Astrocytes (also known collectively as astroglia) are characteristic star-shaped glial cells in the brain. They perform many functions, including the formation of the blood-brain barrier, the provision of nutrients to the nervous tissue, and play a principal role in the repair and scarring process in the brain.
Astrocytes are a sub-type of the glial cells in the brain. They are also known as astrocytic glial cells. Star-shaped, their many processes envelope synapses made by neurons. Astrocytes are classically identified histologically by their expression of glial fibrillary acidic protein (GFAP). Previously in medical science, the neuronal network was considered the only important one, and astrocytes were looked upon as gap fillers. But recently they have been reconsidered and are now thought to play a number of active roles in the brain. Although they aid in the maintenance of the blood-brain barrier, they do not actually form it.
- Structural: involved in the physical structuring of the brain.
- Metabolic support: they provide neurons with nutrients such as glucose.
- Blood-brain barrier: the astrocyte end-feet encircling endothelial cells aid in the maintenance of the blood-brain barrier.
- Transmitter reuptake and release: astrocytes express plasma membrane transporters such as glutamate transporters for several neurotransmitters, including glutamate, ATP and GABA. More recently, astrocytes were shown to release glutamate or ATP in a vesicular, Ca2+-dependent manner.
- Regulation of ion concentration in the extracellular space: astrocytes express potassium channels at a high density. When neurons are active, they release potassium, increasing the local extracellular concentration. Because astrocytes are highly permeable to potassium, they rapidly clear the excess accumulation in the extracellular space. If this function is interfered with, the extracellular concentration of potassium will rise, leading to neuronal depolarization by the Goldman equation. Abnormal accumulation of extracellular potassium is well known to result in epileptic neuronal activity.
- Modulation of synaptic transmission: in the supraoptic nucleus of the hypothalamus, rapid changes in astrocyte morphology have been shown to affect heterosynaptic transmission between neurons.
- Vasomodulation: astrocytes may serve as intermediaries in neuronal regulation of blood flow.
- Promotion of the myelinating activity of oligodendrocytes: electrical activity in neurons causes them to release ATP, which serves as an important stimulus for myelin to form. Surprisingly, the ATP does not act directly on oligodendrocytes. Instead it causes astrocytes to secrete LIM, a regulatory protein that promotes the myelinating activity of oligodendrocytes. This suggest that astrocytes have an executive-coordinating role in the brain.
In the 1990s, following persistent study, a small group of scientists began to uncover evidence that astrocytes signal to neurons and influence their activity. First, cell experiments in petri dishes found that following an increase of the element calcium in astrocytes, there is an increase of calcium in surrounding neurons. This implied some form of communication between the two cell types. Next, scientists found that indeed the calcium increase in astrocytes directly links to changes in neuron activity. In one study of rat cells, microelectrodes measured the electrical impulses that neurons use to signal to each other. In response to the calcium increase in astrocytes, the majority of neurons tested slowed down their signaling activity. A few increased their signaling activity.
Other research is uncovering key molecules that aid the communication. Several studies indicate that following the rise of calcium, astrocytes release the amino acid glutamate, which helps them talk to the neurons. The communication flows both ways, with neurons also being able to talk to the astrocytes through their own glutamate release. Signaling molecules, such as ATP and prostaglandins, also appear to promote the cell-to-cell communication, according to other new investigations.
Determining why the astrocyte chatting occurs and whether it actually affects the neurons' ability to process information, is another area of research. Early studies hint that some of the chatting may aid memory. Adding glutamate to cell samples of astrocytes prompts them to produce special molecules that nourish neurons, known as trophic factors. Other research has found that these molecules are key to memory function. In one recent study, injections of trophic factors into the brains of rats boosted the biological mechanisms known to relate to memory and improved the rats' performance in a memory task. This all may mean that glutamate release from neurons triggers astrocytes to produce trophic factors, which then help neurons process information for memory. Scientists currently are testing this theory.
