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Abstract
Astrocytes are highly complex cells that respond to a variety of external stimulations.
One of the chief functions of astrocytes is to optimize the interstitial space for
synaptic transmission by tight control of water and ionic homeostasis. Several lines
of work have, over the past decade, expanded the role of astrocytes and it is now
clear that astrocytes are active participants in the tri-partite synapse and modulate
synaptic activity in hippocampus, cortex, and hypothalamus. Thus, the emerging concept
of astrocytes includes both supportive functions as well as active modulation of neuronal
output. Glutamate plays a central role in astrocytic-neuronal interactions. This excitatory
amino acid is cleared from the neuronal synapses by astrocytes via glutamate transporters,
and is converted into glutamine, which is released and in turn taken up by neurons.
Furthermore, metabotropic glutamate receptor activation on astrocytes triggers via
increases in cytosolic Ca(2+) a variety of responses. For example, calcium-dependent
glutamate release from the astrocytes modulates the activity of both excitatory and
inhibitory synapses. In vivo studies have identified the astrocytic end-foot processes
enveloping the vessel walls as the center for astrocytic Ca(2+) signaling and it is
possible that Ca(2+) signaling events in the cellular component of the blood-brain
barrier are instrumental in modulation of local blood flow as well as substrate transport.
The hormonal regulation of water and ionic homeostasis is achieved by the opposing
effects of vasopressin and atrial natriuretic peptide on astroglial water and chloride
uptake. In conjuncture, the brain appears to have a distinct astrocytic perivascular
system, involving several potassium channels as well as aquaporin 4, a membrane water
channel, which has been localized to astrocytic endfeet and mediate water fluxes within
the brain. The multitask functions of astrocytes are essential for higher brain function.
One of the major challenges for future studies is to link receptor-mediated signaling
events in astrocytes to their roles in metabolism, ion, and water homeostasis.