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

Polšek, Dora and Bago, Marcel and Živaljić, Marija and Rosenzweig, Ivana and Lacza, Zsombor and Gajović, Srećko (2017) A novel adjustable automated system for inducing chronic intermittent hypoxia in mice. PLoS ONE, 12 (3). e0174896. ISSN 1932-6203

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Abstract

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.

Item Type: Article
Additional Information: © 2017 Polšek et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
MeSH: Animals ; Apoptosis/physiology ; Brain/cytology ; Brain/metabolism ; CA1 Region, Hippocampal/cytology ; CA1 Region, Hippocampal/metabolism ; Dentate Gyrus/cytology ; Dentate Gyrus/metabolism ; Disease Models, Animal ; Hippocampus/cytology ; Hippocampus/metabolism ; Hypoxia/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Neurons/cytology ; Neurons/metabolism ; Sleep Apnea, Obstructive/metabolism ; Sleep Apnea, Obstructive/pathology
Departments: Katedra za histologiju i embriologiju
Depositing User: Martina Žužak
Status: Published
Creators:
CreatorsEmail
Polšek, DoraUNSPECIFIED
Bago, MarcelUNSPECIFIED
Živaljić, MarijaUNSPECIFIED
Rosenzweig, IvanaUNSPECIFIED
Lacza, ZsomborUNSPECIFIED
Gajović, SrećkoUNSPECIFIED
Date: 31 March 2017
Date Deposited: 11 Oct 2017 07:30
Last Modified: 20 Aug 2020 08:51
Subjects: UNSPECIFIED
Related URLs:
URI: http://medlib.mef.hr/id/eprint/2701

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