Astrocytic glutamatergic transporters are involved in Aβ-induced synaptic dysfunction

Brain Res. 2018 Jan 1;1678:129-137. doi: 10.1016/j.brainres.2017.10.011. Epub 2017 Oct 21.


In Alzheimer's disease (AD), dementia severity correlates most strongly with decreased synapse density in the hippocampus and cerebral cortex. Although studies in rodents have established that hippocampal long-term potentiation (LTP) is inhibited by soluble oligomers of beta-amyloid (Aβ), the synaptic mechanisms remain unclear. Here, field excitatory postsynaptic potentials (fEPSP) recordings were made in the CA1 region of mouse hippocampal slices. The medium of APP-expressing CHO cells, which contain soluble forms of Aβ including small oligomers, inhibited LTP and facilitated long-term depression (LTD), thus making the LTP/LTD curve shift toward the right. This phenomenon could be mimicked by the non-selective glutamate transporter inhibitor, DL-TBOA. More specifically, the Aβ impaired LTP and facilitated LTD were occluded by the selective astrocytic glutamate transporter inhibitors, TFB-TBOA. In cultured astrocytes, the Aβ oligomers also decrease astrocytic glutamate transporters (EAAT1, EAAT2) expression. We conclude that soluble Aβ oligomers decrease the activation of astrocytic glutamate transporters, thereby impairing synaptic plasticity.

Keywords: Alzheimer’s disease; Astrocytes; Glutamate transporters; Long-term potentiation; Synaptic plasticity; TBOA.

MeSH terms

  • Alzheimer Disease / metabolism
  • Amino Acid Transport System X-AG / antagonists & inhibitors
  • Amino Acid Transport System X-AG / metabolism*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Astrocytes / metabolism
  • CA1 Region, Hippocampal / metabolism
  • CHO Cells
  • Cricetulus
  • Excitatory Amino Acid Agents / metabolism
  • Excitatory Postsynaptic Potentials / physiology
  • Hippocampus / metabolism
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuronal Plasticity / drug effects
  • Neurons / metabolism
  • Patch-Clamp Techniques
  • Peptide Fragments / metabolism
  • Synapses / metabolism*
  • Synapses / physiology*


  • Amino Acid Transport System X-AG
  • Amyloid beta-Peptides
  • Excitatory Amino Acid Agents
  • Peptide Fragments