Impaired Behavioral Performance after Prolonged Moderate Hypobaric Hypoxic Exposure in Mice

Abstract

Hypobaric hypoxia can be used to simulate the conditions of high altitude to study adaptive responses. The brain is completely reliant on oxygen for oxidative energy metabolism, and even mild decrease in ambient O2 could result in altered function. In this study we investigated specific motor and cognitive performance in mice adapting to moderate hypoxia. Mice (C57BL/6) were exposed to the sea level equivalent of 8% O2 for 3 weeks in hypobaric chambers at a pressure of 300 mmHg (0.4 ATM); littermate normoxic controls were kept in the same location. Motor function was tested using the Rotarod and the inclined‐screen tests. Cognitive function was measured using an object recognition test and a fear conditioning test. Capillary density was estimated from parietal cortical sections. After 2 weeks of hypoxia, the motor performance was declined as represented by decreased latency in the Rotarod test and increased latency in the inclined screen test; the hypoxic mice also performed poorly in the fear conditioning and object recognition tests. Similar to the previous mouse and rat studies, the hypoxic mice went through a decrease in body weight, increases in hematocrit (%, 80 ± 7 vs. 45 ± 1) and an increase in capillary density (N/mm2, 721 ± 63 vs. 533 ± 69) compared to the normoxic controls. Motor and cognitive functions were impaired in the simulated high‐altitude condition despite successful vascular adaptation.