Cumulative Childhood Lead Levels in Relation to Sleep During Adolescence.

STUDY OBJECTIVES: Lead exposure has been linked to adverse cognitive outcomes among children, and sleep disturbances could potentially mediate these relationships. As a first step, whether childhood lead levels are linked to sleep disturbances must be ascertained. Prior studies of lead and sleep are scarce and rely on parent-reported sleep data. METHODS: The study population included 395 participants from the Early Life Exposure in Mexico to Environmental Toxicants project, a group of sequentially enrolled birth cohorts from Mexico City. Blood lead levels measured from ages 1 to 4 years were used to calculate a cumulative measure of early childhood lead levels. Average sleep duration, sleep fragmentation, and movement index were assessed once between the ages of 9 and 18 years with wrist actigraphs worn for a continuous 7-day interval. Linear regression models were fit with average sleep duration, fragmentation, or movement as the outcome and cumulative lead levels divided into quartiles as the exposure, adjusted for age, sex, and maternal education. RESULTS: Mean (standard deviation) age at follow-up was 13.8 (1.9) years, and 48% of participants were boys. Median (interquartile range) cumulative childhood lead level was 13.7 (10.8, 18.0) µg/dL. Patients in the highest quartile of the cumulative childhood lead group had on average 23 minutes less sleep than those in the first quartile in adolescence (95% confidence interval [7, 39]; P, trend = .02). Higher cumulative lead level was associated with higher sleep fragmentation in younger adolescents (younger than 14 years) only (P, interaction = .02). CONCLUSIONS: Shorter sleep duration may represent an as-yet unrecognized adverse consequence of lead exposure in youth.

The erythrocyte membrane stability is associated with sleep time and social jetlag in shift workers.

The osmotic stability of the erythrocyte membrane (OSEM) has been associated with changes in lipid profile, blood glucose and blood pressure. Changes in these parameters are very frequent in shift workers, possibly because of the lack of synchronization of biological rhythms, which results in the social jetlag. However, the existence of association between OSEM and circadian misalignment has not been investigated in this population. Therefore, this study investigated whether shift work, sleep time and social jetlag (SJL) are associated with biochemical and hematological variables. A population consisting of 79 men working at night (n = 37) or during the day (n = 42), aged between 21 and 65 years and with a mean BMI of 27.56 ± 4.0 kg/m2, was investigated cross-sectionally in relation to sleep time, SJL, anthropometric (height, weight and waist circumference) and blood variables, with emphasis on the OSEM. SJL was calculated by the absolute difference between the midpoint of sleep on work and rest days. The Generalized Linear Model (GzLM) was used to investigate the existence of associations between SJL and average sleep time in relation to the analyzed variables. Workers without SJL presented lower baseline lysis values of erythrocytes in isotonic medium in relation to workers with SJL. In addition, workers who slept on average less than 6 hours had higher OSEM, and higher total and LDL-cholesterol in relation to those who slept more than 6 hours, regardless of the shift. It is possible that the association of sleep deprivation and SJL with erythrocyte membrane stability is mediated through changes in the lipid profile.

Adiponectin levels and sleep deprivation in patients with endocrine metabolic disorders.

