Poor quality of sleep in Mexican patients with type 2 diabetes and its association with lack of glycemic control.

AIMS: To determine the association between sleep quality and lack of glycemic control in a Mexican population of type 2 diabetes patients. METHODS: Cross-sectional study. Two hundred two patients between 20 and 60 years old with a previous diagnosis of diabetes were included. Sleep quality was assessed with the Pittsburgh Sleep Quality Index and lack of glycemic control as a glycated hemoglobin A1c level ≥ 7 %. Univariate and multivariate analyses using logistic regression were performed. RESULTS: The study population showed poor sleep quality and a lack of glycemic control of 70.3 % and 69.8 %, respectively. The prevalence of patients with both conditions was 52.5 %. In multivariate analysis, poor sleep quality was significantly associated with a lack of glycemic control (OR = 2.3, p = 0.030). Other associated variables were napping (p = 0.015), diabetes duration (p = 0.011), insulin use (p = 0.024), and diastolic blood pressure ≥ 85 mmHg (p = 0.029). CONCLUSIONS: The prevalence of lack of glycemic control in the study population is high. Poor sleep quality significantly doubles the risk of lack of glycemic control, even in the presence of other risk factors.

Effect of a Hedonic Stimulus on the Sleep Architecture of Male Wistar Rats.

Objective Nocturnal animals forage and eat during the night and sleep during the day. When food is available only for a short period during the day, animals develop a catabolic state and exhibit locomotor behavior before accessing food, termed food anticipatory activity . Consequently, there is a disruption in the sleep pattern. The present study aimed to explore how anticipatory arousal emerges under circadian exposure to a palatable meal (PM) and disrupts sleep architecture. Materials and Methods Adult male Wistar rats were implanted with electrodes for continuous sleep recording and housed under a light/dark 12/12-hour cycle with free access to food and water. After basal recordings, the rats had access to a PM during the light period for eight days. Results The anticipatory arousal started on the third day. On the eighth day, we found an increase in wake time and a decrease in the non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) times 45 minutes before the PM compared with the basal recordings. The REMS transitions (events from NREMS to REMS) showed a significant reduction during the light period of the eighth day of PM. In contrast, the number of NREMS transitions (events from wakefulness to NREMS) remained unchanged. Conclusion The results suggest that palatable food induces a motivational timing that leads the rat to wake by altering the sleep quota.

The Role of Neuroglobin in the Sleep-Wake Cycle.

Neuroglobin (Ngb) is a protein expressed in the central and peripherical nervous systems of the vertebrate. The Ngb has different functions in neurons, including regulating O 2 homeostasis, oxidative stress, and as a neuroprotector after ischemia/hypoxia events. The Ngb is a hemoprotein of the globin family, structurally like myoglobin and hemoglobin. Ngb has higher expression in the cortex, hypothalamus, thalamus, brainstem, and cerebellum in mammals. Interestingly, Ngb immunoreactivity oscillates according to the sleep-wake cycle and decreases after 24 hours of sleep deprivation, suggesting that sleep homeostasis regulates Ngb expression. In addition, Ngb expresses in brain areas related to REM sleep regulation. Therefore, in the present review, we discuss the potential role of the Ngb in the sleep-wake regulation of mammals.

Leptin and adiponectin regulate the activity of nuclei involved in sleep-wake cycle in male rats.

Epidemiological and experimental evidence recognize a relationship between sleep-wake cycles and adiposity levels, but the mechanisms that link both are not entirely understood. Adipose tissue secretes adiponectin and leptin hormones, mainly involved as indicators of adiposity levels and recently associated to sleep. To understand how two of the main adipose tissue hormones could influence sleep-wake regulation, we evaluated in male rats, the effect of direct administration of adiponectin or leptin in the ventrolateral preoptic nuclei (VLPO), a major area for sleep promotion. The presence of adiponectin (AdipoR1 and AdipoR2) and leptin receptors in VLPO were confirmed by immunohistochemistry. Adiponectin administration increased wakefulness during the rest phase, reduced delta power, and activated wake-promoting neurons, such as the locus coeruleus (LC), tuberomammillary nucleus (TMN) and hypocretin/orexin neurons (OX) within the lateral hypothalamus (LH) and perifornical area (PeF). Conversely, leptin promoted REM and NREM sleep, including increase of delta power during NREM sleep, and induced c-Fos expression in VLPO and melanin concentrating hormone expressing neurons (MCH). In addition, a reduction in wake-promoting neurons activity was found in the TMN, lateral hypothalamus (LH) and perifornical area (PeF), including in the OX neurons. Moreover, leptin administration reduced tyrosine hydroxylase (TH) immunoreactivity in the LC. Our data suggest that adiponectin and leptin act as hormonal mediators between the status of body energy and the regulation of the sleep-wake cycle.

