Paradoxical sleep deprivation increases glutamine synthetase in rat brain.

The modifications of glutamine synthetase (GS) level, an enzyme mainly located in astrocytes, were investigated in rat after paradoxical sleep deprivation and during recovery. An immunotitration method was used to evaluate the relative level of GS in brain tissue. At the end of a 24 hrs. paradoxical sleep deprivation, a significant increase in GS level was observed both in the frontoparietal cortex and the locus coeruleus area. 4 hrs. later, during recovery, the GS level returned to control level in the cortex but was lower in the locus coeruleus area.     

Microwave effects on energy metabolism of rat brain

Rat brain was exposed to 591-MHz, continuous-wave (CW) microwaves at 13.8 or 5.0 mW/cm² to determine the effect on nicotinamide adenine dinucleotide, reduced (NADH), adenosine triphosphate (ATP) and creatine phosphate (CP) levels. On initiation of the in vivo microwave exposures, fluorimetrically determined NADH rapidly increased to a maximum of 4.0%–12.5% above pre-exposure control levels at one-half minute, then decreased slowly to 2% above control at three minutes, finally increasing slowly to 5% above control level at five minutes. ATP and CP assays were performed on sham- and microwave-exposed brain at each exposure time. At 13.8 mW/cm², brain CP level was decreased an average of 39.4%, 41.1%, 18.2%, 13.1%, and 36.4% of control at exposure points one-half, one, two three, and five minutes, respectively, and brain ATP concentration was decreased an average of 25.2%, 15.2%, 17.8%, 7.4%, and 11.2% of control at the corresponding exposure periods. ATP and CP levels of rat brain exposed to 591-MHz cw microwaves at 5 mW/cm² for one-half and one minute were decreased significantly below control levels at these exposure times, but were not significantly different from the 13.8 mW/cm² exposures. For all exposures, rectal temperature remained constant. Heat loss through the skull aperture caused brain temperature to decrease during the five-minute exposures. This decrease was the same in magnitude for experimental and control subjects. Changes in NADH, ATP, and CP levels during microwave exposure cannot be attributed to general tissue hyperthermia. The data support the hypothesis that microwave exposure inhibits mitochondrial electron transport chain function, which results in decreased ATP and CP levels in brain.     

Paradoxical sleep deprivation, stress and emotionality in the rat

88 adult male rats were divided into 9 groups. Group I and II served as controls. The rats of group III were repeatedly aroused during 4 days at the very onset of each paradoxical sleep period by direct MRF stimulation. This deprivation reduced the daily amount of paradoxical sleep by 70%, while the slow wave sleep was reduced by 10% only. In group IV, the animals were given food and water for one hour a day only. Groups V and VI were subjected to immobilization and cold stress, respectively. Groups VII, VIII and IX were deprived of paradoxical sleep on platforms of 15, 11 and 6.5 cm in diameter, respectively. Stress was estimated by the classical Selye's triad: weight of adrenals and thymus and gastric ulceration. Emotionality was measured in the open field and also by self-stimulation of the lateral hypothalamus. Neither emotional behaviour disturbances nor stress features were found after paradoxical sleep deprivation in the group III. Moreover, this deprivation induced a slight, though significant, reduction in adrenals weight. Also, no changes in emotional behaviour were noted in the stress-exposed group V and VI. Only the interplay between REM-sleep deprivation and stress on the platforms in groups VII, VIII and especially IX led to a considerable shift in emotionality.     

Enzymes of adenosine metabolism in the brain: diurnal rhythm and the effect of sleep deprivation