BACKGROUND: Sleep abnormalities are frequent in patients with endocrine metabolic disorders (EMD) such as arterial hypertension, diabetes and obesity. Adiponectin is a peptide largely secreted by adipocytes and has various properties e.g. anti-inflammatory, antioxidant, antiatherogenic, pro-angiogenic, vasoprotective and insulin-sensitizing. Adiponectin inversely relates to body weight and when its concentration decreases, the resistin concentration increases resulting in greater insulin resistance. OBJECTIVE: The objective of this study is to examine factors influencing adiponectin levels in a population with EMD. METHODS: This was a cross-sectional evaluation of 332 patients (18 to 80y) presenting arterial hypertension, pre-diabetes, diabetes, and/or obesity. Investigation included clinical evaluation of comorbidities, general blood tests and adiponectin measures (ELISA). Chronic sleep deprivation was determined if habitual sleep was <6 hours >4 days/week. RESULTS: Arterial hypertension (78.5%), type-2 diabetes (82.3%), and overweight (45.0%)/obesity (38.8%) were frequent. Patients with type-2 diabetes tended to have more chronic sleep deprivation (p=0.05). Adiponectin levels increased with age and were inversely correlated with sagittal abdominal diameter (p=0.04) and fasting insulin (p=0.001). Chronic sleep deprivation was associated with higher adiponectin concentration [OR=1.34; CI=1.13-1.58; p<0.005] and this was maintained after adjustment for gender, age, body mass index, menopause, arterial hypertension, American Diabetes Association classification and physical exercise levels [OR=1.38; 0=1.14-1.66: p=0.001]. CONCLUSION: In patients with EMD, adiponectin is influenced not only by obesity but also by age and sleep deprivation. The latter finding may be explained by a compensatory effect or a counter regulation to minimize the harmful effects of sleep deprivation.

Adiponectin levels and sleep deprivation in patients with endocrine metabolic disorders

SUMMARY BACKGROUND: Sleep abnormalities are frequent in patients with endocrine metabolic disorders (EMD) such as arterial hypertension, diabetes and obesity. Adiponectin is a peptide largely secreted by adipocytes and has various properties e.g. anti-inflammatory, antioxidant, antiatherogenic, pro-angiogenic, vasoprotective and insulin-sensitizing. Adiponectin inversely relates to body weight and when its concentration decreases, the resistin concentration increases resulting in greater insulin resistance. OBJECTIVE: The objective of this study is to examine factors influencing adiponectin levels in a population with EMD. METHODS: This was a cross-sectional evaluation of 332 patients (18 to 80y) presenting arterial hypertension, pre-diabetes, diabetes, and/or obesity. Investigation included clinical evaluation of comorbidities, general blood tests and adiponectin measures (ELISA). Chronic sleep deprivation was determined if habitual sleep was <6 hours >4 days/week. RESULTS: Arterial hypertension (78.5%), type-2 diabetes (82.3%), and overweight (45.0%)/obesity (38.8%) were frequent. Patients with type-2 diabetes tended to have more chronic sleep deprivation (p=0.05). Adiponectin levels increased with age and were inversely correlated with sagittal abdominal diameter (p=0.04) and fasting insulin (p=0.001). Chronic sleep deprivation was associated with higher adiponectin concentration [OR=1.34; CI=1.13-1.58; p<0.005] and this was maintained after adjustment for gender, age, body mass index, menopause, arterial hypertension, American Diabetes Association classification and physical exercise levels [OR=1.38; 0=1.14-1.66: p=0.001]. CONCLUSION: In patients with EMD, adiponectin is influenced not only by obesity but also by age and sleep deprivation. The latter finding may be explained by a compensatory effect or a counter regulation to minimize the harmful effects of sleep deprivation.

RESUMO INTRODUÇÃO: Problemas de sono são frequentes em pacientes com distúrbios endócrino-metabólicos (DEM), como hipertensão arterial, diabetes e obesidade. A adiponectina é um peptídeo segregado por adipócitos e apresenta diversas propriedades, como por exemplo, anti-inflamatória, antioxidante, antiaterogênica, pró-angiogênica e vasoprotetora. A adiponectina relaciona-se inversamente com o peso corporal. OBJETIVO: Examinar os fatores que influenciam os níveis de adiponectina em uma população com DEM. MÉTODOS: Trata-se de uma avaliação transversal com 332 pacientes (18 a 80 anos) apresentando hipertensão arterial, pré-diabetes, diabetes e/ou obesidade. A investigação incluiu avaliação clínica de comorbidades, exames de sangue e medidas de adiponectina (Elisa). A restrição crônica do sono foi determinada com o sono habitual <6 horas >4 dias/semana. RESULTADOS: Doenças como hipertensão arterial (78,5%), diabetes tipo 2 (82,3%) e sobrepeso (45,0%)/obesidade (38,8%) foram frequentes. Pacientes com diabetes tipo 2 apresentaram uma tendência na restrição crônica do sono (p=0,05). Os níveis de adiponectina aumentaram com a idade e foram inversamente correlacionados com o diâmetro abdominal sagital (p=0,04) e com a insulina em jejum (p=0,001). A restrição crônica do sono foi associada à maior concentração de adiponectina [OR=1,34; CI=1,13-1,58; p<0,005] e isso foi mantido após ajuste por gênero, idade, índice de massa corporal, menopausa, hipertensão arterial, classificação dos níveis da American Diabetes Association e exercício físico [OR=1,38; CI=1,14-1,66: p=0,001]. CONCLUSÕES: Em pacientes com DEM, a adiponectina é influenciada não apenas pela obesidade, mas também pela idade e pela restrição de sono. O último achado pode ser explicado por um efeito compensatório ou por um regulamento contrário para minimizar os efeitos nocivos da restrição do sono.

