Beta-amyloid prevents excitotoxicity via recruitment of glial glutamate transporters.
Amyloid beta-protein (Abeta), a putative pathogenic endotoxin involved in Alzheimer's disease, induces redistribution of glutamate transporters in astrocytes and promotes their pump activity. Because the transporters are assumed to protect neurons against excitotoxicity by removing extracellular glutamate, we hypothesized that Abeta alters the vulnerability of neurons to glutamate. Cerebrocortical neuron-astroglial co-cultures were exposed to glutamate, the concentration of which was selected so that only 20% of the neurons exhibited degeneration. When cultures were pre-treated with Abeta, exposure to the same "mild" glutamate concentration failed to damage neurons. The Abeta-induced protection was abolished by a glial glutamate transporter inhibitor. Thus, Abeta can alleviate excitotoxicity through glutamate transporter activity. The present results may challenge prevailing concepts that Abeta-induced neuron loss causes Alzheimer's dementia and also provide practical insights into neuro-glial interactions in glutamate toxicity.
D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D003124:Colorimetry; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D016202:N-Methylaspartate / Q000378:metabolism / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D027322:Amino Acid Transport System X-AG; D016229:Amyloid beta-Peptides; D018691:Excitatory Amino Acid Antagonists; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D001224:Aspartic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate