Abstract
Amyloid β-protein (Aβ), 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 Aβ 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 Aβ, exposure to the same "mild" glutamate concentration failed to damage neurons. The Aβ-induced protection was abolished by a glial glutamate transporter inhibitor. Thus, Aβ can alleviate excitotoxicity through glutamate transporter activity. The present results may challenge prevailing concepts that Aβ-induced neuron loss causes Alzheimer's dementia and also provide practical insights into neuro-glial interactions in glutamate toxicity.
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Acknowledgements
The authors are grateful to Dr. T. Shirasawa (Tokyo Metropolitan Institute of Gerontology) for providing synthesized Aβ. This work was supported in part by Grant-in-Aid for Science Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by the Research Grant for Longevity Science (13-2) from the Ministry of Health, Labour and Welfare of Japan.
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Baba, A., Mitsumori, K., Yamada, M.K. et al. β-Amyloid prevents excitotoxicity via recruitment of glial glutamate transporters. Naunyn-Schmiedeberg's Arch Pharmacol 368, 234–238 (2003). https://doi.org/10.1007/s00210-003-0792-6
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DOI: https://doi.org/10.1007/s00210-003-0792-6