Glia
Glia is the generic name for a huge number of cells of several different types that are found in the brain.
They provide support and maintenance for neurons and synapses and are involved in chemical signalling,
but they do not perform electrical signalling like neurons.
Glia cells have often been overlooked in the past as being simply support cells,
but it now seems possible that the unique nature of some types of glial cells found only in the brains of
human and other higher mammals is one of the things that has contributed to the evolutionary
improvement of the brain.
It also seems likely that in the near future we will have treatments for a number of brain disorders
that involve drugs acting on glial cells.
- For a long time glia were thought of as just “scaffolding” for
neurons to keep them in place. However, only in the last twenty years or
so1,
2
it has been discovered that they play a very important role in the brain, helping the formation of
synapse connections between neurons, increasing the strength and speed of neuron signals,
and performing vital brain housekeeping work such as clearing away debris, destroying invading pathogens,
repairing damage and pruning unwanted connections.
- There are almost as many glial cells in the human brain as neurons, somewhere near
86 billion1,
but many are smaller than neurons. Different parts of the brain have different ratios of glia to neurons,
although the reason for this is not understood.
- There are several different types of glial cells, the four main ones are as follows:
- Oligodendrocytes create insulating sleeves of a material called
myelin around the axons of
neurons that protect and insulate the axons so making the electrical signals more
reliable and allowing them to travel much further, faster and more reliably.
Myelin is the so-called “white matter” of the brain and is essential for the proper working of the brain.
One of the diseases caused by damaged myelin is multiple sclerosis.
- Astrocytes have a very close relationship with neurons and synapses and assist with many
important functions
that may influence the strength of synapse connections, and hence affect learning.
They also affect memory by assisting in the formation and pruning of synapses.
Human astrocytes grown in mouse brains
make the mice more intelligent3,
which could indicate that these cells are contributing to the intelligence that is unique to higher mammals.
- Microglia
are the main immune cells of the brain, so are very important in
protecting the brain from infections.
They are involved in promoting the growth of new synapses as well as the pruning of
synapses4,
5.
Microglia fulfil many roles, and problems with their functionality have been suggested as having
a role in a number of diseases
including Alzheimer’s disease.
- NG2-glia
have been likened to stem-cells in the brain because they can transform into different types of glial cells or even (possibly) new neurons,
even in the adult brain6,
7.
The most common type of brain tumour, called glioma,
is caused by the growth of glial cells; neurons
very rarely cause brain tumours.
- Some glia cells are capable of
producing certain neurotransmitters,
so can affect transmission of signals by neurons over quite a wide area by neuromodulation.
Glia can communicate using calcium ions8,
some form synapses to neurons, but glial cells do not generate or pass on electrical signals themselves so are not directly involved in processing data in the brain.
-
^ ^
How many neurons do you have? Some dogmas of quantitative neuroscience under revision - Lent, Azevedo, Andrade-Moraes and Pinto 2011
doi:10.1111/j.1460-9568.2011.07923.x
downloadable here or see
GoogleScholar.
Page 5, second paragraph: “For glial cells, the prevalent dogma poses that the glia/neuron ratio is approximately 10:1 in the brain. However, with the isotropic fractionator, the actual glia/neuron ratio for the whole human brain was shown to be close to 1.”
Page 5, fourth paragraph: “Glial cells cooperate with neurons in the proper function of the nervous system. Their importance has increased recently, well beyond the early conception of their role as a structural 'glue' for the tissue. During development, glial cells act as stem cells and as guidance scaffolds for migrating neurons and growing axons. In adults, they play important roles in synapse physiology, neurovascular interactions, immune mechanisms and circuit stabilization, signal conduction, fiber maintenance and regeneration, and higher information processing. As a whole, the evidence indicates that glial cells do participate actively in the functional computations performed by neurons, circuits, and networks.”
-
^
The interplay between neurons and glia in synapse development and plasticity - Stogsdill and Eroglu 2018
doi: 10.1016/j.conb.2016.09.016
downloadable here or see
GoogleScholar.
Figure 2 at the bottom of page 5 is a useful summary of some of the latest findings. The figure description says:
“(a) Synapse formation is controlled by several astrocyte and microglia-derived soluble factors.
Astrocyte secreted factors regulate synapse formation ...
BDNF released from microglia also control excitatory synapse formation presumably by binding to the TrkB receptor in neurons.
The recruitment of pre and postsynaptic specializations is a key step in synapse development regulated by glia.
(b) Synaptic plasticity is controlled by several glial mechanisms.
Astrocytes regulate synaptic integration through vesicular release of D-serine and potentially via other factors.