Chronic REM Sleep Restriction in Juvenile Male Rats Induces Anxiety-Like Behavior and Alters Monoamine Systems in the Amygdala and Hippocampus.

Adolescence is marked by major physiological changes, including those in the sleep-wake cycle, such as phase delay, which may result in reduced sleep hours. Sleep restriction and/or deprivation in adult rats activate stress response and seem to be a risk factor for triggering emotional disorders. In the present study, we sought to evaluate the behavioral and neurobiological consequences of prolonged REM sleep restriction in juvenile male rats. Immediately after weaning, on postnatal day 21, three males from each litter were submitted to REM sleep deprivation and the other three animals were maintained in their home-cages. REM sleep restriction (REMSR) was accomplished by placing the animals in the modified multiple platform method for 18 h and 6 h in the home-cage, where they could sleep freely; the sleep restriction lasted 21 consecutive days, during which all animals were measured and weighed every 3 days. After the end of this period, all animals were allowed to sleep freely for 2 days, and then the behavioral tests were performed for evaluation of depressive and anxiety-like profiles (sucrose negative contrast test and elevated plus maze, EPM). Blood sampling was performed 5 min before and 30 and 60 min after the EPM for determination of corticosterone plasma levels. The adrenals were weighed and brains collected and dissected for monoamine levels and receptor protein expression. REMSR impaired the physical development of adolescents, persisting for a further week. Animals submitted to REMSR exhibited higher basal corticosterone levels and a greater anxiety index in the EPM, characteristic of an anxious profile. These animals also exhibited higher noradrenaline levels in the amygdala and ventral hippocampus, without any change in the expression of ß1-adrenergic receptors, as well as higher serotonin and reduced turnover in the dorsal hippocampus, with diminished expression of 5-HT1A. Finally, greater concentration of BDNF was observed in the dorsal hippocampus in chronically sleep-restricted animals. Chronic REMSR during puberty impaired physical development and induced anxiety-like behavior, attributed to increased noradrenaline and serotonin levels in the amygdala and hippocampus.

Serum Amyloid A Production Is Triggered by Sleep Deprivation in Mice and Humans: Is That the Link between Sleep Loss and Associated Comorbidities?

Serum amyloid A (SAA) was recently associated with metabolic endotoxemia, obesity and insulin resistance. Concurrently, insufficient sleep adversely affects metabolic health and is an independent predisposing factor for obesity and insulin resistance. In this study we investigated whether sleep loss modulates SAA production. The serum SAA concentration increased in C57BL/6 mice subjected to sleep restriction (SR) for 15 days or to paradoxical sleep deprivation (PSD) for 72 h. Sleep restriction also induced the upregulation of Saa1.1/Saa2.1 mRNA levels in the liver and Saa3 mRNA levels in adipose tissue. SAA levels returned to the basal range after 24 h in paradoxical sleep rebound (PSR). Metabolic endotoxemia was also a finding in SR. Increased plasma levels of SAA were also observed in healthy human volunteers subjected to two nights of total sleep deprivation (Total SD), returning to basal levels after one night of recovery. The observed increase in SAA levels may be part of the initial biochemical alterations caused by sleep deprivation, with potential to drive deleterious conditions such as metabolic endotoxemia and weight gain.

