Gliotransmitters

Activation of CXCR4 Induces Release of Chemical Transmitters (Gliotransmitters) from Glial Cells... 

Mechanisms of Gliotransmitters Release Evidence on CXCR4-Mediated Glutamate Exocytosis from Astrocytes... 

A. Astrocytes Contain and Release Chemical Transmitters (Gliotransmitters)... 

C. Astrocytes Possess Different Exocytotic Organelles and Pathways for Regulated Chemical Transmitters (Gliotransmitters) Release... 

The molecular mechanisms leading to release of gliotransmitters, especially glutamate, from glia are under debate. Accumulating evidence clearly indicates that astrocytes secrete numerous transmitters by Ca2+-dependent exocytosis. This review will discuss the mechanisms underlying the release of chemical transmitters from astrocytes with a particular emphasis to the regulated exocytosis processes. 

Mothet, J. P., Pollegioni, L., Ouanounou, G., Martineau, M., Fossier, P., and Baux, G. (2005). Glutamate receptor activation triggers a calcium-dependent and SNARE protein-dependent release of the gliotransmitter D-serine. Proc. Natl. Acad. Sci. USA 102, 5606-5611. 

The experiments shown above point out that gliosomes represent a highly purified astrocyte-derived subcellular preparation that possess the machinery to actuate exocytotic gliotransmitter release. We tested this hypothesis by monitoring directly the release of glutamate from gliosomes evoked by stimuli that augment the cytosolic ( 2r concentration [C i , by means of different mechanisms, in in vitro release experiments. 

For a growing number of neurotransmitters, direct neurotrophic actions have been reported (for a review see Schwartz, 1992 Schwartz and Tani-waki, 1994). These transmitters are serotonin, acetylcholine, norepinephrine, glutamate and endogenous opioid peptides. Some of these neurotrophic transmitters may also be produced by astrocytes. The family of neurotransmitters synthesized by astrocytes comprises y-aminobutyric acid, glutamate, proenkephalin, neuropeptide Y, somatostatin and others. Martin (1992) has coined the term gliotransmitter for such substances. The role of gliotransmission in development and function of the mature nervous system has not been firmly established yet. It can be anticipated, however, that neurotrophic activity of astroglia-derived transmit-... 

A schematic rendition of the tripartite synapse, emphasizing the role of astrocytes in the management of excess glutamate and gliotransmitter release is described in Fig. 5.2. 

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