Astroglial glutamate transporters in the brain: Regulating neurotransmitter homeostasis and synaptic transmission
Journal of Neuroscience Research. 2017-02-02; 95(11): 2140-2151
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Murphy-Royal C(1)(2), Dupuis J(2)(3), Groc L(2)(3), Oliet SHR(1)(2).
(1)Neurocentre Magendie, Inserm U1215, Bordeaux, France.
(2)Université de Bordeaux, Bordeaux, France.
(3)Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France.
Astrocytes, the major glial cell type in the central nervous system (CNS), are
critical for brain function and have been implicated in various disorders of the
central nervous system. These cells are involved in a wide range of cerebral
processes including brain metabolism, control of central blood flow, ionic
homeostasis, fine-tuning synaptic transmission, and neurotransmitter clearance.
Such varied roles can be efficiently carried out due to the intimate interactions
astrocytes maintain with neurons, the vasculature, as well as with other glial
cells. Arguably, one of the most important functions of astrocytes in the brain
is their control of neurotransmitter clearance. This is particularly true for
glutamate whose timecourse in the synaptic cleft needs to be controlled tightly
under physiological conditions to maintain point-to-point excitatory
transmission, thereby limiting spillover and activation of more receptors. Most
importantly, accumulation of glutamate in the extracellular space can trigger
excessive activation of glutamatergic receptors and lead to excitotoxicity, a
trademark of many neurodegenerative diseases. It is thus of utmost importance for
both physiological and pathophysiological reasons to understand the processes
that control glutamate time course within the synaptic cleft and regulate its
concentrations in the extracellular space. © 2017 Wiley Periodicals, Inc.