Paradoxical Sleep Deprivation Causes Cardiac Dysfunction and the Impairment Is Attenuated by Resistance Training.

BACKGROUND: Paradoxical sleep deprivation activates the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis, subsequently interfering with the cardiovascular system. The beneficial effects of resistance training are related to hemodynamic, metabolic and hormonal homeostasis. We hypothesized that resistance training can prevent the cardiac remodeling and dysfunction caused by paradoxical sleep deprivation. METHODS: Male Wistar rats were distributed into four groups: control (C), resistance training (RT), paradoxical sleep deprivation for 96 hours (PSD96) and both resistance training and sleep deprivation (RT/PSD96). Doppler echocardiograms, hemodynamics measurements, cardiac histomorphometry, hormonal profile and molecular analysis were evaluated. RESULTS: Compared to the C group, PSD96 group had a higher left ventricular systolic pressure, heart rate and left atrium index. In contrast, the left ventricle systolic area and the left ventricle cavity diameter were reduced in the PSD96 group. Hypertrophy and fibrosis were also observed. Along with these alterations, reduced levels of serum testosterone and insulin-like growth factor-1 (IGF-1), as well as increased corticosterone and angiotensin II, were observed in the PSD96 group. Prophylactic resistance training attenuated most of these changes, except angiotensin II, fibrosis, heart rate and concentric remodeling of left ventricle, confirmed by the increased of NFATc3 and GATA-4, proteins involved in the pathologic cardiac hypertrophy pathway. CONCLUSIONS: Resistance training effectively attenuates cardiac dysfunction and hormonal imbalance induced by paradoxical sleep deprivation.

Sleep restriction reduces the survival time and aggravates the neurological dysfunction and memory impairments in an animal model of cerebral hypoperfusion.

Cerebral blood flow is associated with the cerebrovascular prognosis. Sleep restriction (SR) may be a limiting factor of the prognosis after a cerebrovascular event, impairing the neurological recovery. We aimed to investigate the effects of SR on mortality rate and on behavioral and histological parameters of animals submitted to permanent cerebral hypoperfusion. Sixty male Wistar rats were distributed in 4 groups, according to the protocol of common carotid artery occlusion (CCAO) and SR: nSR+nCCAO, SR+nCCAO, nSR+CCAO, and SR+CCAO. The groups SR+nCCAO and SR+CCAO were submitted to SR during 10 days. The cerebral hypoperfusion was induced by the permanent CCAO. Neurological function and memory were assessed over 14 days of cerebral hypoperfusion. Analysis of neuropathological alterations were performed in the CA1 region of hippocampus. The mortality rate was 40% in the nSR+CCAO and SR+CCAO groups. SR significantly reduced the survival time of animals submitted to CCAO. After 7 and 14 days of cerebral hypoperfusion, 11% and 33% of the nSR+CCAO and SR+CCAO animals showed severe neurological dysfunction, respectively. A significant association between a high frequency of memory impairments with the group SR+CCAO was observed. The neuropathological alterations in CA1 region of hippocampus were similar among the groups. SR potentiates the negative effects of cerebral hypoperfusion conditions, suggesting that SR could be a factor associated with a worse prognosis after a cerebrovascular event.

Effects of different periods of paradoxical sleep deprivation and sleep recovery on lipid and glucose metabolism and appetite hormones in rats.

