Ablating ErbB4 in PV neurons attenuates synaptic and cognitive deficits in an animal model of Alzheimer's disease
| Autor: | Ling Zhang, Binggui Sun, Heng Zhang, Tingting Zheng, Dongpi Wang, Frank E. Jones, Xiaoqin Zhang, Yufei Mei, H.G. Pan, Dongming Zhou, Xiao He, Qi Qian |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Receptor ErbB-4 Mouse Long-Term Potentiation Hippocampus Mice Transgenic Plaque Amyloid Biology Receptor tyrosine kinase lcsh:RC321-571 Tissue Culture Techniques ErbB4 Amyloid beta-Protein Precursor 03 medical and health sciences Cognition 0302 clinical medicine Alzheimer Disease Animals Humans Maze Learning lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ERBB4 Spatial Memory Cerebral Cortex Neurons Amyloid beta-Peptides Long-term potentiation Amyloid β Alzheimer's disease Peptide Fragments Blot PV neurons Disease Models Animal HEK293 Cells Parvalbumins 030104 developmental biology nervous system Neurology Synaptic plasticity biology.protein GABAergic Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Neurobiology of Disease, Vol 106, Iss, Pp 171-180 (2017) |
| ISSN: | 0969-9961 |
| DOI: | 10.1016/j.nbd.2017.07.001 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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