Simulated high altitude hypoxia induces anxiety- and depression-like behaviors in mice

Abstract

Objective To determine the effects of simulated altitude hypoxia conditions on anxiety- and depression-like behaviors in mice. Methods C57 adult male mice were divided into 3 groups (n=10): plain control group, 24 h plateau hypoxia group, and 7 d plateau hypoxia group. Behavioral observations were used to detect anxiety-like behaviors, short-term memory, and depression-like behaviors in the mice. Immunohistochemical assay was applied to measure the number of C-Fos, AVP and GR immunoreactive cells in the paraventricular nucleus of the hypothalamus. Enzyme linked immunosorbent assay (ELISA) was adopted to detect the concentrations of adrenocorticotropic hormone (ACTH) and corticosterone in the blood. Results The Results of the elevated plus maze test showed that the mice in the 7 d plateau hypoxia group had a lower percentage of open arm time and increased anxiety-like behavior than those of the control group. Tail suspension test indicated that the mice of the 7 d plateau hypoxia group had more immobile time and increased depression-like behavior than those of the control group (P < 0.01). In the forced swimming test, the 24 h hypoxia group had significantly longer immobility time and increased depression-like behavior than the control group (P < 0.05). Immunohistochemical assay showed that the C-Fos protein in the paraventricular nucleus of the hypothalamus was significantly activated in the 7-d plateau hypoxia group. The numbers of AVP and GR positive neurons were increased in the paraventricular nucleus of the hypothalamus in the 7 d plateau hypoxia group (P < 0.01). Compared with the control group, the ACTH concentration of mice was elevated in the 7 d plateau hypoxia group (P < 0.05), so was the corticosterone concentration in the mice in the 24 h plateau hypoxia group (P < 0.05). Conclusion Rapidly entering the high altitude can cause anxiety- and depression-like behaviors in mice, and the stress responses are regulated by the hypothalamic-pituitary-adrenal axis.

Keywords

• high altitude hypoxia
• anxiety
• depression
• hypothalamus
• mice