Amyloid β peptide (25-35) inhibits Na+-dependent glutamate uptake in rat hippocampal astrocyte cultures

Marni E. Harris, Yaning Wang, Norman W. Pedigo, Kenneth Hensley, D. Allan Butterfield, John M. Carney

Research output: Contribution to journalArticlepeer-review

217 Scopus citations

Abstract

Large numbers of neuritic plaques surrounded by reactive astrocytes are characteristic of Alzheimer's disease (AD). There is a large body of research supporting a causal role for the amyloid β peptide (Aβ), a main constituent of these plaques, in the neuropathology of AD. Several hypotheses have been proposed to explain the toxicity of Aβ including free radical injury and excitotoxicity. It has been reported that treatment of neuronal/astrocytic cultures with Aβ increases the vulnerability of neurons to glutamate- induced cell death. One mechanism that may explain this finding is inhibition of the astrocyte glutamate transporter by Aβ. The aim of the current study was to determine if Aβs inhibit astrocyte glutamate uptake and if this inhibition involves free radical damage to the transporter/astrocytes. We have previously reported that Aβ can generate free radicals, and this radical production was correlated with the oxidation of neurons in culture and inhibition of astrocyte glutamate uptake. In the present study, Aβ (25- 35) significantly inhibited L-glutamate uptake in rat hippocampal astrocyte cultures and this inhibition was prevented by the antioxidant Trolox. Decreases in astrocyte function, in particular L-glutamate uptake, may contribute to neuronal degeneration such as that seen in AD. These results lead to a revised excitotoxicity/free radical hypothesis of Aβ toxicity involving astrocytes.

Original languageEnglish
Pages (from-to)277-286
Number of pages10
JournalJournal of Neurochemistry
Volume67
Issue number1
DOIs
StatePublished - Jul 1996

Keywords

  • Alzheimer's disease
  • Astrocytes
  • Free radicals
  • Glutamate transport

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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