The impact on the quality of life and sleep complaints in a vitiligo sample and the influence of inflammatory cytokines in the interaction between vitiligo and sleep.

INTRODUCTION: Vitiligo is an autoimmune dermatosis that affects quality of life, which englobes sleep quality. Sleep regulates the immune system, including inflammatory cytokines, and other pathways, which may influence vitiligo pathogenesis. OBJECTIVES: To analyze levels of immune serum components (cytokines) in a vitiligo group, and assess whether there was any association with sleep. METHODS: This study comprised 30 vitiligo patients and 26 control individuals. Quality of life and sleep questionnaires were completed [Dermatology Life Quality Index (DLQI), Short-Form Health Survey (SF-36), Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI)]. Seven cytokines have been measured: IFN-γ, interleukin (IL)-4, IL-6, IL-10, IL-17A, IL-12 p40 and TNF-α. RESULTS: The mean age of the vitiligo group was 47.7 years-old, with prevalence of females (66.7 %). Mucosal (70 %), acral (60 %) and focal subtype (53.3 %) predominated. Signs of vitiligo activity were identified in 63.3 % of the disease sample. Total PSQI scores and scores for domain 4 (sleep efficiency) were statistically worse in vitiligo group. The SF-36 and ISI total scores were worse in the vitiligo group, although not statistically significant compared with controls. Four SF-36 domains were statistically worse in vitiligo sample, and the DLQI mean score was mild to moderate (5.57). Cytokine levels were not different between groups, or when associated with PSQI. Higher ISI scores (more severe insomnia) were related to increased IL-17A. Higher IL-4, IL-6 and IL-10 levels were associated with previous phototherapy. CONCLUSIONS: Poor sleep and impaired aspects of quality of life predominated in the vitiligo sample. Insomnia was related to IL-17A increase in vitiligo. Increased levels of IL-4, IL-6 and IL-10 were related to previous ultraviolet B narrow band (UVB-NB) phototherapy, suggesting an interaction of this treatment on immune system. Sleep disruption and the course of vitiligo may have common pathways in respect of circadian cytokines, which may represent an important subject in vitiligo management.

Network analysis of sleep bruxism in the EPISONO adult general population.

Sleep bruxism (SB) has been associated with biological and psychosocial factors. The assessment of SB includes self-report, clinical evaluation, and polysomnography. This study aimed to investigate the associations of self-reported SB with other sleep disorders and demographic, psychological, and lifestyle factors in the adult general population, and to investigate whether self-reported SB and polysomnographically (PSG) confirmed SB provide similar outcomes in terms of their associated factors. We recruited 915 adults from the general population in Sao Paulo, Brazil. All participants underwent a one-night PSG recording and answered questions about sex, age, BMI, insomnia, OSA risk, anxiety, depression, average caffeine consumption, smoking frequency, and alcohol consumption frequency. We investigated the link between SB and the other variables in univariate, multivariate, and network models, and we repeated each model once with self-reported SB and once with PSG-confirmed SB. Self-reported SB was only significantly associated with sex (p = 0.042), anxiety (p = 0.002), and depression (p = 0.03) in the univariate analysis, and was associated with insomnia in the univariate (p < 0.001) and multivariate (ß = 1.054, 95%CI 1.018-1.092, p = 0.003) analyses. Network analysis showed that self-reported SB had a direct positive edge to insomnia, while PSG-confirmed SB was not significantly associated with any of the other variables. Thus, sleep bruxism was positively associated with insomnia only when self-reported, while PSG-confirmed SB was not associated with any of the included factors.

The interplay between X-chromosome functional dosage and circadian regulation in females.

