Ablating ErbB4 in PV neurons attenuates synaptic and cognitive deficits in an animal model of Alzheimer's disease
Accumulation of amyloid β (Aβ) induces neuronal, synaptic, and cognitive deficits in patients and animal models of Alzheimer's disease (AD). The underlying mechanisms, however, remain to be fully elucidated. In the present study, we found that Aβ interacted with ErbB4, a member of the receptor...
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Format: | Article |
Language: | English |
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Elsevier
2017-10-01
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Series: | Neurobiology of Disease |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996117301535 |
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doaj-ba2813ffe31f47f08148beb0e2eb4d45 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Heng Zhang Ling Zhang Dongming Zhou Xiao He Dongpi Wang Hongyu Pan Xiaoqin Zhang Yufei Mei Qi Qian Tingting Zheng Frank E. Jones Binggui Sun |
spellingShingle |
Heng Zhang Ling Zhang Dongming Zhou Xiao He Dongpi Wang Hongyu Pan Xiaoqin Zhang Yufei Mei Qi Qian Tingting Zheng Frank E. Jones Binggui Sun Ablating ErbB4 in PV neurons attenuates synaptic and cognitive deficits in an animal model of Alzheimer's disease Neurobiology of Disease Alzheimer's disease Amyloid β ErbB4 PV neurons Mouse |
author_facet |
Heng Zhang Ling Zhang Dongming Zhou Xiao He Dongpi Wang Hongyu Pan Xiaoqin Zhang Yufei Mei Qi Qian Tingting Zheng Frank E. Jones Binggui Sun |
author_sort |
Heng Zhang |
title |
Ablating ErbB4 in PV neurons attenuates synaptic and cognitive deficits in an animal model of Alzheimer's disease |
title_short |
Ablating ErbB4 in PV neurons attenuates synaptic and cognitive deficits in an animal model of Alzheimer's disease |
title_full |
Ablating ErbB4 in PV neurons attenuates synaptic and cognitive deficits in an animal model of Alzheimer's disease |
title_fullStr |
Ablating ErbB4 in PV neurons attenuates synaptic and cognitive deficits in an animal model of Alzheimer's disease |
title_full_unstemmed |
Ablating ErbB4 in PV neurons attenuates synaptic and cognitive deficits in an animal model of Alzheimer's disease |
title_sort |
ablating erbb4 in pv neurons attenuates synaptic and cognitive deficits in an animal model of alzheimer's disease |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2017-10-01 |
description |
Accumulation of amyloid β (Aβ) induces neuronal, synaptic, and cognitive deficits in patients and animal models of Alzheimer's disease (AD). The underlying mechanisms, however, remain to be fully elucidated. In the present study, we found that Aβ interacted with ErbB4, a member of the receptor tyrosine kinase family and mainly expressed in GABAergic interneurons. Deleting ErbB4 in parvalbumin-expressing neurons (PV neurons) significantly attenuated oligomeric Aβ-induced suppression of long term potentiation (LTP). Furthermore, specific ablation of ErbB4 in PV neurons via Cre/loxP system greatly improved spatial memory and synaptic plasticity in the hippocampus of hAPP-J20 mice. The deposition of Aβ detected by 3D6 and Thioflavin S staining and the proteolytic processing of hAPP analyzed by western blotting were not affected in the hippocampus of hAPP-J20 mice by deleting ErbB4 in PV neurons. Our data suggested that ErbB4 in PV neurons mediated Aβ-induced synaptic and cognitive dysfunctions without affecting Aβ levels. |
topic |
Alzheimer's disease Amyloid β ErbB4 PV neurons Mouse |
url |
http://www.sciencedirect.com/science/article/pii/S0969996117301535 |
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doaj-ba2813ffe31f47f08148beb0e2eb4d452021-03-22T12:45:38ZengElsevierNeurobiology of Disease1095-953X2017-10-01106171180Ablating ErbB4 in PV neurons attenuates synaptic and cognitive deficits in an animal model of Alzheimer's diseaseHeng Zhang0Ling Zhang1Dongming Zhou2Xiao He3Dongpi Wang4Hongyu Pan5Xiaoqin Zhang6Yufei Mei7Qi Qian8Tingting Zheng9Frank E. Jones10Binggui Sun11Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of MOH, Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, ChinaDepartment of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of MOH, Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, ChinaDepartment of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of MOH, Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310058, ChinaDepartment of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of MOH, Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, ChinaDepartment of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of MOH, Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310058, ChinaDepartment of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of MOH, Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, ChinaDepartment of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of MOH, Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, ChinaDepartment of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of MOH, Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, ChinaDepartment of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of MOH, Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, ChinaDepartment of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of MOH, Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, ChinaDepartment of Biochemistry, Tulane University Health Sciences Center, Tulane Cancer Center, New Orleans, LA 70118, USADepartment of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of MOH, Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Corresponding author.Accumulation of amyloid β (Aβ) induces neuronal, synaptic, and cognitive deficits in patients and animal models of Alzheimer's disease (AD). The underlying mechanisms, however, remain to be fully elucidated. In the present study, we found that Aβ interacted with ErbB4, a member of the receptor tyrosine kinase family and mainly expressed in GABAergic interneurons. Deleting ErbB4 in parvalbumin-expressing neurons (PV neurons) significantly attenuated oligomeric Aβ-induced suppression of long term potentiation (LTP). Furthermore, specific ablation of ErbB4 in PV neurons via Cre/loxP system greatly improved spatial memory and synaptic plasticity in the hippocampus of hAPP-J20 mice. The deposition of Aβ detected by 3D6 and Thioflavin S staining and the proteolytic processing of hAPP analyzed by western blotting were not affected in the hippocampus of hAPP-J20 mice by deleting ErbB4 in PV neurons. Our data suggested that ErbB4 in PV neurons mediated Aβ-induced synaptic and cognitive dysfunctions without affecting Aβ levels.http://www.sciencedirect.com/science/article/pii/S0969996117301535Alzheimer's diseaseAmyloid βErbB4PV neuronsMouse |