Elsevier

Metabolism

Volume 55, Supplement 2, October 2006, Pages S20-S23
Metabolism

Sleep deprivation as a neurobiologic and physiologic stressor: allostasis and allostatic load

https://doi.org/10.1016/j.metabol.2006.07.008Get rights and content

Abstract

Sleep has important homeostatic functions, and sleep deprivation is a stressor that has consequences for the brain, as well as many body systems. Whether sleep deprivation is due to anxiety, depression, or a hectic lifestyle, there are consequences of chronic sleep deprivation that impair brain functions and contribute to allostatic load throughout the body. Allostatic load refers to the cumulative wear and tear on body systems caused by too much stress and/or inefficient management of the systems that promote adaptation through allostasis. Chronic sleep deprivation in young healthy volunteers has been reported to increase appetite and energy expenditure, increase levels of proinflammatory cytokines, decrease parasympathetic and increase sympathetic tone, increase blood pressure, increase evening cortisol levels, as well as elevate insulin and blood glucose. Repeated stress in animal models causes brain regions involved in memory and emotions, such as hippocampus, amygdala, and prefrontal cortex, to undergo structural remodeling with the result that memory is impaired and anxiety and aggression are increased. Structural and functional magnetic resonance imaging studies in depression and Cushing's disease, as well as anxiety disorders, provide evidence that the human brain may be similarly affected. Moreover, brain regions such as the hippocampus are sensitive to glucose and insulin, and both type 1 and type 2 diabetes mellitus are associated with cognitive impairment and (for type 2 diabetes mellitus) increased risk for Alzheimer's disease. Animal models of chronic sleep deprivation indicate that memory is impaired along with depletion of glycogen stores and increases in oxidative stress and free radical production. Taken together, these changes in brain and body are further evidence that sleep deprivation is a chronic stressor and that the resulting allostatic load can contribute to cognitive problems, which can, in turn, further exacerbate pathways that lead to disease.

Introduction

From the personal experience of sleep deprivation and then subsequently “getting a good night's sleep,” there can be little doubt that sleep plays a role in maintaining a good mood and cognitive acuity, as well as in promoting physiologic balance and resilience. These impressions are supported by studies of endocrine function and metabolism, as well as from investigations of sleep deprivation effects on cognitive and neural function. This includes research on the brain that shows a variety of substantial changes resulting from sleep restriction, with reversal after recovery sleep. This article reviews selected aspects of the current state of knowledge in this area and then evaluates what is known using the model of allostasis and allostatic load, which emphasizes the “wear and tear” on the brain and body from coping with stress.

Section snippets

Allostasis and allostatic overload

The maintenance of homeostasis is an active process that requires the output of mediators such as those of the autonomic nervous system, and the neuroendocrine and immune systems.

This process is called “allostasis,” or “maintaining homeostasis through change” [1], [2], [3]. The mediators of allostasis work as a nonlinear network (Fig. 1), meaning that too much or too little of each mediator can have harmful consequences by perturbing the entire network. This is because the mediators

Metabolic and hormonal responses to sleep deprivation

Sleep deprivation produces an allostatic overload that can have deleterious consequences. Sleep restriction to 4 hours of sleep per night increases blood pressure, decreases parasympathetic tone, increases evening cortisol and insulin levels, and promotes increased appetite, possibly through the elevation of ghrelin, a pro-appetitive hormone, and decrease in levels of leptin [15], [16], [17]. Proinflammatory cytokine levels are increased, along with performance in tests of psychomotor

Neural responses to sleep deprivation

The brain is the master regulator of the neuroendocrine, autonomic, and immune systems, along with behaviors that contribute to unhealthy or healthy lifestyles, which, in turn, influence the physiologic processes of allostasis [1]. Alterations in brain function by chronic stress can therefore have direct and indirect effects on the cumulative allostatic overload. Allostatic overload resulting from chronic stress in animal models causes atrophy of neurons in the hippocampus and prefrontal

Interpretation

Sleep deprivation studies in animals have involved radically different methods ranging from the flower pot or treadmill to the use of novelty or gentle stimulation for shorter time intervals. In spite of these different methods, which differ in the amount of physical stress, locomotor activity, and other variables, there is a consistent pattern of results for cognitive function, namely, impairment of learning and retention. For the brain, measures of proinflammatory cytokines have shown an

Conclusions

Sleep is believed to be a neural state during which consolidation of declarative memories are taking place [40]. Sleep deprivation, even for the course of the active period of the day, increases the homeostatic drive to sleep, with resulting changes in proinflammatory cytokines and glycogen levels. Moreover, relatively brief deprivation of sleep promotes an exacerbation of these processes with progressively more severe physiologic, neurobiologic, and behavioral consequences as the sleep

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