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A novel adjustable automated system for inducing chronic intermittent hypoxia in mice
Dora Polšek1, Marcel Bago2,3, Marija Živaljić1
1Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.
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.
Insights
A new automated system effectively models obstructive sleep apnea in mice by inducing intermittent hypoxia. This model showed increased hippocampal neuron apoptosis, validating its use for studying sleep apnea
Area of Science:
- Neuroscience
- Sleep Medicine
- Animal Models
Background:
- Sleep apnea is a common, underdiagnosed condition causing sleep disruption and intermittent hypoxia.
- It is a significant risk factor for cardiovascular diseases and Alzheimer's Dementia.
- Reliable animal models are crucial for understanding sleep apnea's associated disorders.
Purpose of the Study:
- To develop and validate an automated system for inducing intermittent hypoxia in mice.
- To establish a reliable animal model for obstructive sleep apnea research.
- To investigate the effects of intermittent hypoxia on hippocampal neuron apoptosis.
Main Methods:
- An automated hypoxic chamber was designed for precise control of oxygen levels and exposure duration.
- Mice were exposed to intermittent hypoxia (5-7% O2 for 90s, alternating with 21% O2) for 8 hours daily over three weeks.
- Histological comparison of hippocampal regions between treated and control mice was performed.
Main Results:
- The system reliably induced precise intermittent hypoxia without adverse side effects.
- Mice exposed to intermittent hypoxia exhibited significantly higher apoptotic neurons in all hippocampal regions (CA1, CA3, DG) compared to controls.
- The dentate gyrus showed a higher baseline apoptotic neuron count than CA1 and CA3 regions.
Conclusions:
- The developed hypoxic chamber offers a fast, adjustable, and reliable model for obstructive sleep apnea.
- Increased hippocampal neuron apoptosis validates the model's efficacy.
- This model aids in studying the neuropathological consequences of sleep apnea.