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Women's mood at high altitude. sexual dimorphism in hypoxic stress modulation by the tryptophan-melatonin axis

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FRONTIERS IN PHYSIOLOGY
卷 13, 期 -, 页码 -

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FRONTIERS MEDIA SA
DOI: 10.3389/fphys.2022.1099276

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women's mood; high altitude; serotonin; tryptophan; REM sleep; thermogenesis

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Sexual (and gender)-dimorphism in tolerance to hypobaric hypoxia has become increasingly important for monitoring human activities at high altitudes. The prevalence of anxiety and depression in women is already double than that of men at low altitudes, and it is expected to increase even more at high altitudes. This study explores the potential involvement of the tryptophan-melatonin axis in mood changes caused by exposure to hypobaric hypoxia, highlighting the anxiogenic effects of high altitude exposure. The study suggests that sex-related differences in neural network organization and hormonal changes, as well as the overexpression effects of a 5-HT transporter protein, may contribute to mood alterations in women exposed to high altitude. Proper care for women at high altitudes should include monitoring of hormonal cycles and consideration of targeted antidepressant treatments.
Sexual (and gender)-dimorphism in tolerance to hypobaric hypoxia increasingly matters for a differential surveillance of human activities at high altitude (HA). At low altitudes, the prevalence of anxiety and depression in women has already been found to double when compared with men; it could be expected to even increase on exposure to HA. In purposefully caring for the health of women at HA, the present work explores the potential involvement of the tryptophan (Trp)-melatonin axis in mood changes on exposure to hypobaric hypoxia. The present work highlights some already known anxiogenic effects of HA exposure. Hypoxia and insomnia reduce serotonin (5-HT) availability; the latter defect being expressed as failure of brown adipose tissue (BAT) activation and mood disorders. Rapid eye movement (REM) sleep organization and synapsis restoration that are additionally affected by hypoxia impair memory consolidation. Affective complaints may thus surge, evolving into anxiety and depression. Sex-related differences in neural network organization and hormonal changes during the menstrual cycle, and certainly also during the life cycle, underscore the possibility of 5-HT-related mood alterations, particularly in women on HA exposure. The mean brain rate of 5-HT synthesis at sea level is already 1.5-fold higher in males than in females. sexual dimorphism also evidences the overexpression effects of SERT, a 5-HT transporter protein. Gonadal and thyroid hormones, as influenced by HA exposure, further modulate 5-HT availability and its effects in women. Besides caring for adequate oxygenation and maintenance of one's body core temperature, special precautions concerning women sojourning at HA should include close observations of hormonal cycles and, perhaps, also trials with targeted antidepressants.

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