Hypomyelination, memory impairment, and blood-brain barrier permeability in a model of sleep apnea

Brain Res. 2015 Feb 9:1597:28-36. doi: 10.1016/j.brainres.2014.11.052. Epub 2014 Dec 5.

Abstract

We investigated the effect of intermittent hypoxia, mimicking sleep apnea, on axonal integrity, blood-brain barrier permeability, and cognitive function of mice. Forty-seven C57BL mice were exposed to intermittent or sham hypoxia, alternating 30s of progressive hypoxia and 30s of reoxigenation, during 8h/day. The axonal integrity in cerebellum was evaluated by transmission electron microscopy. Short- and long-term memories were assessed by novel object recognition test. The levels of endothelin-1 were measured by ELISA. Blood-brain barrier permeability was quantified by Evans Blue dye. After 14 days, animals exposed to intermittent hypoxia showed hypomyelination in cerebellum white matter and higher serum levels of endothelin-1. The short and long-term memories in novel object recognition test was impaired in the group exposed to intermittent hypoxia as compared to controls. Blood-brain barrier permeability was similar between the groups. These results indicated that hypomyelination and impairment of short- and long-term working memories occurred in C57BL mice after 14 days of intermittent hypoxia mimicking sleep apnea.

Keywords: Blood–brain barrier; Endothelin-1; Hypomyelination; Intermittent hypoxia; Sleep apnea; Working memory.

MeSH terms

  • Animals
  • Axons / ultrastructure
  • Blood-Brain Barrier / physiopathology*
  • Blood-Brain Barrier / ultrastructure
  • Capillary Permeability / physiology
  • Cerebellum / physiopathology
  • Cerebellum / ultrastructure
  • Cerebrum / physiopathology
  • Disease Models, Animal
  • Endothelin-1 / blood
  • Enzyme-Linked Immunosorbent Assay
  • Evans Blue
  • Hypoxia / pathology
  • Hypoxia / physiopathology*
  • Male
  • Memory Disorders / pathology
  • Memory Disorders / physiopathology*
  • Memory, Short-Term / physiology
  • Mice, Inbred C57BL
  • Myelin Sheath / ultrastructure
  • Neuropsychological Tests
  • Recognition, Psychology / physiology
  • Sleep Apnea Syndromes / pathology
  • Sleep Apnea Syndromes / physiopathology*
  • White Matter / physiopathology
  • White Matter / ultrastructure

Substances

  • Endothelin-1
  • Evans Blue