Ablating ErbB4 in PV neurons attenuates synaptic and cognitive deficits in an animal model of Alzheimer's disease

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

Neurobiology of Disease (Oct 2017)

Ablating ErbB4 in PV neurons attenuates synaptic and cognitive deficits in an animal model of Alzheimer's disease

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

Affiliations

Heng Zhang: Department 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
Ling Zhang: Department 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
Dongming Zhou: Department 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, China
Xiao He: Department 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
Dongpi Wang: Department 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, China
Hongyu Pan: Department 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
Xiaoqin Zhang: Department 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
Yufei Mei: Department 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
Qi Qian: Department 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
Tingting Zheng: Department 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
Frank E. Jones: Department of Biochemistry, Tulane University Health Sciences Center, Tulane Cancer Center, New Orleans, LA 70118, USA
Binggui Sun: Department 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.

Journal volume & issue: Vol. 106
pp. 171 – 180

Abstract

Read online

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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

About the journal

Abstract

Keywords