Synaptic plasticity is regulated in the visual cortex by astrocytic hevin and microglial P2Y12.
(c) Elimination of weak synapses is controlled by microglia through the complement proteins C1q, C3 and C4 and their microglial receptors.
Astrocytes engulf and remove unwanted synapses via MEGF10 and MERTK pathways.”
-
^
A Competitive Advantage by Neonatally Engrafted Human Glial Progenitors Yields Mice Whose Brains Are Chimeric for Human Glia - Windrem, Schanz, Morrow, Munir, Chandler-Militello, Wang and Goldman 2014
doi:10.1523/JNEUROSCI.1510-14.2014
downloadable here or see
GoogleScholar.
Page 16159, right-hand column, second sentence under the heading “Discussion”:
“We found that a large proportion of glial cells within the recipient mice, often all GPCs and a large proportion of astrocytes, and oligodendrocytes as well, when using hypomyelinated hosts, were ultimately replaced by human donor-derived cells. The extent of this colonization of the mouse brain by human glia appeared so robust that we quantitatively evaluated the absolute numbers, relative proportions, and geographic distributions of human donor cells in the neonatally engrafted recipients.”
...continuing on page 16160, right-hand column:
“As a result, the greater structural complexity of human astrocytes relative to those of rodents is accompanied by functional differences: human astrocytes propagate Ca2+ wave significantly faster than rodents, and human glial chimeric mice exhibit both enhanced long-term potentiation and facilitated learning in a variety of conditioned response paradigms and cognitive tasks.”
-
^
Microglia: New Roles for the Synaptic Stripper
- Kettenmann, Kirchhoff and Verkhratsky 2013
doi: 10.1016/j.neuron.2012.12.023
downloadable here or see
GoogleScholar.
Page 10, third sentence of abstract:
“In the normal brain microglia were considered 'resting', but it has recently become evident that they constantly scan the brain environment and contact synapses. Activated microglia can remove damaged cells as well as dysfunctional synapses, a process termed 'synaptic stripping.' Here we summarize evidence that molecular pathways
characterized in pathology are also utilized by microglia in the normal and developing brain to influence synaptic development and connectivity, and therefore should become targets of future research.”
-
^
Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
- Paolicelli et al. 2011
doi: 10.1126/science.1202529
downloadable here or see
GoogleScholar.
Page 1456, third sentence of abstract:
“Here, we show that microglia actively engulf synaptic material and play a major role in synaptic pruning during postnatal development in mice.”
-
^
Oligodendrocyte Development and Plasticity
- Bergles and Richardson 2016
doi: 10.1101/cshperspect.a020453
downloadable here or see
GoogleScholar.
Page 1, first paragraph of main text:
“Oligodendrocytes (OLs), the myelin-forming cells of the central nervous system (CNS), develop from glial progenitor cells, known as 'oligodendrocyte precursor cells' (OPCs), which arise from several parts of the ventricular germinal zones of the embryonic neural tube. OPCs proliferate and migrate away from these zones into developing gray and white matter before differentiating into myelin-forming OLs. However, unlike most progenitors, OPCs remain abundant in the adult CNS, where they retain the ability to generate new OLs that allow rapid regeneration of myelin that might be lost through normal aging or disease, as well as changing the pattern of myelination in response to life experience.... OPCs have also been referred to as 'NG2 cells' (because they express the NG2 proteoglycan on their surface)...”
Page 12, first paragraph:
“...there has been a recent report that OPCs can produce new neurons in the adult hypothalamus...”
-
^
Lineage, Fate, and Fate Potential of NG2-glia
- Nishiyama1, Boshans, Goncalves, Wegrzyn and Patel 2016
doi: 10.1016/j.brainres.2015.08.013
downloadable here or see
GoogleScholar.
Page 1, first paragraph of introduction:
“NG2 cells represent a fourth resident glial cell population in the mammalian central nervous system (CNS) that is distinct from astrocytes, mature oligodendrocytes, and microglia. They are defined as non-neuronal, non-vascular glial cells in the CNS parenchyma that express the NG2 antigen and the alpha receptor for platelet-derived growth factor (Pdgfra). They are distributed widely throughout both gray and white matter. They generate oligodendrocytes in culture and in vivo and hence are often equated with oligodendrocyte precursor cells (OPCs).”
-
^
The Other Brain - Douglas Fields, speaking on The Leonard Lopate Show on WNYC radio on January 22nd 2010.
Particularly 4'05" in podcast:
“Glia communicate with chemical signalling, and they communicate by sending waves of calcium ions from one cell to another.”
Page last uploaded
Sat Mar 2 02:55:42 2024 MST
