Ablating ErbB4 in PV neurons attenuates synaptic and cognitive deficits in an animal model of Alzheimer's disease
Ablating ErbB4 in PV neurons attenuates synaptic and cognitive deficits in an animal model of Alzheimer's disease
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DOI：
10.1016/j.nbd.2017.07.001
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发表时间：
2017-10-01
影响因子：
6.1
通讯作者：
Sun, Binggui
中科院分区：
文献类型：
--
作者：
Zhang, Heng;Zhang, Ling;Sun, Binggui
淀粉样蛋白（A β）的积累在阿尔茨海默病患者和动物模型中诱导神经元、突触和认知缺陷（A β）。然而，潜在的机制仍有待充分阐明。在本研究中，我们发现A β与ErbB4相互作用，ErbB4是酪氨酸激酶受体家族的成员，主要表达于gaba能间神经元。在表达小蛋白的神经元（PV神经元）中删除ErbB4可显著减弱寡聚A β诱导的长时程增强（LTP）抑制。此外，通过Cre/loxP系统特异性消融PV神经元中的ErbB4可显著改善hap - j20小鼠海马的空间记忆和突触可塑性。通过删除PV神经元中的ErbB4, 3d - 6和硫黄素S染色检测的A β沉积和western blotting分析的hAPP蛋白水解加工在hap - j20小鼠海马中不受影响。我们的数据表明，PV神经元中的ErbB4介导了A β诱导的突触和认知功能障碍，而不影响A β水平。(C) 2017爱思唯尔公司版权所有。
Accumulation of amyloid beta (A beta) induces neuronal, synaptic, and cognitive deficits in patients and animal models of Alzheimer's disease (A beta). The underlying mechanisms, however, remain to be fully elucidated. In the present study, we found that A beta interacted with ErbB4, a member of the receptor tyrosine kinase family and mainly expressed in GABAergic intemeurons. Deleting ErbB4 in parvalbumin-expressing neurons (PV neurons) significantly attenuated oligomeric A beta-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 A beta 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 A beta-induced synaptic and cognitive dysfunctions without affecting A beta levels. (C) 2017 Elsevier Inc. All rights reserved.