Adenosine plays a role in promoting sleep, an effect that is thought to be mediated in the basal forebrain. Adenosine levels vary in this region with prolonged wakefulness in a unique way. The basis for this is unknown. We examined, in rats, the activity of the major metabolic enzymes for adenosine - adenosine deaminase, adenosine kinase, ecto- and cytosolic 5'-nucleotidase - in sleep/wake regulatory regions as well as cerebral cortex, and how the activity varies across the day and with sleep deprivation. There were robust spatial differences for the activity of adenosine deaminase, adenosine kinase, and cytosolic and ecto-5'-nucleotidase. However, the basal forebrain was not different from other sleep/wake regulatory regions apart from the tuberomammillary nucleus. All adenosine metabolic enzymes exhibited diurnal variations in their activity, albeit not in all brain regions. Activity of adenosine deaminase increased during the active period in the ventrolateral pre-optic area but decreased significantly in the basal forebrain. Enzymatic activity of adenosine kinase and cytosolic-5'-nucleotidase was higher during the active period in all brain regions tested. However, the activity of ecto-5'-nucleotidase was augmented during the active period only in the cerebral cortex. This diurnal variation may play a role in the regulation of adenosine in relationship to sleep and wakefulness across the day. In contrast, we found no changes specifically with sleep deprivation in the activity of any enzyme in any brain region. Thus, changes in adenosine with sleep deprivation are not a consequence of alterations in adenosine enzyme activity.     

长期异相睡眠剥夺对大鼠能量代谢及血清甲状腺素水平的影响

目的：探讨长期异相睡眠剥夺对大鼠能量代谢及血清甲状腺素水平的影响。方法：采用小平台水环境法建立长期异相睡眠剥夺大鼠模型;检测其能量代谢变化;放射免疫法检测血清中甲状腺素水平。结果：睡眠剥夺后大鼠摄食量由（75.06±25.37）g/（d.kg）增加到（122.30±20.43）g/（d.kg）,体重由（360.89±43.01）g减轻到（295.97±37.95）g,体温由（37.62±1.12）℃先升高到（39.00±0.87）℃后又降低至（37.72±0.84）℃,基础代谢率由（1.69±0.36）mlO2/（g.h）增加到（2.40±0.09）mlO2/（g.h）与对照组相比差异显著（P〈0.05）;血清中游离三碘甲状腺原氨酸（FT3）水平由（3.38±0.88）pmol/L降低到（2.38±0.83）pmol/L,游离甲状腺素（FT4）由（14.62±3.62）pmol/L降低到（8.26±2.80）pmol/L与对照组相比差异显著（P〈0.05）。结论：长期异相睡眠剥夺可以显著影响大鼠的能量代谢和血清甲状腺素水平。     

Galanin-like peptide in the brain: effects on feeding, energy metabolism and reproduction

The hypothalamus plays an important role in the regulation of feeding behavior, energy metabolism and reproduction. A novel peptide containing 60 amino acid peptide and a non-amidated C-terminus is produced in the hypothalamic arcuate nucleus (ARC) and has been named galanin-like peptide (GALP) on the basis of a portion of this peptide being homologous with galanin. It acts in the central nervous system (CNS), where it is involved in the regulation of feeding behavior. GALP-producing neurons make neuronal networks with several feeding related peptide-producing neurons. Since GALP is involved in the control of food intake and energy balance, it is possible that it plays an important role in the development of obesity. Furthermore, GALP regulates plasma lateral hypothalamus (LH) levels via the activation of gonadotropin-releasing hormone (GnRH)-producing neurons, suggesting that GALP is active in the reproductive system. Thus, interesting findings on the roles of GALP have made across a number of physiological systems. This review will attempt to summarize the research carried out to date on these areas. Because GALP may be involved in feeding behavior, energy metabolism and reproduction, further studies on the morphology and function of GALP-containing neurons in the CNS should increase our understanding of the role of GALP in brain function.     

Glucocorticoids influence brain glycogen levels during sleep deprivation

We investigated whether glucocorticoids [i.e., corticosterone (Cort) in rats] released during sleep deprivation (SD) affect regional brain glycogen stores in 34-day-old Long-Evans rats. Adrenalectomized (with Cort replacement; Adx+) and intact animals were sleep deprived for 6 h beginning at lights on and then immediately killed by microwave irradiation. Brain and liver glycogen and glucose and plasma glucose levels were measured. After SD in intact animals, glycogen levels decreased in the cerebellum and hippocampus but not in the cortex or brain stem. By contrast, glycogen levels in the cortex of Adx+ rats increased by 43% (P < 0.001) after SD, while other regions were unaffected. Also in Adx+ animals, glucose levels were decreased by an average of 28% throughout the brain after SD. Intact sleep-deprived rats had elevations of circulating Cort, blood, and liver glucose that were absent in intact control and Adx+ animals. Different responses between brain structures after SD may be due to regional variability in metabolic rate or glycogen metabolism. Our findings suggest that the elevated glucocorticoid secretion during SD causes brain glycogenolysis in response to energy demands.     

