Impact of Bariatric Surgery on Circulating Metabolites and Cognitive Performance.

INTRODUCTION: Bariatric surgery is an effective intervention to reduce obesity and improve associated comorbidities. However, its effects on cognitive function are still the subject of debate. Given that the bioavailability of circulating metabolites can influence brain metabolism and cognitive performance, we aimed to assess the effects of bariatric surgery on plasma metabolic profiles and cognitive performance. METHODS: We recruited 26 women undergoing gastric bypass surgery. We conducted anthropometric assessments and collected plasma samples for metabolomic analysis. A set of 4 cognitive tests were used to evaluate cognitive performance. Participants were reevaluated 1 year post-surgery. RESULTS: After surgery, attention capacity and executive function were improved, while immediate memory had deteriorated. Regarding metabolic profile, reduction of beta-tocopherol and increase of serine, glutamic acid, butanoic acid, and glycolic acid were observed. To better understand the relationship between cognitive function and metabolites, a cluster analysis was conducted to identify more homogeneous subgroups based on the cognitive performance. We identified cluster 1, which did not show changes in cognitive performance after surgery, and cluster 2, which showed improved attention and executive function, but reduced performance in the immediate memory test. Thus, cluster 2 was more homogeneous group that replicated the results of non-clustered subjects. Analysis of the metabolic profile of cluster 2 confirmed serine, glutamic acid, and glycolic acid as potential metabolites associated with cognitive performance. CONCLUSIONS: Metabolites identified in this study have potential for biomarkers and alternative therapeutic target to prevent obesity-related cognitive decline. KEY POINTS: • Attention capacity and executive function were improved 12 months post bariatric surgery. • Immediate memory was worsened 12 months post bariatric surgery. • Serine, glutamic acid, and glycolic acid are potential metabolites linked to the alteration of cognitive performance.

Effect of Testosterone on the Thyroarytenoid Muscle and Lamina Propria of Female Rat Vocal Folds.

OBJECTIVE: To analyze the effects of androgen therapy on the thyroarytenoid (TA) muscle, expression of androgen receptors (ARs) and hyaluronic acid (HA) concentration in the vocal folds (VFs) of adult female rats. METHODS: Twenty-one adult female Wistar rats were divided into experimental and control groups. The experimental group received weekly intramuscular injections of nandrolone decanoate for 9 weeks. Following euthanasia and dissection of the VFs, histomorphometric analysis of the TA muscle, immunohistochemical evaluation of ARs, and measurement of HA concentration using the ELISA-like fluorimetric method were performed. RESULTS: The experimental group exhibited a significantly larger mean fiber cross-sectional area in the TA muscle compared to the control group (434.3 ± 68.6 µm2 versus 305.7 ± 110.1 µm2; p = 0.029), indicating muscle hypertrophy. There was no significant difference in the number of muscle fibers. The experimental group showed higher expression of ARs in the lamina propria (62.0% ± 30.3% versus 22.0% ± 22.8%; p = 0.046) and in the TA muscle (45.0% ± 22.6% versus 18.3% ± 9.8%; p = 0.024). There was no significant difference in the concentration of HA. CONCLUSION: Exposure of adult female rats to androgen therapy resulted in hypertrophy of the TA muscle and increased expression of ARs in the VFs. The TA muscle seems to be the primary target of testosterone action in the VF, and the up-regulation of ARs might contribute to the persistent deepening of the voice. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2316-2321, 2024.

Beneficial Short-Term Effects of Bariatric Surgery on Nutritional Inflammatory Profile and Metabolic Biomarkers.

PURPOSE: Bariatric surgery (BS) has several potential metabolic benefits. However, little is known about its impact on changes in the inflammatory potential of diet and its effect on inflammatory and metabolic markers. This study aimed to assess the short-term beneficial effects of BS on dietary inflammatory potential and inflammatory and metabolic markers. MATERIALS AND METHODS: Participants (n = 20) were evaluated 3 months before and after BS. Body mass, body mass index, anthropometric measurements, fat mass, fat-free mass, visceral fat, skeletal muscle mass, basal metabolic rate, serum lipids, HOMA-IR, QUICKI and inflammatory markers, including leptin, adiponectin, adiponectin/leptin ratio and plasminogen activator inhibitor-1 (PAI-1), were evaluated. Diet data were collected using a 3-day diet record and the dietary inflammatory index (DII®) and energy-adjusted dietary inflammatory index (E-DIITM) scores were computed. RESULTS: There was a reduction in DII® (2.56 vs 2.13) and E-DIITM (2.18 vs 0.45) indicating an improvement in inflammatory nutritional profile. Moreover, there were increases in the adiponectin/leptin ratio (0.08 vs 0.21) and QUICKI scores (0.31 vs 0.37), and reductions in leptin (36.66 vs 11.41 ng/ml) and HOMA-IR scores (3.93 vs 1.50). There were also improvements in body composition and anthropometric parameters. CONCLUSIONS: BS promotes changes in metabolic profile, inflammatory state and food intake and these modifications appeared to be associated with improvements in diet-related inflammation, an increase in the adiponectin/leptin ratio and a reduction in leptin. These results contribute to knowledge on the contribution bariatric surgery can make to the treatment of obesity and the reduction of related comorbidities.

Sleep deprivation modulates APOE and LDL receptor-related protein 1 through thyroid hormone T4 and impairs Aß clearance in hippocampus of rats.

Alzheimer's disease is the most common form of dementia. One of its pathological hallmarks is Aß accumulation, which is influenced by APOE genotype and expression, as well as by sleep homeostasis. However, conflicting mechanisms for APOE roles in Aß clearance have been reported, and the relationship between APOE and sleep also remains unclear. In this study, we aimed to investigate how hormonal alteration caused by sleep deprivation affects APOE and its receptors in rats, and to evaluate the role of different cell types in Aß clearance. Paradoxical sleep deprivation for 96 h increased Aß level in hippocampus with concomitant reduction of APOE and LRP1 at the time point within the resting period. Sleep deprivation also significantly reduced T4 levels in both active and resting times. To evaluate the effect of T4 variation, C6 glial cells and primary brain endothelial cells were treated with T4. High T4 level (300 ng/mL) increased APOE, but reduced LRP1 and LDL-R in C6 cells, while in primary endothelial cells, LDL-R levels were increased. Treatment of C6 cells with exogenous APOE reduced LRP1 and Aß uptake. These results suggest that T4 modulates LRP1 and LDL-R in both cell types, but in the opposite manner, thus, sleep deprivation might modify the ratio of the receptors in blood-brain barrier and glial cells by altering T4 levels. Considering that LRP1 and LDL-R are important for Aß clearance, sleep deprivation might also affect the degree of participation of glia in Aß clearance, and consequently, turnover of Aß in the brain.

Severe Obesity in Women Can Lead to Worse Memory Function and Iron Dyshomeostasis Compared to Lower Grade Obesity.

Objective: Obesity is one of the modifiable risk factors for dementia. Insulin resistance, the abundance of advanced glycated end-products, and inflammation are some of the mechanisms associated with the lower cognitive performance observed in obesity. This study aims to evaluate the cognitive function of subjects with distinct degrees of obesity, comparing class I and II obesity (OBI/II) to class III obesity (OBIII), and to investigate metabolic markers that can distinguish OBIII from OBI/II. Study Design. This is a cross-sectional study, in which 45 females with BMI varying from 32.8 to 51.9 kg/m2 completed a set of 4 cognitive tests (verbal paired-associate test, stroop color, digit span, and Toulouse-Pieron cancellation test) and their plasma metabolites, enzymes, and hormones related to glycemia, dyslipidemia, and liver function, as well as the biomarkers of iron status, were concomitantly analyzed. Results: OBIII showed lower scores in the verbal paired-associate test compared to OBI/II. In other cognitive tests, both groups showed similar performance. OBIII presented a lower iron status compared to OBI/II based on total iron binding capacity, degree of transferrin saturation, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin. The levels of indicators for glycemia, liver function, and lipid metabolism were similar in both groups. Analysis of plasma metabolites showed that OBIII had lower levels of pyroglutamic acid, myoinositol, and aspartic acid and higher levels of D-ribose than OBI/II. Conclusion: Iron is an essential micronutrient for several metabolic pathways. Thus, iron dyshomeostasis observed in severe obesity may aggravate the cognitive impairment by altering metabolic homeostasis and enhancing oxidative stress. These findings can contribute to searching for biomarkers that indicate cognitive performance in the population with obesity.

Paradoxical sleep deprivation induces tissue changes in the parotid gland of rats.

PURPOSE: This study aimed to evaluate if paradoxical sleep deprivation induces some tissue changes in the parotid gland of rats. METHODS: A total of 24 male Wistar rats were distributed into the following groups, as follows: Group 1-Control (CTRL; n = 8); Group 2-Sleep deprivation (PS; n = 8): the animals were submitted to Paradoxical Sleep deprivation for 96 h and Group 3-Recovery (R; n = 8): the animals were submitted to sleep loss for 96 h, followed by a period of 96 h without any intervention. The following parameters were evaluated: microscopic analysis, immunohistochemistry for Caspase-3, Ki-67, and COX-2 and gene expression of cytochrome C, TNF-α, and Interleukins 6, 10. RESULTS: The results pointed out acinar atrophy, and the presence of cytoplasmic vacuoles in the parenchyma of the experimental groups. In the same groups, there was differential expression of interleukins 6, 10 and TNF-α. Apoptosis was also increased by means of cleaved caspase 3 expression. The cellular proliferation (ki-67 expression) was increased the R group. CONCLUSION: Taken together, sleep deprivation induces tissue degeneration, inflammatory process, as well as activate apoptosis in the parotid gland of rats.

Inflammatory activity and apoptosis are associated with tissue degeneration in the submandibular gland of rats submitted to paradoxical sleep deprivation.

The aim of this study was to evaluate if paradoxical sleep deprivation is able to induce tissue degeneration, inflammatory activity and apoptosis in the submandibular gland of rats. A total of 24 male Wistar rats were distributed into the following groups: group 1-control (CTRL; n = 8): the animals were not submitted to any procedures; group 2-sleep deprivation (PS; n = 8): the animals were submitted to paradoxical sleep deprivation for 96 h and group 3-recovery (R; n = 8): the animals were submitted to sleep deprivation for 96 h, followed by a period of 96 h without any intervention. The following parameters were evaluated: histopathological analysis, immunohistochemistry for Ki-67, COX-2 and cleaved caspase-3 and gene expression of TNF-α, Interleukin 6 (IL-6), Interleukin 10 (IL-10) and cytochrome C by real-time PCR. The results pointed out cytoplasmic vacuoles and congested vessels in the parenchyma of submandibular gland the in PS and R groups. The expression of interleukins 6, 10 and TNF-ɑ was differentially expressed in the PS and R groups. Apoptosis was also triggered by means of increasing cleaved caspase-3 and cytochrome c expression. The cellular proliferation (Ki-67 index) was also positive in the R group. Taken together, our results demonstrate that sleep deprivation is capable of promoting tissue degeneration in the submandibular gland, as a result of inflammatory response and cellular death in rats.

High and fluctuating levels of ovarian hormones induce an anxiogenic effect, which can be modulated under stress conditions: Evidence from an assisted reproductive rodent model.

Elevated levels of endogenous ovarian hormones are conditions commonly experienced by women undergoing assisted reproductive technologies (ART). Additionally, infertility-associated stress and treatment routines are factors that together may have a highly negative impact on female emotionality, which can be aggravated when several cycles of ART are needed to attempt pregnancy. This study aimed to investigate the effect of high and fluctuating levels of gonadal hormones induced by repeated ovarian stimulation on the stress response in rodents. To mimic the context of ART, female rats were exposed to an unpredictable chronic mild stress (UCMS) paradigm for four weeks. During this time, three cycles of ovarian stimulation (superovulation) (150 IU/Kg of PMSG and 75 IU/Kg of hCG) were applied, with intervals of two estrous cycles between them. The rats were distributed into four groups: Repeated Superovulation/UCMS; Repeated Superovulation/No Stress; Saline/UCMS; and Saline/No Stress. Anxiety-like and depressive-like behaviors were evaluated in a light-dark transition box and by splash test, respectively. Corticosterone, estradiol, progesterone, and biometric parameters were assessed. Data were analyzed using a two-way Generalized Linear Model (GzLM). Our results showed that repeated ovarian stimulation exerts by itself an expressive anxiogenic effect. Surprisingly, when high and fluctuating levels of ovarian hormones were combined with chronic stress, anxiety-like behavior was no longer observed, and a depressive-like state was not detected. Our findings suggest that females subjected to emotional overload induced by repeated ovarian stimulation and chronic stress seem to trigger the elaboration of adaptive coping strategies.

Histopathological changes and oxidative damage in type I and type II muscle fibers in rats undergoing paradoxical sleep deprivation.

BACKGROUND: previous studies have shown that muscle atrophy is observed after sleep deprivation (SD) protocols; however, the mechanisms responsible are not fully understood. Muscle trophism can be modulated by several factors, including energy balance (positive or negative), nutritional status, oxidative stress, the level of physical activity, and disuse. The metabolic differences that exist in different types of muscle fiber may also be the result of different adaptive responses. To better understand these mechanisms, we evaluated markers of oxidative damage and histopathological changes in different types of muscle fibers in sleep-deprived rats. METHODS: Twenty male Wistar EPM-1 rats were randomly allocated in two groups: a control group (CTL group; n = 10) and a sleep deprived group (SD group; n = 10). The SD group was submitted to continuous paradoxical SD for 96  h; the soleus (type I fibers) and plantar (type II fiber) muscles were analyzed for histopathological changes, trophism, lysosomal activity, and oxidative damage. Oxidative damage was assessed by lipid peroxidation and nuclear labeling of 8-OHdG. RESULTS: The data demonstrated that SD increased the nuclear labeling of 8-OHdG and induced histopathological changes in both muscles, being more evident in the soleus muscle. In the type I fibers there was signs of tissue degeneration, inflammatory infiltrate and tissue edema. Muscle atrophy was observed in both muscles. The concentration of malondialdehyde, and cathepsin L activity only increased in type I fibers after SD. CONCLUSION: These data indicate that the histopathological changes observed after 96 h of SD in the skeletal muscle occur by different processes, according to the type of muscle fiber, with muscles predominantly composed of type I fibers undergoing greater oxidative damage and catabolic activity, as evidenced by a larger increase in 8-OHdG labeling, lipid peroxidation, and lysosomal activity.

Sleep Deprivation Interferes with JAK/STAT Signaling Pathway and Myogenesis in the Masseter Muscle of Rats.

OBJECTIVES: The aim of the study was to study the Janus kinase/tyrosine kinase-activated transduction factor (JAK/STAT) signaling pathway and myogenesis on the masseter muscle after sleep deprivation and to investigate the role of stress in this scenario. SUBJECTS AND METHODS: A total of 18 male Wistar rats were divided into the following groups: control (n = 6): animals were not submitted to any procedures, and paradoxical sleep deprivation and vehicle (PSD + V; n = 6): animals were subjected to PSD for 96 h and (PSD + MET; n = 6): animals were subjected to PSD for 96 h with administration of metyrapone. Paradoxical sleep deprivation was performed by the modified multiple platforms method. Histopathological analysis, histomorphometry, and immunohistochemistry were performed. RESULTS: The results showed the presence of inflammatory infiltrate in the PSD + V and PSD + MET groups and atrophy. Histomorphometry showed that the cellular profile area decreased, while cellular density increased in both experimental groups. Expression of p-STAT 3, MyoD, and MyoG increased in the PSD + V group, while the PSD + MET group showed increased expression of IL-6 and p-STAT 3. CONCLUSION: Our results suggest that sleep deprivation induces an inflammatory response and atrophy in the masseter muscle of rats.

A single ovarian stimulation, as performed in assisted reproductive technologies, can modulate the anxiety-like behavior and neuronal activation in stress-related brain areas in rats.

Infertility affects about 8 to 12% of couples of childbearing age around the world, and is recognized as a global public health issue by the WHO. From a psychosocial perspective, infertile individuals experience intense psychological distress, related to emotional disorders, which have repercussions on marital and social relationships. The symptoms persist even after seeking specialized treatment, such as assisted reproductive technologies (ART). While the stress impact of ART outcome has been comprehensively studied, the role of supraphysiological concentrations of gonadal hormones on stress response, remains to be elucidated. This study aimed to evaluate the effect of a single ovarian stimulation on the stress response in rats. To mimic the context of ART in rodents, female rats were submitted to the superovulation (150 UI/kg of PMSG and 75 UI/kg of hCG) and then to psychogenic stress (restraint stress for 30 min/day, repeated for three days). Anxiety-like behavior was evaluated in the elevated plus-maze, and neuronal activation in the stress-related brain areas assessed by Fos protein immunoreactivity. Corticosterone, estradiol, progesterone and corpora lutea were quantified. Data were analyzed using Generalized Linear Model (GzLM). Our findings indicate anxiolytic-like and protective effects of supraphysiological concentrations of gonadal hormones induced by a single ovarian stimulation on stress response. An activation of hypothalamus-pituitary-adrenal response inhibitory pathways, with participation of the prefrontal cortex, basomedial amygdala, lateral septum, medial preoptic area, dorsomedial and paraventricular hypothalamus, was detected.

Effects of Sleep Deprivation on Acute Skeletal Muscle Recovery after Exercise.

PURPOSE: Sleep is considered essential for muscle recovery, mainly due to its effect on hormone secretion. Total sleep deprivation or restriction is known to alter not only blood hormones but also cytokines that might be related to skeletal muscle recovery. This study aimed to evaluate whether total sleep deprivation after eccentric exercise-induced muscle damage (EEIMD) modifies the profiles of blood hormones and cytokines. METHODS: In two separate conditions, with a crossover and randomized model, 10 men (age, 24.5 ± 2.9 yr; body mass index, 22.7 ± 2.3 kg·m) performed a unilateral EEIMD protocol that comprised 240 eccentric contractions of the knee extensor muscles using an isokinetic dynamometer. In one condition, a "muscle damage" protocol was followed by 48 h of total sleep deprivation and 12 h of normal sleep (DEPRIVATION). In the other condition, the same muscle damage protocol was conducted, followed by three nights of regular sleep (SLEEP). Isometric muscle voluntary contraction tests and blood samples were collected serially throughout the protocol and analyzed for creatine kinase, free and total testosterone, IGF-1, cortisol, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, receptor antagonist of IL-1 and IL-10. RESULTS: Muscle voluntary contraction and serum creatine kinase increased equally over the study period in both conditions. From the cytokines evaluated, only IL-6 increased in DEPRIVATION. No differences were detected in testosterone levels between conditions, but IGF-1, cortisol, and cortisol/total testosterone ratio were higher in DEPRIVATION. CONCLUSIONS: Total sleep deprivation after EEIMD does not delay muscle strength recovery but modifies inflammatory and hormonal responses.

Paradoxical sleep deprivation induces differential biological response in rat masticatory muscles: Inflammation, autophagy and myogenesis.

BACKGROUND: The aim of this study was to evaluate whether sleep deprivation (SD) induces inflammation, autophagy and myogenesis in the following masticatory muscles: masseter and temporal. METHODS: In this study, 18 animals were randomly distributed into three groups: control group (CTL, n = 6), SD for 96 hours (SD96, n = 6), and SD for 96 hours and more 96 hours of sleep recovery (SD96 + R, n = 6). RESULTS: In the histopathological analysis, SD 96 was able to induce inflammation in masseter and temporal. Nevertheless, the lack of inflammatory process was evidenced to the masseter in the group SD96 + R. Upregulation of TNF-alpha production was detected in the SD96 group, while SD96 + R decreased TNF immunoexpression for both skeletal muscles evaluated. MyoD and myogenin increased in rats submitted to SD96. By contrast, the levels of MyoD decreased in the group SD96 + R. Myogenin pointed out high immunoexpression in SD96 + R groups. In temporal, pAkt decreased in animals submitted to SD96, but it increased in the group SD96 + R. The levels of LC3 protein increased in both skeletal muscles studied, and masseter decreased LC3 protein expression in the SD96 + R. CONCLUSION: In summary, our results demonstrate that SD is able to induce inflammation, atrophy and myogenesis in rat masticatory muscles, being more intense in temporal when compared to masseter.

Physical activity as a moderator for obstructive sleep apnoea and cardiometabolic risk in the EPISONO study.

Obstructive sleep apnoea (OSA) is positively associated with cardiometabolic diseases; however, high levels of physical activity could decrease the incidence of OSA and associated comorbidities.In this study we aimed to examine the incidence of OSA in relation to physical activity, and its role as a protective factor in individuals with OSA on the incidence of cardiometabolic diseases, in an 8-9-year follow-up study. We analysed data of 658 volunteers from the São Paulo Epidemiologic Sleep Study (EPISONO), a cohort study of individuals aged 20-80 years, collected through polysomnography, the International Physical Activity Questionnaire and an assessment of cardiometabolic profile.Active subjects had a lower risk of developing OSA compared with nonactive subjects (relative risk 0.877, 95% CI 0.296-0.855) and there was a reduced risk of developing type 2 diabetes mellitus in active/apnoeic subjects (relative risk 0.493, 95% CI 0.252-0.961) compared with nonactive subjects. Metabolic equivalent was negatively associated to cardiometabolic markers, such as C-reactive protein (exp(B)=0.720; p=0.001), interleukin-6 (exp(B)=0.991; p=0.03), insulin (exp(B)=0.982; p=0.03), triglycerides (exp(B)=0.997; p<0.001), homeostasis model assessment for insulin resistance (exp(B)≤0.946; p<0.024), quantitative insulin sensitivity check index (exp(B)=992.4; p<0.001) and mean arterial pressure (exp(B)=0.987; p=0.001).Physical activity was a protective factor against type 2 diabetes mellitus in apnoeic individuals; moreover, being active reduced the risk of developing OSA and was associated with a better cardiometabolic profile.

Sleep deprivation induces pathological changes in rat masticatory muscles: Role of Toll like signaling pathway and atrophy.

The aim of this study was to evaluate the Toll like signaling pathway and atrophy after sleep deprivation (SD) in rat masticatory muscles: masseter and temporal. A total of 24 animals was distributed into three groups: Control group (CTL, n = 8), subjected to SD for 96 h (SD96, n = 8) and subjected to SD for 96 h more 96 h of sleep recovery (SD96 + R, n = 8). Histopathological analysis revealed the presence of acute inflammatory cells, congested vessels, fibrosis, and high cellularity in the skeletal muscle fibers from masseter and temporal submitted to SD. These morphological alterations were not observed in the control group since neither inflammatory cells nor congested vessels were observed to this group. In the group SD96 + R, the absence of inflammation was noticed to the masseter only. In this group, COX-2 and TNF-alpha downregulation were detected when comparing to control group. MyD88 and pIKK decreased in SD96 and SD96 + R groups being pNFKBp50 downregulatated in SD96 + R. MyD88 expression increased in rats submitted to SD96 and SD96 + R in temporal when compared to control group. On the other hand, pIKK decreased the protein expression in groups SD96 and SD96 + R while pNFKBp50 showed a decreased protein expression in group SD96 only. The activation of atrophy by means of MAFbx upregulation was detected in temporal muscle in SD96 and SD96 + R when compared to control. In summary, our results show that SD is able to induce morphological alterations in rat masticatory muscles. Toll like signaling pathway and atrophy play important roles in ethiopathogenesis induced by SD, being dependent of skeletal muscle type.

REM sleep deprivation impairs muscle regeneration in rats.

INTRODUCTION: The aim was observe the influence of sleep deprivation (SD) and sleep recovery on muscle regeneration process in rats submitted to cryolesion. METHODS: Thirty-two Wistar rats were randomly allocated in four groups: control (CTL), SD for 96 h (SD96), control plus sleep recovery period (CTL + R) and SD96h plus 96 h of sleep recovery (SD96 + R). The animals were submitted to muscle injury by cryolesioning, after to SD and sleep recovery. RESULTS: The major outcomes of this study were the reduction of muscular IGF-1 in both legs (injured and uninjured) and a delay in muscle regeneration process of animals submitted to SD compared to animals that slept, with increase connective tissue, inflammatory infiltrate and minor muscle fibers. CONCLUSIONS: SD impairs muscle regeneration in rats, moreover reduces muscular IGF-1 and sleep recovery was able to restore it to basal levels, but it was not enough to normalize the muscle regeneration.

Efeito do Treinamento Resistido na Contratilidade Miocárdica In Vitro após a Privação de Sono / Effect Of Resistance Training On Myocardial Contractility In Vitro After Sleep Deprivation

Fundamento: O treinamento resistido promove benefícios à saúde cardiovascular, a qual é influenciada pela privação de sono. Objetivo: Investigar o efeito prévio do treinamento resistido de alta intensidade sobre a contratilidade miocárdica de ratos privados de sono paradoxal. Métodos: Quarenta ratos machos Wistar foram distribuídos nos grupos controle (CTRL), treinamento resistido (TRES), privação de sono paradoxal por 96 horas (PSP96) e treinamento resistido seguido de privação de sono paradoxal por 96 horas (TRES/PSP96). O treinamento resistido foi de alta intensidade, por 8 semanas, 5x/semana. Vinte e quatro horas após a última sessão de treinamento, os grupos PSP96 e TRES/PSP96 foram submetidos ao protocolo de privação de sono paradoxal e em seguida foi realizado o estudo in vitro da mecânica contrátil do músculo papilar isolado. Resultados: Em comparação ao CTRL, os grupos PSP96 e TRES/PSP96 apresentaram menor comprimento do músculo papilar e aumento da área de secção transversa. Associado a essas alterações, verificou-se a diminuição das derivadas temporais da força na contração e relaxamento em todas as condições avaliadas. Somente o grupo PSP96 apresentou redução da tensão de repouso e lentidão no tempo de relaxamento, sendo este último atenuado pelo treinamento resistido prévio. Conclusão: O treinamento resistido prévio à PSP foi parcialmente protetor contra as alterações contráteis do músculo papilar, minimizando a lentidão no tempo de relaxamento. Assim, o caráter de alta intensidade do protocolo adotado parece não proteger plenamente o tecido cardíaco frente a PSP

Background: Resistance training promotes cardiovascular health benefits that may affected by sleep deprivation. Objective: To evaluate the effect of high-intensity resistance training on myocardial contractility in rats subsequently subjected to paradoxical sleep deprivation. Methods: Forty male Wistar rats were distributed into control group (CTRL), resistance training (REST), 96-hour paradoxical sleep deprivation (PSD96) and resistance training followed by 96-hour paradoxical sleep deprivation (REST/PSD96). The animals underwent highintensity resistance training for 8 weeks, 5x/week. Twenty-four hours after the last training session, the PSD96 and REST/PSD96 groups were submitted to paradoxical sleep deprivation, which was followed by the in vitro study of isolated papillary muscle contractile mechanics. Results: In comparison with the CTRL group, a lower papillary muscle length and increased cross sectional area were found in PSD96 and RETS/PSD96, which were associated with decreased temporal parameters of contraction force and relaxation. Decreased resting tension and slowing of relaxation time were found in the PSD96 group only. This effect was attenuated by previous resistance training. Conclusion: Resistance training partially prevented contractile changes induced by PSD, minimizing the slowing in relaxation time. Thus, high-intensity exercise seems to not fully protect the cardiac tissue from PSD-induced effects

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.

Leucine supplementation is anti-atrophic during paradoxical sleep deprivation in rats.

The purpose of this study was to identify sleep deprivation-induced atrophy and the muscle-specific fiber types affected and to determine the effects of leucine supplementation on atrophy and pertinent portions of the pathways of muscle protein synthesis and degradation in rats. A total of 46 Wistar rats were distributed in four groups: control (CTL), leucine supplementation (LEU), sleep deprivation (SD), and leucine supplementation + sleep deprivation (LEU + SD). Leucine supplementation was by gavage (1.35 g/kg/daily), and the animals were subjected to SD for 96 h. Testosterone and corticosterone concentrations, along with proteins involved in protein synthesis and degradation and proteasome activity levels, were measured in the gastrocnemius (GA) muscle. Myosin ATPase staining was used to evaluate the different muscle fibers. After sleep deprivation, GA muscle and body masses decreased in the SD group compared to the CTL, LEU, and LEU + SD groups. There was no difference between groups in type I fiber cross-sectional area (CSA). The CSAs for type IIa fibers were lower in the SD and LEU + SD groups vs. the CTL and LEU groups, while the IIb fiber CSA was lower in the SD group vs. the CSAs in all other groups. The phospho (p)-Akt levels were lower in the SD and LEU + SD groups vs. the CTL and LEU groups. The p-mTORC1 levels were higher in the LEU, SD, and LEU + SD groups vs. the CTL group. The p-p70S6k levels were higher in the LEU and LEU + SD groups; the 4E-BP1 levels were higher in the SD and LEU + SD groups compared to those in the CTL and LEU groups, and the p-4E-BP1 levels were higher in the LEU and SD groups compared to those in the CTL group and even higher in the LEU + SD group compared to those in the LEU and SD groups. Ubiquitinated proteins, LC3, and p62/SQSTM, and proteasome activity levels were higher in the SD and LEU + SD groups vs. the LEU and CTL groups. Sleep deprivation led to the atrophy of IIa and IIb muscle fibers; however, leucine supplementation prevented muscle loss and type IIb fiber atrophy.