Cargando…
Impairments of spatial memory in an Alzheimer’s disease model via degeneration of hippocampal cholinergic synapses
Choline acetyltransferase neurons in the vertical diagonal band of Broca (vChATs) degenerate in the early stage of Alzheimer’s disease (AD). Here, we report that vChATs directly innervate newly generated immature neurons (NGIs) in the dorsal hippocampus (dNGIs) of adult mice and regulate both the dN...
| Autores principales: | , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2017
|
| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698429/ https://www.ncbi.nlm.nih.gov/pubmed/29162816 http://dx.doi.org/10.1038/s41467-017-01943-0 |
| _version_ | 1783280762084130816 |
|---|---|
| author | Zhu, Houze Yan, Huanhuan Tang, Na Li, Xinyan Pang, Pei Li, Hao Chen, Wenting Guo, Yu Shu, Shu Cai, You Pei, Lei Liu, Dan Luo, Min-Hua Man, Hengye Tian, Qing Mu, Yangling Zhu, Ling-Qiang Lu, Youming |
| author_facet | Zhu, Houze Yan, Huanhuan Tang, Na Li, Xinyan Pang, Pei Li, Hao Chen, Wenting Guo, Yu Shu, Shu Cai, You Pei, Lei Liu, Dan Luo, Min-Hua Man, Hengye Tian, Qing Mu, Yangling Zhu, Ling-Qiang Lu, Youming |
| author_sort | Zhu, Houze |
| collection | PubMed |
| description | Choline acetyltransferase neurons in the vertical diagonal band of Broca (vChATs) degenerate in the early stage of Alzheimer’s disease (AD). Here, we report that vChATs directly innervate newly generated immature neurons (NGIs) in the dorsal hippocampus (dNGIs) of adult mice and regulate both the dNGIs survival and spatial pattern separation. In a mouse model that exhibits amyloid-β plaques similar to AD patients, cholinergic synaptic transmission, dNGI survival and spatial pattern separation are impaired. Activation of vChATs with theta burst stimulation (TBS) that alleviates the decay in cholinergic synaptic transmission effectively protects against spatial pattern separation impairments in the AD mice and this protection was completely abolished by inhibiting the dNGIs survival. Thus, the impairments of pattern separation-associated spatial memory in AD mice are in part caused by degeneration of cholinergic synaptic transmission that modulates the dNGIs survival. |
| format | Online Article Text |
| id | pubmed-5698429 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2017 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-56984292017-11-24 Impairments of spatial memory in an Alzheimer’s disease model via degeneration of hippocampal cholinergic synapses Zhu, Houze Yan, Huanhuan Tang, Na Li, Xinyan Pang, Pei Li, Hao Chen, Wenting Guo, Yu Shu, Shu Cai, You Pei, Lei Liu, Dan Luo, Min-Hua Man, Hengye Tian, Qing Mu, Yangling Zhu, Ling-Qiang Lu, Youming Nat Commun Article Choline acetyltransferase neurons in the vertical diagonal band of Broca (vChATs) degenerate in the early stage of Alzheimer’s disease (AD). Here, we report that vChATs directly innervate newly generated immature neurons (NGIs) in the dorsal hippocampus (dNGIs) of adult mice and regulate both the dNGIs survival and spatial pattern separation. In a mouse model that exhibits amyloid-β plaques similar to AD patients, cholinergic synaptic transmission, dNGI survival and spatial pattern separation are impaired. Activation of vChATs with theta burst stimulation (TBS) that alleviates the decay in cholinergic synaptic transmission effectively protects against spatial pattern separation impairments in the AD mice and this protection was completely abolished by inhibiting the dNGIs survival. Thus, the impairments of pattern separation-associated spatial memory in AD mice are in