Together the research is not only making researchers rethink how the brain operates, but also how to treat it when it malfunctions. For one, if the research on astrocytes' connection to memory pans out, then the cells may make good targets for treatment of memory disorders such as Alzheimer's disease. Astrocytes' relationship to glutamate also may make them good targets for clinical intervention since several brain disorders have been tied to glutamate problems. For example, some scientists believe that when the brain is infected by the AlDS-causing HIV virus or deprived of oxygen from lack of blood flow due to a stroke, a release of excess glutamate causes neurons to die. Agents that target astrocytes might help limit the glutamate overflow and prevent the cell death.
Furthermore, studies are underway to determine whether astroglia play an instrumental role in depression, based on the link between diabetes and depression. Altered CNS glucose metabolism is seen in both these conditions, and the astroglial cells are the only cells with insulin receptors in the brain.
An increase in intracellular calcium concentration can propagate outwards through this syncytium. Mechanisms of calcium wave propagation include diffusion of IP3 through gap junctions and extracellular ATP signalling. Calcium elevations are the primary known axis of activation in astrocytes, and are necessary and sufficient for some types of astrocytic glutamate release.
There are several different ways to classify astrocytes:
by Lineage and antigenic phenotype
These have been established by classic work by Raff et al in early 1980s on Rat optic nerves.
- Type 1: Antigenically Ran2+, GFAP+, FGFR3+, A2B5- thus resembling the "type 1 astrocyte" of the postnatal day 7 rat optic nerve. These can arise from the tripotential glial restricted precursor cells (GRP), but not from the bipotential O2A/OPC (oligodendrocyte, type 2 astrocyte precursor, also called Oligodendrocye progenitor cell) cells.
- Type 2: Antigenically A2B5+, GFAP+, FGFR3-, Ran 2-. These cells can develop in vitro from the either tripotential GRP (probably via O2A stage) or from bipotential O2A cells (which some people think may in turn have been derived from the GRP) or in vivo when the these progenitor cells are transplanted into lesion sites (but probably not in normal development, at least not in the rat optic nerve). Type-2 astrocytes are the major astrocytic component in postnatal optic nerve cultures that are generated by O2A cells grown in the presence of fetal calf serum but are not thought to exist in vivo (Fulton et al., 1992).
- Type I: Those astrocytes are in direct contact with blood capillaries through astrocytique pod. They are actively helping neuronal metabolism and glucose delivery.
- Type II: Type II astrocytes surrounds neurons and synaptic gap. This coverage varies from 1 to 100%.
by Anatomical Classification
- Protoplasmic: found in grey matter and have many branching processes whose end-feet envelop synapses. Some protoplasmic astrocytes are generated by multipotent subventricular zone progenitor cells (Levison and Goldman, 1993; Zerlin et al., 1995).
- Fibrous: found in white matter and have long thin unbranched processes whose end-feet envelop nodes of Ranvierand also they play an important on humans brain. Some fibrous astrocytes are generated by radial glia (Choi and Lapham, 1978; Schmechel and Rakic, 1979; Misson et al., 1988; Voigt, 1989; Goldman, 1996
by Transporter/receptor classification
- GluT type: express glutamate transporters (EAAT1/SLC1A3 and EAAT2/SLC1A2) and respond to synaptic release of glutamate by transporter currents
- GluR type: express glutamate receptors (mostly mGluR and AMPA type) and respond to synaptic release of glutamate by channel-mediated currents and IP3-dependent Ca2+ transients
Bergmann glia, a type of glia also known as radial epithelial cells (as named by Camillo Golgi), are astrocytes in the cerebellum that have their cell bodies in the Purkinje cell layer and processes that extend into the molecular layer, terminating with bulbous endfeet at the pial surface. Bergmann glia express high densities of glutamate transporters that limit diffusion of the neurotransmitter glutamate during its release from synaptic terminals. Besides their role in early development of the cerebellum, Bergmann glia are also required for the pruning or addition of synapses.
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