Astrocyte

Astrocytes (or astroglia) are star-shaped glial cells in the brain and spinal cord. They provide metabolic support for the epithelial cells that form the blood-brain barrier, provide nutrients to the nervous tissue, and thay have a major role in repair and regeneration in the brain. They also intercommunicate with neurones, and have an important role in the uptake and degradation of neurotransmitters released by neurons into the extracellular space.

Description

Astrocytes are a sub-type of glial cells. Their primary processes are star-shaped, and numerous fine processes largely fill the space between the "star beams" to create a spongiform shape. Fine distal processes of the astrocyte envelop, or "ensheath" neurons and their axons. Proximity and interaction between synaptic elements and astrocytic processes gave rise to a concept of "tripartite synapse". The degree of synapse ensheathing varies between brain areas and between individual synapses, and it can also change in an activity-dependent manner, allowing for structural plasticity of tripartite synapse. Astrocytes express many different receptors for peptides and other signalling molecules that are released by neurons, and these signals regulate their shape and function.

Classically, astrocytes are identified histologically by their expression of the intermediate filament glial fibrillary acidic protein (GFAP), although the level of GFAP expression varies widely between astrocytes. Two forms of astrocytes exist in the CNS, fibrous and protoplasmic. Fibrous astrocytes are usually located within white matter, have relatively few organelles, and have long, unbranched processes. This type often has "vascular feet", also called endfeet, that connect the astrocyte to the outside of capillary wall. Protoplasmic astrocytes, found in grey matter, have more organelles, and short,highly branched processes. When in proximity to the pia mater, astrocytes send out their processes to form the pia-glial membrane.

Formerly, glia were looked upon as gap fillers in the CNS, playing essentially a supportive, structural role, and providing neurons with nutrients such as glucose (the name 'glia' originating from the Greek for glue, and for many years they viewed simply as the brain's packing material) . However, astrocytic networks are now thought to play a number of active roles in the brain, including the secretion and uptake of neurotransmitters, "siphoning" K⁺ ions away from synapses, regulation of synaptogenesis, modulation of synaptic transmission, short- and long-term synaptic plasticity, neuro-vascular coupling, and maintenance of the blood-brain barrier.

Astrocytes express plasma membrane transporters such as glutamate transporters for several neurotransmitters, including glutamate, ATP and GABA. More recently, astrocytes have been shown shown to release glutamate or ATP in a Ca²⁺-dependent manner.

Astrocytes express a high density of potassium channels. When neurons are active, they release potassium into the extracellular space; astrocytes can rapidly clear this excess accumulation to maintain the ionic composition of extracellular fluid. If this function is interfered with, the extracellular concentration of potassium will rise, leading to neuronal depolarization , and can result in epileptic neuronal activity.

In the supraoptic nucleus and paraventricular nucleus of the hypothalamus, astrocytic processes ensheathe the somata and dendrites of oxytocin- and vasopressin- secreting neurons. Rapid changes in the morphology of these astrocytes occur in a variety of different physiological states, including during lactation, which is associated with high demand for oxytocin, and after dehydration, which is associated with high demand for vasopressin. These changes affect dendro-dendritic intercommunication between the neurons, and also affevt afferent synaptic transmission to them, by altering the availability of transmitter released at synapses.

• Vasomodulation: astrocytes may serve as intermediaries in neuronal regulation of blood flow.

Electrical activity in neurons causes them to release ATP, which serves as an important stimulus for myelin to form. Surprisingly, ATP does not act directly on oligodendrocytes; instead it causes astrocytes to secrete the cytokine leukemia inhibitory factor, a regulatory protein that promotes the myelinating activity of oligodendrocytes.

When nerve cells are injured, astrocytes become phagocytic to ingest them . The astrocytes then fill up the space to form a glial scar, repairing the area and replacing the CNS cells that cannot regenerate.

Astrocytes are important in regulating neural stem cells. The human brain contains numerous neural stem cells, which are kept in a dormant state by chemical signals (ephrin-A2 and ephrin-A3) from the astrocytes. Astrocytes can activate the stem cells to transform into working neurons by dampening the release of ephrin-A2 and ephrin-A3.

Calcium waves

Astrocytes are linked by gap junctions, creating an electrically coupled syncytium. Waves of intracellular calcium 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.

Classification

There are several ways to classify astrocytes:

By lineage and antigenic phenotype

1. 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 cells).
2. Type 2: Antigenically A2B5⁺, GFAP⁺, FGFR3^-, Ran 2^-. These cells can develop in vitro from the either tripotential GRP or from bipotential O2A cells or in vivo when the these progenitor cells are transplanted into lesion sites.

Anatomically

1. 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.
2. Fibrous: found in white matter, these have long thin unbranched processes whose end-feet envelop nodes of Ranvier. Some fibrous astrocytes are generated by radial glia.

By transporter/receptor expression

1. GluT type: express glutamate transporters (EAAT1/Template:Gene and EAAT2/Template:Gene)
2. GluR type: express glutamate receptors (mostly mGluR and AMPA type); these respond to glutamate by channel-mediated currents and IP3-dependent calcium transients

Bergmann glia

Bergmann 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 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.

Pathology

Astrocytomas are primary intracranial tumors derived from astrocyte cells of the brain. Under the 1993 World Health Association criteria, a glioblastoma can be considered a "high-grade" (Grade IV) astrocytoma; grade III anaplastic astrocytomas are also malignant. The lower-grade astrocytomas may progress to higher-grade