Volumetric Differences in Cerebellum and Brainstem in Patients with Migraine: A UK Biobank Study.

Background: The cerebellum and the brainstem are two brain structures involved in pain processing and modulation that have also been associated with migraine pathophysiology. The aim of this study was to investigate possible associations between the morphology of the cerebellum and brainstem and migraine, focusing on gray matter differences in these brain areas. Methods: The analyses were based on data from 712 individuals with migraine and 45,681 healthy controls from the UK Biobank study. Generalized linear models were used to estimate the mean gray matter volumetric differences in the brainstem and the cerebellum. The models were adjusted for important biological covariates such as BMI, age, sex, total brain volume, diastolic blood pressure, alcohol intake frequency, current tobacco smoking, assessment center, material deprivation, ethnic background, and a wide variety of health conditions. Secondary analyses investigated volumetric correlation between cerebellar sub-regions. Results: We found larger gray matter volumes in the cerebellar sub-regions V (mean difference: 72 mm3, 95% CI [13, 132]), crus I (mean difference: 259 mm3, 95% CI [9, 510]), VIIIa (mean difference: 120 mm3, 95% CI [0.9, 238]), and X (mean difference: 14 mm3, 95% CI [1, 27]). Conclusions: Individuals with migraine show larger gray matter volumes in several cerebellar sub-regions than controls. These findings support the hypothesis that the cerebellum plays a role in the pathophysiology of migraine.

Migraine, inflammatory bowel disease and celiac disease: A Mendelian randomization study.

OBJECTIVE: To assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease. BACKGROUND: Migraine has been linked to IBD and celiac disease in observational studies, but whether this link may be explained by a shared genetic basis or could be causal has not been established. The presence of a causal association could be clinically relevant, as treating one of these medical conditions might mitigate the symptoms of a causally linked condition. METHODS: Linkage disequilibrium score regression and two-sample bidirectional Mendelian randomization analyses were performed using summary statistics from cohort-based genome-wide association studies of migraine (59,674 cases; 316,078 controls), IBD (25,042 cases; 34,915 controls) and celiac disease (11,812 or 4533 cases; 11,837 or 10,750 controls). Migraine with and without aura were analyzed separately, as were the two IBD subtypes Crohn's disease and ulcerative colitis. Positive control analyses and conventional Mendelian randomization sensitivity analyses were performed. RESULTS: Migraine was not genetically correlated with IBD or celiac disease. No evidence was observed for IBD (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.99-1.02, p = 0.703) or celiac disease (OR 1.00, 95% CI 0.99-1.02, p = 0.912) causing migraine or migraine causing either IBD (OR 1.08, 95% CI 0.96-1.22, p = 0.181) or celiac disease (OR 1.08, 95% CI 0.79-1.48, p = 0.614) when all participants with migraine were analyzed jointly. There was some indication of a causal association between celiac disease and migraine with aura (OR 1.04, 95% CI 1.00-1.08, p = 0.045), between celiac disease and migraine without aura (OR 0.95, 95% CI 0.92-0.99, p = 0.006), as well as between migraine without aura and ulcerative colitis (OR 1.15, 95% CI 1.02-1.29, p = 0.025). However, the results were not significant after multiple testing correction. CONCLUSIONS: We found no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease, although we obtained some indications of causal associations with migraine subtypes.

Effect of worry, depression, and sensitivity to environmental stress owing to neurotic personality on risk of cardiovascular disease: A Mendelian randomization study.

OBJECTIVE: This study investigated the putative causal link between neuroticism (using three genetically distinct subclusters namely depressed affect, worry, and sensitivity to environmental stress and adversity [SESA]) and cardiovascular disease (CVD). METHOD: A two-sample bi-directional Mendelian randomization (MR) approach was used. Genetic instruments were extracted from publically available GWAS summary statistics. RESULTS: In forward MR analyses with neuroticism subclusters as exposures, no causal associations between worry or SESA cluster and any of the CVD traits were observed (p > .05 for all). However, a higher risk of having heart failure (odds ratio (95% confidence interval):1.32(1.12 to 1.56); p = .0011) and myocardial infarction (1.47[1.18 to 1.83]; p = 6.3 × 10-4) associated with depressed affect cluster was observed. In reverse MR analyses with CVD traits as exposures, no significant associations were observed (p > .05 for all). CONCLUSIONS: Individuals with high neuroticism who are more susceptible to depressive symptoms are at higher risk for developing heart failure and myocardial infarction and should be more carefully evaluated for CVD risk in clinical settings. These individuals can potentially benefit from interventions aimed at reducing depressive symptoms to decrease CVD risk. There is no evidence to suggest that being sensitive to environmental stressors or being more worried can increase the risk for CVD.

