[Role of glutamate transporters in astrocytes].
L-glutamate is the primary excitatory neurotransmitter in the mammalian central nervous system and has also been implicated as a potent neurotoxin. To ensure a high signal-to-noise ratio during synaptic transmission and to prevent neuronal damage that might occur as a result of excessive activation of glutamate receptors, the extracellular glutamate concentration is tightly controlled by glutamate transporters in the plasma membrane of neurons and the surrounding glial cells. Five subtypes of glutamate transporters have been identified and characterized by molecular cloning. Recent studies of glutamate transporters using the genetic knockout strategy indicate that glial, but not neuronal, glutamate transporters play critical roles in maintaining the extracellular glutamate concentrations and are thereby essential for both normal synaptic transmission and protection of neurons against glutamate excitotoxicity. Furthermore, we have recently demonstrated that glial glutamate transporters are necessary for brain development through regulation of extracellular glutamate concentration and mediate a functional metabolic crosstalk between neurons and astrocytes. Changes involving altered glutamate signaling are found in CNS disorders including depression, schizophrenia, and several neurodegenerative diseases. Therefore, the design of compounds capable of modulating glutamate uptake represents a novel strategy for the treatment of these CNS disorders.
Tanaka
Kohichi
K
Laboratory of Molecular Neuroscience, School of Biomedical Science, Tokyo Medical & Dental University, 1-5-45 Yushima, Bunkyo ku, Tokyo 113-8519, Japan.
D027322:Amino Acid Transport System X-AG / Q000172:deficiency / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001921:Brain / Q000254:growth & development; D016923:Cell Death; D002493:Central Nervous System Diseases / Q000188:drug therapy / Q000209:etiology; D015195:Drug Design; D005971:Glutamates / Q000378:metabolism / Q000633:toxicity; D051379:Mice; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology; D017470:Receptors, Glutamate / Q000378:metabolism; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology
D027322:Amino Acid Transport System X-AG; D005971:Glutamates; D017470:Receptors, Glutamate