title: A novel adjustable automated system for inducing chronic intermittent hypoxia in mice.
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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Dora
authors.initials: D
authors.lastname: Polšek
authors.affiliation: Institute of Clinical Experimental Research, Semmelweis University, Budapest, Hungary.|University of Physical Education, Budapest, Hungary.
authors.forename: Marcel
authors.initials: M
authors.lastname: Bago
authors.affiliation: Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Marija
authors.initials: M
authors.lastname: Živaljić
authors.affiliation: Sleep and Brain Plasticity Centre, Department of Neuroimaging, King's College London, London, United Kingdom.|Sleep Disorders Centre, Guy's and St Thomas's Hospitals NHS Trust, London, United Kingdom.
authors.forename: Ivana
authors.initials: I
authors.lastname: Rosenzweig
authors.affiliation: Institute of Clinical Experimental Research, Semmelweis University, Budapest, Hungary.
authors.forename: Zsombor
authors.initials: Z
authors.lastname: Lacza
authors.affiliation: Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Srećko
authors.identifier: http://orcid.org/0000-0001-8668-5239
authors.initials: S
authors.lastname: Gajović
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020181:Sleep Apnea, Obstructive / Q000378:metabolism / Q000473:pathology