Astroglia Cells

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

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.