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MicroRNA-195 prevents dendritic degeneration and neuron death in rats following chronic brain hypoperfusion
Impaired synaptic plasticity and neuron loss are hallmarks of Alzheimer’s disease and vascular dementia. Here, we found that chronic brain hypoperfusion (CBH) by bilateral common carotid artery occlusion (2VO) decreased the total length, numbers and crossings of dendrites and caused neuron death in...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520902/ https://www.ncbi.nlm.nih.gov/pubmed/28569780 http://dx.doi.org/10.1038/cddis.2017.243 |
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author | Chen, Xin Jiang, Xue-Mei Zhao, Lin-Jing Sun, Lin-Lin Yan, Mei-Ling Tian, You Zhang, Shuai Duan, Ming-Jing Zhao, Hong-Mei Li, Wen-Rui Hao, Yang-Yang Wang, Li-Bo Xiong, Qiao-Jie Ai, Jing |
author_facet | Chen, Xin Jiang, Xue-Mei Zhao, Lin-Jing Sun, Lin-Lin Yan, Mei-Ling Tian, You Zhang, Shuai Duan, Ming-Jing Zhao, Hong-Mei Li, Wen-Rui Hao, Yang-Yang Wang, Li-Bo Xiong, Qiao-Jie Ai, Jing |
author_sort | Chen, Xin |
collection | PubMed |
description | Impaired synaptic plasticity and neuron loss are hallmarks of Alzheimer’s disease and vascular dementia. Here, we found that chronic brain hypoperfusion (CBH) by bilateral common carotid artery occlusion (2VO) decreased the total length, numbers and crossings of dendrites and caused neuron death in rat hippocampi and cortices. It also led to increase in N-terminal β-amyloid precursor protein (N-APP) and death receptor-6 (DR6) protein levels and in the activation of caspase-3 and caspase-6. Further study showed that DR6 protein was downregulated by miR-195 overexpression, upregulated by miR-195 inhibition, and unchanged by binding-site mutation and miR-masks. Knockdown of endogenous miR-195 by lentiviral vector-mediated overexpression of its antisense molecule (lenti-pre-AMO-miR-195) decreased the total length, numbers and crossings of dendrites and neuron death, upregulated N-APP and DR6 levels, and elevated cleaved caspase-3 and caspase-6 levels. Overexpression of miR-195 using lenti-pre-miR-195 prevented these changes triggered by 2VO. We conclude that miR-195 is involved in CBH-induced dendritic degeneration and neuron death through activation of the N-APP/DR6/caspase pathway. |
format | Online Article Text |
id | pubmed-5520902 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-55209022017-07-27 MicroRNA-195 prevents dendritic degeneration and neuron death in rats following chronic brain hypoperfusion Chen, Xin Jiang, Xue-Mei Zhao, Lin-Jing Sun, Lin-Lin Yan, Mei-Ling Tian, You Zhang, Shuai Duan, Ming-Jing Zhao, Hong-Mei Li, Wen-Rui Hao, Yang-Yang Wang, Li-Bo Xiong, Qiao-Jie Ai, Jing Cell Death Dis Original Article Impaired synaptic plasticity and neuron loss are hallmarks of Alzheimer’s disease and vascular dementia. Here, we found that chronic brain hypoperfusion (CBH) by bilateral common carotid artery occlusion (2VO) decreased the total length, numbers and crossings of dendrites and caused neuron death in rat hippocampi and cortices. It also led to increase in N-terminal β-amyloid precursor protein (N-APP) and death receptor-6 (DR6) protein levels and in the activation of caspase-3 and caspase-6. Further study showed that DR6 protein was downregulated by miR-195 overexpression, upregulated by miR-195 inhibition, and unchanged by binding-site mutation and miR-masks. Knockdown of endogenous miR-195 by lentiviral vector-mediated overexpression of its antisense molecule (lenti-pre-AMO-miR-195) decreased the total length, numbers and crossings of dendrites and neuron death, upregulated N-APP and DR6 levels, and elevated cleaved caspase-3 and caspase-6 levels. Overexpression of miR-195 using lenti-pre-miR-195 prevented these changes triggered by 2VO. We conclude that miR-195 is involved in CBH-induced dendritic degeneration and neuron death through activation of the N-APP/DR6/caspase pathway. Nature Publishing Group 2017-06 2017-06-01 /pmc/articles/PMC5520902/ /pubmed/28569780 http://dx.doi.org/10.1038/cddis.2017.243 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Chen, Xin Jiang, Xue-Mei Zhao, Lin-Jing Sun, Lin-Lin Yan, Mei-Ling Tian, You Zhang, Shuai Duan, Ming-Jing Zhao, Hong-Mei Li, Wen-Rui Hao, Yang-Yang Wang, Li-Bo Xiong, Qiao-Jie Ai, Jing MicroRNA-195 prevents dendritic degeneration and neuron death in rats following chronic brain hypoperfusion |
title | MicroRNA-195 prevents dendritic degeneration and neuron death in rats following chronic brain hypoperfusion |
title_full | MicroRNA-195 prevents dendritic degeneration and neuron death in rats following chronic brain hypoperfusion |
title_fullStr | MicroRNA-195 prevents dendritic degeneration and neuron death in rats following chronic brain hypoperfusion |
title_full_unstemmed | MicroRNA-195 prevents dendritic degeneration and neuron death in rats following chronic brain hypoperfusion |
title_short | MicroRNA-195 prevents dendritic degeneration and neuron death in rats following chronic brain hypoperfusion |
title_sort | microrna-195 prevents dendritic degeneration and neuron death in rats following chronic brain hypoperfusion |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520902/ https://www.ncbi.nlm.nih.gov/pubmed/28569780 http://dx.doi.org/10.1038/cddis.2017.243 |
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