Effectiveness of exercise and pramipexole in the treatment of restless leg syndrome: Implications on the dopaminergic system and PTPRD.

OBJECTIVE: Dopaminergic dysfunction, iron reduction and variations in the PTPRD gene (protein tyrosine phosphatase receptor type delta) may be associated with restless leg syndrome (RLS). Here, we evaluate the effect of pramipexole (PPX) and exercise on genes and proteins associated with RLS and on sleep patterns in spontaneously hypertensive rats (SHR). METHODS: Animals were distributed into 4 groups: 1) Control (CTRL); 2) Exercise (EX); 3) Exercise and pramipexole (EX + PPX); and 4) Pramipexole (PPX). PPX treatment was performed daily (0.125 mg/kg), while exercise was conducted over 5 sessions per week, both for 4 weeks. RESULTS: EX + PPX increased the protein levels of PTPRD, reduced the protein levels of the enzyme tyrosine hydroxylase (TH) and improved sleep parameters in both cycles; on the other hand, the use of PPX reduced mRNA and protein levels of PTPRD and TH but improved the sleep pattern in the light cycle. However, in the dark cycle, pramipexole caused the worsening of symptoms. CONCLUSIONS: We suggest that the improvement in sleep pattern by EX + PPX may be associated with the increased protein levels of PTPRD and that EX + PPX can reverse the negative effects of PPX.

Effect of a probiotic fermented milk supplementation on behavior and sleep.

This study attempted to analyze the effect of supplementing Wistar-Kyoto rats with fermented milk containing the probiotic Bifidobacterium animalis BB-12 and pomegranate juice on the microbiota-gut-brain axis of rats, with special focus on their behavior, sleep patterns, and response to stress. This study was divided into two experiments: (1) For the behavioral analysis the animals were divided into two groups: Fermented probiotic milk (BB + 1) and control (BB-). (2) For the sleep analysis the animals were divided into two groups: Fermented probiotic milk (BB + 2) and control (H2O). For the behavioral analysis, the open field method was used, which evaluates the behavior after ten, twenty, and thirty days of supplementation. For sleep analysis, the animals were submitted to implantation of electrodes and 24 h polysomnography, followed by 48 h sleep deprivation (REM) and 48 h polysomnography, then euthanized 100 days after the beginning of the experiment. In addition, animal feces were collected before and after sleep deprivation to assess its effects on the microbiota. A decrease in anxiety-related behaviors was observed in the supplemented animals and an increase in sleep efficiency and a reduction in the number of awakenings of the animals before deprivation. It has also been observed that sleep deprivation decreased the amount of total bacterial DNA. The number of copies of genomes of the genus Bifidobacterium did not differ in both groups.

Immune status, well-being and gut microbiota in military supplemented with synbiotic ice cream and submitted to field training: a randomised clinical trial.

Strenuous physical activity, sleep deprivation and psychological stress are common features of military field training. The present study aimed to evaluate the effects of supplementation with a synbiotic ice cream on salivary IgA, gastrointestinal symptoms, well-being indicators and gut microbiota in young military participants undergoing field training. Sixty-five military completed the study: one group was supplemented for 30 d with synbiotic ice cream containing: 2·1 × 108 CFU/g for Lactobacillus acidophilus LA-5 and 2·7 × 109 CFU/g for Bifidobacterium animalis BB-12 and 2·3 g of inulin in the 60 g of ice cream at manufacture, and the other with a placebo ice cream. Volunteers were evaluated at pre-supplementation (baseline), post-supplementation and after a 5-d military training. Bifidobacterium and Lactobacillus genera were measured in stool samples and both showed a higher differential abundance post-supplementation and training. Salivary IgA and gastrointestinal symptoms decreased at post-training in both groups (P < 0·05; main effect of time); however, supplementation with synbiotic did not mitigate this effect. Tenseness and sleepiness were decreased in the synbiotic-treated group, but not in the placebo group at post-military training (P = 0·01 and 0·009, respectively; group × time effect). The other well-being indicators were not affected by the synbiotic supplementation. In conclusion, 30 d of synbiotic ice cream supplementation containing inulin, L. acidophilus LA-5 and B. animalis BB-12 favourably modulated gut microbiota and improved tenseness and sleepiness in healthy young military undergoing a 5-d field training. These improvements may be relevant to this population as they may influence the decision-making process in an environment of high physical and psychological stress.

PTPRD as a candidate druggable target for therapies for restless legs syndrome?

