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An enriched environment prevents cognitive impairment in an Alzheimer’s disease model by enhancing the secretion of exosomal microRNA-146a from the choroid plexus
Alzheimer’s disease (AD) is characterized by the extensive deposition of amyloid-β plaques and neurofibrillary tangles. We previously found that preserved function of astrocytes is associated with cognitively normal subjects with AD pathology. Here we show that an enriched environment (EE) can preve...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474441/ https://www.ncbi.nlm.nih.gov/pubmed/34589894 http://dx.doi.org/10.1016/j.bbih.2020.100149 |
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author | Nakano, Masako Kubota, Kenta Hashizume, Shin Kobayashi, Eiji Chikenji, Takako S. Saito, Yuki Fujimiya, Mineko |
author_facet | Nakano, Masako Kubota, Kenta Hashizume, Shin Kobayashi, Eiji Chikenji, Takako S. Saito, Yuki Fujimiya, Mineko |
author_sort | Nakano, Masako |
collection | PubMed |
description | Alzheimer’s disease (AD) is characterized by the extensive deposition of amyloid-β plaques and neurofibrillary tangles. We previously found that preserved function of astrocytes is associated with cognitively normal subjects with AD pathology. Here we show that an enriched environment (EE) can prevent cognitive impairment in AD model mice by ameliorating astrocytic inflammation and increasing synaptic density in the subiculum area of the hippocampus. In AD model mice treated with an EE, increased levels of microRNA (miR)-146a and down-regulation of NF-κB were observed in the hippocampus. In addition, increased levels of interferon (IFN)-γ were seen in serum from mice exposed to an EE. In vitro, enhanced miR-146a expression was observed in exosomes derived from the choroid plexus (CP) after IFN-γ treatment. In further in vitro experiments, we transfected miR-146a into Aβ/lipopolysaccharide-induced inflammatory astrocytes and showed that miR-146a ameliorated astrocytic inflammation by down-regulating tumor necrosis factor receptor-associated factor 6 and NF-κB. The present study indicates that following an EE, exosomal miR-146a derived from the CP cells is a key factor in ameliorating astrocytic inflammation, leading to synaptogenesis and correction of cognitive impairment. |
format | Online Article Text |
id | pubmed-8474441 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-84744412021-09-28 An enriched environment prevents cognitive impairment in an Alzheimer’s disease model by enhancing the secretion of exosomal microRNA-146a from the choroid plexus Nakano, Masako Kubota, Kenta Hashizume, Shin Kobayashi, Eiji Chikenji, Takako S. Saito, Yuki Fujimiya, Mineko Brain Behav Immun Health Full Length Article Alzheimer’s disease (AD) is characterized by the extensive deposition of amyloid-β plaques and neurofibrillary tangles. We previously found that preserved function of astrocytes is associated with cognitively normal subjects with AD pathology. Here we show that an enriched environment (EE) can prevent cognitive impairment in AD model mice by ameliorating astrocytic inflammation and increasing synaptic density in the subiculum area of the hippocampus. In AD model mice treated with an EE, increased levels of microRNA (miR)-146a and down-regulation of NF-κB were observed in the hippocampus. In addition, increased levels of interferon (IFN)-γ were seen in serum from mice exposed to an EE. In vitro, enhanced miR-146a expression was observed in exosomes derived from the choroid plexus (CP) after IFN-γ treatment. In further in vitro experiments, we transfected miR-146a into Aβ/lipopolysaccharide-induced inflammatory astrocytes and showed that miR-146a ameliorated astrocytic inflammation by down-regulating tumor necrosis factor receptor-associated factor 6 and NF-κB. The present study indicates that following an EE, exosomal miR-146a derived from the CP cells is a key factor in ameliorating astrocytic inflammation, leading to synaptogenesis and correction of cognitive impairment. Elsevier 2020-09-22 /pmc/articles/PMC8474441/ /pubmed/34589894 http://dx.doi.org/10.1016/j.bbih.2020.100149 Text en © 2020 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Full Length Article Nakano, Masako Kubota, Kenta Hashizume, Shin Kobayashi, Eiji Chikenji, Takako S. Saito, Yuki Fujimiya, Mineko An enriched environment prevents cognitive impairment in an Alzheimer’s disease model by enhancing the secretion of exosomal microRNA-146a from the choroid plexus |
title | An enriched environment prevents cognitive impairment in an Alzheimer’s disease model by enhancing the secretion of exosomal microRNA-146a from the choroid plexus |
title_full | An enriched environment prevents cognitive impairment in an Alzheimer’s disease model by enhancing the secretion of exosomal microRNA-146a from the choroid plexus |
title_fullStr | An enriched environment prevents cognitive impairment in an Alzheimer’s disease model by enhancing the secretion of exosomal microRNA-146a from the choroid plexus |
title_full_unstemmed | An enriched environment prevents cognitive impairment in an Alzheimer’s disease model by enhancing the secretion of exosomal microRNA-146a from the choroid plexus |
title_short | An enriched environment prevents cognitive impairment in an Alzheimer’s disease model by enhancing the secretion of exosomal microRNA-146a from the choroid plexus |
title_sort | enriched environment prevents cognitive impairment in an alzheimer’s disease model by enhancing the secretion of exosomal microrna-146a from the choroid plexus |
topic | Full Length Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474441/ https://www.ncbi.nlm.nih.gov/pubmed/34589894 http://dx.doi.org/10.1016/j.bbih.2020.100149 |
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