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 affe...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
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| Online Access: | https://doi.org/10.1016/j.trci.2019.10.003 |
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| author | Hiromitsu Tanaka Daiki Sakaguchi Tomoo Hirano |
| author_facet | Hiromitsu Tanaka Daiki Sakaguchi Tomoo Hirano |
| author_sort | Hiromitsu Tanaka |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-bf8fa1a5072e4fe7bc3d66473c3e560d |
| institution | DOAJ |
| issn | 2352-8737 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| spelling | doaj-art-bf8fa1a5072e4fe7bc3d66473c3e560d2025-08-20T03:22:00ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372019-01-015179780810.1016/j.trci.2019.10.003Amyloid‐β oligomers suppress subunit‐specific glutamate receptor increase during LTPHiromitsu Tanaka0Daiki Sakaguchi1Tomoo Hirano2Department of BiophysicsGraduate School of Science, Kyoto UniversitySakyo‐kuKyoto606‐8502JapanDepartment of BiophysicsGraduate School of Science, Kyoto UniversitySakyo‐kuKyoto606‐8502JapanDepartment of BiophysicsGraduate School of Science, Kyoto UniversitySakyo‐kuKyoto606‐8502JapanAbstract 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.https://doi.org/10.1016/j.trci.2019.10.003Amyloid‐β oligomersAlzheimer's diseaseAMPA‐type glutamate receptorLong‐term potentiationHippocampusExocytosis |
| spellingShingle | Hiromitsu Tanaka Daiki Sakaguchi Tomoo Hirano Amyloid‐β oligomers suppress subunit‐specific glutamate receptor increase during LTP Alzheimer’s & Dementia: Translational Research & Clinical Interventions Amyloid‐β oligomers Alzheimer's disease AMPA‐type glutamate receptor Long‐term potentiation Hippocampus Exocytosis |
| title | Amyloid‐β oligomers suppress subunit‐specific glutamate receptor increase during LTP |
| title_full | Amyloid‐β oligomers suppress subunit‐specific glutamate receptor increase during LTP |
| title_fullStr | Amyloid‐β oligomers suppress subunit‐specific glutamate receptor increase during LTP |
| title_full_unstemmed | Amyloid‐β oligomers suppress subunit‐specific glutamate receptor increase during LTP |
| title_short | Amyloid‐β oligomers suppress subunit‐specific glutamate receptor increase during LTP |
| title_sort | amyloid β oligomers suppress subunit specific glutamate receptor increase during ltp |
| topic | Amyloid‐β oligomers Alzheimer's disease AMPA‐type glutamate receptor Long‐term potentiation Hippocampus Exocytosis |
| url | https://doi.org/10.1016/j.trci.2019.10.003 |
| work_keys_str_mv | AT hiromitsutanaka amyloidboligomerssuppresssubunitspecificglutamatereceptorincreaseduringltp AT daikisakaguchi amyloidboligomerssuppresssubunitspecificglutamatereceptorincreaseduringltp AT tomoohirano amyloidboligomerssuppresssubunitspecificglutamatereceptorincreaseduringltp |