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

Neurobiology of Disease

Xiao He¹  Xiaoqin Zhang¹  Binggui Sun²  Qi Qian²  Ling Zhang²  Tingting Zheng²  Dongming Zhou²  Hongyu Pan²  Frank E. Jones²  Heng Zhang²  Dongpi Wang²  Yufei Mei² 

[1] Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China;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;

关键词: Alzheimer's disease;    Amyloid β;    ErbB4;    PV neurons;    Mouse;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown