The Puzzle of Decreased Homeostatic Slow Wave Sleep in Aging
Year: 2012
Type: dissertation
Abstract: Slow wave sleep is the most important part of sleep, yet it decreases with aging. Staying awake puts pressure on the neurons of the brain s arousal systems, e.g. on the cortically projecting neurons of the basal forebrain. During wakefulness, these neurons are active and excite the cortex, thereby enhancing behavioral arousal. Sleep quality and duration are compromised with increasing age. Elderly people often experience these symptoms as sleep problems and contact medical professionals. Treatment of the condition is difficult without basic knowledge of the natural course of sleep changes during aging. Sleep is regulated by two main processes: the circadian process, which defines the time when to sleep, and the homeostatic process, which defines how much sleep is needed. Changes in the circadian system with aging have been studied more extensively than changes in sleep homeostasis. Homeostatic processes couple changes in wake duration and quality to changes in slow wave sleep. Sleep pressure accumulates in the course of waking and induces sleep. Increases in basal forebrain neuronal activity during prolonged waking will increase sleep pressure through site-specific accumulation of the sleep-inducing molecules nitric oxide and adenosine. Simultaneously, progressive use-dependent changes in cortical plasticity lead to a net increase in synaptic weight, as reflected in the increased expression of synaptic molecules such as the brain-derived neurotrophic factor. Slow wave sleep serves to downscale the synaptic strength to a sustainable level, this way reducing sleep pressure. The aim of this thesis was to find out whether the homeostatic slow wave sleep response decreases with age and if so, why. We also investigated the molecular mechanisms involved in such a decrease. Specifically, we studied what aging does to the active wake and sleep pressure underlying the slow wave sleep response, and whether this response can be experimentally restored. We found that both the high cortical EEG theta power (7-9 Hz) and the basal forebrain neuronal activity, as assessed by lactate release, decrease with age, suggesting that the decrease in slow wave sleep is partly due to age-related changes in wake quality and cortical arousal. Aging also decreased the build-up of sleep pressure, as indicated by the less pronounced increase in the basal forebrain nitric oxide and adenosine concentrations and in also the cortical brain-derived neurotrophic factor expression, which all correlate with the intensity of slow wave sleep. Sleep latency, which decreases with increasing sleep pressure, was less reduced in the aged following prolonged waking, which further suggests a lower sleep pressure in the aged. Finally, experimental stimulation of the basal forebrain neurons by the glutamate receptor agonist N-Methyl-D-aspartate in aged subjects failed to increase active wake, and experimental inhibition of the neurons by nitric oxide failed to increase slow wave sleep. Both results indicate a reduced sensitivity of the aged brain to the effects of sleep pressure-inducing molecules. Together, the results show that the reduction of the slow wave sleep response with aging is due to a reduced sleep need, reflecting cellular and molecular changes in the aged brain.
Source: Työväentutkimus Vuosikirja
Author: Kirsi-Marja Rytkönen
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1514179409