PURPOSE: Biological factors and mechanisms that drive higher prevalence of insomnia in females are poorly understood. This study focused on the neurological consequences of X-chromosome functional imbalances between sexes. METHODS: Benefited from publicly available large-scale genetic, transcriptional and epigenomic data, we curated and contrasted different gene lists: (1) X-liked genes, including assignments for X-chromosome inactivation patterns and disease associations; (2) sleep-associated genes; (3) gene expression markers for the suprachiasmatic nucleus. RESULTS: We show that X-linked markers for the suprachiasmatic nucleus are significantly enriched for clinically relevant genes in the context of rare genetic syndromes and brain waves modulation. CONCLUSION: Considering female-specific patterns on brain transcriptional programs becomes essential when designing health care strategies for mental and sleep illnesses with sex bias in prevalence.

The relationship between irritable bowel syndrome, the gut microbiome, and obstructive sleep apnea: the role of the gut-brain axis.

Sleep disruption, especially that resulting from obstructive sleep apnea (OSA) - a widely prevalent sleep disorder - can lead to important systemic repercussions. We raise a subject of current interest, namely the possible relationship between sleep in general, OSA, and irritable bowel syndrome (IBS), an intestinal disease that can be made worse by stressful events. The intermittent hypoxia caused by OSA can induce alterations in the gut microbiota, which can lead to the dysregulation of the gut-brain axis and the worsening of IBS. This may be considered to be a circular relationship, with OSA playing a crucial role in the worsening of bowel symptoms, which in turn have a negative effect on sleep. Thus, based on previous evidence, we suggest that improving sleep quality could be a key to disrupting this relationship of IBS aggravation and OSA.

How do phases of the menstrual cycle affect sleep? A polysomnographic study of the EPISONO database.

PURPOSE: Our study aimed to evaluate the impact of the menstrual cycle stages, especially menses, on sleep, inflammatory mediators, fatigue, anxiety, depression, and quality of life. METHODS: We used data from the EPISONO study cohort, selecting 96 women who had undergone one-night polysomnography. The women were distributed in three groups according to the time point of the menstrual cycle on the polysomnography night: menses, mid/late follicular phase, and luteal phase. The volunteers completed questionnaires related to sleep quality, daytime sleepiness, insomnia, fatigue, anxiety, depression, and quality of life. Blood samples were collected to analyze interleukin 6, tumor necrosis factor-alpha, and C-reactive protein. RESULTS: Sleep efficiency was statistically higher in women in the mid/late follicular group (89.9% ± 9.6) compared to menstrual (83.0% ± 10.8) and luteal (83.7% ± 12.7) groups. The mid/late follicular group presented a statistically significant reduction in sleep onset latency (7.1 ± 7.1 min) compared to the menstrual (22.3 ± 32.4 min) and luteal groups (15.9 ± 14.7 min). No statistical differences among the three groups were observed in other polysomnographic parameters, inflammatory mediators, daytime sleepiness, insomnia, fatigue, anxiety, depression, and quality of life. CONCLUSIONS: Our findings demonstrate that the mid/late follicular phase might be beneficial for women's sleep, although there were no statistically changes in inflammatory mediators among the groups.

Insomnia Symptoms and Menstrual Health: Is There a Link in Women During Reproductive Phase of Life?

OBJECTIVES: To investigate the association between insomnia severity symptoms and menstrual health, fatigue and anxiety symptoms in women at reproductive age. METHOD: We used data from EPISONO (2007), an epidemiological study from the city of São Paulo, Brazil. Women completed the Insomnia Severity Index (ISI), the Chalder Fatigue Scale (CFS), and the Beck Anxiety Inventory (BAI) to obtain information about insomnia, fatigue, and anxiety symptoms. For menstrual health, we collected information using our Institutional Women's Questionnaire about menstrual flow and duration, the presence of pain during menstruation and menstrual cycle regularity. The statistical analysis was performed using ordinal logistic regression, considering p < .05. RESULTS: Of the 1,042 participants, only 282 women met the inclusion criteria to participate in this study. The mean age was 34.4 years (SD ± 8.36), and the body mass index (BMI) was 25.7 (SD ± 5.39). According to the model, a 1-unit higher CFS score increased the odds of having more insomnia symptoms in the ISI (OR = 1.170; 95% CI=[1.073; 1.279]; p < .001). In the same way, a 1-unit higher BAI score increased the chance of presenting insomnia symptoms, according to the ISI (OR = 1.072; 95% CI=[1.042; 1.104]; p < .001). The menstrual variables did not represent statistical significance in the model. CONCLUSIONS: Fatigue and anxiety symptoms were associated with insomnia symptoms; however, no association was observed between menstrual health and insomnia. The need to examine sleep when there are sleep complaints is essential to provide an accurate diagnosis that facilitates appropriate treatment and to provide better sleep quality for women.

