Abnormal dendritic calcium activity and synaptic depotentiation occur early in a mouse model of Alzheimer’s disease
Abstract Background Alzheimer’s disease (AD) is characterized by amyloid deposition, tangle formation as well as synapse loss. Synaptic abnormalities occur early in the pathogenesis of AD. Identifying early synaptic abnormalities and their underlying mechanisms is likely important for the prevention...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2017-11-01
|
Series: | Molecular Neurodegeneration |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s13024-017-0228-2 |
id |
doaj-7a924d09f8b749d2aee61762c03c021c |
---|---|
record_format |
Article |
spelling |
doaj-7a924d09f8b749d2aee61762c03c021c2020-11-24T22:02:26ZengBMCMolecular Neurodegeneration1750-13262017-11-0112111510.1186/s13024-017-0228-2Abnormal dendritic calcium activity and synaptic depotentiation occur early in a mouse model of Alzheimer’s diseaseYang Bai0Miao Li1Yanmei Zhou2Lei Ma3Qian Qiao4Wanling Hu5Wei Li6Zachary Patrick Wills7Wen-Biao Gan8Drug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate SchoolDrug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate SchoolDrug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate SchoolDrug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate SchoolDrug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate SchoolDrug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate SchoolDrug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate SchoolDepartment of Neurobiology, University of PittsburghDrug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate SchoolAbstract Background Alzheimer’s disease (AD) is characterized by amyloid deposition, tangle formation as well as synapse loss. Synaptic abnormalities occur early in the pathogenesis of AD. Identifying early synaptic abnormalities and their underlying mechanisms is likely important for the prevention and treatment of AD. Methods We performed in vivo two-photon calcium imaging to examine the activities of somas, dendrites and dendritic spines of layer 2/3 pyramidal neurons in the primary motor cortex in the APPswe/PS1dE9 mouse model of AD and age-matched wild type control mice. We also performed calcium imaging to determine the effect of Aβ oligomers on dendritic calcium activity. In addition, structural and functional two-photon imaging were used to examine the link between abnormal dendritic calcium activity and changes in dendritic spine size in the AD mouse model. Results We found that somatic calcium activities of layer 2/3 neurons were significantly lower in the primary motor cortex of 3-month-old APPswe/PS1dE9 mice than in wild type mice during quiet resting, but not during running on a treadmill. Notably, a significantly larger fraction of apical dendrites of layer 2/3 pyramidal neurons showed calcium transients with abnormally long duration and high peak amplitudes during treadmill running in AD mice. Administration of Aβ oligomers into the brain of wild type mice also induced abnormal dendritic calcium transients during running. Furthermore, we found that the activity and size of dendritic spines were significantly reduced on dendritic branches with abnormally prolonged dendritic calcium transients in AD mice. Conclusion Our findings show that abnormal dendritic calcium transients and synaptic depotentiation occur before amyloid plaque formation in the motor cortex of the APPswe/PS1dE9 mouse model of AD. Dendritic calcium transients with abnormally long durations and high amplitudes could be induced by soluble Aβ oligomers and contribute to synaptic deficits in the early pathogenesis of AD.http://link.springer.com/article/10.1186/s13024-017-0228-2Alzheimer’s diseaseDendritic calcium activityTwo-photon imagingAPPswe/PS1dE9Soluble Aβ oligomersSynaptic depotentiation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yang Bai Miao Li Yanmei Zhou Lei Ma Qian Qiao Wanling Hu Wei Li Zachary Patrick Wills Wen-Biao Gan |
spellingShingle |
Yang Bai Miao Li Yanmei Zhou Lei Ma Qian Qiao Wanling Hu Wei Li Zachary Patrick Wills Wen-Biao Gan Abnormal dendritic calcium activity and synaptic depotentiation occur early in a mouse model of Alzheimer’s disease Molecular Neurodegeneration Alzheimer’s disease Dendritic calcium activity Two-photon imaging APPswe/PS1dE9 Soluble Aβ oligomers Synaptic depotentiation |