part caused by degeneration of cholinergic synaptic transmission that modulates the dNGIs survival. Nature Publishing Group UK 2017-11-22 /pmc/articles/PMC5698429/ /pubmed/29162816 http://dx.doi.org/10.1038/s41467-017-01943-0 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article Zhu, Houze Yan, Huanhuan Tang, Na Li, Xinyan Pang, Pei Li, Hao Chen, Wenting Guo, Yu Shu, Shu Cai, You Pei, Lei Liu, Dan Luo, Min-Hua Man, Hengye Tian, Qing Mu, Yangling Zhu, Ling-Qiang Lu, Youming Impairments of spatial memory in an Alzheimer’s disease model via degeneration of hippocampal cholinergic synapses |
| title | Impairments of spatial memory in an Alzheimer’s disease model via degeneration of hippocampal cholinergic synapses |
| title_full | Impairments of spatial memory in an Alzheimer’s disease model via degeneration of hippocampal cholinergic synapses |
| title_fullStr | Impairments of spatial memory in an Alzheimer’s disease model via degeneration of hippocampal cholinergic synapses |
| title_full_unstemmed | Impairments of spatial memory in an Alzheimer’s disease model via degeneration of hippocampal cholinergic synapses |
| title_short | Impairments of spatial memory in an Alzheimer’s disease model via degeneration of hippocampal cholinergic synapses |
| title_sort | impairments of spatial memory in an alzheimer’s disease model via degeneration of hippocampal cholinergic synapses |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698429/ https://www.ncbi.nlm.nih.gov/pubmed/29162816 http://dx.doi.org/10.1038/s41467-017-01943-0 |
| work_keys_str_mv | AT zhuhouze impairmentsofspatialmemoryinanalzheimersdiseasemodelviadegenerationofhippocampalcholinergicsynapses AT yanhuanhuan impairmentsofspatialmemoryinanalzheimersdiseasemodelviadegenerationofhippocampalcholinergicsynapses AT tangna impairmentsofspatialmemoryinanalzheimersdiseasemodelviadegenerationofhippocampalcholinergicsynapses AT lixinyan impairmentsofspatialmemoryinanalzheimersdiseasemodelviadegenerationofhippocampalcholinergicsynapses AT pangpei impairmentsofspatialmemoryinanalzheimersdiseasemodelviadegenerationofhippocampalcholinergicsynapses AT lihao impairmentsofspatialmemoryinanalzheimersdiseasemodelviadegenerationofhippocampalcholinergicsynapses AT chenwenting impairmentsofspatialmemoryinanalzheimersdiseasemodelviadegenerationofhippocampalcholinergicsynapses AT guoyu impairmentsofspatialmemoryinanalzheimersdiseasemodelviadegenerationofhippocampalcholinergicsynapses AT shushu impairmentsofspatialmemoryinanalzheimersdiseasemodelviadegenerationofhippocampalcholinergicsynapses AT caiyou impairmentsofspatialmemoryinanalzheimersdiseasemodelviadegenerationofhippocampalcholinergicsynapses AT peilei impairmentsofspatialmemoryinanalzheimersdiseasemodelviadegenerationofhippocampalcholinergicsynapses AT liudan impairmentsofspatialmemoryinanalzheimersdiseasemodelviadegenerationofhippocampalcholinergicsynapses AT luominhua impairmentsofspatialmemoryinanalzheimersdiseasemodelviadegenerationofhippocampalcholinergicsynapses AT manhengye impairmentsofspatialmemoryinanalzheimersdiseasemodelviadegenerationofhippocampalcholinergicsynapses AT tianqing impairmentsofspatialmemoryinanalzheimersdiseasemodelviadegenerationofhippocampalcholinergicsynapses AT muyangling impairmentsofspatialmemoryinanalzheimersdiseasemodelviadegenerationofhippocampalcholinergicsynapses AT zhulingqiang impairmentsofspatialmemoryinanalzheimersdiseasemodelviadegenerationofhippocampalcholinergicsynapses AT luyouming impairmentsofspatialmemoryinanalzheimersdiseasemodelviadegenerationofhippocampalcholinergicsynapses |