Effects of chronic sleep fragmentation on wake-active neurons and the hypercapnic arousal response.

STUDY OBJECTIVES: Delayed hypercapnic arousals may occur in obstructive sleep apnea. The impaired arousal response is expected to promote more pronounced oxyhemoglobin desaturations. We hypothesized that long-term sleep fragmentation (SF) results in injury to or dysfunction of wake-active neurons that manifests, in part, as a delayed hypercapnic arousal response. DESIGN: Adult male mice were implanted for behavioral state recordings and randomly assigned to 4 weeks of either orbital platform SF (SF4wk, 30 events/h) or control conditions (Ct4wk) prior to behavioral, histological, and locus coeruleus (LC) whole cell electrophysiological evaluations. MEASUREMENTS AND RESULTS: SF was successfully achieved across the 4 week study, as evidenced by a persistently increased arousal index, P < 0.01 and shortened sleep bouts, P < 0.05, while total sleep/wake times and plasma corticosterone levels were unaffected. A multiple sleep latency test performed at the onset of the dark period showed a reduced latency to sleep in SF4wk mice (P < 0.05). The hypercapnic arousal latency was increased, Ct4wk 64 ± 5 sec vs. SF4wk 154 ± 6 sec, P < 0.001, and remained elevated after a 2 week recovery (101 ± 4 sec, P < 0.001). C-fos activation in noradrenergic, orexinergic, histaminergic, and cholinergic wake-active neurons was reduced in response to hypercapnia (P < 0.05-0.001). Catecholaminergic and orexinergic projections into the cingulate cortex were also reduced in SF4wk (P < 0.01). In addition, SF4wk resulted in impaired LC neuron excitability (P < 0.01). CONCLUSIONS: Four weeks of sleep fragmentation (SF4wk) impairs arousal responses to hypercapnia, reduces wake neuron projections and locus coeruleus neuronal excitability, supporting the concepts that some effects of sleep fragmentation may contribute to impaired arousal responses in sleep apnea, which may not reverse immediately with therapy.

Daytime sleepiness in obesity: mechanisms beyond obstructive sleep apnea--a review.

Increasing numbers of overweight children and adults are presenting to sleep medicine clinics for evaluation and treatment of sleepiness. Sleepiness negatively affects quality of life, mental health, productivity, and safety. Thus, it is essential to comprehensively address all potential causes of sleepiness. While many obese individuals presenting with hypersomnolence will be diagnosed with obstructive sleep apnea and their sleepiness will improve with effective therapy for sleep apnea, a significant proportion of patients will continue to have hypersomnolence. Clinical studies demonstrate that obesity without sleep apnea is also associated with a higher prevalence of hypersomnolence and that bariatric surgery can markedly improve hypersomnolence before resolution of obstructive sleep apnea. High fat diet in both humans and animals is associated with hypersomnolence. This review critically examines the relationships between sleepiness, feeding, obesity, and sleep apnea and then discusses the hormonal, metabolic, and inflammatory mechanisms potentially contributing to hypersomnolence in obesity, independent of sleep apnea and other established causes of excessive daytime sleepiness.

Review of sleep disorders.

Sleep disorders are common and may result in significant morbidity. Examples of the major sleep disturbances in primary care practice include insomnia; sleep-disordered breathing, such as obstructive sleep apnea; central nervous system hypersomnias, including narcolepsy; circadian rhythm sleep disturbances; parasomnias, such as REM sleep behavior disorder; and sleep-related movement disorders, including restless legs syndrome. Diagnosis is based on meticulous inventory of the clinical history and careful physical examination. In some cases referral to a sleep laboratory for further evaluation with polysomnography, a sleep study, is indicated.