Homocysteine as a predictor of apnea-hypopnea index in obstructive sleep apnea: a longitudinal epidemiological study (EPISONO).

BACKGROUND: Obstructive sleep apnea (OSA) affects nearly 1 billion people globally, and has established links with cardiovascular and neurocognitive complications. Although it has some limitations, the apnea-hypopnea index (AHI) is commonly used to gauge OSA severity and therapeutic response. Homocysteine (Hcy) metabolism, when impaired, can elicit cellular senescence mechanisms that may be shared with OSA. Hence, our objective was to explore the role of Hcy concentrations both as a predictor of AHI values and as a potential risk factor for OSA. METHODS: Involving 1042 volunteers aged 20 to 80 years, the initial study (2007) included polysomnographic evaluations, questionnaires on sleep and general health, as well as biochemical analyses. After an 8-year interval, 715 participants from the initial study were invited for a follow-up assessment in 2015. RESULTS: Our findings showed that Hcy was a predictor for an increased AHI, and AHI increased over time. Individuals with plasma Hcy concentrations ≥ 15 µmol/L experienced an average AHI increase of 7.43 events/hour ([beta coefficient] ß = 7.43; 95%CI 2.73 to 12.13) over time, compared to those with plasma concentrations < 10 µmol/L. A similar trend was apparent in those with plasma Hcy concentrations between 10 ≥ and < 15 µmol/L, who had an AHI increase with an average beta coefficient of 3.20 events/hour (95%CI 1.01 to 5.39) compared to those with plasma Hcy concentrations < 10 µmol/L. CONCLUSIONS: In summary, our study suggests that increased plasma Hcy concentrations could be considered a risk factor for the development of OSA. These findings highlight that elevated plasma Hcy concentrations can predict the severity of OSA, underscoring their correlation with the AHI.

Genetic basis of sleep phenotypes and rare neurodevelopmental syndromes reveal shared molecular pathways.

Sleep-related phenotypes have been frequently reported in early on-set epileptic encephalopathies and in developmental delay syndromes, in particular in syndromes related to autism spectrum disorder. Yet the convergent pathogenetic mechanisms between these comorbidities are largely unknown. We first performed a gene enrichment study that identified shared risk genes among rare epileptic encephalopathies/neurodevelopmental disorders, rare developmental delay genetic syndromes and sleep disturbances. We then determined cellular and molecular pathways enriched among genes shared between sleep phenotypes and those two early onset mental illnesses, aiming to identify genetic disparities and commonalities among these phenotypic groups. The sleep gene set was observed as significantly overlapped with the two gene lists associated to rare genetic syndromes (i.e., epileptic encephalopathies/neurodevelopmental disorders and developmental delay gene sets), suggesting shared genetic contribution. Similarities across significantly enriched pathways between the two intersect lists comprehended mostly synapse-related pathways, such as retrograde endocannabinoid signaling, serotonergic, and GABAergic synapse. Network analysis indicates epileptic encephalopathies/neurodevelopmental disorders versus sleep-specific clusters and developmental delay versus sleep-specific clusters related to synaptic and transcriptional regulation, respectively. Longstanding functional patterns previously described in epileptic encephalopathies and neurodevelopmental disorders genetic architecture were recaptured after dissecting the overlap between the genes associated to those developmental phenotypes and sleep disturbances, suggesting that during neurodevelopment different molecular and functional mechanisms are related to alterations on circadian rhythm. The overlapping gene set and biological pathways highlighted by this study may serve as a primer for new functional investigations of shared molecular mechanisms between sleep disturbances and rare developmental syndromes.