The gene that encodes the protein tyrosine phosphatase D (PTPRD) may be related to brain circuits associated with sleep, and has been seen as an interesting molecule, a "druggable" drug target. This gene is a potential candidate for increasing therapeutic advances in restless legs syndrome, a sleep-related movement disorder, that manifests as an uncontrollable desire to move limbs (legs) to relieve uncomfortable sensations. Changes in the PTPRD gene expression may increase the chance of developing this syndrome. Treatment with pramipexole is used in restless legs syndrome. This study aims to verify the effect of treatment with pramipexole on the PTPRD expression, as well as on the sleep pattern in an animal model for restless legs syndrome. For this, an animal model of sleep-related movement disorders (spontaneously hypertensive rats) was distributed in groups: (a) spontaneously hypertensive rats-control; (b) spontaneously hypertensive rats-pramipexole (0.125 mg kg-1 for 4 weeks). The analyses of PTPRD gene and protein expression were performed in the striatum and spinal cord by quantitative real-time polymerase chain reaction and indirect enzyme-linked immunosorbent assay, respectively. Electrocorticographic and electromyographic analyses were performed. There was no difference in the PTPRD mRNA levels, as well as in the protein levels, although a tendency has been observed for decreased gene expression in the striatum and increased protein expression in the spinal cord in the spontaneously hypertensive rats-pramipexole group. Pramipexole improved the animals' sleep pattern. Thus, the treatment with pramipexole in the evaluated dose and time tended to alter the expression of the PTPRD protein in the spinal cord, in addition to significantly improving the sleep pattern.

Can physical exercise have a protective effect in an animal model of sleep-related movement disorder?

The purpose of the present study was to determine whether physical exercise (PE) has a protective effect in an experimental animal model of sleep-related movement disorder (A11 dopaminergic nuclei lesions with 6-OHDA). Rats were divided into four groups (Control PE-CTRL/PE, SHAM/PE, A11 lesion/NPE, A11 lesion/PE). Two experiments were performed: (1) the rats underwent PE before (2 weeks) and after (4 weeks) the A11 lesion; and (2) the rats underwent PE only after (4 weeks) the A11 lesion. Electrode insertion surgery was performed and sleep analyses were conducted over a period of 24h (baseline and after PE) and analyzed in 6 blocks of 4h. The results demonstrated that the A11 lesion produced an increased percentage of wakefulness in the final block of the dark period (3-7am) and a significant enhancement of the number of limb movements (LM) throughout the day. Four weeks of PE was important for reducing the number of LMs in the A11 lesion group in the rats that performed PE before and after the A11 lesion. However, in the analysis of the protective effect of PE on LM, the results showed that the number of LMs was lower at baseline in the group that had performed 2 weeks of PE prior to the A11 lesion than in the group that had not previously performed PE. In conclusion, these findings consistently demonstrate that non-pharmacological manipulations had a beneficial effect on the symptoms of sleep-related movement disorder.

Incremental exercise test for the evaluation of peak oxygen consumption in paralympic swimmers.

BACKGROUND: Peak oxygen consumption (VO2peak) is a fundamental parameter used to evaluate physical capacity. The objective of this study was to explore two types of incremental exercise tests used to determine VO2peak in four Paralympic swimmers: arm ergometer testing in the laboratory and testing in the swimming pool. METHODS: On two different days, the VO2peak values of the four athletes were measured in a swimming pool and by a cycle ergometer. The protocols identified the VO2peak by progressive loading until the volitional exhaustion maximum was reached. The results were analyzed using the paired Student's t-test, Cohen's d effect sizes and a linear regression. RESULTS: The results showed that the VO2peak values obtained using the swimming pool protocol were higher (P=0.02) than those obtained by the arm ergometer (45.8±19.2 vs. 30.4±15.5; P=0.02), with a large effect size (d=3.20). When analyzing swimmers 1, 2, 3 and 4 individually, differences of 22.4%, 33.8%, 60.1% and 27.1% were observed, respectively. CONCLUSIONS: Field tests similar to the competitive setting are a more accurate way to determine the aerobic capacity of Paralympic swimmers. This approach provides more sensitive data that enable better direction of training, consequently facilitating improved performance.

Spontaneously hypertensive rats: possible animal model of sleep-related movement disorders.

Clinical experience suggests that restless legs syndrome (RLS), periodic leg movement (PLM), and attention-deficit hyperactivity disorder (ADHD) may co-occur in both children and adults. The purpose of the present study was to provide an electrocorticography and electromyography evaluation of the spontaneously hypertensive rat (SHR) to investigate the potential of this rat strain as an animal model of RLS-PLM. Initial work focused on evaluating sleep patterns and limb movements during sleep in SHR, having normotensive Wistar rats (NWR) as control, followed by comparison of two treatments (pharmacological-dopaminergic agonist treatment and nonpharmacological-chronic physical exercise), known to be clinically beneficial for sleep-related movement disorders. The captured data strengthen the association between SHR and RLS-PLM, revealing a significant reduction on sleep efficiency and slow wave sleep and an increase on wakefulness and limb movements for the SHR group during the dark period, as compared to the NWR group, effects that have characteristics that are strikingly consistent with RLS-PLM. The pharmacological and nonpharmacological manipulations validated these results. The present findings suggest that the SHR may be a useful putative animal model to study sleep-related movement disorders mechanisms.