Sleep loss and addiction.

Reducing sleep hours is a risk factor for developing cardiovascular, metabolic, and psychiatric disorders. Furthermore, previous studies have shown that reduction in sleep time is a factor that favors relapse in addicted patients. Additionally, animal models have demonstrated that both sleep restriction and sleep deprivation increase the preference for alcohol, methylphenidate, and the self-administration of cocaine. Therefore, the present review discusses current knowledge about the influence of sleep hours reduction on addictivebehaviors; likewise, we discuss the neuronal basis underlying the sleep reduction-addiction relationship, like the role of the orexin and dopaminergic system and neuronal plasticity (i.e., delta FosB expression). Potentially, chronic sleep restriction could increase brain vulnerability and promote addictive behavior.

Neurobiology of Dream Activity and Effects of Stimulants on Dream.

The sleep-wake cycle is the result of the activity of multiple neurobiological network interactions. The dreaming feature is one interesting sleep on that represents sensorial components, mostly visual perceptions, accompaniedby intense emotions. Further complexity has been added to the topic of the neurobiological mechanism of dream generation by the current data suggesting drugs' influence on dream generation. Here, we discuss the review of some of the neurobiological mechanisms of the regulation of dream activity, with special emphasis on the effects of stimulants on dreaming.

The role of growth hormone in hippocampal function.

Growth hormone is a multifunctional molecule with broad cellular targets. This pituitary hormone is currently used as a therapeutic agent against several brain injuries due to its neurotrophic activity. The hippocampus is one of the brain regions where the growth hormone plays a role in normal and pathologic conditions. This brain structure is associated with several cognitive functions such as learning, memory, and mood, which are frequently affected by brain traumatism. The present chapter describes the experimental and clinical evidence that supports a central role of growth hormone in the hippocampus functionality.

Stimulants and Depressor Drugs in the Sleep-wake Cycle Modulation: The Case of Alcohol and Cannabinoids.

A complex neurobiological network drives the sleep-wake cycle. In addition, external stimuli, including stimulants or depressor drugs, also influence the control of sleep. Here we review the recent advances that contribute to the comprehensive understanding of the actions of stimulants and depressor compounds, such as alcohol and cannabis, in sleep regulation. The objective of this review is to highlight the neurobiological mechanism engaged by alcohol and cannabis in sleep control.

Health-Related Fitness as a Predictor of Anxiety Levels Among School Adolescents: An observational cross-sectional study.

Background: There is an inverse association between cardiorespiratory fitness and general anxiety levels in adolescents. Obesity also is associated with a higher risk of anxiety in this population. However, little is known about the association between other health-related fitness elements with anxiety symptoms in this population. The authors explored the relationship between health-related fitness and anxiety symptoms in a large sample of Brazilian youth. Methods: This was an observational cross-sectional study with a sample comprised of 257 school adolescents, who were 136 girls (52.9%) and 121 boys (47.1%). The health-related fitness elements were evaluated by FitnessGram® test and anxiety levels by Multidimensional Anxiety Scale for Children - 39. Hierarchical regression analyses were used to determine the association between health-related fitness elements and anxiety symptoms in both sexes. Results: In male adolescents, only the cardiorespiratory fitness was significantly associated with anxiety symptoms (F(1, 119) = 6.472; P = 0.012; R2 = 0.052; adjusted R2 = 0.044). In turn, the anxiety symptoms showed an inverse small relationship with cardiorespiratory fitness (r = - 0.227; P < 0.01). However, in female adolescents, no association was found between health-related fitness elements and anxiety symptoms. Conclusion: The level of cardiorespiratory fitness may represent a marker of anxiety in male adolescents.

Maternal Separation Modifies the Activity of Social Processing Brain Nuclei Upon Social Novelty Exposure.

Maternal separation has been shown to disrupt proper brain development and maturation, having profound consequences on the neuroendocrine systems in charge of the stress response, and has been shown to induce behavioral and cognitive abnormalities. At the behavioral level, maternal separation has been shown to increase offensive play-fighting in juvenile individuals and reduce social interest in adulthood. Since most of the studies that have evaluated the consequences of maternal separation on social behavior have focused on behavioral analysis, there is a need for a further understanding of the neuronal mechanisms underlying the changes in social behavior induced by maternal separation. Therefore, the aim of the present research was to assess the long-term effects of maternal separation on social interaction behavior and to assess the activity of several brain regions involved in the processing of social cues and reward upon social novelty exposure, using c-Fos immunohistochemistry as a marker of neuronal activity. Male Wistar rats were subjected to 4 h maternal separation during the neonatal period, 9:00 h-13:00 h from postnatal day 1 to 21, and exposed to social novelty during adulthood. After social novelty exposure, brains were fixed and coronal sections of the medial amygdala, lateral septum (LS), paraventricular nucleus of the hypothalamus, nucleus accumbens, and medial prefrontal cortex were obtained for c-Fos immunohistochemistry. Maternally separated rats spent less time investigating the novel peer, suggesting that maternal separation reduces social approach motivation. Furthermore, maternal separation reduced the number of c-Fos positive cells of the medial amygdala, paraventricular nucleus of the hypothalamus, LS, nucleus accumbens, and medial prefrontal cortex upon social novelty exposure. These findings suggest that maternal separation can reduce the plastic capacity of several brain nuclei, which constitute a physiological basis for the emergence of behavioral disorders presented later in life reported to be linked to early life adversity.

CD38 Correlates with an Immunosuppressive Treg Phenotype in Lupus-Prone Mice.

CD38 is a transmembrane glycoprotein expressed by T-cells. It has been reported that patients with systemic lupus erythematosus (SLE) showed increased CD38+CD25+ T-cells correlating with immune activation and clinical signs. Contrariwise, CD38 deficiency in murine models has shown enhanced autoimmunity development. Recent studies have suggested that CD38+ regulatory T-cells are more suppressive than CD38- regulatory T-cells. Thus, we have suggested that CD38 overexpression in SLE patients could play a role in regulating immune activation cells instead of enhancing it. This study found a correlation between CD38 with FoxP3 expression and immunosuppressive molecules (CD69, IL-10, CTLA-4, and PD-1) in T-cells from lupus-prone mice (B6.MRL-Faslpr/J). Additionally, B6.MRL-Faslpr/J mice showed a decreased proportion of CD38+ Treg cells regarding wild-type mice (WT). Furthermore, Regulatory T-Cells (Treg cells) from CD38-/- mice showed impairment in expressing immunosuppressive molecules and proliferation after stimulation through the T-cell receptor (TCR). Finally, we demonstrated an increased ratio of IFN-γ/IL-10 secretion in CD38-/- splenocytes stimulated with anti-CD3 compared with the WT. Altogether, our data suggest that CD38 represents an element in maintaining activated and proliferative Treg cells. Consequently, CD38 could have a crucial role in immune tolerance, preventing SLE development through Treg cells.

Maternal behavior, novelty confrontation, and subcortical c-Fos expression during lactation period are shaped by gestational environment.

The environmental context during gestation may modulate the postpartum variations in maternal behaviors observed within different animal species. Most of our experimental knowledge on this phenomenon and its physiological effects have been gained by confronting the pregnant mother with stressful situations, with the consensual results indicating a reduced maternal behavior and a hyper reactivity of stress-related neural paths. Here, in contrast, by exposing nulliparous rats strictly during pregnancy to a standard laboratory environment (STD) or a highly stimulating sensory and social environment (EE), we investigated the hypothesis that subjects frequently exposed to social stimuli and novel situations during pregnancy will show postpartum changes in subcortical brain areas' activity related to the processing of social stimuli and novelty, such that there will be modifications in maternal behavior. We found that EE mothers doubled the levels of licking and grooming, and active hovering over pups during the first postpartum week than STD dams, without a difference in the time of contact with the pups. Associated with these behaviors, EE dams showed increased c-Fos immunoreaction in hypothalamic nuclei and distinct responses in amygdalar nuclei, than STD dams. In the maternal defensive test, EE dams tripled the levels of aggressive behaviors of the STD rats. Additionally, in two different tests, EE mothers showed lower levels of postpartum anxiety-like behaviors when confronted with novel situations. Our results demonstrate that the activity of brain areas related to social behavior is adaptable by environmental circumstances experienced during gestation, presumably to prepare the progeny for these particular conditions.

Increased alcohol consumption in sleep-restricted rats is mediated by delta FosB induction.

