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Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-β Precursor Protein/Presenilin 2 Mouse Model of Alzheimer's Disease
Presenilin 1 and presenilin 2 (PS1 and PS2) play a critical role in γ-secretase-mediated cleavage of amyloid-β precursor protein (APP) and the subsequent generation of β-amyloid peptides. The purpose of the present study was to test whether PS2 mutation accelerates the onset of contextual fear memor...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733185/ https://www.ncbi.nlm.nih.gov/pubmed/29333315 http://dx.doi.org/10.1155/2017/8584205 |
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author | Kishimoto, Yasushi Fukumoto, Kai Nagai, Mika Mizuguchi, Ayaka Kobashi, Yuiko |
author_facet | Kishimoto, Yasushi Fukumoto, Kai Nagai, Mika Mizuguchi, Ayaka Kobashi, Yuiko |
author_sort | Kishimoto, Yasushi |
collection | PubMed |
description | Presenilin 1 and presenilin 2 (PS1 and PS2) play a critical role in γ-secretase-mediated cleavage of amyloid-β precursor protein (APP) and the subsequent generation of β-amyloid peptides. The purpose of the present study was to test whether PS2 mutation accelerates the onset of contextual fear memory deficits in a mouse model of AD that expresses a mutation (K670N/M671L) of the human APP with the Swedish mutation (Tg2576 mice). In the present study, an APP/PS2 double-transgenic mouse model (PS2Tg2576) was generated by crossbreeding transgenic mice carrying the human mutant PS2 (N141I) with Tg2576 mice. Contextual fear conditioning was tested in PS2Tg2576 mice aged 3, 4, 6, and 10–12 months. PS2Tg2576 mice showed a tendency of lower freezing behavior as early as 3 months of age, but significant memory impairment was observed from the age of 4 months. The cognitive impairment was more prominent at ages of 6 and 10–12 months. In contrast, Tg2576 mice aged 3 and 4 months exhibited successful acquisition of contextual fear learning, but Tg2576 mice aged 6 months or older showed significantly impaired fear memory. These results show that PS2 mutation significantly accelerates the onset of fear memory deficits in the APP AD model mice. |
format | Online Article Text |
id | pubmed-5733185 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-57331852018-01-14 Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-β Precursor Protein/Presenilin 2 Mouse Model of Alzheimer's Disease Kishimoto, Yasushi Fukumoto, Kai Nagai, Mika Mizuguchi, Ayaka Kobashi, Yuiko Int J Alzheimers Dis Research Article Presenilin 1 and presenilin 2 (PS1 and PS2) play a critical role in γ-secretase-mediated cleavage of amyloid-β precursor protein (APP) and the subsequent generation of β-amyloid peptides. The purpose of the present study was to test whether PS2 mutation accelerates the onset of contextual fear memory deficits in a mouse model of AD that expresses a mutation (K670N/M671L) of the human APP with the Swedish mutation (Tg2576 mice). In the present study, an APP/PS2 double-transgenic mouse model (PS2Tg2576) was generated by crossbreeding transgenic mice carrying the human mutant PS2 (N141I) with Tg2576 mice. Contextual fear conditioning was tested in PS2Tg2576 mice aged 3, 4, 6, and 10–12 months. PS2Tg2576 mice showed a tendency of lower freezing behavior as early as 3 months of age, but significant memory impairment was observed from the age of 4 months. The cognitive impairment was more prominent at ages of 6 and 10–12 months. In contrast, Tg2576 mice aged 3 and 4 months exhibited successful acquisition of contextual fear learning, but Tg2576 mice aged 6 months or older showed significantly impaired fear memory. These results show that PS2 mutation significantly accelerates the onset of fear memory deficits in the APP AD model mice. Hindawi 2017 2017-11-27 /pmc/articles/PMC5733185/ /pubmed/29333315 http://dx.doi.org/10.1155/2017/8584205 Text en Copyright © 2017 Yasushi Kishimoto et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Kishimoto, Yasushi Fukumoto, Kai Nagai, Mika Mizuguchi, Ayaka Kobashi, Yuiko Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-β Precursor Protein/Presenilin 2 Mouse Model of Alzheimer's Disease |
title | Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-β Precursor Protein/Presenilin 2 Mouse Model of Alzheimer's Disease |
title_full | Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-β Precursor Protein/Presenilin 2 Mouse Model of Alzheimer's Disease |
title_fullStr | Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-β Precursor Protein/Presenilin 2 Mouse Model of Alzheimer's Disease |
title_full_unstemmed | Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-β Precursor Protein/Presenilin 2 Mouse Model of Alzheimer's Disease |
title_short | Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-β Precursor Protein/Presenilin 2 Mouse Model of Alzheimer's Disease |
title_sort | early contextual fear memory deficits in a double-transgenic amyloid-β precursor protein/presenilin 2 mouse model of alzheimer's disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733185/ https://www.ncbi.nlm.nih.gov/pubmed/29333315 http://dx.doi.org/10.1155/2017/8584205 |
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