author_facet |
Yang Bai Miao Li Yanmei Zhou Lei Ma Qian Qiao Wanling Hu Wei Li Zachary Patrick Wills Wen-Biao Gan |
author_sort |
Yang Bai |
title |
Abnormal dendritic calcium activity and synaptic depotentiation occur early in a mouse model of Alzheimer’s disease |
title_short |
Abnormal dendritic calcium activity and synaptic depotentiation occur early in a mouse model of Alzheimer’s disease |
title_full |
Abnormal dendritic calcium activity and synaptic depotentiation occur early in a mouse model of Alzheimer’s disease |
title_fullStr |
Abnormal dendritic calcium activity and synaptic depotentiation occur early in a mouse model of Alzheimer’s disease |
title_full_unstemmed |
Abnormal dendritic calcium activity and synaptic depotentiation occur early in a mouse model of Alzheimer’s disease |
title_sort |
abnormal dendritic calcium activity and synaptic depotentiation occur early in a mouse model of alzheimer’s disease |
publisher |
BMC |
series |
Molecular Neurodegeneration |
issn |
1750-1326 |
publishDate |
2017-11-01 |
description |
Abstract Background Alzheimer’s disease (AD) is characterized by amyloid deposition, tangle formation as well as synapse loss. Synaptic abnormalities occur early in the pathogenesis of AD. Identifying early synaptic abnormalities and their underlying mechanisms is likely important for the prevention and treatment of AD. Methods We performed in vivo two-photon calcium imaging to examine the activities of somas, dendrites and dendritic spines of layer 2/3 pyramidal neurons in the primary motor cortex in the APPswe/PS1dE9 mouse model of AD and age-matched wild type control mice. We also performed calcium imaging to determine the effect of Aβ oligomers on dendritic calcium activity. In addition, structural and functional two-photon imaging were used to examine the link between abnormal dendritic calcium activity and changes in dendritic spine size in the AD mouse model. Results We found that somatic calcium activities of layer 2/3 neurons were significantly lower in the primary motor cortex of 3-month-old APPswe/PS1dE9 mice than in wild type mice during quiet resting, but not during running on a treadmill. Notably, a significantly larger fraction of apical dendrites of layer 2/3 pyramidal neurons showed calcium transients with abnormally long duration and high peak amplitudes during treadmill running in AD mice. Administration of Aβ oligomers into the brain of wild type mice also induced abnormal dendritic calcium transients during running. Furthermore, we found that the activity and size of dendritic spines were significantly reduced on dendritic branches with abnormally prolonged dendritic calcium transients in AD mice. Conclusion Our findings show that abnormal dendritic calcium transients and synaptic depotentiation occur before amyloid plaque formation in the motor cortex of the APPswe/PS1dE9 mouse model of AD. Dendritic calcium transients with abnormally long durations and high amplitudes could be induced by soluble Aβ oligomers and contribute to synaptic deficits in the early pathogenesis of AD. |
topic |
Alzheimer’s disease Dendritic calcium activity Two-photon imaging APPswe/PS1dE9 Soluble Aβ oligomers Synaptic depotentiation |
url |
http://link.springer.com/article/10.1186/s13024-017-0228-2 |
work_keys_str_mv |
AT yangbai abnormaldendriticcalciumactivityandsynapticdepotentiationoccurearlyinamousemodelofalzheimersdisease AT miaoli abnormaldendriticcalciumactivityandsynapticdepotentiationoccurearlyinamousemodelofalzheimersdisease AT yanmeizhou abnormaldendriticcalciumactivityandsynapticdepotentiationoccurearlyinamousemodelofalzheimersdisease AT leima abnormaldendriticcalciumactivityandsynapticdepotentiationoccurearlyinamousemodelofalzheimersdisease AT qianqiao abnormaldendriticcalciumactivityandsynapticdepotentiationoccurearlyinamousemodelofalzheimersdisease AT wanlinghu abnormaldendriticcalciumactivityandsynapticdepotentiationoccurearlyinamousemodelofalzheimersdisease AT weili abnormaldendriticcalciumactivityandsynapticdepotentiationoccurearlyinamousemodelofalzheimersdisease AT zacharypatrickwills abnormaldendriticcalciumactivityandsynapticdepotentiationoccurearlyinamousemodelofalzheimersdisease AT wenbiaogan abnormaldendriticcalciumactivityandsynapticdepotentiationoccurearlyinamousemodelofalzheimersdisease |
_version_ |
1725835840516521984 |