FUNCTIONAL CONSEQUENCES OF SUSTAINED SLEEP-DEPRIVATION IN THE RAT

Sleep deprivation disrupts vital biological processes that are necessa ry for cognitive ability and physical health, but the physiological ch anges that underlie these outward effects are largely unknown. The pur pose of the present studies in the laboratory rat is to prolong sleep deprivation to delineate the pathophysiology and to determine its medi ation. In the rat, the course of prolonged sleep deprivation has a syn dromic nature and eventuates in a life-threatening state. An early and central symptom of sleep deprivation is a progressive increase in per ipheral energy expenditure to nearly double normal levels. An attempt to alleviate this negative energy balance by feeding rats a balanced d iet that is high in its efficiency of utilization prolongs survival an d attenuates or delays development of malnutrition-like symptoms, indi cating that several symptoms can be manipulated to some extent by ener gy and nutrient consumption. Most changes in neuroendocrine parameters appear to be responses to metabolic demands, such as increased plasma catecholamines indicating sympathetic activation. Plasma total thyroi d hormones, however, decline to severely low levels; a metabolic compl ication that is associated with other sleep deprivation-induced sympto ms, such as a decline in body temperature to hypothermic levels despit e increased energy expenditure. Metabolic mapping of the brain reveale d a dissociation between the energy metabolism of the brain and that o f the body. Sleep deprivation's effects on cerebral structures are het erogenous and unidirectional toward decreased functional activity. The hypometabolic brain structures are concentrated in the hypothalamus, thalamus and limbic system, whereas few regions in the rest of the bra in and none in the medulla, are affected. Correspondence can be found between some of the affected cerebral structures and several of the pe ripheral symptoms, such as hyperphagia and possible heat retention pro blems. The factor predisposing to mortality is a decreased resistance to infection. Lethal opportunistic organisms are permitted to infect t he bloodstream, which presumably results in a cascade of toxic-like re actions. Host defense is thus the first system to fail. There is neith er fever nor marked tissue inflammatory reactions typical of infectiou s disease states, suggesting that sleep deprivation is immunosuppressi ve. Each of the four major abnormalities identified-(1) a deep negativ e energy balance and associated malnutrition; (2) heterogeneous decrea ses in cerebral function; (3) low thyroid hormone concentrations; and (4) decreased resistance to infection-can be viewed as having an early origin during the sleep deprivation process to signify the foremost p athogenic situation to which the other abnormalities might be secondar ily related. The findings therefore remain somewhat equivocal for a un itary function for sleep, but can support putative roles for sleep in thermoregulation, energy conservation, immune system integrity and tis sue restoration.