Age-related changes in hippocampal AD pathology, actin remodeling proteins and spatial memory behavior of male APP/PS1 mice
Copyright © 2019 Elsevier B.V. All rights reserved..
Alzheimer's disease (AD) is the most common form of dementia in the elderly, characterized by amyloid-beta (Aβ) plaques and tau neurofibrillary tangles (NFTs). Synaptic plasticity impairment is one of the early pathological events in AD. Transgenic APP/PS1 mice that overproduce Aβ are one of the most extensively used AD animal models. Many studies have investigated the roles of NTF-related p-Tau, non-amyloidogenic ADAM10, amyloidogenic BACE1, Aβ proteolytic NEP and IDE in certain ages of APP/PS1 mice as well as dendritic spine-related Rictor and Profilin-1 in normal mice, but there are few studies exploring the age-related changes of these molecules in the hippocampus of APP/PS1 mice. Furthermore, current studies regarding when memory impairment occurs in these mice are controversial. Thus, we examined the changes of these molecules in APP/PS1 and control mice using Western blot in mice 2-month-old (2 m) to 10 m of age and behavior changes using the Morris water maze from 4 m to 8 m. The results showed that in APP/PS1 mice, significant changes of hippocampal p-Tau, Aβ, ADAM10, BACE1 and Rictor occurred at 6 m, NEP at 8 m, and IDE and Profilin-1 at 10 m. In control mice, changes of p-Tau, ADAM10, and BACE1 occurred at 8 m and NEP at 10 m, while IDE, Rictor and Profilin-1 remained unchanged. Importantly, the Morris water maze test revealed that spatial memory impairment was detected at 8 m but not 4 or 6 m. The above findings clearly evidence that neurochemical changes overtly precede cognitive dysfunctions in this AD model and provide novel knowledge for a better understanding of the molecular events driving AD.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:376 |
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| Enthalten in: |
Behavioural brain research - 376(2019) vom: 30. Dez., Seite 112182 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sun, Huan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 17.09.2020 Date Revised 17.09.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbr.2019.112182 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM300814895 |
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| 245 | 1 | 0 | |a Age-related changes in hippocampal AD pathology, actin remodeling proteins and spatial memory behavior of male APP/PS1 mice |
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| 500 | |a published: Print-Electronic | ||
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| 520 | |a Copyright © 2019 Elsevier B.V. All rights reserved. | ||
| 520 | |a Alzheimer's disease (AD) is the most common form of dementia in the elderly, characterized by amyloid-beta (Aβ) plaques and tau neurofibrillary tangles (NFTs). Synaptic plasticity impairment is one of the early pathological events in AD. Transgenic APP/PS1 mice that overproduce Aβ are one of the most extensively used AD animal models. Many studies have investigated the roles of NTF-related p-Tau, non-amyloidogenic ADAM10, amyloidogenic BACE1, Aβ proteolytic NEP and IDE in certain ages of APP/PS1 mice as well as dendritic spine-related Rictor and Profilin-1 in normal mice, but there are few studies exploring the age-related changes of these molecules in the hippocampus of APP/PS1 mice. Furthermore, current studies regarding when memory impairment occurs in these mice are controversial. Thus, we examined the changes of these molecules in APP/PS1 and control mice using Western blot in mice 2-month-old (2 m) to 10 m of age and behavior changes using the Morris water maze from 4 m to 8 m. The results showed that in APP/PS1 mice, significant changes of hippocampal p-Tau, Aβ, ADAM10, BACE1 and Rictor occurred at 6 m, NEP at 8 m, and IDE and Profilin-1 at 10 m. In control mice, changes of p-Tau, ADAM10, and BACE1 occurred at 8 m and NEP at 10 m, while IDE, Rictor and Profilin-1 remained unchanged. Importantly, the Morris water maze test revealed that spatial memory impairment was detected at 8 m but not 4 or 6 m. The above findings clearly evidence that neurochemical changes overtly precede cognitive dysfunctions in this AD model and provide novel knowledge for a better understanding of the molecular events driving AD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a A-beta metabolism | |
| 650 | 4 | |a APP/PS1 mice | |
| 650 | 4 | |a Actin polymerization | |
| 650 | 4 | |a Alzheimer’s disease | |
| 650 | 4 | |a Rictor | |
| 650 | 4 | |a Tau protein | |
| 650 | 7 | |a Actins |2 NLM | |
| 650 | 7 | |a Amyloid beta-Peptides |2 NLM | |
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| 650 | 7 | |a Amyloid Precursor Protein Secretases |2 NLM | |
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| 700 | 1 | |a Liu, Mengying |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yutong |e verfasserin |4 aut | |
| 700 | 1 | |a Lan, Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Lian, Biyao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Chengjun |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jiqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yan |e verfasserin |4 aut | |
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