Neurochemical alterations in frontal cortex of the rat after one week of hypobaric hypoxia.
Residing at high altitude may lead to reduced blood oxygen saturation in the brain and altered metabolism in frontal cortical brain areas, probably due to chronic hypobaric hypoxia. These changes may underlie the increased rates of depression and suicidal behavior that have been associated with life at higher altitudes. To test the hypothesis that hypobaric hypoxia is responsible for development of mood disorders due to alterations in neurochemistry, we assessed depression-like behavior in parallel to levels of brain metabolites in rats housed at simulated altitude. 32 female Sprague Dawley rats were housed either in a hypobaric hypoxia chamber at 10,000 ft of simulated altitude for 1 week or at local conditions (4500 ft of elevation in Salt Lake City, Utah). Depression-like behavior was assessed using the forced swim test (FST) and levels of neurometabolites were estimated by in vivo proton magnetic resonance spectroscopy in the frontal cortex, the striatum and the hippocampus at baseline and after a week of exposure to hypobaric hypoxia. After hypoxia exposure the animals demonstrated increased immobility behavior and shortened latency to immobility in the FST. Elevated ratios of myo-inositol, glutamate, and the sum of myo-inositol and glycine to total creatine were observed in the frontal cortex of hypoxia treated rats. A decrease in the ratio of alanine to total creatine was also noted. This study shows that hypoxia induced alterations in frontal lobe brain metabolites, aggravated depression-like behavior and might be a factor in increased rates of psychiatric disorders observed in populations living at high altitudes.
Brain Institute, University of Utah, 383 Colorow Drive, Salt Lake City 84108, UT USA. Electronic address: basilevsis@yahoo.com.
Olena V
OV
Bogdanova
Department of Bioengineering, University of Utah, 36 S. Wasatch Drive, Salt Lake City 84112, UT USA.
Osama
O
Abdullah
Brain Institute, University of Utah, 383 Colorow Drive, Salt Lake City 84108, UT USA; Psychiatry Department, University of Utah, 383 Colorow Drive, Salt Lake City 84108, UT USA.
Shami
S
Kanekar
INRA, Nutrition et Neurobiologie Intégrée and University Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 146 rue Léo-Saignat, Bordeaux Cedex 33076, France.
Volodymyr B
VB
Bogdanov
Brain Institute, University of Utah, 383 Colorow Drive, Salt Lake City 84108, UT USA; Department of Radiology, University of Utah, 30 North 1900 East, Salt Lake City 84132, UT USA.
Andrew P
AP
Prescot
Brain Institute, University of Utah, 383 Colorow Drive, Salt Lake City 84108, UT USA; Psychiatry Department, University of Utah, 383 Colorow Drive, Salt Lake City 84108, UT USA; VISN19 MIRECC Salt Lake City UAMC, 500 Foothill Drive, Salt Lake City 84148, UT USA.
Perry F
PF
Renshaw
D000409:Alanine / Q000378:metabolism; D000531:Altitude; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D003866:Depressive Disorder / Q000209:etiology* / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism*; D007294:Inositol / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming; D013997:Time Factors
D018698:Glutamic Acid; D007294:Inositol; D003401:Creatine; D000409:Alanine; D005998:Glycine
Behavior; Depression; Hypobaric hypoxia; Proton magnetic resonance spectroscopy