Importance of astrocytic inactivation of synaptically released glutamate for cell survival in the central nervous system--are astrocytes vulnerable to low intracellular glutamate concentrations?
Multiple levels of neuron-astrocyte interactions do exist at glutamatergic synapses, glial glutamate transporters being involved in most of them. Inactivation of synaptically released glutamate is not only important for the phasic aspect of glutamatergic transmission but also for astrocyte metabolism, which supply neurons with different metabolic precursors, and for cell survival in the central nervous system. Alteration of glutamate transport, which leads to abnormally high extracellular glutamate levels, has been involved in numerous neurodegenerative diseases. There are different ways by which elevated extracellular levels of glutamate can be toxic. Excitotoxic mechanisms, involving overstimulation of glutamate receptors, have been shown to induce the death of neurons and oligodendrocytes, but not of astrocytes. Oxidative glutamate toxicity, which can affect every cell type of the central nervous system, is currently viewed as the consequence of altered cystine transport, leading in turn to reduced glutathione synthesis and oxidative stress. This review summarizes the functional implications of astroglial glutamate transport and the consequences of its alteration. Emphasis is laid on our recent finding that alteration of glutamate transport, by depleting intracellular stores of glutamate, can induce oxidative toxicity in astrocytes. The consequences for the other cell types of the central nervous system are discussed in terms of neuron dependency on astrocytes for glutathione synthesis and therefore oxidative stress protection.
Had-Aissouni
Laurence
L
LNCF, CNRS, 31 chemin Joseph Aiguier, F-13402 Marseille cedex 20, France. had@lncf.cnrs-mrs.fr
Ré
Diane-Bérangère
DB
Nieoullon
André
A
Kerkerian-Le Goff
Lydia
L
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D013569:Synapses / Q000378:metabolism*
D018698:Glutamic Acid