text.skipToContent text.skipToNavigation
Need help? Please contact us

Astrocyte biology

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 astrocytes.

The fibrous glia cell is usually located within white matter, has relatively few organelles, and exhibits 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 cells are the most prevalent and are found in grey matter tissue. They possess larger quantities of organelles and exhibit short and highly branched tertiary processes.

The radial glia cell is 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 cells 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. 

Key functions of astrocytes

Astrocyte functional interactions with surround cell types

Astrocytes perform many functions like, biochemical support of endothelial cells that form the blood–brain barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, and have a role in the repair and scarring process of the brain and spinal cord following traumatic injuries.

Function details

  • Structural: Astrocytes 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 glycogenesis. The astrocytes next to neurons in the frontal cortex and hippocampus store and release glycogen. Thus, astrocytes can fuel neurons with glucose during periods of high rate of glucose consumption and glucose shortage.
  • Metabolic Support: Astrocytes provide neurons with nutrients such as lactate.
  • Blood–Brain Barrier: The blood–brain barrier (BBB) is a tightly regulated interface in the Central Nervous System (CNS) that regulates the exchange of molecules in and out from the brain thus maintaining the CNS homeostasis. It is mainly composed of endothelial cells (ECs), pericytes and astrocytes that create a neurovascular unit (NVU) with the adjacent neurons. Astrocytes are essential for the formation and maintenance of the BBB by providing secreted factors that lead to the adequate association between the cells of the BBB and the formation of strong tight junctions.
  • Regulation of blood flow: Astrocytes make extensive contacts and have multiple bidirectional interactions with blood vessels, including regulation of local CNS blood flow. Astrocytes produce and release various molecular mediators, such prostaglandins (PGE), nitric oxide (NO), and arachidonic acid (AA), that can increase or decrease CNS blood vessel diameter and blood flow in a coordinated manner. Moreover, astrocytes may be primary mediators of changes in local CNS blood flow in response to changes in neuronal activity. Astrocytes have processes in contact with both blood vessels and synapses. Via these contacts, astrocytes titrate blood flow in relation to levels of synaptic activity.
  • Transmitter uptake and release: Astrocytes express plasma membrane transporters such as glutamate transporters for uptake & release of 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. 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 ectonucliotidases to yield adenosine. Adenosine acts on neuronal adenosine receptors to inhibit synaptic transmission.
  • 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.
  • Nervous system repair: Upon injury to nerve cells within the central nervous system, astrocytes fill up the space to form a glial scar, repairing the area by transformation into neurons

Astrocytes in neuropathology

Astrocytes are fundamental for the control of brain homeostasis and they also represent an important part of the intrinsic brain defense system. Brain insults of multiple etiologies trigger an evolutionary conserved astroglial defense response generally referred to as reactive astrogliosis. 

Astrogliosis is essential for both limiting the areas of damage (by scar formation through anisomorphic astrogliosis) and for the post-insult remodeling and recovery of neural function (by isomorphic astrogliosis). Astrocytes are involved in all types of brain pathologies from acute lesions (trauma or stroke) to chronic neurodegenerative processes such as Alexander’s disease, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and psychiatric diseases.

The pathologically relevant neuroglial processes are many, and they include various programs of activation, which are essential for limiting the areas of damage, producing neuro-immune responses and for the post-insult remodeling and recovery of neural function. Studies also emphasized the role of astroglial degeneration and atrophy in the early stages of various neurodegenerative disorders, which may be important for cognitive impairments. Astroglial cells determine to a very large extent the progression and the outcome of neurological diseases.

Research applications with astrocytes

Astrocyte mediated neurotoxicity assessment represents an important part of drug safety evaluation, as well as being a significant focus of environmental protection efforts. Additionally, neurotoxicity is also a well-accepted in vitro marker of the development of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Studies have suggested that the use of astrocytes in an in vitro neurotoxicity test system may prove more relevant to human CNS structure and function than neuronal cells alone. High Content Analysis based assays by co-culture of neurons and astrocytes, enables simultaneous analysis of neurotoxicity, neurite outgrowth, gliosis, neuronal and astrocytic morphology and its development in a wide variety of cellular models, representing a novel, non-subjective, high-throughput assay for neurotoxicity assessment. This holds great potential for enhanced detection of neurotoxicity and improved productivity in neuroscience research and drug discovery. In addition, functional studies of receptors expressed by astrocytes and their responses can be studied in real time in astrocyte cultures, giving indications of their functional roles and identification of potent drug candidates for neurodegenerative disorders.

Astrocytes have been co-cultured with neurons on a confluent layer of astrocytes. Neuron and astrocyte co-culture studies help to examine cell surface molecule expression and trophic factor release. Alternatively, astrocytes can be cultured in plates, where inserts with neurons, oligodendrocytes, neuronal stem cells, microglia or endothelial cells are added, so that they share the same medium, but are grown in separate layers. A more dynamic in vivo-like environment is thus created for the cells, enabling the researcher to investigate cell-type specific effects separately.


