Cargando…

A novel adjustable automated system for inducing chronic intermittent hypoxia in mice

BACKGROUND: Sleep apnea is a chronic, widely underdiagnosed condition characterized by disruption of sleep architecture and intermittent hypoxia due to short cessations of breathing. It is a major independent risk factor for myocardial infarction, congestive heart failure and stroke as well as one o...

Descripción completa

Detalles Bibliográficos
Autores principales: Polšek, Dora, Bago, Marcel, Živaljić, Marija, Rosenzweig, Ivana, Lacza, Zsombor, Gajović, Srećko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376321/
https://www.ncbi.nlm.nih.gov/pubmed/28362813
http://dx.doi.org/10.1371/journal.pone.0174896
_version_ 1782519139511828480
author Polšek, Dora
Bago, Marcel
Živaljić, Marija
Rosenzweig, Ivana
Lacza, Zsombor
Gajović, Srećko
author_facet Polšek, Dora
Bago, Marcel
Živaljić, Marija
Rosenzweig, Ivana
Lacza, Zsombor
Gajović, Srećko
author_sort Polšek, Dora
collection PubMed
description BACKGROUND: Sleep apnea is a chronic, widely underdiagnosed condition characterized by disruption of sleep architecture and intermittent hypoxia due to short cessations of breathing. It is a major independent risk factor for myocardial infarction, congestive heart failure and stroke as well as one of the rare modifiable risk factors for Alzheimer’s Dementia. Reliable animal disease models are needed to understand the link between sleep apnea and the various clinically linked disorders. NEW METHOD: An automated system for inducing hypoxia was developed, in which the major improvement was the possibility to efficiently adjust the length and intensity of hypoxia in two different periods. The chamber used a small volume of gas allowing for fast exchanges of different oxygen levels. The mice were kept in their cages adapted with the system on the cage lid. As a proof of principle, they were exposed to a three week period of intermittent hypoxia for 8 hours a day, with 90 s intervals of 5, 7% and 21% oxygen to validate the model. Treated (n = 8) and control mice (no hypoxia, n = 7) were handled in the same manner and their hippocampal brain regions compared by histology. RESULTS: The chamber provided a fast, reliable and precise intermittent hypoxia, without inducing noticeable side effects to the animals. The validation experiment showed that apoptotic neurons in the hippocampus were more numerous in the mice exposed to intermittent hypoxia than in the control group, in all tested hippocampal regions (cornu ammonis 1 (CA1) P <0.001; cornu ammonis 3 (CA3) P <0.001; and dentate gyrus (DG) P = 0.023). In both, control and hypoxic conditions, there was a significantly higher number of apoptotic neurons in the DG compared to the CA1 and CA3 subfields (P <0.001). CONCLUSION: The new design of a hypoxic chamber provides a fast, adjustable and reliable model of obstructive sleep apnea, which was validated by apoptosis of hippocampal neurons.
format Online
Article
Text
id pubmed-5376321
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-53763212017-04-07 A novel adjustable automated system for inducing chronic intermittent hypoxia in mice Polšek, Dora Bago, Marcel Živaljić, Marija Rosenzweig, Ivana Lacza, Zsombor Gajović, Srećko PLoS One Research Article BACKGROUND: Sleep apnea is a chronic, widely underdiagnosed condition characterized by disruption of sleep architecture and intermittent hypoxia due to short cessations of breathing. It is a major independent risk factor for myocardial infarction, congestive heart failure and stroke as well as one of the rare modifiable risk factors for Alzheimer’s Dementia. Reliable animal disease models are needed to understand the link between sleep apnea and the various clinically linked disorders. NEW METHOD: An automated system for inducing hypoxia was developed, in which the major improvement was the possibility to efficiently adjust the length and intensity of hypoxia in two different periods. The chamber used a small volume of gas allowing for fast exchanges of different oxygen levels. The mice were kept in their cages adapted with the system on the cage lid. As a proof of principle, they were exposed to a three week period of intermittent hypoxia for 8 hours a day, with 90 s intervals of 5, 7% and 21% oxygen to validate the model. Treated (n = 8) and control mice (no hypoxia, n = 7) were handled in the same manner and their hippocampal brain regions compared by histology. RESULTS: The chamber provided a fast, reliable and precise intermittent hypoxia, without inducing noticeable side effects to the animals. The validation experiment showed that apoptotic neurons in the hippocampus were more numerous in the mice exposed to intermittent hypoxia than in the control group, in all tested hippocampal regions (cornu ammonis 1 (CA1) P <0.001; cornu ammonis 3 (CA3) P <0.001; and dentate gyrus (DG) P = 0.023). In both, control and hypoxic conditions, there was a significantly higher number of apoptotic neurons in the DG compared to the CA1 and CA3 subfields (P <0.001). CONCLUSION: The new design of a hypoxic chamber provides a fast, adjustable and reliable model of obstructive sleep apnea, which was validated by apoptosis of hippocampal neurons. Public Library of Science 2017-03-31 /pmc/articles/PMC5376321/ /pubmed/28362813 http://dx.doi.org/10.1371/journal.pone.0174896 Text en © 2017 Polšek et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Polšek, Dora
Bago, Marcel
Živaljić, Marija
Rosenzweig, Ivana
Lacza, Zsombor
Gajović, Srećko
A novel adjustable automated system for inducing chronic intermittent hypoxia in mice
title A novel adjustable automated system for inducing chronic intermittent hypoxia in mice
title_full A novel adjustable automated system for inducing chronic intermittent hypoxia in mice
title_fullStr A novel adjustable automated system for inducing chronic intermittent hypoxia in mice
title_full_unstemmed A novel adjustable automated system for inducing chronic intermittent hypoxia in mice
title_short A novel adjustable automated system for inducing chronic intermittent hypoxia in mice
title_sort novel adjustable automated system for inducing chronic intermittent hypoxia in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376321/
https://www.ncbi.nlm.nih.gov/pubmed/28362813
http://dx.doi.org/10.1371/journal.pone.0174896
work_keys_str_mv AT polsekdora anoveladjustableautomatedsystemforinducingchronicintermittenthypoxiainmice
AT bagomarcel anoveladjustableautomatedsystemforinducingchronicintermittenthypoxiainmice
AT zivaljicmarija anoveladjustableautomatedsystemforinducingchronicintermittenthypoxiainmice
AT rosenzweigivana anoveladjustableautomatedsystemforinducingchronicintermittenthypoxiainmice
AT laczazsombor anoveladjustableautomatedsystemforinducingchronicintermittenthypoxiainmice
AT gajovicsrecko anoveladjustableautomatedsystemforinducingchronicintermittenthypoxiainmice
AT polsekdora noveladjustableautomatedsystemforinducingchronicintermittenthypoxiainmice
AT bagomarcel noveladjustableautomatedsystemforinducingchronicintermittenthypoxiainmice
AT zivaljicmarija noveladjustableautomatedsystemforinducingchronicintermittenthypoxiainmice
AT rosenzweigivana noveladjustableautomatedsystemforinducingchronicintermittenthypoxiainmice
AT laczazsombor noveladjustableautomatedsystemforinducingchronicintermittenthypoxiainmice
AT gajovicsrecko noveladjustableautomatedsystemforinducingchronicintermittenthypoxiainmice