Influence of gonadal hormones on the behavioral effects of intermittent hypoxia in mice

Jan 2, 2015American journal of physiology. Regulatory, integrative and comparative physiology

How sex hormones affect behavior changes from repeated low oxygen in mice

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Abstract

Ovariectomy paired with intermittent hypoxia exposure impaired spatial learning and memory in female mice.

Obstructive sleep apnea is associated with repetitive upper airway obstruction and intermittent hypoxia during sleep.
The severity of obstructive sleep apnea is greater in postmenopausal women compared to premenopausal women.
Estrogens may protect against hippocampal morphological and behavioral changes induced by intermittent hypoxia.
Intact male mice exposed to intermittent hypoxia exhibited impaired learning and memory compared to those in room air.
Changes in learning and memory were linked to reductions in the length of specific dendrites in the hippocampus.

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Obstructive sleep apnea (OSA) is characterized by repetitive upper airway obstruction resulting in cyclic intermittent hypoxia (IH) during sleep in affected individuals. OSA occurs more frequently in postmenopausal than premenopausal women and the severity of OSA increases after menopause. Gonadal hormones can influence brain and behavior; testosterone and estrogens in particular can enhance spatial learning and memory. We hypothesized that estrogens may protect mice from IH-induced hippocampal morphological and behavioral changes. To test this hypothesis we exposed intact or gonadectomized male and female mice to room air or IH [15 cycles/h, 8 h/day, fraction of inspired oxygen (FiO 2) nadir of 5%] for a total of 30 days. During the final 4 days of IH, mice were tested for anxiety- and depressive-like behaviors. After cessation of IH exposure mice were tested on the Barnes maze and passive avoidance tests to assess learning and memory. Ovariectomy paired with IH treatment, impaired spatial learning and memory compared to all other female groups. Intact male mice receiving IH treatment also had impaired learning and memory compared with intact or castrated male mice exposed to room air. Learning and memory changes were mirrored by changes in basilar dendritic length of the CA1 region of the hippocampus. These data suggest that estrogens provide protection against IH-induced deficits, whereas androgens partially exacerbate IH-induced deficits on learning and memory.

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Influence of gonadal hormones on the behavioral effects of intermittent hypoxia in mice

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