Temperature effects on energy metabolism: a dynamic system analysis.

Q(10) factors are widely used as indicators of the magnitude of temperature-induced changes in physico-chemical and physiological rates. However, there is a long-standing debate concerning the extent to which Q(10) values can be used to derive conclusions about energy metabolism regulatory control. The main point of this disagreement is whether or not it is fair to use concepts derived from molecular theory in the integrative physiological responses of living organisms. We address this debate using a dynamic systems theory, and analyse the behaviour of a model at the organismal level. It is shown that typical Q(10) values cannot be used unambiguously to deduce metabolic rate regulatory control. Analytical constraints emerge due to the more formal and precise equation used to compute Q(10), derived from a reference system composed from the metabolic rate and the Q(10). Such an equation has more than one unknown variable and thus is unsolvable. This problem disappears only if the Q(10) is assumed to be a known parameter. Therefore, it is concluded that typical Q(10) calculations are inappropriate for addressing questions about the regulatory control of a metabolism unless the Q(10) values are considered to be true parameters whose values are known beforehand. We offer mathematical tools to analyse the regulatory control of a metabolism for those who are willing to accept such an assumption.     

Human brain glycogen content and metabolism: implications on its role in brain energy metabolism

The adult brain relies on glucose for its energy needs and stores it in the form of glycogen, primarily in astrocytes. Animal and culture studies indicate that brain glycogen may support neuronal function when the glucose supply from the blood is inadequate and/or during neuronal activation. However, the concentration of glycogen and rates of its metabolism in the human brain are unknown. We used in vivo localized 13C-NMR spectroscopy to measure glycogen content and turnover in the human brain. Nine healthy volunteers received intravenous infusions of [1-(13)C]glucose for durations ranging from 6 to 50 h, and brain glycogen labeling and washout were measured in the occipital lobe for up to 84 h. The labeling kinetics suggest that turnover is the main mechanism of label incorporation into brain glycogen. Upon fitting a model of glycogen metabolism to the time courses of newly synthesized glycogen, human brain glycogen content was estimated at approximately 3.5 micromol/g, i.e., three- to fourfold higher than free glucose at euglycemia. Turnover of bulk brain glycogen occurred at a rate of 0.16 micromol.g-1.h-1, implying that complete turnover requires 3-5 days. Twenty minutes of visual stimulation (n=5) did not result in detectable glycogen utilization in the visual cortex, as judged from similar [13C]glycogen levels before and after stimulation. We conclude that the brain stores a substantial amount of glycogen relative to free glucose and metabolizes this store very slowly under normal physiology.     

Rapid eye movement (rem) sleep deprivation: effect on acid mucopolysaccharides in rat brain.

The effect of rapid eye movement (REM) sleep deprivation on the total content and proportion of different mucopolysaccharides (AMPS) containing uronic acid in rat brain was studied. REM sleep deprivation was induced by the water tank methods. Five experimental groups of animals were used: control, stressed, REM sleep deprived, post-stress sleeping and post-deprivation sleeping rats. No changes of AMPS were observed in any of the experimental groups when the whole brain was analysed. A significant increase of AMPS was found in the cerebral hemispheres of stressed and REM deprived rats. A significant decrease of AMPS was observed in the cerebellum and brain stem. A further increase of AMPS was found in the cerebral hemispheres after the rebound of REM sleep following its deprivation, and after the recovery sleep following the stress. A significant increase of AMPS was found in the brain stem of rats allowed to recuperate after REM deprivation or stress as compared with the stressed and REM deprived animals. Recovery sleep induced a significant increase of AMPS in the cerebellum in previously stressed rats, while previously REM deprived rats exhibited a further decrease of AMPS from control values. The possible functional meaning of these results is discussed in relation to the role of REM sleep in protein synthesis and learning and memory processes. Intriguing, well-controlled positive findings and the fact that no experimental design is known where stress is minimal while REM deprivation is 100 per cent, justify and encourage continued efforts in studying the biochemical state of the brain during sleep and/or its alterations.     

