ref>

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.<ref>{{cite book|last=Koob|first=Andrew|title=The Root of Thought|date=2009|publisher=FT Press|isbn=978-0-13-715171-4 |page=186}}</ref>

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.<ref>{{cite web| last = Aw| first = B.L| title = 5 Reasons why Glial Cells Were So Critical to Human Intelligence.| url = http://scientificbrains.com/5-reaons-why-glial-cells-were-so-critical-to-human-intelligence/| website = Scientific Brains| access-date = 5 January 2015| archive-date = 1 May 2015| archive-url = https://web.archive.org/web/20150501184148/http://scientificbrains.com/5-reaons-why-glial-cells-were-so-critical-to-human-intelligence/| url-status = live}}</ref> Moreover, evidences are demonstrating the active role of glia, in particular astroglia, in cognitive processes like learning and memory.<ref>{{cite book |doi=10.1093/acprof:oso/9780195152227.003.0014 |chapter-url=https://www.researchgate.net/publication/286097769 |chapter=Quantal Release of Transmitter: Not Only from Neurons but from Aastrocytes as Well? |title=Neuroglia |year=2004 |last1=Volterra |first1=Andrea |last2=Meldolesi |first2=Jacopo |pages=190–201 |isbn=978-0-19-515222-7 }}</ref><ref>{{cite journal |doi=10.1016/j.tins.2006.08.004 |url=https://www.urmc.rochester.edu/MediaLibraries/URMCMedia/labs/nedergaard-lab/documents/Astrocytic-Complexity.pdf |title=Astrocytic complexity distinguishes the human brain |year=2006 |last1=Oberheim |first1=Nancy Ann |last2=Wang |first2=Xiaohai |last3=Goldman |first3=Steven |last4=Nedergaard |first4=Maiken |journal=Trends in Neurosciences |volume=29 |issue=10 |pages=547–53 |pmid=16938356 |s2cid=17945890 |access-date=2023-02-21 |archive-date=2023-02-21 |archive-url=https://web.archive.org/web/20230221161909/https://www.urmc.rochester.edu/MediaLibraries/URMCMedia/labs/nedergaard-lab/documents/Astrocytic-Complexity.pdf |url-status=live }}</ref>

== See also ==
* [[Oligodendrocyte progenitor cell]]
* [[List of human cell types derived from the germ layers]]

== References ==
{{Reflist|30em}}

===Bibliography===
* {{cite book |last=Brodal |first=Per|author-link=Per Alf Brodal|chapter=Glia |title=The central nervous system: structure and function |publisher=Oxford University Press |year=2010 |isbn=978-0-19-538115-3 |page=19 |chapter-url=https://books.google.com/books?id=iJjI6yDNmr8C&pg=PA19}}
* Kettenmann and Ransom, ''Neuroglia'', Oxford University Press, 2012, {{ISBN|978-0-19-979459-1}} |http://ukcatalogue.oup.com/product/9780199794591.do#.UVcswaD3Ay4| {{Webarchive|url=https://web.archive.org/web/20140304225402/http://ukcatalogue.oup.com/product/9780199794591.do#.UVcswaD3Ay4{{!}} |date=2014-03-04 }}
* {{Cite book|title=Neuroscience |edition=5th |last=Puves|first=Dale|publisher=Sinauer Associates|year=2012|isbn=978-0-87893-646-5|pages=560–80}}

== Further reading ==
* {{cite journal |author=Barres BA |author-link=Ben Barres|title=The mystery and magic of glia: a perspective on their roles in health and disease |journal=Neuron |volume=60 |issue=3 |pages=430–40 |date=November 2008 |pmid=18995817 |doi=10.1016/j.neuron.2008.10.013|doi-access=free }}
* [http://pfrieger.gmxhome.de/work/publications/pfrieger_2002.pdf Role of glia in synapse development] {{Webarchive|url=https://web.archive.org/web/20120207052455/http://pfrieger.gmxhome.de/work/publications/pfrieger_2002.pdf |date=2012-02-07 }}
* {{cite journal |last=Overstreet |first=LS |title=Quantal transmission: not just for neurons |journal=Trends in Neurosciences |volume=28 |issue=2 |pages=59–62 |date=February 2005 |pmid=15667925 |doi=10.1016/j.tins.2004.11.010|s2cid=40224065 }}
* {{cite journal |author=Peters A |title=A fourth type of neuroglial cell in the adult central nervous system |journal=Journal of Neurocytology |volume=33 |issue=3 |pages=345–57 |date=May 2004 |pmid=15475689 |doi=10.1023/B:NEUR.0000044195.64009.27|s2cid=39470375 }}
* {{cite journal |vauthors=Volterra A, Steinhäuser C |title=Glial modulation of synaptic transmission in the hippocampus |journal=Glia |volume=47 |issue=3 |pages=249–57 |date=August 2004 |pmid=15252814 |doi=10.1002/glia.20080|s2cid=10169165 }}
* {{cite journal |vauthors=Huang YH, Bergles DE |title=Glutamate transporters bring competition to the synapse |journal=Current Opinion in Neurobiology |volume=14 |issue=3 |pages=346–52 |date=June 2004 |pmid=15194115 |doi=10.1016/j.conb.2004.05.007|s2cid=10725242 }}
* [https://web.archive.org/web/20070927162621/http://www.anioman.com/Profile.php?viewedArtistID=1793201250&gallery=&page=1&back=1 Artist ADSkyler] (uses concepts of neuroscience and found inspiration from Glia)

== External links ==
{{Commons category|Glia}}
* [http://www.wnyc.org/story/59905-the-other-brain/ "The Other Brain"] {{Webarchive|url=https://web.archive.org/web/20170109022838/http://www.wnyc.org/story/59905-the-other-brain/ |date=2017-01-09 }}{{snd}}''[[Leonard Lopate|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."
* [http://www.networkglia.eu/en/ "Network Glia"] {{Webarchive|url=https://web.archive.org/web/20210424154033/http://www.networkglia.eu/en/ |date=2021-04-24 }} A homepage devoted to glial cells.

{{Nervous tissue}}
{{Authority control}}

[[Category:Glial cells]]