The reduction of sleep hours is a public health problem in contemporary society. It is estimated that humans sleep between 1.5 and 2 h less, per night, than 100 years ago. The reduction of sleep hours is a risk factor for developing cardiovascular, metabolic, and psychiatric problems. Previous studies have shown that low sleep quality is a factor that favors relapse in addicted patients. In rodents, sleep deprivation increases the preference for methylphenidate and the self-administration of cocaine. However, it is unknown whether chronic sleep restriction induces voluntary alcohol consumption in rats and whether alcohol intake is associated with delta FosB expression in the brain reward circuit. Potentially, chronic sleep restriction could make the brain vulnerable and consequently promote addictive behavior. Therefore, the present study's objective was to evaluate alcohol consumption in a chronic sleep restriction model and determine the expression of delta FosB in brains of adult rats. For this purpose, male Wistar rats (300-350 g body weight) were divided into four experimental groups (n = 6 each group): control (without manipulation), sleep restriction (SR) for 7 days, SR and ethanol exposure (Ethanol + SR), and a group with just ethanol exposure (Ethanol). At the end of the management, rats were sacrificed, and the brains were dissected and processed for immunohistochemical detection of delta FosB. The results showed that SR stimulates alcohol consumption compared to unrestricted-sleep rats and induces a significant increase in the number of delta FosB-positive cells in brain nuclei within the motivation/brain reward circuit. These results suggest that chronic reduction of sleep hours is a risk factor for developing a preference for alcohol consumption.

Sleep Recovery Restored Neuroglobin Immunoreactivity in Rat LDTg-PPTg Nuclei.

Neuroglobin (Ngb) is a protein member of the globin family, expressed mainly in the central and peripheral nervous system. It is involved in the transport of oxygen in response to hypoxic/ischemic and oxidative stress-related insults. We recently showed that sleep deprivation reduces the number of Ngb-positive cells in brain areas related to sleep. However, it is poorly understood whether Ngb expression correlates with sleep occurrence. Here, we aimed to study if sleep recovery produced by 24 h of sleep deprivation restores the number of Ngb-positive cells in the pedunculopontine tegmentum (PPTg) and laterodorsal tegmentum (LDTg), brain areas related to sleep-wake regulation. Male Wistar rats were sleep-deprived for 24 h using the gentle handling method. After sleep deprivation, rats were allowed a sleep recovery for three or six hours. After sleep recovery, rats were euthanized, and their brains processed for Ngb immunohistochemistry. We found that a 3 h sleep recovery is enough to restore the number of Ngb-positive cells in all the analyzed areas. A similar result was observed after a 6 h sleep recovery. These results suggest that Ngb expression is sleep dependent. We suggest that Ngb expression is involved in preventing cell damage due to prolonged wakefulness.

Naringenin mitigates autoimmune features in lupus-prone mice by modulation of T-cell subsets and cytokines profile.

Naringenin is flavonoid mainly found in citrus fruits which has shown several biological properties. In this work, we evaluated the therapeutic potential of the flavonoid Naringenin. Five-month-old B6.MRL-Faslpr/J lupus-prone mice were administered daily orally with Naringenin for seven months. We showed that Naringenin treatment at 50 or 100 mg/kg inhibited the splenomegaly and decreased the levels of anti-nuclear and anti-dsDNA autoantibodies. Furthermore, a reduction in serum concentration of TNF-α, IFN-γ and IL-6 was observed in the mice provided with Naringenin. Interestingly, serum levels of IL-10 increased. Naringenin decreased the frequency and absolute numbers of splenic effector memory T cells. Additionally, in order to be able to evaluate whether Naringenin prevented kidney damage, twelve-week-old MRL/MpJ-Faslpr/J mice, an accelerated lupus model, were orally administered with Naringenin at 100 mg/kg for six weeks. Surprisingly, Naringenin treatment prevented kidney damage and reduced the development of fibrosis similar to cyclophosphamide group. Moreover, Naringenin treatment increased the percentage of regulatory T cells in this aggressive model of lupus. Together, these results suggest a potential ability of Naringenin to reduce the autoimmunity in lupus-prone mice by modulation of T-cell subsets and cytokines profile that mitigate the development of important lupus clinical manifestations.

c-Fos immunoreactivity in the hypothalamus and reward system of young rats after social novelty exposure.

