astrocyte astrocyte astrocytes (from ancient greek ἄστρον, ástron, "star" + κύτος, kútos, "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. they perform many functions, including biochemical control of endothelial cells that form the blood–brain barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, regulation of cerebral blood flow, and a role in the repair and scarring process of the brain and spinal cord following infection and traumatic injuries. the proportion of astrocytes in the brain is not well defined; depending on the counting technique used, studies have found that the astrocyte proportion varies by region and ranges from 20% to around 40% of all glia. another study reports that astrocytes are the most numerous cell type in the brain. astrocytes are the major source of cholesterol in the central nervous system. apolipoprotein e transports cholesterol from astrocytes to neurons and other glial cells, regulating cell signaling in the brain. astrocytes in humans are more than twenty times larger than in rodent brains, and make contact with more than ten times the number of synapses. "cajal cell" redirects here. for the cell in the gastrointestinal tract, see interstitial cell of cajal. astrocytean astrocyte from a rat brain grown in tissue culture and stained with antibodies to gfap (red) and vimentin (green). both proteins are present in large amounts in the intermediate filaments of this cell, so the cell appears yellow. the blue material shows dna visualized with dapi stain, and reveals the nucleus of the astrocyte and of other cells. image courtesy of encor biotechnology inc.detailslocationbrain and spinal cordidentifierslatinastrocytusmeshd001253neurolex idsao1394521419thh2.00.06.2.00002, h2.00.06.2.01008 fma54537anatomical terms of microanatomy research since the mid-1990s has shown that astrocytes propagate intercellular ca2+ waves over long distances in response to stimulation, and, similar to neurons, release transmitters (called gliotransmitters) in a ca2+-dependent manner. data suggest that astrocytes also signal to neurons through ca2+-dependent release of glutamate. such discoveries have made astrocytes an important area of research within the field of neuroscience. structure astrocytes (green) in the context of neurons (red) in a mouse cortex cell culture 23-week-old fetal brain culture human astrocyte astrocytes (red-yellow) among neurons (green) in the living cerebral cortex astrocytes are a sub-type of glial cells in the central nervous system. they are also known as astrocytic glial cells. star-shaped, their many processes envelop synapses made by neurons. in humans, a single astrocyte cell can interact with up to 2 million synapses at a time. astrocytes are classically identified using histological analysis; many of these cells express the intermediate filament glial fibrillary acidic protein (gfap). several forms of astrocytes exist in the central nervous system including fibrous (in white matter), protoplasmic (in grey matter), and radial. the fibrous glia are usually located within white matter, have relatively few organelles, and exhibit long unbranched cellular processes. this type often has astrocytic endfoot processes that physically connect the cells to the outside of capillary walls when they are in proximity to them. the protoplasmic glia are the most prevalent and are found in grey matter tissue, possess a larger quantity of organelles, and exhibit short and highly branched tertiary processes. the radial glial cells are disposed in planes perpendicular to the axes of ventricles. one of their processes abuts the pia mater, while the other is deeply buried in gray matter. radial glia are mostly present during development, playing a role in neuron migration. müller cells of the retina and bergmann glia cells of the cerebellar cortex represent an exception, being present still during adulthood. when in proximity to the pia mater, all three forms of astrocytes send out processes to form the pia-glial membrane. development astrocytes are depicted in red. cell nuclei are depicted in blue. astrocytes were obtained from brains of newborn mice. astrocytes are macroglial cells in the central nervous system. astrocytes are derived from heterogeneous populations of progenitor cells in the neuroepithelium of the developing central nervous system. there is remarkable similarity between the well known genetic mechanisms that specify the lineage of diverse neuron subtypes and that of macroglial cells. just as with neuronal cell specification, canonical signaling factors like sonic hedgehog (shh), fibroblast growth factor (fgfs), wnts and bone morphogenetic proteins (bmps), provide positional information to developing macroglial cells through morphogen gradients along the dorsal–ventral, anterior–posterior and medial–lateral axes. the resultant patterning along the neuraxis leads to segmentation of the neuroepithelium into progenitor domains (p0, p1 p2, p3 and pmn) for distinct neuron types in the developing spinal cord. on the basis of several studies it is now believed that this model also applies to macroglial cell specification. studies carried out by hochstim and colleagues have demonstrated that three distinct populations of astrocytes arise from the p1, p2 and p3 domains. these subtypes of astrocytes can be identified on the basis of their expression of different transcription factors (pax6, nkx6.1) and cell surface markers (reelin and slit1). the three populations of astrocyte subtypes which have been identified are 