Do nocturnal asthma attacks influence sleep parameters and inflammatory markers? A cross-sectional population-based study.

PURPOSE: To evaluate the effects of nocturnal asthma on sleep parameters and inflammatory markers according to the severity of the condition in participants in the São Paulo Epidemiologic Sleep Study (EPISONO). METHODS: Data from the 2007 and 2018 editions of the EPISONO study were utilized. Subjects completed validated sleep and respiratory questionnaires, underwent nocturnal polysomnography and spirometry tests, and provided blood samples for the assessment of inflammatory parameters. RESULTS: Of 72 participants (67% women), 53% (n = 38) had intermittent nocturnal asthma symptoms and 47% (n = 34) had persistent asthma (mild, moderate, and severe). Individuals with persistent nocturnal symptoms had a higher body mass index (BMI), were more likely to have respiratory symptoms, and had worse lung function, a higher apnea-hypopnea index (AHI), and higher desaturation index than individuals with intermittent nocturnal symptoms. Positive associations were identified between nocturnal asthma and obstructive sleep apnea (OSA). A higher frequency of OSA was observed in participants with persistent asthma and participants with OSA were more likely to have persistent than intermittent asthma. However, there were no significant differences between the immunological parameters of those with intermittent or persistent asthma. CONCLUSIONS: This study highlights the relevance of nocturnal symptoms as a valuable indicator of asthma severity. The findings also add to the existing body of evidence linking nocturnal asthma and OSA.

The influence of age on the frequency of rhythmic masticatory muscle activity during sleep in general population differs from that in clinical research samples.

BACKGROUND: During sleep, limb and jaw muscle motor activity can be quantified by electromyography (EMG). The frequency of periodic limb activity during sleep increases with age in both the general and clinical research populations. The literature is controversial regarding stability, over age, of the frequency of rhythmic masticatory muscle activity (RMMA), which is one biomarker of sleep bruxism (SB). OBJECTIVES: The purpose of this retrospective sleep laboratory study was to assess if any change in RMMA frequency occurs over age in the general population (GP) and two clinical research (CR) samples. METHODS: RMMA signals from polysomnography (PSG) recordings of 465 individuals, irrespective of SB awareness, were analysed. The sample comprised 164 individuals from the GP of Sao Paulo, and 301 individuals from Montreal and Osaka CR samples. Data were divided into two subgroups, younger (15-39) and older (40-80) participants. RMMA was classified as low frequency (<2 events/h) or high (≥2 events/h). Pearson correlation (R) and B (slope) analyses were performed with power estimations. RESULTS: In the GP sample, no significant change over age was noted in the RMMA index/year. In the CR samples, a significant reduction was observed in the RMMA index/year (-0.05) with age (R2  = .042; p < .001; 3.5 to 1.5 RMMA/h from 20 to 60 years old). CONCLUSIONS: In the GP, the RMMA index remained stable over age. In the CR samples, a significant, reduction was observed. Prospective studies with multiple home sleep recordings, in both general and clinical research populations, are needed before extrapolating from the present findings.

Sleep loss and the skin: Possible effects of this stressful state on cutaneous regeneration during nocturnal dermatological treatment and related pathways.

