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

Date Published: March 31, 2017

Publisher: Public Library of Science

Author(s): Dora Polšek, Marcel Bago, Marija Živaljić, Ivana Rosenzweig, Zsombor Lacza, Srećko Gajović, Manabu Sakakibara.


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.

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.

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). 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.

Partial Text

Sleep apnea is characterized by periodical cessation of breathing with a reduction in nasal airflow less than 30 percent of its normal level. It is present in three forms: central, obstructive or mixed. In central sleep apnea, the feedback mechanism in the respiratory centers of the ventrolateral medulla fails, resulting in a reduced or absent drive to breathe during sleep. The more common obstructive sleep apnea (OSA) is characterized by reduction in airflow to the lungs that occurs during sleep as a result of occlusion or narrowing of the respiratory tract at the pharyngeal level [1]. In all cases, sleep apnea leads to intermittent hypoxia, hypercapnia and subsequent reoxygenation as well as a disruption of sleep architecture. OSA has been reported to affect middle-aged and older individuals, with the prevalence recently estimated to be around 22% in men and 17% in women [2].

The design of a new hypoxic chamber provided a fast, adjustable and compact model of obstructive sleep apnea, which was validated by showing apoptosis of neurons in the hippocampus.




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