Sleep has a fundamental role in the regulation of energy balance, and it is an essential and natural process whose precise impacts on health and disease have not yet been fully elucidated. The aim of this study was to assess the consequences of different periods of paradoxical sleep deprivation (PSD) and recovery from PSD on lipid profile, oral glucose tolerance test (OGTT) results, and changes in insulin, corticosterone, ghrelin, and leptin concentrations. Three-month-old male Wistar rats weighing 250-350 g were submitted to 24, 96, or 192 h of PSD or 192 h of PSD with 480 h of recovery. The PSD was induced by the multiple platforms method. Subsequently, the animals were submitted to an OGTT. One day later, the animals were killed and the levels of triglycerides, total cholesterol, lipoproteins (low-density lipoprotein, very-low-density lipoprotein, and high-density lipoprotein), insulin, ghrelin, leptin, and corticosterone in plasma were quantified. There was a progressive decrease in body weight with increasing duration of PSD. The PSD induced basal hypoglycemia over all time periods evaluated. Evaluation of areas under the curve revealed progressive hypoglycemia only after 96 and 192 h of PSD. There was an increase in corticosterone levels after 192 h of PSD. We conclude that PSD induces alterations in metabolism that are reversed after a recovery period of 20 days.

Sex-related effects of sleep deprivation on depressive- and anxiety-like behaviors in mice.

Anxiety and depressive symptoms are generated after paradoxical sleep deprivation (PSD). However, it is not clear whether PSD produces differential effects between females and males. The aim of this study was to assess the effect of PSD on anxiety- and depressive-like behaviors between sexes. Male and female BALB/c mice were divided in three groups: the control group, the 48-h PSD group and the 96-h PSD group. Immediately after PSD protocols, the forced swimming and open field test were applied. Sucrose consumption test was used to evaluate the middle-term effect of PSD. We found that corticosterone serum levels showed significant differences in the 96-h PSD females as compared to 96-h PSD males. In the open-field test, the 48-h and 96-h PSD females spent more time at the periphery of the field, and showed high locomotion as compared to males. In the elevated plus maze, the 48-h PSD females spent more time in closed arms than males, which is compatible with anxiety-like behavior. The forced swim test indicated that the 96-h PSD males spent more time swimming as compared to the 96-h PSD females. Remarkably, the 96-h PSD males had lower sucrose intake than the 96-h PSD females, which suggest that male mice have proclivity to develop a persistent depressive-like behavior late after PSD. In conclusion, male mice showed a significant trend to depressive-like behaviors late after sleep deprivation. Conversely, female have a strong tendency to display anxiety- and depressive-like behaviors immediately after sleep deprivation.

Could BDNF be involved in compensatory mechanisms to maintain cognitive performance despite acute sleep deprivation? An exploratory study.

BACKGROUND: Neuroimaging studies suggest that acute sleep deprivation can lead to adaptations, such as compensatory recruitment of cerebral structures, to maintain cognitive performance despite sleep loss. However, the understanding of the neurochemical alterations related to these adaptations remains incomplete. OBJECTIVE: Investigate BDNF levels, cognitive performance and their relations in healthy subjects after acute sleep deprivation. METHODS: Nineteen sleep deprived (22.11±3.21years) and twenty control (25.10±4.42years) subjects completed depression, anxiety and sleep quality questionnaires. Sleep deprived group spent a full night awake performing different playful activities to keep themselves from sleeping. Attention, response inhibition capacity and working memory (prefrontal cortex-dependent) were assessed with Stroop and Digit Span tests. Declarative memory (hippocampus-dependent) was assessed with Logical Memory test. Serum BDNF was measured by sandwich ELISA. Data were analyzed with independent samples T-test, ANOVA, ANCOVA and curve estimation regressions. p<0.05 was deemed statistically significant. RESULTS: The sleep deprived group showed higher BDNF levels and normal performance on attention, response inhibition capacity and working memory. However, declarative memory was impaired. A sigmoidal relation between BDNF and Stroop Test scores was found. CONCLUSIONS: Increased BDNF could be related, at least in part, to the maintenance of normal prefrontal cognitive functions after sleep deprivation. This potential relation should be further investigated.

Impairment of male reproductive function after sleep deprivation.

