Astrocyte

Astrocytes (Astro from Greek astron = star and cyte from Greek 'kytos' = cavity but also means cell), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. 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 40% of all glia. Overall, astrocytes outnumber neurons by over fivefold. They perform many functions, including biochemical support of endothelial cells that form the blood–brain barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, and a role in the repair and scarring process of the brain and spinal cord following traumatic injuries. Astrocytes (Astro from Greek astron = star and cyte from Greek 'kytos' = cavity but also means cell), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. 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 40% of all glia. Overall, astrocytes outnumber neurons by over fivefold. They perform many functions, including biochemical support of endothelial cells that form the blood–brain barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, and a role in the repair and scarring process of the brain and spinal cord following traumatic injuries. 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. 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. 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 'vascular feet' 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. 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. 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. Astrocytes are linked by gap junctions, creating an electrically coupled (functional) syncytium. Because of this ability of astrocytes to communicate with their neighbors, changes in the activity of one astrocyte can have repercussions on the activities of others that are quite distant from the original astrocyte. An influx of Ca2+ ions into astrocytes is the essential change that ultimately generates calcium waves. Because this influx is directly caused by an increase in blood flow to the brain, calcium waves are said to be a kind of hemodynamic response function. An increase in intracellular calcium concentration can propagate outwards through this functional syncytium. Mechanisms of calcium wave propagation include diffusion of calcium ions and 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. Given the importance of calcium signaling in astrocytes, tight regulatory mechanisms for the progression of the spatio-temporal calcium signaling have been developed. Via mathematical analysis it has been shown that localized inflow of Ca2+ ions yields a localized raise in the cytosolic concentration of Ca2+ ions. Moreover, cytosolic Ca2+ accumulation is independent of every intracellular calcium flux and depends on the Ca2+ exchange across themembrane, cytosolic calcium diffusion, geometry of the cell, extracellular calcium perturbation, and initial concentrations. Within the dorsal horn of the spinal cord, activated astrocytes have the ability to respond to almost all neurotransmitters and, upon activation, release a multitude of neuroactive molecules such as glutamate, ATP, nitric oxide (NO), and prostaglandins (PG), which in turn influences neuronal excitability. The close association between astrocytes and presynaptic and postsynaptic terminals as well as their ability to integrate synaptic activity and release neuromodulators has been termed the tripartite synapse. Synaptic modulation by astrocytes takes place because of this three-part association. Astrocytomas are primary intracranial tumors derived from astrocytes cells of the brain. It is also possible that glial progenitors or neural stem cells give rise to astrocytomas.