Repeated mild hypoxic exposures decrease anxiety-like behavior in the adult mouse together with an increased brain adrenomedullin gene expression

Behav Brain Res. 2012 Apr 21;230(1):78-84. doi: 10.1016/j.bbr.2012.01.054. Epub 2012 Feb 7.


Whereas severe hypoxia is known to contribute to neuronal death and to lead to neurological disturbances, mild hypoxia can also induce beneficial effects through endogenous adaptive responses. The aim of this study was to investigate the effects of mild hypoxia (8% O(2)) on cognitive and emotional behavior in the adult mouse. To this end, mice were submitted to repeated mild hypoxia exposure or normoxia during 6 weeks and underwent behavioral testing during the last 3 weeks. Hypoxia decreased anxiety-like behavior in the light/dark transition test, enhanced, albeit modestly, non-spatial recognition memory, but did not alter spontaneous locomotor activity, nor spatial learning. On additional mice, whole brain adrenomedullin mRNA expression was found to be increased at D1, D25 and D41 after hypoxia initiation and vascular endothelial growth factor (VEGF) mRNA expression was increased at only on D41. This work shows that repeated mild hypoxic exposure decreases anxiety-related behavior and points out hypoxia inducible factor-1 (HIF-1) target genes, particularly adrenomedullin, as potential mediator candidate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenomedullin / genetics
  • Adrenomedullin / metabolism*
  • Analysis of Variance
  • Animals
  • Anxiety Disorders / physiopathology*
  • Brain / metabolism*
  • Gene Expression Regulation / physiology*
  • Hypoxia / pathology*
  • Hypoxia / physiopathology*
  • Hypoxia-Inducible Factor 1 / genetics
  • Hypoxia-Inducible Factor 1 / metabolism
  • Locomotion / physiology
  • Male
  • Maze Learning / physiology
  • Mice
  • RNA, Messenger / metabolism
  • Recognition, Psychology / physiology
  • Time Factors
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism


  • Hypoxia-Inducible Factor 1
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Adrenomedullin