Socialization is an adaptive behavior during the early stages of life because it helps young animals become independent and determines healthy adult social behavior. Therefore, it is probable that the brain areas involved in the processing of social stimuli are more sensitive to social novelty during early life stages. To test this hypothesis, four groups of young male rats were exposed to different socioenvironmental stimuli; nonsocial physical novelty, social familiarity, social novelty, and a control group which received no stimulation. After stimuli exposure, brains were fixed and cut in coronal sections for c-Fos immunohistochemistry. The number of c-Fos-immunoreactive (c-Fos-ir) neurons in the paraventricular nucleus and supraoptic nucleus, the main producers of oxytocin and vasopressin, was compared, as well as in the nucleus accumbens and ventral pallidum, the main areas involved in reinforced behavior. A significantly higher number of c-Fos-ir neurons were found in animals exposed to social novelty in all areas, except in the supraoptic nucleus. In particular, the increase in c-Fos-ir in the paraventricular nucleus seems to be selective in response to social novelty, while the increase of c-Fos-ir in the nucleus accumbens and ventral pallidum suggests that social novelty during youth is a highly rewarding stimulus compared with social familiarity and nonsocial physical novelty.

Effect of orange juice and tryptamine on the behavior and c-fos expression of Wistar rats.

Recent reports have shown that commercial orange juice is rich in biogenic amines. Consumption of foods containing large amounts of biogenic amines increase hypertensive crisis and high levels of histamine and tyramine, which have been implicated as causative agents in a number of food poisoning episodes. In addition, accumulation of tryptamine in plasma may be associated with mood disorders. The aim of this study was to determine whether chronic administration of orange juice extract and tryptamine affects the behavior and c-fos expression in the rat. For this purpose, Wistar male rats were injected with saline solution, tryptamine or orange juice extract. Sucrose preference test and elevated plus maze were evaluated to determine hedonic and anxiety behavior, respectively. Rats treated with orange juice extract showed increased anxiety behavior and sucrose consumption, similar to those treated with tryptamine. In addition, dorsal raphe nucleus, accumbens nucleus, and hippocampus showed an increase of c-fos positive cells in rats treated with orange juice extract. In conclusion, the chronic and lengthy consumption of orange juice or their derivatives in the diet could be a factor responsible to induce mood disorders and may promote excess caloric consumption.

Characterization of sleep-pattern and neuro-immune-endocrine markers at 24 hour post-injection of a single low dose of lipopolysaccharide in male Wistar rats.

The long-term effect of immune system activation by a low dose of lipopolysaccharide on neuro-immune-endocrine regulation is unclear. Sleep, neurotransmitter concentrations, TNF-α, and corticosterone levels were evaluated in male Wistar rats implanted with conventional sleep recordings. In this work, we found that REM sleep was reduced in the first 4 h post-injection, without affecting the total sleep time, while adrenaline concentration was reduced in the hippocampus at 24 h post-injection of LPS. Our results demonstrated that, although the acute immune response was not evident 24 h after the injection of LPS, it was able to promote the reduction of AD in the hippocampus, which may explain in part the depressive behavior reported in rodents following LPS administration.

Intracerebroventricular administration of growth hormone induces morphological changes in pyramidal neurons of the hippocampus and prefrontal cortex in adult rats.

A growing body of evidence suggests that growth hormone (GH) affects synaptic plasticity at both the molecular and electrophysiological levels. However, unclear is whether plasticity that is stimulated by GH is associated with changes in neuron structure. This study investigated the effect of intracerebroventricular (ICV) administration of GH on the morphology of pyramidal neurons of the CA1 region of the dorsal hippocampus and layer III of the prefrontal cortex. Male Wistar rats received daily ICV injections of GH (120 ng) for 7 days, and they were euthanized 21 days later. Changes in neuronal morphology were evaluated using Golgi-Cox staining and subsequent Sholl analysis. GH administration increased total dendritic length in the CA1 region of the dorsal hippocampus and prefrontal cortex. The Sholl analysis revealed an increase in dendritic length of the third to eighth branch orders in the hippocampus and from the third to sixth branch orders in the prefrontal cortex. Interestingly, GH treatment increased the density of dendritic spines in both brain regions, favoring the presence of mushroom-like spines only in the CA1 hippocampal region. Our results indicated that GH induces changes in the length of dendritic trees and the density of dendritic spines in two high-plasticity brain regions, suggesting that GH-induced synaptic plasticity at the molecular and electrophysiological levels may be associated with these structural changes in neurons.