Cutaneous homeostasis can be modulated by sleep. Although there is little evidence about the efficacy of medications topically applied in the morning compared to those administered in the evening, they are commonly prescribed to be used overnight. Poor sleep may affect the tegument, but its repercussion on dermatological therapy is not clear. This communication aims to carry out an overview on the relationship between sleep and the skin, particularly in respect of the effectiveness of topical substances during the night versus the day; and the possible impact of sleep dysregulation on these treatments. Features related to this external organ, involving hydration, blood flow, and the permeability of the superficial barrier have physiological variations in sleep period. Our hypothesis is that sleep loss could alter drug absorption in the dermis and impair the success of the treatment. This can depend on the integrity of the mechanical skin barrier, and the enzymatic process after drug penetration, which may be influenced by the circadian rhythm. We raise the role of sleep disturbance in relation to skin aging and the cutaneous microbiota. The organ integrity and local immunology can be guided by sleep distress, which can modify the control of dermatological diseases. Future comparative analyses are warranted to explore the possible changes of the integumentary system influenced by circadian rhythm, and interference in response to topical dermal treatments. We emphasize the importance of sufficient sleep to improve the clinical management of several dermatosis and cosmetic complaints that need percutaneous therapeutics.

Bidirectional Association Between Sleep Quality and Low Back Pain in Older Adults: A Longitudinal Observational Study.

OBJECTIVE: To investigate the bidirectional relationship by determining whether baseline sleep quality predicts pain intensity and whether baseline pain intensity predicts sleep quality in older individuals with chronic low back pain (LBP). DESIGN: A prospective longitudinal cohort study with a 6-month follow-up period. SETTING: Community. PARTICIPANTS: Older adults with LBP aged 60 years or older (N=215). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Data collection occurred at baseline and at 6 months. Pain intensity and sleep quality were measured in both time points of assessment using the numeric pain rating scale (range, 0-10) and the Pittsburg Sleep Quality Index. At baseline, we also collected information on demographic anthropometric variables, cognitive status, depression, and comorbidities. Multivariable linear regression analyses adjusted for potential covariates were performed. RESULTS: A total of 215 individuals with LBP were recruited. Poor sleep quality at baseline predicted high pain intensity at 6 months (ß coefficient, 0.18; 95% confidence interval [CI], 0.07-0.30). High pain intensity at baseline predicted poor sleep quality 6 months later (ß coefficient, 0.14; 95% CI, 0.01-0.26). CONCLUSION: Our findings give some support to the bidirectional relationship between pain and sleep quality in older individuals with LBP. This bidirectional relationship may be used as prognostic information by clinicians when managing patients with LBP.

Role of epigenetic regulatory enzymes in animal models of mania induced by amphetamine and paradoxical sleep deprivation.

It is known that bipolar disorder has a multifactorial aetiology where the interaction between genetic and environmental factors is responsible for its development. Because of this, epigenetics has been largely studied in psychiatric disorders. The present study aims to evaluate the effects of histone deacetylase inhibitors on epigenetic enzyme alterations in rats or mice submitted to animal models of mania induced by dextro-amphetamine or sleep deprivation, respectively. Adult male Wistar rats were subjected to 14 days of dextro-amphetamine administration, and from the eighth to the fourteenth day, the animals were treated with valproate and sodium butyrate in addition to dextro-amphetamine injections. Adult C57BL/6 mice received 7 days of valproate or sodium butyrate administration, being sleep deprived at the last 36 hr of the protocol. Locomotor and exploratory activities of rats and mice were evaluated in the open-field test, and histone deacetylase, DNA methyltransferase, and histone acetyltransferase activities were assessed in the frontal cortex, hippocampus, and striatum. Dextro-amphetamine and sleep deprivation induced hyperactivity and increased histone deacetylase and DNA methyltransferase activities in the animal's brain. Valproate and sodium butyrate were able to reverse hyperlocomotion induced by both animal models, as well as the alterations on histone deacetylase and DNA methyltransferase activities. There was a positive correlation between enzyme activities and number of crossings for both models. Histone deacetylase and DNA methyltransferase activities also presented a positive correlation between theirselves. These results suggest that epigenetics can play an important role in BD pathophysiology as well as in its treatment.

Effects of sleep deprivation on maternal behaviour in animal models: A systematic review and meta-analysis.