1) dorsally located va1 astrocytes, derived from p1 domain, express pax6 and reelin 2) ventrally located va3 astrocytes, derived from p3, express nkx6.1 and slit1 and 3) and intermediate white-matter located va2 astrocyte, derived from the p2 domain, which express pax6, nkx6.1, reelin and slit1. after astrocyte specification has occurred in the developing cns, it is believed that astrocyte precursors migrate to their final positions within the nervous system before the process of terminal differentiation occurs. function metabolic interactions between astrocytes and neurons astrocytes help form the physical structure of the brain, and are thought to play a number of active roles, including the secretion or absorption of neural transmitters and maintenance of the blood–brain barrier. the concept of a tripartite synapse has been proposed, referring to the tight relationship occurring at synapses among a presynaptic element, a postsynaptic element and a glial element. structural: they are involved in the physical structuring of the brain. astrocytes get their name because they are "star-shaped". they are the most abundant glial cells in the brain that are closely associated with neuronal synapses. they regulate the transmission of electrical impulses within the brain. glycogen fuel reserve buffer: astrocytes contain glycogen and are capable of gluconeogenesis. the astrocytes next to neurons in the frontal cortex and hippocampus store and release glucose. thus, astrocytes can fuel neurons with glucose during periods of high rate of glucose consumption and glucose shortage. a recent research on rats suggests there may be a connection between this activity and physical exercise. metabolic support: they provide neurons with nutrients such as lactate. glucose sensing: normally associated with neurons, the detection of interstitial glucose levels within the brain is also controlled by astrocytes. astrocytes in vitro become activated by low glucose and are in vivo this activation increases gastric emptying to increase digestion. blood–brain barrier: the astrocyte end-feet encircling endothelial cells were thought to aid in the maintenance of the blood–brain barrier, but recent research indicates that they do not play a substantial role; instead, it is the tight junctions and basal lamina of the cerebral endothelial cells that play the most substantial role in maintaining the barrier. however, 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. transmitter uptake 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. (this has been disputed for hippocampal astrocytes.) 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. in the hippocampus, astrocytes suppress synaptic transmission by releasing atp, which is hydrolyzed by ectonucleotidases to yield adenosine. adenosine acts on neuronal adenosine receptors to inhibit synaptic transmission, thereby increasing the dynamic range available for ltp. 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. however, the atp does not act directly on oligodendrocytes. instead, it causes astrocytes to secrete cytokine leukemia inhibitory factor (lif), a regulatory protein that promotes the myelinating activity of oligodendrocytes. this suggests that astrocytes have an executive-coordinating role in the brain. nervous system repair: upon injury to nerve cells within the central nervous system, astrocytes fill up the space to form a glial scar, and may contribute to neural repair. the role of astrocytes in cns regeneration following injury is not well understood though. the glial scar has traditionally been described as an impermeable barrier to regeneration, thus implicating a negative role in axon regeneration. however, recently, it was found through genetic ablation studies that astrocytes are actually required for regeneration to occur. more importantly, the authors found that the astrocyte scar is actually essential for stimulated axons (that axons that have been coaxed to grow via neurotrophic supplementation) to extend through the injured spinal cord. astrocytes that have been pushed into a reactive phenotype (termed astrogliosis, defined by upregulation of gfap expression, a definition still under debate) may actually be toxic to neurons, releasing signals that can kill neurons. much work, however, remains to elucidate their role in nervous system injury. long-term potentiation: scientists debate whether astrocytes integrate learning and memory in the hippocampus. recently it has been shown that engrafting human glial progenitor cell in the nascent mice brains will cause the cells to differentiate into astrocytes. after differentiation these cells increase ltp and improve memory performance in the mice. circadian clock: astrocytes alone are sufficient to drive the molecular oscillations in the scn and circadian behavior in mice, and thus can autonomously initiate and sustain complex mammalian behavior. the switch of the nervous system: based on the evidence listed below, it has been recently conjectured in, that macro glia (and astrocytes in particular) act both as a lossy neurotransmitter capacitor and as the logical switch of the nervous system. i.e., macroglia either block or enable the propagation of the stimulus along the nervous system, depending on their membrane state and the level of the stimulus. fig. 6 the conjectured switching role of glia in the biological neural detection scheme as suggested by nossenson et al. evidence supporting the switch and lossy capacitor role of glia as suggested in evidence typedescription