Paradoxical effects of copper and manganese on brain mitochondrial function

Defects in the mitochondrial genome have been associated with Parkinson's and Alzheimer's disease, and apoptosis can be triggered by the presence of energetically compromised mitochondria. Thus, in this study we have examined whether the divalent cations Cu2+ and Mn2+ could influence mitochondrial function in vitro. Mitochondrial electron transport was dose and time dependently reduced by Cu2+ to a greater extent with succinate as a substrate. Following a 60 min preincubation period, Mn2+ dose dependently inhibited electron transport to a greater extent with lactate and malate. In contrast, paradoxical effects were seen following a 5 min preincubation period with Mn2+. Cu2+ dose-dependently reduced NADH-dependent lactate dehydrogenase (LDH) activity, with almost complete inhibition apparent at 10 microM. An initial induction of LDH by 10 microM Mn2+ was partially reversed by higher concentrations of the metal. Cu2+ dose-dependently reduced flavin adenine dinucleotide (FAD)-dependent monoamine oxidase A (MAO-A) activity in a time-independent manner, with an IC50 value approximately 20 microM, whereas Mn2+ had no effect. In conclusion, it is proposed that Cu2+ and Mn2+ have differential effects on nicotinamide adenine dinucleotide (NAD) and FAD-dependent mitochondrial enzymes at the level of the essential cofactors. Cu2+ appears to exert an inhibitory effect on both NAD and FAD-dependent enzymes, but predominantly against the latter, including MAO-A and succinate dehydrogenase. The complex responses to Mn2+ may be due to dose-related effects on the interconversion of NAD and NADH and reversible enzymatic reactions employing this nucleotide cofactor.     

Aging worsens the effects of sleep deprivation on postural control

Falls increase with age and cause significant injuries in the elderly. This study aimed to determine whether age modulates the interactions between sleep deprivation and postural control and to evaluate how attention influences these interactions in the elderly. Fifteen young (24±2.7 y.o.) and 15 older adults (64±3.2 y.o.) stood still on a force plate after a night of sleep and after total sleep deprivation. Center of pressure range and velocity were measured with eyes open and with eyes closed while participants performed an interference task, a control task, and no cognitive task. Sleep deprivation increased the antero-posterior range of center of pressure in both age groups and center of pressure speed in older participants only. In elderly participants, the destabilizing effects of sleep deprivation were more pronounced with eyes closed. The interference task did not alter postural control beyond the destabilization induced by sleep loss in older subjects. It was concluded that sleep loss has greater destabilizing effects on postural control in older than in younger participants, and may therefore increase the risk of falls in the elderly.     

Effect of sleep deprivation on cholesterol metabolism and triglyceridaemia in male volunteers

The effect of 5-day sleep deprivation (SD) on cholesterol metabolism, together with triglyceridaemia, was studied in seven healthy male volunteers. A 3-day control period was followed by 5 days (120 h) complete SD and 4 days recovery. Blood was collected at 9 a.m. and at 9 p.m. Vastus lateralis muscle biopsy was performed during the control period, on the 5th day of SD, and on day 3 of recovery. The value of muscle cholesterol was related to the non-collagen protein content. The plasma triglycerides (TG) varied in a circadian biorhythm, the amplitude of which declined gradually during SD. The morning triglyceridaemia was significantly decreased on days 3-5 of SD (35%-79% of initial values). On days 4 and 5 of SD, plasma cholesterol fell significantly to 78% and 88% of control values, respectively. The ratio of its esterified to unesterified fractions remained unchanged throughout SD. Basal activity of lecithin cholesterol acyltransferase (LCAT) showed no diurnal biorhythm; on the last 2 days of SD, LCAT activity fell significantly to 71%-80%. In contrast, the decrease in fractional esterification rate (FER) was insignificant. In the vastus lateralis muscle, total cholesterol (TC) was decreased by 40% at the end of SD, the reduction being greater for cholesterol esters (CE) (by 63%) than for free cholesterol (FC) (by 36%). The relative proportion of CE significantly decreased from an initial 14.7% to 9.2% on the last day of SD. During recovery after SD, plasma cholesterol and TG slowly returned to normal. LCAT activity and FER recovered quickly, within 48 h.(ABSTRACT TRUNCATED AT 250 WORDS)