Pregnancy is a period of numerous physical and emotional changes in women's lives, including alterations in sleep patterns and worsening of pre-existing sleep disturbances, which possibly lead to impaired postpartum maternal behaviour and mother-infant relationship. The effects of sleep deprivation during pregnancy in maternal behaviour have been evaluated in preclinical studies, but have provided inconsistent results. Thus, in the present study, we aimed to evaluate the effects of sleep deprivation during pregnancy on maternal behaviour of animals through a systematic review and meta-analyses. After a two-step selection process, six articles were included, all of them describing rat studies. The most frequently used method of sleep deprivation was rapid eye movement sleep restriction, using the multiple-platform method. Four meta-analyses were performed, none of them presenting significant impact of sleep deprivation on maternal behaviour, failing to reproduce the results observed in previous clinical studies. In conclusion, our results show a lack of translational applicability of animal models to evaluate the effects of sleep deprivation during pregnancy on maternal behaviour.

Disruption of neocortical synchronisation during slow-wave sleep in the rotenone model of Parkinson's disease.

Parkinson's disease motor dysfunctions are associated with improperly organised neural oscillatory activity. The presence of such disruption at the early stages of the disease in which altered sleep is one of the main features could be a relevant predictive feature. Based on this, we aimed to investigate the neocortical synchronisation dynamics during slow-wave sleep (SWS) in the rotenone model of Parkinson's disease. After rotenone administration within the substantia nigra pars compacta, one group of male Wistar rats underwent sleep-wake recording. Considering the association between SWS oscillatory activity and memory consolidation, another group of rats underwent a memory test. The fine temporal structure of synchronisation dynamics was evaluated by a recently developed technique called first return map. We observed that rotenone administration decreased the time spent in SWS and altered the power spectrum within different frequency bands, whilst it increased the transition rate from a synchronised to desynchronised state. This neurotoxin also increased the probability of longer and decreased the probability of shorter desynchronisation events. At the same time, we observed impairment in object recognition memory. These findings depict an electrophysiological fingerprint represented by a disruption in the typical oscillatory activity within the neocortex at the early stages of Parkinson's disease, concomitant with a decrease in the time spent in SWS and impairment in recognition memory.

Sleep deficit in COVID-19 health-care workers may increase the infection risk.

The COVID-19 pandemic has had negative effects on health-care workers. The rapid growth of the disease has led to overwhelmed health-care systems, overcrowded hospitals, an insufficient number of health-care professionals and shortages of medical equipment. The potential exposure of front-line health-care workers during the COVID-19 outbreak has led to self-isolation and the appearance of adverse feelings such as stress, anxiety and fear. All these factors, combined with an increased workload and extra and changed shifts, are determinants of a sleep-loss process that may result in insomnia. The exacerbated pro-inflammatory milieu caused by insomnia and sleep deprivation present in health professionals may therefore make them more prone to developing severe COVID-19 if infected and/or aggravate the symptoms of the disease. Keeping these professionals healthy and doing everything possible to prevent them from being infected with COVID-19 should be a top priority. As part of this effort, we must be aware of the important effects of insomnia on the immune systems of these professionals and take all possible measures to counter these effects.

Invariant Natural Killer T cells resilience to paradoxical sleep deprivation-associated stress.