OBJECTIVE: To evaluate the influence of sleep loss on sexual behavior, hormone levels, sperm parameters, and testis-specific gene expression in male rats. DESIGN: Experimental research. SETTING: Animal laboratory. ANIMAL(S): Male adult Wistar-Hannover rats. INTERVENTION(S): Sexually experienced rats were subjected to paradoxic sleep deprivation (PSD) for 96 hours or sleep restriction (SR) for 21 days or kept in their home cage as control (CTRL). MAIN OUTCOME MEASURE(S): Sexual behavior, hormone levels, sperm parameters and expression of stress and nitric oxide-related genes were evaluated. RESULT(S): PSD significantly decreased sexual behavior compared with the CTRL group, whereas SR had no effect. The PSD group had significantly lower testosterone levels than the CTRL group. Both PSD and SR groups had lower sperm viabilities than the CTRL group. The decrease in the number of live sperm compared with the CTRL group was larger in the PSD group than in the SR group. Regarding testicular gene expression, both PSD and SR led to an increase of iNOS and hydroxysteroid 11ß-dehydrogenase 1 expressions compared with the CTRL group. These changes were more pronounced in the PSD group. A significant increase in endothelial nitric oxide synthase expression was observed in the PSD groups compared with the CTRL group. No changes were observed in dimethylarginine dimethylaminohydrolase 1 and casein kinase 2ß-polypeptide expressions. CONCLUSION(S): Sleep loss can promote marked changes in the male reproductive system of rats, particularly affecting spermatic function in part by interfering in the testicular nitric oxide pathway.

Sleep deprivation alters thyroid hormone economy in rats.

NEW FINDINGS: What is the central question of this study? The relationship between the thyroid system and sleep deprivation has seldom been assessed in the literature, and mounting evidence exists that sleep disturbances influence human lifestyles. The aim of this study was to investigate the hypothalamic-pituitary-thyroid axis and thyroid hormone metabolism in sleep-deprived and sleep-restricted rats. What is the main finding and its importance? Central hypothyroidism and high thyroxine (T4 ) to 3,5,3'-triiodothyronine (T3 ) activation in brown adipose tissue were observed following sleep deprivation. Sleep-restricted rats exhibited normal thyroid-stimulating hormone and T4 concentrations despite increased circulating T3 . Sleep recovery for 24 h did not normalize the high T3 concentrations, suggesting that high T3 is a powerful counterregulatory mechanism activated following sleep deprivation. Modern life has shortened sleep time, and the consequences of sleep deprivation have been examined in both human subjects and animal models. As the relationship between thyroid function and sleep deprivation has not been fully investigated, the aim of this study was to assess the hypothalamic-pituitary-thyroid axis and thyroid hormone metabolism following paradoxical sleep deprivation (PSD) and sleep restriction (SR) in rats. The effects of a 24 h rebound period were also studied. Male Wistar rats (200-250 g, n = 10 per group) were subjected to sleep deprivation via the modified multiple platform method. Rats were assigned to the following seven groups: control, PSD for 24 or 96 h, 24 or 96 h of sleep deprivation with rebound (PSD24R and PSD96R), SR for 21 days (SR21) and SR21 with rebound (SR21R). Blood samples were collected to determine the 3,5,3'-triiodothyronine (T3 ), thyroxine (T4 ) and thyroid-stimulating hormone concentrations. Brown adipose tissue iodothyronine deiodinase type 2 (D2) activity was also evaluated. Body weight gain was dramatically reduced (by ∼50-100%) in all sleep-deprived and sleep-restricted rats; rebound restored this parameter in only the PSD24R group. The serum TSH and T4 concentrations decreased, whereas T3 increased in both the PSD24 and PSD96 groups compared with control animals (P < 0.05). Only PSD24R and PSD96R normalized T4 and thyroid-stimulating hormone concentrations, respectively, independently of the higher circulating T3 concentrations (∼20-30%) noted in all groups compared with control animals (P < 0.05). Brown adipose tissue D2 activity increased in the PSD 24 and 96 h groups (∼10 times), and PSD24R was more effective than PSD96R at restoring basal brown adipose tissue D2 activity. Our data suggest that thyroid hormone metabolism adapts to sleep deprivation-induced hypothalamic-pituitary-thyroid alterations and increases T4 to T3 activation peripherally, thereby increasing circulating T3 in rats.

