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SerpinA3N deficiency deteriorates impairments of learning and memory in mice following hippocampal stab injury
Traumatic brain injury is a global leading cause of disability and death, which puts patients at high risk for developing dementia. Early intervention is believed as the key to minimize the development of brain damages that could aggravate the symptoms. Here, we report that the serine protease inhib...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501238/ https://www.ncbi.nlm.nih.gov/pubmed/33014432 http://dx.doi.org/10.1038/s41420-020-00325-8 |
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author | Wang, Zhi-Meng Liu, Cong Wang, Ying-Ying Deng, Yu-Sen He, Xuan-Cheng Du, Hong-Zhen Liu, Chang-Mei Teng, Zhao-Qian |
author_facet | Wang, Zhi-Meng Liu, Cong Wang, Ying-Ying Deng, Yu-Sen He, Xuan-Cheng Du, Hong-Zhen Liu, Chang-Mei Teng, Zhao-Qian |
author_sort | Wang, Zhi-Meng |
collection | PubMed |
description | Traumatic brain injury is a global leading cause of disability and death, which puts patients at high risk for developing dementia. Early intervention is believed as the key to minimize the development of brain damages that could aggravate the symptoms. Here, we report that the serine protease inhibitor SerpinA3N is upregulated in hippocampal neurons in the early stage of hippocampal stab injury (HSI), while its deficiency causes a greater degree of neuronal apoptosis and severer impairments of spatial learning and memory in mice after HSI. We further show that MMP2 is a key substrate of SerpinA3N, and MMP2 specific inhibitor (ARP100) can protect against neuronal apoptosis and cognitive dysfunction in mice after HSI. These findings demonstrate a critical role for SerpinA3N in neuroprotection, suggesting that SerpinA3N and MMP2 inhibitors might be a novel therapeutic agents for neurotrauma. |
format | Online Article Text |
id | pubmed-7501238 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75012382020-10-01 SerpinA3N deficiency deteriorates impairments of learning and memory in mice following hippocampal stab injury Wang, Zhi-Meng Liu, Cong Wang, Ying-Ying Deng, Yu-Sen He, Xuan-Cheng Du, Hong-Zhen Liu, Chang-Mei Teng, Zhao-Qian Cell Death Discov Article Traumatic brain injury is a global leading cause of disability and death, which puts patients at high risk for developing dementia. Early intervention is believed as the key to minimize the development of brain damages that could aggravate the symptoms. Here, we report that the serine protease inhibitor SerpinA3N is upregulated in hippocampal neurons in the early stage of hippocampal stab injury (HSI), while its deficiency causes a greater degree of neuronal apoptosis and severer impairments of spatial learning and memory in mice after HSI. We further show that MMP2 is a key substrate of SerpinA3N, and MMP2 specific inhibitor (ARP100) can protect against neuronal apoptosis and cognitive dysfunction in mice after HSI. These findings demonstrate a critical role for SerpinA3N in neuroprotection, suggesting that SerpinA3N and MMP2 inhibitors might be a novel therapeutic agents for neurotrauma. Nature Publishing Group UK 2020-09-18 /pmc/articles/PMC7501238/ /pubmed/33014432 http://dx.doi.org/10.1038/s41420-020-00325-8 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Wang, Zhi-Meng Liu, Cong Wang, Ying-Ying Deng, Yu-Sen He, Xuan-Cheng Du, Hong-Zhen Liu, Chang-Mei Teng, Zhao-Qian SerpinA3N deficiency deteriorates impairments of learning and memory in mice following hippocampal stab injury |
title | SerpinA3N deficiency deteriorates impairments of learning and memory in mice following hippocampal stab injury |
title_full | SerpinA3N deficiency deteriorates impairments of learning and memory in mice following hippocampal stab injury |
title_fullStr | SerpinA3N deficiency deteriorates impairments of learning and memory in mice following hippocampal stab injury |
title_full_unstemmed | SerpinA3N deficiency deteriorates impairments of learning and memory in mice following hippocampal stab injury |
title_short | SerpinA3N deficiency deteriorates impairments of learning and memory in mice following hippocampal stab injury |
title_sort | serpina3n deficiency deteriorates impairments of learning and memory in mice following hippocampal stab injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501238/ https://www.ncbi.nlm.nih.gov/pubmed/33014432 http://dx.doi.org/10.1038/s41420-020-00325-8 |
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