Abbott NJ. Astrocyte–endothelial interactions and blood–brain barrier permeability. Journal of Anatomy 2002. 200: 629–638

Anderl JL, Redpath aS, Ball AJ. A neuronal and astrocyte co-culture assay for high content analysis of neurotoxicity. Journal of Visualized. Experiments 2009. 27: e1173

Brand FJ 3rd, de Rivero Vaccari JC, Mejias NH, Alonso OF, de Rivero Vaccari JP. RIG-I contributes to the innate immune response after cerebral ischemia. Journal of Inflammation 2015. 12: 52

Carroll-Anzinger D, Kumar A Adarichev V, Kashanchi F, Al-Harthi L. Human immunodeficiency virus-restricted replication in astrocytes and the ability of gamma interferon to modulate this restriction are regulated by a downstream effector of the wnt signaling pathway. Journal of Virology 2007. 6: 5864–5871

Chung RS, Penkowa M, dittmann J, King CE, Bartlett C, Asmussen JW, Hidalgo J, Carrasco J, Leung YKJ, Walker AK, Fung SJ, Dunlop Sa, Fitzgerald M, Beazley LD, Chuah MI, Vickers JC, West AK. Redefining the role of metallothionein within the injured brain. The Journal of Biological Chemistry 2008. 283: 22; 15349–15358

Fiacco TA, Agulhon C, McCarthy KD. Sorting out Astrocyte Physiology from Pharmacology. Annual Review of Pharmacology & Toxicology 2009. 49 (1): 151–74

Figley CR & Stroman PW. The role(s) of astrocytes and astrocyte activity in neurometabolism, neurovascular coupling, and the production of functional neuroimaging signals. European Journal of Neuroscience 2011. 33: 4: 577–588

Hamby ME and Sofroniew MV. Reactive astrocytes as therapeutic targets for CNS disorders. Neurotherapeutics 2010. 7: 494-506

Heni M, Hennige AM, Peter A, Siegel-Axel D, Ordelheide AM, Krebs N, Machicao F, Fritsche A, Häring HU, Staiger H. Insulin promotes glycogen storage and cell proliferation in primary human astrocytes. PLOS ONE 2011. 6: 6; e21594

Kettenmann H, Ransom B. The concept of neuroglia: a historical perspective. In: Kettenmann H, Ransom BR, editors. Neuroglia. 2nd ed. New York: Oxford University Press 2005. 1–16

Lange SC, Bak LK, Waagepetersen HS, Schousboe A, Norrenberg MD. Primary cultures of astrocytes: Their value in understanding astrocytes in health and disease. Neurochemical Research 2012. 37; 11; 2569–2588

Molofsky AV, Krencik R, Ullian EM, Tsai HH, Deneen B, Richardson WD, Barres BA, Rowitch DH. Astrocytes and disease: a neurodevelopmental perspective. Genes & Development 2009. 26: 891–907

Nedergaard M, Ransom B, Goldman SA. New roles for astrocytes: redefining the functional architecture of the brain. Trends in Neurosciences 2003. 26: 523–530

Nishimura M, Doi K, Kishimoto S, Koshitani O, Naito S, Yamauchi A. Pharmacological assessment of ARTCEREB irrigation and perfusion solution for cerebrospinal surgery using primary cultures of rat brain cells. The Journal of Toxicological Sciences 2010. 35: 4: 447-457

Oberheim NA, Wang X, Goldman S, Nedergaard M. Astrocytic complexity distinguishes the human brain. Trends in Neurosciences 2006. 29: 547–553

Sofroniew MV, Vinters HV. Astrocytes: biology and pathology. Acta Neuropatholgica 2010. 119: 7–35

Vartak-Sharma N, Gelman BB, Joshi C, Borgamann, Ghorpade A. Astrocyte elevated gene-1 is a novel modulator of HIV-1-associated neuroinflammation via regulation of nuclear factor-B signaling and excitatory amino acid transporter-2 repression. The Journal of Biological Chemistry 2014. 289; 28: 19599–19612

Venkatesh K, Srikanth L, Vengamma B, Chandrasekhar C, Sanjeevkumar A, Prasad BCM, Sarma PVGK. In vitro differentiation of cultured human CD34+ cells into astrocytes. Neurology India 2013. 61 (4): 383–388

Xing F, Kobayashi A, Okuda H, Watabe M, Pai SK, Pandey PR, Hirota S, Wilber A, Mo YY, Moore BE, Liu W, Fukuda K, Iiizumi M, Sharma S, Liu Y, Wu K, Peralta E, Watabe K. Reactive astrocytes promote the metastatic growth of breast cancer stem-like cells by activating Notch signalling in brain. EMBO Molecular Medicine 2013. 5; 384-396

Yu P, Wang H, Katagiri Y, Geller HM. An in vitro model of reactive astrogliosis and its effect on neuronal growth. Methods in Molecular Biology 2012. 814: 327–340