Amyloid-β1-42 slows clearance of synaptically released glutamate by mislocalizing astrocytic GLT-1

Annalisa Scimemi, James S. Meabon, Randall (Randy) Woltjer, Jane M. Sullivan, Jeffrey S. Diamond, David G. Cook

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

GLT-1, the major glutamate transporter in the adult brain, is abundantly expressed in astrocytic processes enveloping synapses. By limiting glutamate escape into the surrounding neuropil, GLT-1 preserves the spatial specificity of synaptic signaling. Here we show that the amyloid-β peptide A β1-42 markedly prolongs the extracellular lifetime of synaptically released glutamate by reducing GLT-1 surface expression in mouse astrocytes and that this effect is prevented by the vitamin E derivative Trolox. These findings indicate that astrocytic glutamate transporter dysfunction may play an important role in the pathogenesis of Alzheimer's disease and suggest possible mechanisms by which several current treatment strategies could protect against the disease.

Original languageEnglish (US)
Pages (from-to)5312-5318
Number of pages7
JournalJournal of Neuroscience
Volume33
Issue number12
DOIs
StatePublished - Mar 20 2013

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Amino Acid Transport System X-AG
Amyloid
Glutamic Acid
Neuropil
Vitamin E
Astrocytes
Synapses
Alzheimer Disease
Brain
6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid
peptide A

ASJC Scopus subject areas

  • Neuroscience(all)

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Amyloid-β1-42 slows clearance of synaptically released glutamate by mislocalizing astrocytic GLT-1. / Scimemi, Annalisa; Meabon, James S.; Woltjer, Randall (Randy); Sullivan, Jane M.; Diamond, Jeffrey S.; Cook, David G.

In: Journal of Neuroscience, Vol. 33, No. 12, 20.03.2013, p. 5312-5318.

Research output: Contribution to journalArticle

Scimemi, Annalisa ; Meabon, James S. ; Woltjer, Randall (Randy) ; Sullivan, Jane M. ; Diamond, Jeffrey S. ; Cook, David G. / Amyloid-β1-42 slows clearance of synaptically released glutamate by mislocalizing astrocytic GLT-1. In: Journal of Neuroscience. 2013 ; Vol. 33, No. 12. pp. 5312-5318.
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