Gabriela Matos

Association between leisure time, physical activity, and mood disorder levels in individuals with epilepsy

The aim of this study was to investigate the association between physical activity levels (occupational, sports, and leisure time activities), depression, anxiety, and epilepsy. The behavioral outcomes of individuals with epilepsy (E) were also compared with healthy control subjects (C). The sample included 31 individuals with epilepsy (12 with idiopathic generalized epilepsy and 19 with partial epilepsy) and 31 control subjects. Self-rating questionnaires were used to assess mood (State-Trait Anxiety Inventory and Beck Depression Inventory), anxiety, and depression as well as habitual physical activity. Patients with epilepsy were more severely impaired compared to control subjects in both mood questionnaires and presented higher levels of depression (35%), state anxiety (18%), and trait anxiety (12.6%) when compared to the C group. Although physical activity level did not differ significantly between groups, linear regression analyses showed that the physical activity leisure level predicted 31% of depression levels and 26% of anxiety levels in the E group. These data suggest that low levels of physical activity may be considered a risk factor for the development of depression and anxiety and can play an important role in the quality of life of individuals with epilepsy.

Sleep, epilepsy and translational research: What can we learn from the laboratory bench?

The relationship between sleep and epilepsy has been known since ancient times, and the modulating effects of both on each other have been widely described in clinical studies. However, the mechanisms of this correlation remain unclear. Translational research is essential for filling the gaps in our knowledge, and for developing better therapeutic approaches to improve the quality of life of epileptic patients. Excellent animal models of epilepsy are available for the investigation of various aspects of epilepsy, such as epileptogenesis and hippocampal sclerosis. These models also show an association between sleep and epilepsy, suggesting that they are suitable for translational research on this relationship. While some knowledge has been obtained from preclinical studies, the topic remains relatively unexplored. In terms of the role of sleep in modulating seizure susceptibility in epilepsy, animal sleep research is a major tool. In this review, we focus on the intricate relationship between sleep and epilepsy in the preclinical setting, using a translational science approach.

Sleep and epilepsy: Exploring an intriguing relationship with a translational approach

The relationship between sleep and epilepsy has been well established. There is a high prevalence of sleep disturbances in epilepsy, which are associated with a decreased quality of life of individuals with epilepsy. In view of this fact, preclinical research is necessary to address many gaps in knowledge. For instance, it is well known that sleep deprivation can trigger seizures; however, this is a complex pathophysiological event. In this context, there are many valuable animal models of epilepsy that reproduce clinical symptoms and can be used. Investigations using animal models that simulate clinical epilepsy are imperative. Furthermore, preclinical studies that reveal mechanisms related to sleep-epilepsy interactions are very important. Results of such studies can, in turn, improve the understanding of epilepsy itself and can be useful in developing new antiepileptic drugs and preventive measures to control seizures. Preclinical research should be performed using a translational framework with experimental designs that can lead to advances in the quality of life of individuals with epilepsy. In view of the fact that more than 50 million of people are affected by epilepsy around the world, understanding the relationship between sleep and epilepsy is imperative.

Modafinil ameliorates cognitive deficits induced by maternal separation and sleep deprivation

Animals exposed to an early adverse event may be more susceptible to a second source of stress later in life, and these stressors may have additive deleterious effects. Sleep deprivation is known to be a stressor, affecting multiple body functions such as the cognition. Modafinil enhances working memory and attention in healthy non-sleep deprived subjects and in animal models of sleep deprivation. The first aim of the present study was to investigate the effects of maternal separation (MS) combined with paradoxical sleep deprivation (PSD) in adulthood on recognition memory in rats. Second, we aimed to evaluate whether the administration of modafinil would be able to ameliorate memory deficits induced by MS and PSD. Wistar rat pups were initially distributed into MS and handling (H) groups, with their litters standardized in 4 females and 4 males. In adulthood, the male rats were submitted to PSD or control condition, being redistributed afterwards in modafinil- or vehicle-treatment immediately after the training session of object recognition task. PSD did not potentiate the cognitive deficit due to MS. However, modafinil was able to recover memory impairments associated to PSD and also to MS in the neonatal period. This study demonstrates for the first time that modafinil ameliorates cognitive deficits associated to MS and to PSD in adulthood, independent from MS in the neonatal period.

