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α2-Antiplasmin as a potential regulator of the spatial memory process and age-related cognitive decline
α2-Antiplasmin (α2AP), a principal physiological plasmin inhibitor, is mainly produced by the liver and kidneys, but it is also expressed in several parts of the brain, including the hippocampus and cerebral cortex. Our previous study demonstrated that α2AP knockout mice exhibit spatial memory impai...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566027/ https://www.ncbi.nlm.nih.gov/pubmed/33059734 http://dx.doi.org/10.1186/s13041-020-00677-3 |
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author | Kawashita, Eri Ishihara, Keiichi Miyaji, Haruko Tanishima, Yu Kiriyama, Akiko Matsuo, Osamu Akiba, Satoshi |
author_facet | Kawashita, Eri Ishihara, Keiichi Miyaji, Haruko Tanishima, Yu Kiriyama, Akiko Matsuo, Osamu Akiba, Satoshi |
author_sort | Kawashita, Eri |
collection | PubMed |
description | α2-Antiplasmin (α2AP), a principal physiological plasmin inhibitor, is mainly produced by the liver and kidneys, but it is also expressed in several parts of the brain, including the hippocampus and cerebral cortex. Our previous study demonstrated that α2AP knockout mice exhibit spatial memory impairment in comparison to wild-type mice, suggesting that α2AP is necessary for the fetal and/or neonatal development of the neural network for spatial memory. However, it is still unclear whether α2AP plays a role in the memory process. The present study demonstrated that adult hippocampal neurogenesis and remote spatial memory were enhanced by the injection of an anti-α2AP neutralizing antibody in WT mice, while the injection of α2AP reduced hippocampal neurogenesis and impaired remote spatial memory, suggesting that α2AP is a negative regulator in memory processing. The present study also found that the levels of α2AP in the brains of old mice were higher than those in young mice, and a negative correlation between the α2AP level and spatial working memory. In addition, aging-dependent brain oxidative stress and hippocampal inflammation were attenuated by α2AP deficiency. Thus, an age-related increase in α2AP might cause cognitive decline accompanied by brain oxidative stress and neuroinflammation. Taken together, our findings suggest that α2AP is a key regulator of the spatial memory process, and that it may represent a promising target to effectively regulate healthy brain aging. |
format | Online Article Text |
id | pubmed-7566027 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-75660272020-10-20 α2-Antiplasmin as a potential regulator of the spatial memory process and age-related cognitive decline Kawashita, Eri Ishihara, Keiichi Miyaji, Haruko Tanishima, Yu Kiriyama, Akiko Matsuo, Osamu Akiba, Satoshi Mol Brain Research α2-Antiplasmin (α2AP), a principal physiological plasmin inhibitor, is mainly produced by the liver and kidneys, but it is also expressed in several parts of the brain, including the hippocampus and cerebral cortex. Our previous study demonstrated that α2AP knockout mice exhibit spatial memory impairment in comparison to wild-type mice, suggesting that α2AP is necessary for the fetal and/or neonatal development of the neural network for spatial memory. However, it is still unclear whether α2AP plays a role in the memory process. The present study demonstrated that adult hippocampal neurogenesis and remote spatial memory were enhanced by the injection of an anti-α2AP neutralizing antibody in WT mice, while the injection of α2AP reduced hippocampal neurogenesis and impaired remote spatial memory, suggesting that α2AP is a negative regulator in memory processing. The present study also found that the levels of α2AP in the brains of old mice were higher than those in young mice, and a negative correlation between the α2AP level and spatial working memory. In addition, aging-dependent brain oxidative stress and hippocampal inflammation were attenuated by α2AP deficiency. Thus, an age-related increase in α2AP might cause cognitive decline accompanied by brain oxidative stress and neuroinflammation. Taken together, our findings suggest that α2AP is a key regulator of the spatial memory process, and that it may represent a promising target to effectively regulate healthy brain aging. BioMed Central 2020-10-15 /pmc/articles/PMC7566027/ /pubmed/33059734 http://dx.doi.org/10.1186/s13041-020-00677-3 Text en © The Author(s) 2020 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Kawashita, Eri Ishihara, Keiichi Miyaji, Haruko Tanishima, Yu Kiriyama, Akiko Matsuo, Osamu Akiba, Satoshi α2-Antiplasmin as a potential regulator of the spatial memory process and age-related cognitive decline |
title | α2-Antiplasmin as a potential regulator of the spatial memory process and age-related cognitive decline |
title_full | α2-Antiplasmin as a potential regulator of the spatial memory process and age-related cognitive decline |
title_fullStr | α2-Antiplasmin as a potential regulator of the spatial memory process and age-related cognitive decline |
title_full_unstemmed | α2-Antiplasmin as a potential regulator of the spatial memory process and age-related cognitive decline |
title_short | α2-Antiplasmin as a potential regulator of the spatial memory process and age-related cognitive decline |
title_sort | α2-antiplasmin as a potential regulator of the spatial memory process and age-related cognitive decline |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566027/ https://www.ncbi.nlm.nih.gov/pubmed/33059734 http://dx.doi.org/10.1186/s13041-020-00677-3 |
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