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.

Short-term sleep deprivation reinstates memory retrieval in mice: the role of corticosterone secretion.

While the effects of sleep deprivation (SD) on the acquisition and consolidation phases of memory have been extensively characterized, its effects on memory retrieval remain overlooked. SD alone is a stressor, and stress-activated glucocorticoids promote bimodal effects on memory. Because we have recently demonstrated that 72h SD impairs memory retrieval in the plus-maze discriminative avoidance task (PM-DAT) in mice, this study investigated whether shorter SD periods would facilitate retrieval. In Experiment I, the temporal forgetting curve of the PM-DAT was determined and an interval between training/testing in which retrieval was no longer present was used in all subsequent experiments. In Experiments II and III, retrieval performance and corticosterone concentration, respectively, were quantified in mice that were sleep deprived for 12 or 24h before testing. In Experiments IV and V, the effects of the corticosterone synthesis inhibitor metyrapone were evaluated on 12h SD-induced retrieval reinstatement and corticosterone concentration enhancement, respectively. Experiment VI determined whether pre-test acute administration of exogenous corticosterone would mimic the facilitatory effects of 12h SD on retrieval. Thirty days after training, mice presented poor performance of the task; however, SD for 12h (but not for 24) before testing reinstated memory retrieval. This facilitatory effect was accompanied by increased corticosterone concentration, abolished by metyrapone, and mimicked by pre-test acute corticosterone administration. Collectively, short-term SD can facilitate memory retrieval by enhancing corticosterone secretion. This facilitatory effect is abolished by longer periods of SD.

More than hormones: sex differences in cardiovascular parameters after sleep loss in rats.

Although the influence of sex on sleep pattern and cardiovascular parameters is well known, knowledge regarding the effects of sleep loss on heart responses in both sexes is scarce. The present study investigated the effects of paradoxical sleep deprivation (PSD) and chronic sleep restriction (SR) on cardiovascular parameters and adrenocorticotropic hormone (ACTH) levels in male and female rats. Both groups were randomly assigned to PSD for 96 h, SR for 21 days or home-cage control. Mean arterial pressure (MAP), heart rate (HR), baroreflex sensitivity (bradycardia and tachycardia responses) and ACTH levels were evaluated. The results showed that PSD induced a significant increase in HR and ACTH levels in both sexes, although male rats presented higher levels of ACTH hormone compared to females. In addition to sex-specific responses, PSD decreased the tachycardia only in male rats. SR, induced a significant increase in MAP and decrease in bradycardia in both sexes. Male rats were more affected by sleep deprivation protocols than females for MAP, bradycardia response, and ACTH levels. The results showed that the effects of sleep loss on cardiovascular parameters are associated with the protocol of sleep deprivation and that sex can modulate these effects. We suggested this experimental model as a suitable tool for further investigations of the relationship between cardiovascular parameters and sleep.

Sleep loss and cytokines levels in an experimental model of psoriasis.

Up to 80% of people develop a cutaneous condition closely connected to their exposure to stressful life events. Psoriasis is a chronic recurrent inflammatory skin disorder with multifactorial etiology, including genetic background, environmental factors, and immune system disturbances with a strong cytokine component. Moreover, psoriasis is variably associated with sleep disturbance and sleep deprivation. This study evaluated the influence of sleep loss in the context of an animal model of psoriasis by measuring cytokine and stress-related hormone levels. Male adult Balb/C mice with or without psoriasis were subjected to 48 h of selective paradoxical sleep deprivation (PSD). Sleep deprivation potentiated the activities of kallikrein-5 and kallikrein-7 in the skin of psoriatic groups. Also, mice with psoriasis had significant increases in specific pro-inflammatory cytokines (IL-1ß, IL-6 and IL-12) and decreases in the anti-inflammatory cytokine (IL-10) after PSD, which were normalized after 48 h of sleep rebound. Linear regression showed that IL-2, IL-6 and IL-12 levels predicted 66% of corticosterone levels, which were selectively increased in psoriasis mice subject to PSD. Kallikrein-5 was also correlated with pro-inflammatory cytokines, explaining 58% of IL-6 and IL-12 variability. These data suggest that sleep deprivation plays an important role in the exacerbation of psoriasis through modulation of the immune system in the epidermal barrier. Thus, sleep loss should be considered a risk factor for the development of psoriasis.