Do circadian preferences influence the sleep patterns of night shift drivers?

OBJECTIVE: The objective of this study was to analyze the effect of individual circadian preferences of drivers with fixed night work schedules on sleep patterns. SUBJECTS AND METHODS: A total of 123 professional drivers, 32 indifferent preference drivers and 91 morning preference drivers of an intermunicipality and interstate bus transportation company were evaluated. All drivers underwent polysomnographic recordings after their shifts. Furthermore, they filled out a questionnaire that contained sociodemographic and health questions. The Horne and Östberg questionnaire was used to assess the subjects' morningness-eveningness preference. RESULTS: The mean age was 42.54 ± 6.98 years and 82 (66.66%) of the drivers had worked for ≥15 years. A significant effect on rapid eye movement (REM) was observed in the morning preference drivers. They showed an increased sleep latency and an REM sleep percentage of 5% of the total REM time. This reveals a significant effect on sleep architecture associated with work time. CONCLUSION: The drivers reported that morning preference had a significant effect on their sleep pattern indicating less REM sleep and longer REM sleep latency in the morning preference group. Thus, it is important to evaluate interactions between individual aspects of health and other parameters, such as sleep quality and work organizational factors, to promote night shift workers' health and well-being.

Prevalence of and risk factors for obstructive sleep apnea syndrome in Brazilian railroad workers.

OBJECTIVE: This study evaluated the prevalence of, and the risk factors for, obstructive sleep apnea syndrome (OSAS) among Brazilian railroad workers. METHODS: Male railroad workers (745) from a railway company in Brazil were analyzed after responding to questionnaires about their demographics, sleep habits, excessive daytime sleepiness (Epworth), and the likelihood of having apnea (Berlin). We also performed polysomnography and measured anthropometric data for all of the railroad workers. RESULTS: The results showed that 261 (35.03%) of the railroad workers presented with OSAS. These railroad workers were older (OSAS: 38.53±10.08 versus non-OSAS: 33.99±8.92 years), more obese according to body mass index (27.70±4.38 versus 26.22±3.92 kg/m(2)), and employed for a longer period of time (14.32±9.13 years) compared with those without OSAS (10.96±7.66 years). Among those with OSAS, 9.5% were smokers and 54.7% reported alcohol use. The associated risk factors were age (OR=2.51, 95% CI=1.76-3.57), BMI (OR=1.56, 95% CI=1.04-2.34), alcohol use (OR=1.28, 95% CI=0.90-1.81), and a high chance of having sleep apnea, as assessed by the Berlin questionnaire (OR=2.19, 95% CI=1.49-3.21). CONCLUSION: The prevalence of OSAS in Brazilian railroad workers was higher than that observed in the general population but similar to that found in the population of the city of São Paulo, Brazil. These results suggest that age, BMI, a high risk of developing apnea through subjective self-reporting (Berlin), and alcohol use are associated with a higher risk of developing OSAS. These data reinforce the need to be more attentive to this population because they have a higher propensity for accidents.

Characteristics of muscle fibers in rats with limb movements during sleep after spinal cord injury.

BACKGROUND/AIMS: Previous studies have demonstrated that spinal cord injury (SCI) results in changes in sleep patterns through increased arousals and limb movements during sleep. Dramatic changes in muscle myosin heavy-chain isoforms have also been reported. The aim of this study was to investigate the characteristics of muscle fibers after SCI in rats with limb movements during sleep. METHODS: Forty male Wistar rats were divided into four groups: SHAM, SCI 3, 7 and 15 days. Animals were subjected to electrode insertion surgery, 24-hour baseline sleep recording, SCI, and subsequent sleep recording for 3, 7, or 15 consecutive days. In addition, the gastrocnemius muscle and spinal cord were collected for histopathological/histochemical analyses. RESULTS: Our results indicate a rapid and progressive decrease in the cross-sectional area of type I fibers in the gastrocnemius muscle (35.76-24.74 µm(2)) after SCI. Additionally, we found SCI-induced changes in sleep patterns. Following SCI, we also observed limb movements in sleeping rats, as well as significant negative moderate correlations between type I fibers and limb movement. CONCLUSION: Our study strengthened the hypothesis by correlation between changes in types of muscle fiber (decline in type I fibers) and an increase in limb movements during sleep after SCI.

