Lanterna Rally

Author: Taryn G. Aubrecht

Publisher:

Published: 2015

Total Pages:

ISBN-13:

Obstructive sleep apnea (OSA) is an increasingly prevalent health problem, leading to periods of intermittent hypoxia (IH) during sleep. IH was used to model severe OSA in mice for my studies (15 cycles/h, 8 h/day, FIO2 nadir of 5%). OSA and dim light at night (dLAN) have both been independently associated with alterations in mood and cognition. In Chapter 2, I aimed to determine whether dLAN would interact with IH, to alter behavioral, cognitive, and affective responses. Adult male mice were housed in either standard lighting conditions (14:10; 150 lux:0 lux) or dLAN (150 lux:5 lux), and then were then exposed to IH for 3 weeks. The combination of IH and dLAN provokes negative effects on affect and cognition and reduced neuronal cell body area in the CA1 and 3 of the hippocampus. Prior studies have demonstrated both protective and harmful consequences of IH exposure prior to middle cerebral artery occlusion (MCAO); Chapter 3 extends this research by examining the effects of timing of IH on stroke-related neuronal death and neuroinflammation. The effects of ischemic outcome were dependent on duration of the IH exposure prior to MCAO; there was a significant reduction in stroke-induced infarct size after 11 days of IH exposure and 3 days of Air exposure following MCAO relative to Air/Air exposure. Likewise, interleukin (IL)-6 mRNA expression in the ipsilateral hemisphere was significantly reduced among mice exposed to 11 days of IH/Air relative to Air/Air mice. However, the protective effects of IH were no longer apparent among mice exposed to 20 days of IH prior to MCAO. Together, these data suggest that the protective effects of acute IH may be associated with reduced post-stroke proinflammatory cytokine expression; additionally, IH loses its protective quality following chronic exposure, such as might be experienced by people with obstructive sleep apnea. OSA occurs more frequently in postmenopausal than premenopausal women and the severity of OSA increase after menopause. Gonadal hormones can influence brain and behavior; testosterone and estrogens in particular can enhance spatial learning and memory. In Chapter 4, I hypothesized that estrogens may protect mice from IH-induced hippocampal morphological and behavioral changes. I exposed intact or gonadectomized male and female mice to room air or IH for 30 days. Ovariectomy paired with IH treatment, impaired spatial learning and memory compared to all other female groups. Intact male mice exposed to IH impaired learning and memory compared to male mice exposed to room air. Learning and memory changes in female mice were mirrored by changes in basilar dendritic length of the CA1 region of the hippocampus. In Chapter 5, I examined the effects of dihydrotestosterone (DHT), a non-aromatizable androgen, on learning and memory performance in female mice. Ovariectomized mice with DHT capsules were protected from IH-induced spatial learning and memory deficits following 30 days of treatment. IH combined with other factors like, light at night and hormone removal produce behavior more consistent with OSA symptoms. When assessing individuals with OSA it is important to consider their environment, age, sex, and hormonal status.