Amyloid-β oligomers suppress subunit-specific glutamate receptor increase during LTP

• Tanaka, Hiromitsu

  Department of Biophysics, Graduate School of Science, Kyoto University

• Sakaguchi, Daiki

  Department of Biophysics, Graduate School of Science, Kyoto University

• Hirano, Tomoo

  Department of Biophysics, Graduate School of Science, Kyoto University

Bibliographic Information

Other Title

• Amyloid‐β oligomers suppress subunit‐specific glutamate receptor increase during LTP

Abstract

Introduction: Amyloid‐β oligomers (AβOs) are assumed to impair the ability of learning and memory by suppressing the induction of synaptic plasticity, such as long‐term potentiation (LTP) in the early stage of Alzheimer's disease. However, the direct molecular mechanism of how AβOs affect excitatory synaptic plasticity remains to be elucidated. Methods: In order to study the effects of AβOs on LTP‐associated changes of AMPA (alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid)‐type glutamate receptor (AMPAR) movement, we performed live‐cell imaging of fluorescently labeled AMPAR subunit GluA1 or GluA2 with total internal reflection fluorescence microscopy. Results: Incubation of cultured hippocampal neurons with AβOs for 1–2 days inhibited the increase in GluA1 number and GluA1 exocytosis frequency in both postsynaptic and extrasynaptic membranes during LTP. In contrast, AβOs did not inhibit the increase in GluA2 number or exocytosis frequency. Discussion: These results suggest that AβOs primarily inhibit the increase in the number of GluA1 homomers and suppress hippocampal LTP expression.

Journal

• Alzheimer's and Dementia: Translational Research and Clinical Interventions

  Alzheimer's and Dementia: Translational Research and Clinical Interventions 5 (1), 797-808, 2019

  Elsevier Inc

Keywords

• Amyloid‐β oligomers
• Alzheimer's disease
• AMPA‐type glutamate receptor
• Long‐term potentiation
• Hippocampus
• Exocytosis
• Total internal reflection fluorescence microscopy

Details

• CRID: 1051412328400138880
• NII Article ID: 120007006206
• ISSN: 23528737
• DOI: 10.1016/j.trci.2019.10.003
• HANDLE: 2433/255887
• Web Site: https://api.elsevier.com/content/article/PII:S2352873719300836?httpAccept=text/xml
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• Web Site: https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1016%2Fj.trci.2019.10.003
• Web Site: https://onlinelibrary.wiley.com/doi/pdf/10.1016/j.trci.2019.10.003
• Web Site: https://onlinelibrary.wiley.com/doi/full-xml/10.1016/j.trci.2019.10.003
• Web Site: https://onlinelibrary.wiley.com/doi/am-pdf/10.1016%2Fj.trci.2019.10.003
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN