Vitamin E supplementation inhibits muscle damage and inflammation after moderate exercise in hypoxia.

BACKGROUND: Exercise under hypoxic conditions represents an additional stress in relation to exercise in normoxia. Hypoxia induces oxidative stress and inflammation as mediated through tumour necrosis factor (TNF)-α release that might be exacerbated through exercise. In addition, vitamin E supplementation might attenuate oxidative stress and inflammation resulting from hypoxia during exercise. The present study aimed to evaluate the effects of vitamin E supplementation (250 mg) on inflammatory parameters and cellular damage after exercise under hypoxia simulating an altitude of 4200 m. METHODS: Nine volunteers performed three sessions of 60 min of exercise (70% maximal oxygen uptake) interspersed for 1 week under normoxia, hypoxia and hypoxia after vitamin E supplementation 1 h before exercise. Blood was collected before, immediately after and at 1 h after exercise to measure inflammatory parameters and cell damage. RESULTS: Percentage oxygen saturation of haemoglobin decreased after exercise and recovered 1 h later in the hypoxia + vitamin condition (P < 0.05). Supplementation decreased creatine kinase (CK)-TOTAL, CK-MB and lactate dehydrogenase 1 h after exercise (P < 0.05). The exercise in hypoxia increased interleukin (IL)-6, TNF-α, IL-1ra and IL-10 immediately after exercise (P < 0.05). Supplementation reversed the changes observed after exercise in hypoxia without supplementation (P < 0.05). CONCLUSIONS: We conclude that 250 mg of vitamin E supplementation at 1 h before exercise reduces cell damage markers after exercise in hypoxia and changes the concentration of cytokines, suggesting a possible protective effect against inflammation induced by hypoxia during exercise.

Sleep disorder or simple sleep ontogeny? Tendency for morningness is associated with worse sleep quality in the elderly

The objective of this study was to evaluate the alterations in sleep and circadian parameters during the aging process. The study sample comprises volunteers older than 18 up to 90 years of age that answered the Pittsburgh Sleep Quality Index (PSQI) and the Horne and Östberg circadian preference questionnaire. We observed that the shift to morningness with increasing age is associated with a significant worsening in sleep quality. We discuss that this sleep profile characterized by morningness and worse sleep quality observed in elderly, when compared to younger people, reflects not necessarily a pathological state, but an expected profile for this age group.

Effects of a physical fitness program on memory and blood viscosity in sedentary elderly men

The aim of this study was to investigate the effects of a 6-month exercise program on cognitive function and blood viscosity in sedentary elderly men. Forty-six healthy inactive men, aged 60–75 years were randomly distributed into a control group (n=23) and an experimental group (n=23). Participants underwent blood analysis and physical and memory evaluation, before and after the 6-month program of physical exercise. The control group was instructed not to alter its everyday activities; the experimental group took part in the fitness program. The program was conducted using a cycle ergometer, 3 times per week on alternate days, with intensity and volume individualized at ventilatory threshold 1. Sessions were continuous and maximum duration was 60 min each. There was significant improvement in memory (21%; P<0.05), decreased blood viscosity (−19%; P<0.05), and higher aerobic capacity (48%; P<0.05) among participants in the experimental group compared with the control group. These data suggest that taking part in an aerobic physical fitness program at an intensity corresponding to ventilatory threshold-1 may be considered a nonmedication alternative to improve physical and cognitive function.

The role of progesterone in memory: an overview of three decades.

Memory comprises acquisition, consolidation and retrieval of information. Many substances can influence these different phases. It is well demonstrated that sex hormones, mainly estrogen, impact cognitive function. More recently, progesterone has also been documented as playing an important role in cognition, since it influences brain regions involved in memory. Currently, many women are under hormone treatment, which contain progesterone to decrease the risk of development of endometrial cancer. This affords the opportunity to study the real effects of this hormonal replacement on cognition. There are many contradictory results regarding the role of progesterone in memory. Therefore, the aim of this review was to synthesize these studies using the new perspective of the influence of hormone replacement on cognition in women.

Is lack of sleep capable of inducing DNA damage in aged skin?

Skin naturally changes with age, becoming more fragile. Various stimuli can alter skin integrity. The aim of this study was to evaluate whether sleep deprivation affects the integrity of DNA in skin and exacerbates the effects of aging. Fifteen-month old female Hairless mice underwent 72 h of paradoxical sleep deprivation or 15 days of chronic sleep restriction. Punch biopsies of the skin were taken to evaluate DNA damage by single cell gel (comet) assay. Neither paradoxical sleep deprivation nor sleep restriction increased genetic damage, measured by tail movement and tail intensity values. Taken together, the findings are consistent with the notion that aging overrides the effect of sleep loss on the genetic damage in elderly mice.

The beneficial effects of massage therapy for insomnia in postmenopausal women.

With increases life expectancy, the incidence of undesirable manifestations of menopause has increased as well. The effects of lost ovarian function include progressive decrease in estradiol secretion, trophic changes in the breast, vasomotor symptoms, anxiety, depression, and sleep disorders. Insomnia, which has physiological consequences and can result in a loss of quality of life, is prevalent in women after menopause. Hormone therapy has been widely used to reduce menopausal symptoms, but its use in recent years has been questioned because of the reported risks of cardiovascular events and increased incidence of tumors. This controversy has generated significant interest in non-hormonal treatments among both physicians and patients. Our previous research has shown a positive effect of massage therapy on menopausal symptoms. We explored the hypothesis that massage therapy would produce beneficial effects in postmenopausal women through inflammatory and immunological changes. Recent results from self-report questionnaires have shown improvements in sleep pattern and quality of life following massage therapy. These findings demonstrate the effectiveness of massage therapy for the treatment of postmenopausal symptoms, particularly insomnia, and indicate that it is a promising line of research.

The association between TNF-α and erectile dysfunction complaints.

Inflammatory markers like tumour necrosis factor-alpha (TNF-α) have been related to erectile dysfunction (ED) and may interact with other cardiovascular risk factors such as obstructive sleep apnoea syndrome (OSAS). The aim of this study was to examine the inflammatory, metabolic and hormonal profile of men with or without ED complaints and/or OSAS recruited through the Epidemiologic Sleep Study (EPISONO). A sample of 363 men completed sexual questionnaires for ED and had physical and blood examinations. OSAS was evaluated by polysomnography and clinical assessment. The blood samples were used for determination of TNF-α, interleukin-6, leptin, cholesterol and fractions, triglycerides, homocysteine, glucose and hormonal levels. After controlling for confounding factors, men with ED complaints presented higher systolic blood pressure and TNF-α, independent of OSAS. Significant interaction between ED and OSAS was only observed for neck circumference, which was higher in ED men with OSAS than men with OSAS without ED and men with ED without OSAS. Binary logistic regression showed that the predictor factors for ED were age >43 years, myocardial infarction events, TNF-α and systolic blood pressure. Finally, a receiver-operating characteristics curve suggested a cut-off point of 9.95 pg/mL for TNF-α with sensitivity of 60% and specificity of 59% in men with ED complaints. Furthermore, there was a significant association between high levels of TNF-α (>9.95 pg/mL) and the presence of ED complaints. The results showed that there was an association between TNF-α levels and ED complaints in men independent of OSAS.

Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission

Impaired cholinergic neurotransmission can affect memory formation and influence sleep-wake cycles (SWC). In the present study, we describe the SWC in mice with a deficient vesicular acetylcholine transporter (VAChT) system, previously characterized as presenting reduced acetylcholine release and cognitive and behavioral dysfunctions. Continuous, chronic ECoG and EMG recordings were used to evaluate the SWC pattern during light and dark phases in VAChT knockdown heterozygous (VAChT-KDHET, n=7) and wild-type (WT, n=7) mice. SWC were evaluated for sleep efficiency, total amount and mean duration of slow-wave, intermediate and paradoxical sleep, as well as the number of awakenings from sleep. After recording SWC, contextual fear-conditioning tests were used as an acetylcholine-dependent learning paradigm. The results showed that sleep efficiency in VAChT-KDHET animals was similar to that of WT mice, but that the SWC was more fragmented. Fragmentation was characterized by an increase in the number of awakenings, mainly during intermediate sleep. VAChT-KDHET animals performed poorly in the contextual fear-conditioning paradigm (mean freezing time: 34.4±3.1 and 44.5±3.3 s for WT and VAChT-KDHET animals, respectively), which was followed by a 45% reduction in the number of paradoxical sleep episodes after the training session. Taken together, the results show that reduced cholinergic transmission led to sleep fragmentation and learning impairment. We discuss the results on the basis of cholinergic plasticity and its relevance to sleep homeostasis. We suggest that VAChT-KDHET mice could be a useful model to test cholinergic drugs used to treat sleep dysfunction in neurodegenerative disorders.

Resistance exercise improves hippocampus-dependent memory

It has been demonstrated that resistance exercise improves cognitive functions in humans. Thus, an animal model that mimics this phenomenon can be an important tool for studying the underlying neurophysiological mechanisms. Here, we tested if an animal model for resistance exercise was able to improve the performance in a hippocampus-dependent memory task. In addition, we also evaluated the level of insulin-like growth factor 1/insulin growth factor receptor (IGF-1/IGF-1R), which plays pleiotropic roles in the nervous system. Adult male Wistar rats were divided into three groups (N = 10 for each group): control, SHAM, and resistance exercise (RES). The RES group was submitted to 8 weeks of progressive resistance exercise in a vertical ladder apparatus, while the SHAM group was left in the same apparatus without exercising. Analysis of a cross-sectional area of the flexor digitorum longus muscle indicated that this training period was sufficient to cause muscle fiber hypertrophy. In a step-through passive avoidance task (PA), the RES group presented a longer latency than the other groups on the test day. We also observed an increase of 43 and 94% for systemic and hippocampal IGF-1 concentration, respectively, in the RES group compared to the others. A positive correlation was established between PA performance and systemic IGF-1 (r = 0.46, P < 0.05). Taken together, our data indicate that resistance exercise improves the hippocampus-dependent memory task with a concomitant increase of IGF-1 level in the rat model. This model can be further explored to better understand the effects of resistance exercise on brain functions.

Pain-related diseases and sleep disorders

Pain and sleep share mutual relations under the influence of cognitive and neuroendocrine changes. Sleep is an important homeostatic feature and, when impaired, contributes to the development or worsening of pain-related diseases. The aim of the present review is to provide a panoramic view for the generalist physician on sleep disorders that occur in pain-related diseases within the field of Internal Medicine, such as rheumatic diseases, acute coronary syndrome, digestive diseases, cancer, and headache.

Pain-related diseases and sleep disorders.

Pain and sleep share mutual relations under the influence of cognitive and neuroendocrine changes. Sleep is an important homeostatic feature and, when impaired, contributes to the development or worsening of pain-related diseases. The aim of the present review is to provide a panoramic view for the generalist physician on sleep disorders that occur in pain-related diseases within the field of Internal Medicine, such as rheumatic diseases, acute coronary syndrome, digestive diseases, cancer, and headache.

Spatial memory is improved by aerobic and resistance exercise through divergent molecular mechanisms.

A growing body of scientific evidence indicates that exercise has a positive impact on human health, including neurological health. Aerobic exercise, which is supposed to enhance cardiovascular functions and metabolism, also induces neurotrophic factors that affect hippocampal neurons, thereby improving spatial learning and memory. Alternatively, little is known about the effect of resistance exercise on hippocampus-dependent memory, although this type of exercise is increasingly recommended to improve muscle strength and bone density and to prevent age-related disabilities. Therefore, we evaluated the effects of resistance training on spatial memory and the signaling pathways of brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1), comparing these effects with those of aerobic exercise. Adult male Wistar rats underwent 8 weeks of aerobic training on a treadmill (AERO group) or resistance training on a vertical ladder (RES group). Control and sham groups were also included. After the training period, both AERO and RES groups showed improved learning and spatial memory in a similar manner. However, both groups presented distinct signaling pathways. Although the AERO group showed increased level of IGF-1, BDNF, TrkB, and ß-CaMKII (calcium/calmodulin-dependent kinase II) in the hippocampus, the RES group showed an induction of peripheral and hippocampal IGF-1 with concomitant activation of receptor for IGF-1 (IGF-1R) and AKT in the hippocampus. These distinct pathways culminated in an increase of synapsin 1 and synaptophysin expression in both groups. These findings demonstrated that both aerobic and resistance exercise can employ divergent molecular mechanisms but achieve similar results on learning and spatial memory.

A link between sleep loss, glucose metabolism and adipokines

The present review evaluates the role of sleep and its alteration in triggering problems of glucose metabolism and the possible involvement of adipokines in this process. A reduction in the amount of time spent sleeping has become an endemic condition in modern society, and a search of the current literature has found important associations between sleep loss and alterations of nutritional and metabolic contexts. Studies suggest that sleep loss is associated with problems in glucose metabolism and a higher risk for the development of insulin resistance and type 2 diabetes mellitus. The mechanism involved may be associated with the decreased efficacy of regulation of the hypothalamus-pituitary-adrenal axis by negative feedback mechanisms in sleep-deprivation conditions. In addition, changes in the circadian pattern of growth hormone (GH) secretion might also contribute to the alterations in glucose regulation observed during sleep loss. On the other hand, sleep deprivation stress affects adipokines - increasing tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and decreasing leptin and adiponectin -, thus establishing a possible association between sleep-debt, adipokines and glucose metabolism. Thus, a modified release of adipokines resulting from sleep deprivation could lead to a chronic sub-inflammatory state that could play a central role in the development of insulin resistance and type 2 diabetes mellitus. Further studies are necessary to investigate the role of sleep loss in adipokine release and its relationship with glucose metabolism.

A link between sleep loss, glucose metabolism and adipokines.

The present review evaluates the role of sleep and its alteration in triggering problems of glucose metabolism and the possible involvement of adipokines in this process. A reduction in the amount of time spent sleeping has become an endemic condition in modern society, and a search of the current literature has found important associations between sleep loss and alterations of nutritional and metabolic contexts. Studies suggest that sleep loss is associated with problems in glucose metabolism and a higher risk for the development of insulin resistance and type 2 diabetes mellitus. The mechanism involved may be associated with the decreased efficacy of regulation of the hypothalamus-pituitary-adrenal axis by negative feedback mechanisms in sleep-deprivation conditions. In addition, changes in the circadian pattern of growth hormone (GH) secretion might also contribute to the alterations in glucose regulation observed during sleep loss. On the other hand, sleep deprivation stress affects adipokines - increasing tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and decreasing leptin and adiponectin -, thus establishing a possible association between sleep-debt, adipokines and glucose metabolism. Thus, a modified release of adipokines resulting from sleep deprivation could lead to a chronic sub-inflammatory state that could play a central role in the development of insulin resistance and type 2 diabetes mellitus. Further studies are necessary to investigate the role of sleep loss in adipokine release and its relationship with glucose metabolism.

Sleep and muscle recovery: endocrinological and molecular basis for a new and promising hypothesis.

Sleep is essential for the cellular, organic and systemic functions of an organism, with its absence being potentially harmful to health and changing feeding behavior, glucose regulation, blood pressure, cognitive processes and some hormonal axes. Among the hormonal changes, there is an increase in cortisol (humans) and corticosterone (rats) secretion, and a reduction in testosterone and Insulin-like Growth Factor 1, favoring the establishment of a highly proteolytic environment. Consequently, we hypothesized that sleep debt decreases the activity of protein synthesis pathways and increases the activity of degradation pathways, favoring the loss of muscle mass and thus hindering muscle recovery after damage induced by exercise, injuries and certain conditions associated with muscle atrophy, such as sarcopenia and cachexia.

Inflammatory markers are associated with inhibitory avoidance memory deficit induced by sleep deprivation in rats.

Sleep deprivation (SD) causes detrimental effects to the body, such as memory impairment and weight loss. SD also changes the concentration of inflammatory mediators such as cytokines, which, in turn, can affect cognitive functioning. Thus, the objective of this study was to investigate the involvement of these inflammatory mediators in inhibitory avoidance memory deficit in sleep-deprived rats. Male Wistar rats were deprived of sleep by the modified multiple platform method for 96 h, while their respective controls remained in their housing cages. To assess memory after SD, all animals underwent training, followed by the inhibitory avoidance task test 24h later. Also, the weight of each animal was recorded daily. In the first experiment, animals received an acute administration of lipopolysaccharide (LPS, 50 or 75 µg/kg i.p.) 3h before the inhibitory avoidance training. In the experiment 2, the animals received acute or chronic administration of anti-IL-6 antibody (Ab, 2 µg/kg i.p.). The acute administration was performed 3h before the inhibitory avoidance training, while the chronic treatment administrations were performed daily during the SD period. The 75 µg/kg dose of LPS, but not the 50 µg/kg dose, caused a significant attenuation of memory impairment in the sleep-deprived animals. Although the treatments with the anti-IL-6 Ab did not produce any significant changes in cognitive performance, the Ab attenuated weight loss in sleep-deprived animals. Taken together, these results suggest the involvement of inflammatory mediators in the modulation of memory deficit and weight loss that are observed in sleep-deprived rats.

Plasma iron levels appraised 15 days after spinal cord injury in a limb movement animal model.

STUDY DESIGN: Experimental, controlled trial. OBJECTIVES: The purpose of this study was to evaluate plasma iron and transferrin levels in a limb movement animal model with spinal cord injury (SCI). SETTING: Universidade Federal de São Paulo, Departamento de Psicobiologia. METHODS: In all, 72 male Wistar rats aged 90 days were divided into four groups: (1) acute SCI (1 day, SCI1), (2) 3 days post-SCI (SCI3), (3) 7 days post-SCI (SCI7) and (4) 15 days post-SCI (SCI15). Each of these groups had corresponding control (CTRL) and SHAM groups. Plasma iron and transferrin levels of the different groups were analyzed using a one-way analysis of variance (ANOVA) followed by Tukey's test. RESULTS: We found a significant reduction in iron plasma levels after SCI compared with the CTRL group: SCI1 (CTRL: 175±10.58 µg dl(-1); SCI: 108.28±11.7 µg dl(-1)), SCI3 (CTRL: 195.5±11.00 µg dl(-1); SCI: 127.88±12.63 µg dl(-1)), SCI7 (CTRL: 186±2.97 µg dl(-1); SCI: 89.2±15.39 µg dl(-1)) and SCI15 (CTRL: 163±5.48 µg dl(-1); SCI: 124.44±10.30 µg dl(-1)) (P<0.05; ANOVA). The SHAM1 group demonstrated a reduction in iron plasma after acute SCI (CTRL: 175±10.58 µg dl(-1); SHAM: 114.60±7.81 µg dl(-1)) (P<0.05; ANOVA). CONCLUSION: Reduced iron metabolism after SCI may be one of the mechanisms involved in the pathogenesis of sleep-related movement disorders.

Effects of isoflavone on the learning and memory of women in menopause: a double-blind placebo-controlled study

Hormone decline is common to all women during aging and, associated with other factors, leads to cognitive impairment. Its replacement enhances cognitive performance, but not all women present a clinical and family or personal history that justifies its use, mainly women with a history of cancer. The aim of this study was to determine whether a daily oral dose of 80 mg of isoflavone extract for 4 months can produce benefits in women with low hormone levels, contributing to improvement in cognitive aspects. The sample comprised 50- to 65-year-old women whose menstruation had ceased at least 1 year before and who had not undergone hormone replacement. The volunteers were allocated to two groups of 19 individuals each, i.e., isoflavone and placebo. There was a weak correlation between menopause duration and low performance in the capacity to manipulate information (central executive). We observed an increase in the capacity to integrate information in the group treated with isoflavone, but no improvement in the capacity to form new memories. We did not observe differences between groups in terms of signs and symptoms suggestive of depression according to the Geriatric Depression Scale. Our results point to a possible beneficial effect of isoflavone on some abilities of the central executive. These effects could also contribute to minimizing the impact of memory impairment. Further research based on controlled clinical trials is necessary to reach consistent conclusions.