Cargando…
Involvement of Hepcidin in Cognitive Damage Induced by Chronic Intermittent Hypoxia in Mice
Obstructive sleep apnea (OSA) patients exhibit different degrees of cognitive impairment, which is related to the activation of reactive oxygen species (ROS) production by chronic intermittent hypoxia (CIH) and the deposition of iron in the brain. As a central regulator of iron homeostasis, whether...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357469/ https://www.ncbi.nlm.nih.gov/pubmed/34394834 http://dx.doi.org/10.1155/2021/8520967 |
_version_ | 1783737133540835328 |
---|---|
author | Zhao, Ya-Shuo Tan, Miao Song, Ji-Xian An, Ji-Ren Yang, Xin-Yue Li, Wen-Ya Guo, Ya-Jing Ji, En-Sheng |
author_facet | Zhao, Ya-Shuo Tan, Miao Song, Ji-Xian An, Ji-Ren Yang, Xin-Yue Li, Wen-Ya Guo, Ya-Jing Ji, En-Sheng |
author_sort | Zhao, Ya-Shuo |
collection | PubMed |
description | Obstructive sleep apnea (OSA) patients exhibit different degrees of cognitive impairment, which is related to the activation of reactive oxygen species (ROS) production by chronic intermittent hypoxia (CIH) and the deposition of iron in the brain. As a central regulator of iron homeostasis, whether hepcidin is involved in OSA-induced cognitive impairment has not been clarified. In order to simulate OSA, we established the mouse model by reducing the percentage of inspired O(2) (FiO(2)) from 21% to 5%, 20 times/h for 8 h/day. We found hepcidin was rising during CIH, along with increasing iron levels and neuron loss. Then, we constructed a mouse with astrocyte-specific knockdown hepcidin gene (shHamp). During CIH exposure, the shHamp mice showed a lower level of total iron and neuronal iron in the hippocampus, via stabilizing ferroportin 1 (FPN1) and decreasing L-ferritin (FTL) levels, when compared with wild-type (WT) mice. Furthermore, the shHamp mice showed a decrease of ROS by downregulating the elevated NADPH oxidase (NOX2) and 4-hydroxynonenal (4-HNE) levels mediated by CIH. In addition, the shHamp mice presented improved cognitive deficit by improving synaptic plasticity and BDNF expression in the hippocampus when subjected to CIH. Therefore, our data revealed that highly expressed hepcidin might promote the degradation of FPN1, resulting in neuronal iron deposition, oxidative stress damage, reduced synaptic plasticity, and impaired cognitive performance during CIH exposure. |
format | Online Article Text |
id | pubmed-8357469 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-83574692021-08-12 Involvement of Hepcidin in Cognitive Damage Induced by Chronic Intermittent Hypoxia in Mice Zhao, Ya-Shuo Tan, Miao Song, Ji-Xian An, Ji-Ren Yang, Xin-Yue Li, Wen-Ya Guo, Ya-Jing Ji, En-Sheng Oxid Med Cell Longev Research Article Obstructive sleep apnea (OSA) patients exhibit different degrees of cognitive impairment, which is related to the activation of reactive oxygen species (ROS) production by chronic intermittent hypoxia (CIH) and the deposition of iron in the brain. As a central regulator of iron homeostasis, whether hepcidin is involved in OSA-induced cognitive impairment has not been clarified. In order to simulate OSA, we established the mouse model by reducing the percentage of inspired O(2) (FiO(2)) from 21% to 5%, 20 times/h for 8 h/day. We found hepcidin was rising during CIH, along with increasing iron levels and neuron loss. Then, we constructed a mouse with astrocyte-specific knockdown hepcidin gene (shHamp). During CIH exposure, the shHamp mice showed a lower level of total iron and neuronal iron in the hippocampus, via stabilizing ferroportin 1 (FPN1) and decreasing L-ferritin (FTL) levels, when compared with wild-type (WT) mice. Furthermore, the shHamp mice showed a decrease of ROS by downregulating the elevated NADPH oxidase (NOX2) and 4-hydroxynonenal (4-HNE) levels mediated by CIH. In addition, the shHamp mice presented improved cognitive deficit by improving synaptic plasticity and BDNF expression in the hippocampus when subjected to CIH. Therefore, our data revealed that highly expressed hepcidin might promote the degradation of FPN1, resulting in neuronal iron deposition, oxidative stress damage, reduced synaptic plasticity, and impaired cognitive performance during CIH exposure. Hindawi 2021-08-04 /pmc/articles/PMC8357469/ /pubmed/34394834 http://dx.doi.org/10.1155/2021/8520967 Text en Copyright © 2021 Ya-Shuo Zhao et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Zhao, Ya-Shuo Tan, Miao Song, Ji-Xian An, Ji-Ren Yang, Xin-Yue Li, Wen-Ya Guo, Ya-Jing Ji, En-Sheng Involvement of Hepcidin in Cognitive Damage Induced by Chronic Intermittent Hypoxia in Mice |
title | Involvement of Hepcidin in Cognitive Damage Induced by Chronic Intermittent Hypoxia in Mice |
title_full | Involvement of Hepcidin in Cognitive Damage Induced by Chronic Intermittent Hypoxia in Mice |
title_fullStr | Involvement of Hepcidin in Cognitive Damage Induced by Chronic Intermittent Hypoxia in Mice |
title_full_unstemmed | Involvement of Hepcidin in Cognitive Damage Induced by Chronic Intermittent Hypoxia in Mice |
title_short | Involvement of Hepcidin in Cognitive Damage Induced by Chronic Intermittent Hypoxia in Mice |
title_sort | involvement of hepcidin in cognitive damage induced by chronic intermittent hypoxia in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357469/ https://www.ncbi.nlm.nih.gov/pubmed/34394834 http://dx.doi.org/10.1155/2021/8520967 |
work_keys_str_mv | AT zhaoyashuo involvementofhepcidinincognitivedamageinducedbychronicintermittenthypoxiainmice AT tanmiao involvementofhepcidinincognitivedamageinducedbychronicintermittenthypoxiainmice AT songjixian involvementofhepcidinincognitivedamageinducedbychronicintermittenthypoxiainmice AT anjiren involvementofhepcidinincognitivedamageinducedbychronicintermittenthypoxiainmice AT yangxinyue involvementofhepcidinincognitivedamageinducedbychronicintermittenthypoxiainmice AT liwenya involvementofhepcidinincognitivedamageinducedbychronicintermittenthypoxiainmice AT guoyajing involvementofhepcidinincognitivedamageinducedbychronicintermittenthypoxiainmice AT jiensheng involvementofhepcidinincognitivedamageinducedbychronicintermittenthypoxiainmice |