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.

Impairment of Sexual Function in Rats with Epilepsy

INTRODUCTION Epilepsy is a chronic disease that affects men and women of all ages, with different levels of severity. Many individuals with epilepsy also suffer from impairments in sexual function. However, it is difficult to differentiate between the impact of the disease and the impact of antiepileptic drugs on sexual function in human subjects. AIMS To evaluate sexual behavior in adult male rats submitted to chronic pilocarpine-induced epilepsy. METHODS First, non-epileptic rats were exposed to nine training sessions to acquire sexual experience, and their baseline sexual performance was evaluated. Then, the same rats were given pilocarpine to induce status epilepticus followed by chronic epilepsy. Once the animals had developed spontaneous recurrent seizures, their sexual behavior was evaluated during three sessions. MAIN OUTCOME MEASURES Examine changes in latencies to first mount, intromission, and ejaculation, and the total number of mounts, intromissions, and ejaculations. RESULTS All outcome measures related to sexual motivation and sexual performance were markedly impaired during chronic epilepsy compared with the baseline and the control group. CONCLUSION These findings will aid in understanding the interaction between sexual behavior and epilepsy, as well as encouraging further experimental studies in human patients with epilepsy suffering from sexual dysfunction.

Behavioral and genetic effects promoted by sleep deprivation in rats submitted to pilocarpine-induced status epilepticus

The interaction between sleep deprivation and epilepsy has been well described in electrophysiological studies, but the mechanisms underlying this association remain unclear. The present study evaluated the effects of sleep deprivation on locomotor activity and genetic damage in the brains of rats treated with saline or pilocarpine-induced status epilepticus (SE). After 50 days of pilocarpine or saline treatment, both groups were assigned randomly to total sleep deprivation (TSD) for 6 h, paradoxical sleep deprivation (PSD) for 24 h, or be kept in their home cages. Locomotor activity was assessed with the open field test followed by resection of brain for quantification of genetic damage by the single cell gel electrophoresis (comet) assay. Status epilepticus induced significant hyperactivity in the open field test and caused genetic damage in the brain. Sleep deprivation procedures (TSD and PSD) did not affect locomotor activity in epileptic or healthy rats, but resulted in significant DNA damage in brain cells. Although PSD had this effect in both vehicle and epileptic groups, TSD caused DNA damage only in epileptic rats. In conclusion, our results revealed that, despite a lack of behavioral effects of sleep deprivation, TSD and PSD induced genetic damage in rats submitted to pilocarpine-induced SE.

Changes in gene expression in the frontal cortex of rats with pilocarpine-induced status epilepticus after sleep deprivation

Sleep and epilepsy present a bidirectional interaction. Sleep complaints are common in epilepsy, and sleep deprivation may provoke seizures. However, the mechanisms underlying this relationship are unknown. Thus, this study investigated the effects of paradoxical sleep deprivation (PSD24h) and total sleep deprivation (TSD6h) in the expression of genes related to reactive oxygen species and nitric oxide production in the frontal cortex of a rodent model of temporal lobe epilepsy (PILO). The data show that PILO rats had increased NOX-2 expression and decreased SOD expression, independent of sleep. Higher NOX-2 expression was observed only in PILO rats subjected to the control condition and TSD6h. Also, eNOS and DDAH1 were increased in the PILO group submitted to TSD6h. Moreover, CAT expression in the frontal cortex of PILO rats submitted to PSD24h was reduced compared to that of PILO rats that were not sleep-deprived. The molecular changes found in the frontal cortex of PILO rats following sleep deprivation suggest a mechanism via oxidative stress.

Lights out! It is time for bed. Warning: obstructive sleep apnea increases risk of sudden death in people with epilepsy.

Universidade Federal de Sao Paulo, Escola Paulista Med, Disciplina Neurol Expt, UNIFESP EPM, BR-04023900 Sao Paulo, Brazil

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.