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The GLT‐1 and GLAST Glutamate Transporters Are Expressed on Morphologically Distinct Astrocytes and Regulated by Neuronal Activity in Primary Hippocampal Cocultures

2000; Wiley; Volume: 75; Issue: 3 Linguagem: Inglês

10.1046/j.1471-4159.2000.0751076.x

1471-4159

Carla Perego, C. Vanoni, M Bossi, Silvia Massari, H. Basudev, Renato Longhi, Grazia Pietrini,

Neurogenesis and neuroplasticity mechanisms

Abstract: The GLT‐1 and GLAST astroglial transporters are the glutamate transporters mainly involved in maintaining physiological extracellular glutamate concentrations. Defects in neurotransmitter glutamate transport may represent an important component of glutamate‐induced neurodegenerative disorders (such as amyotrophic lateral sclerosis) and CNS insults (ischemia and epilepsy). We characterized the protein expression of GLT‐1 and GLAST in primary astrocyte—neuron cocultures derived from rat hippocampal tissues during neuron differentiation/maturation. GLT‐1 and GLAST are expressed by morphologically distinct glial fibrillary acidic protein‐positive astrocytes, and their expression correlates with the status of neuron differentiation/maturation and activity. Up‐regulation of the transporters paralleled the content of the synaptophysin synaptic vesicle marker p38, and down‐regulation was a consequence of glutamate‐induced neuronal death or the reduction of synaptic activity. Finally, soluble factors in neuronal‐conditioned media prevented the down‐regulation of the GLT‐1 and GLAST proteins. Although other mechanisms may participate in regulating GLT‐1 and GLAST in the CNS, our data indicate that soluble factors dependent on neuronal activity play a major regulating role in hippocampal cocultures.