Sleep deprivation alters rat ventral prostate morphology, leading to glandular atrophy: a microscopic study contrasted with the hormonal assays.

We investigated the effect of 96 h paradoxical sleep deprivation (PSD) and 21-day sleep restriction (SR) on prostate morphology using stereological assays in male rats. After euthanasia, the rat ventral prostate was removed, weighed, and prepared for conventional light microscopy. Microscopic analysis of the prostate reveals that morphology of this gland was altered after 96 h of PSD and 21 days of SR, with the most important alterations occurring in the epithelium and stroma in the course of both procedures compared with the control group. Both 96 h PSD and 21-day SR rats showed lower serum testosterone and higher corticosterone levels than control rats. The significance of our result referring to the sleep deprivation was responsible for deep morphological alterations in ventral prostate tissue, like to castration microscopic modifications. This result is due to the marked alterations in hormonal status caused by PSD and SR.

Influence of food restriction on lipid profile and spontaneous glucose levels in male rats subjected to paradoxical sleep deprivation.

OBJECTIVES: The purpose of this study was to determine the paired consequences of food restriction and paradoxical sleep deprivation on lipid profile and spontaneous glucose levels in male rats. METHOD: Food restriction began at weaning, with 6 g of food being provided per day, which was subsequently increased by 1 g per week until reaching 15 g per day by the eighth week. At adulthood, both rats subjected to food restriction and those fed ad libitum were exposed to paradoxical sleep deprivation for 96 h or were maintained in their home-cage groups. RESULTS: Animals subjected to food restriction exhibited a significant increase in high-density lipoprotein levels compared to animals that were given free access to food. After the paradoxical sleep deprivation period, the food-restricted animals demonstrated reduced concentrations of high-density lipoprotein relative to their respective controls, although the values for the food-restricted animals after sleep deprivation were still higher than those for the ad libitum group. The concentration of low-density lipoproteins was significantly increased in sleep-deprived animals fed the ad libitum diet. The levels of triglycerides, very low-density lipoproteins, and glucose in food-restricted animals were each decreased compared to both ad libitum groups. CONCLUSION: These results may help to illustrate the mechanisms underlying the relationship between sleep curtailment and metabolism and may suggest that, regardless of sleep deprivation, dietary restriction can minimize alterations in parameters related to cardiovascular risk.

Bone marrow and peripheral white blood cells number is affected by sleep deprivation in a murine experimental model.

Sleep deficit and related disorders are becoming increasingly prevalent in modern life and an extensive literature has documented that acute or chronic sleep deprivation can lead to several physiological consequences. Here, we evaluated the effects of sleep deprivation on hematopoietic composition of either bone marrow or peripheral blood. Mice were subjected to paradoxical sleep deprivation (PSD) for 72 h by modified multiple platform method, with or without an additional sleep recovery (SR) period of 10 days. PSD decreased total cellularity of the bone marrow and peripheral blood concomitantly. Subsequent analysis of cell composition showed that absolute number of hematopoietic stem/progenitor cells and colony-forming units was decreased. Moreover, the absolute number of granulocytes and monocytes in bone marrow was reduced in PSD group. These alterations were paralleled by an accumulation of neutrophils and monocytes in peripheral blood. PSD also induced lymphopenia in the circulation. To the best of our knowledge, this is the first study that demonstrates the importance of sleep on the hematopoietic microenvironment and provides new insights into the relationship between sleep and the immune system.