Evaluation of periodic limb movements in a putative animal model of restless leg syndrome.

Restless leg syndrome (RLS) is a major healthcare burden with increasing prevalence. It has been demonstrated that periodic limb movements (PLM) can occur as an isolated phenomenon, but they are often associated with this syndrome and are the only symptom of this disorder that can be measured electrophysiologically. The aim of this study was to examine the sleep-wake behavior and the presence of limb movement in a rat model of RLS induced by lesioning the A11 dopaminergic nuclei with the neurotoxin 6-hydroxydopamine (6-OHDA). Rats were implanted with electrodes for electrocorticography and electromyography. Sleep recordings were monitored during light/dark periods lasting 12 hours each and were evaluated on days 7, 15, and 28 after injection of the drug or phosphate-buffered saline (PBS). A control group that did not receive any injection was also included. Wakefulness percentages were generated for 4-hour segments of the dark period, yielding the following 3 bins: 7 PM to 11 PM, 11 PM to 3 AM, and 3 PM to 7 PM. Additionally, slow wave sleep, paradoxical sleep, wakefulness, and limb movements were evaluated over the entire 12 hours of the light/dark cycle. All A11-lesioned rats exhibited an increased percentage of wakefulness during the last block of the dark period, as would be expected for an animal model of this syndrome. In addition, at all time points after lesioning, these animals presented increased frequencies of limb movement during both the light and the dark periods. These alterations were reversed by the acute administration of the dopaminergic agonist pramipexole. This animal model strengthens the notion that 6-OHDA-induced A11 lesions can be a valid animal model for RLS and PLM.

Exercise training improves sleep pattern and metabolic profile in elderly people in a time-dependent manner.

Aging and physical inactivity are two factors that favors the development of cardiovascular disease, metabolic syndrome, obesity, diabetes, and sleep dysfunction. In contrast, the adoption a habitual of moderate exercise may present a non-pharmacological treatment alternative for sleep and metabolic disorders. We aimed to assess the effects of moderate exercise training on sleep quality and on the metabolic profile of elderly people with a sedentary lifestyle. Fourteen male sedentary, healthy, elderly volunteers performed moderate training for 60 minutes/day, 3 days/week for 24 wk at a work rate equivalent to the ventilatory aerobic threshold. The environment was kept at a temperature of 23 ± 2 °C, with an air humidity 60 ± 5%. Blood and polysomnographs analysis were collected 3 times: at baseline (1 week before training began), 3 and 6 months (after 3 and 6 months of training). Training promoted increasing aerobic capacity (relative VO2, time and velocity to VO2max; p < 0.05), and reduced serum NEFA, and insulin concentrations as well as improved HOMA index (p < 0.05), and increased adiponectin levels (p < 0.05), after 3 months of training when compared with baseline data. The sleep parameters, awake time and REM sleep latency were decreased after 6 months exercise training (p < 0.05) in relation baseline values. Our results demonstrate that the moderate exercise training protocol improves the sleep profile in older people, but the metabolism adaptation does not persist. Suggesting that this population requires training strategy modifications as to ensure consistent alterations regarding metabolism.

Sleep complaints and polysomnographic findings: a study of nuclear power plant shift workers.

The literature widely recognizes that shift workers have more health complaints than the general population. The objective of this study was to describe the prevalence of sleep complaints and verify the polysomnographic (PSG) variables of shift workers in two Brazilian nuclear power plants. We carried out a subjective evaluation with a sleep questionnaire. Based on these results, the interviewees that reported sleep-related complaints were referred for polysomnographic evaluation. Of the 327 volunteers initially evaluated by the sleep questionnaire, 113 (35%) reported sleep complaints; they were significantly older, had higher body mass index (BMI), and worked more years on shifts than those without sleep complaints. Of these 113, 90 met criteria for various sleep disorders: 30 (9%) showed obstructive sleep apnea (OSA), 18 (5.5%) showed limb movement, and 42 (13%) evidenced both sleep problems and had a significantly higher proportion of sleep stage 1 and arousals compared with the 23 shift workers that had no indices of sleep problems. The present study found that 90 (27.5%) of the evaluated participants met the PSG criteria of some type of clinical sleep disorder. This high proportion should be investigated for associations with other aspects of work, such as working hours, working schedule, years performing shift work, and access to health services. Due to the strong association between sleep disorders and the incidence of fatigue and sleepiness, the evaluation of the sleep patterns and complaints of shift workers is essential and should be considered to be one of the basic strategies of industry to prevent accidents.