Although several studies demonstrate that stressful situations, such as sleep disturbances, negatively impact the innate and adaptive arms of the immune system, their influence on invariant Natural Killer T (iNKT) cells remains unclear. iNKT cells are CD1d-restricted innate T cells that recognize glycolipid antigens and rapidly produce polarizing cytokines being key players in several immune responses, and a potential target for immunotherapy. iNKT cells differ in several aspects from conventional T lymphocytes, including a unique dependence on CD1d-expressing double-positive (DP) thymocytes for intrathymic maturation. As a consequence of stress, DP thymocytes undergo glucocorticoid-induced apoptosis, which might compromise iNKT developmental pathway. Therefore, we used a paradoxical sleep deprivation (SD) model to determine the impact of sleep disturbance on iNKT cell biology. After 72 h of SD, C57Bl/6 mice exhibited a significant increase in systemic glucocorticoid levels and thymus atrophy. Despite marked decrease in the number of DP thymocytes, the ratio CD1d+/CD1d- was higher in SD mice, and the number of thymic iNKT cells remained unaltered, suggesting that SD did not compromise the iNKT developmental pathway. In contrast, SD reduced hepatic IFN-γ, but not, IL-4-producing iNKT cells, without further effect in the spleen. Despite this fact, SD did not affect stimulation of IFN-γ production by iNKT cells, or cytokine release, in response to α-galactosylceramide, a specific antigen. Furthermore, although SD impaired splenic NK cells activity against tumor cells, it did not affect iNKT cell-specific cytotoxicity. Thus, our study shows that SD-induced stress did not impair the iNKT cells' responses to a cognate antigen.

Efficacy of folic acid as an adjunct to lithium therapy on manic-like behaviors, oxidative stress and inflammatory parameters in an animal model of mania.

Evaluate the efficacy of folic acid (FA) as a therapeutic adjunct to lithium (Li) on the manic-like behaviors as well as parameters of oxidative stress and inflammation in an animal model of mania induced by m-amphetamine (m-AMPH). Wistar rats first received m-AMPH or saline (NaCl 0.9%, Sal) for 14 days. Between the 8th and 14th day, rats were treated with water, Li, FA or a combination of thereof drugs (Li + FA). Manic-like behaviors were assessed in the open-field test. Oxidative stress and inflammation parameters were assessed in the frontal cortex, striatum, and hippocampus. Administration of m-AMPH in rats significantly enhanced the exploratory and locomotor behaviors, as well as the risk-taking and stereotypic behaviors. Li + FA reversed these behavioral alterations elicited by m-AMPH. Administration of this psychostimulant also increased oxidative damage to lipids and proteins, whereas Li + FA reversed these oxidative damages. m-AMPH also induced an increase in the glutathione peroxidase (GPx) activity and a decrease in the glutathione reductase (GR) activity. Li + FA reversed the alteration in GR activity, but not in GPx activity. In addition, m-AMPH increased the IL-1ß and TNF-α levels in the rat brain; Li + FA combined therapy reversed the alterations on these inflammatory parameters. FA administration per se reduced the increased TNF-α content induced by m-AMPH. Present study provides evidence that FA is effective as an adjunct to Li standard therapy on manic-like behaviors, oxidative stress and inflammatory parameters in a model of mania induced by m-AMPH.

The effects of cannabidiol on male reproductive system: A literature review.

Cannabidiol (CBD) is one of the most abundant phytocannabinoids present in the plant Cannabis sativa (marijuana). There have been several studies of CBD in the last few decades, mainly focused on its neuroprotective properties, particularly after the identification of the endocannabinoid system and its participation in the central nervous system. On the other hand, the peripheral effects of CBD, particularly on reproductive physiology, were also evidenced. A narrative review was conducted using the PubMed database to identify studies that analyzed the pharmacological effects of CBD on the male reproductive system of vertebrates and invertebrates. Thirty-two citations (in vivo and in vitro) were identified. Among the vertebrates, the studies were carried out with men, monkeys, rats and mice. Studies with invertebrates are centered exclusively on the sea urchin. The CBD treatment periods include mostly acute and subacute evaluations. Exposure to CBD is associated with a reduction in mammalian testis size, the number of germ and Sertoli cells in spermatogenesis, fertilization rates, and plasma concentrations of hypothalamic, pituitary and gonadal hormones. Moreover, chronic doses of CBD have impaired sexual behavior in mice. From the studies identified in this review, it is possible to conclude that CBD has negative effects on the reproductive system of males. However, knowledge is still limited, and additional research is required to elucidate fully the mechanisms of action, as well as the reversibility of CBD effects on the reproductive system.