Evidence of a Causal Link Between the Well-Being Spectrum and the Risk of Myocardial Infarction: A Mendelian Randomization Study.

Epidemiological studies have provided extensive evidence regarding the role of psychological risk factors in the pathogenesis of cardiovascular disease (CVD), but whether these associations are causal in nature is still unknown. We aimed to investigate whether the association between the wellbeing spectrum (WBS; derived from four psychological traits including life satisfaction, positive affect, neuroticism, and depressive symptoms) and CVD risk is causal. By employing a two-sample Mendelian randomization (MR) approach, the effect of the WBS on four CVD outcomes, including atrial fibrillation, heart failure, myocardial infarction, and ischemic stroke, was investigated. The genetically predicted WBS was associated with 38% lower risk for heart failure (odds ratio (OR): 0.62; 95% confidence interval [CI]: 0.50-0.78; P: 2.2 × 10-5) and 40% reduced risk of myocardial infarction (OR: 0.60; 95% CI: 0.47-0.78; P: 1.1 × 10-4). Of the WBS constituent traits, only depressive symptoms showed a positive causal association with heart failure and myocardial infarction. Neither WBS nor WBS constituent traits were associated with atrial fibrillation and ischemic stroke. In multivariable MR analyses, when genetic instruments for traditional CVD risk factors were also taken into consideration, the WBS was causally associated with a reduced risk for heart failure (OR: 0.72; 95% CI: 0.58-0.88; P: 0.001) and myocardial infarction (OR: 0.67; 95% CI: 0.52-0.86; P: 0.002). This study provides evidence that a higher WBS is causally associated with a decreased risk of developing CVD and, more specifically, myocardial infarction; moreover, the association is mainly driven by depressive symptoms. These results support current guidelines that suggest improving psychological wellbeing may help in reducing the burden of cardiovascular disease.

Association between migraine prevalence, treatment with proton-pump inhibitors and CYP2C19 phenotypes in UK Biobank.

Proton-pump inhibitors (PPIs) are used to suppress gastric acid secretion in several gastrointestinal conditions. While these drugs are generally well tolerated, their long-term use may be associated with different adverse effects, including migraine. We analyzed the association between treatment with PPIs (omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole) and migraine prevalence in the UK Biobank cohort through a cross-sectional analysis (using baseline data for 468,280 participants, 16,390 of whom had migraine) and a longitudinal analysis (including 145,007 participants with no migraine at baseline, of whom 3786 had probable migraine without aura [MWOA] and 9981 probable migraine with aura [MWA] or both MWOA and MWA at an average follow-up time of 10.06 years). We also evaluated the modulating role of the metabolizer phenotype of CYP2C19, the major enzyme involved in PPI clearance. Treatment with PPIs was associated with higher migraine prevalence at baseline (odds ratio [OR] = 1.25, p < 0.0001). CYP2C19 rapid metabolizer phenotype was associated with lower prevalence of migraine exclusively in participants treated with PPIs (OR = 0.89, p = 0.029). In addition, treatment with PPIs was associated with higher incidence of both probable MWOA (OR = 1.24, p = 0.002) and MWA (OR = 1.43, p < 0.0001) at follow-up. Treatment with PPIs and CYP2C19 poor metabolizer status were associated with higher incidence of probable chronic migraine exclusively in men. Our results suggest a significant association between treatment with PPIs and migraine in this large population-based cohort and support a potential relevant role of gender and CYP2C19 phenotype.

Migraine as a risk factor for mixed symptoms of peripartum depression and anxiety in late pregnancy: A prospective cohort study.

BACKGROUND: Migraine has been identified as a risk factor for peripartum depression. However, little is known about the contribution of anxiety to this association or potential changes throughout the peripartum period. METHODS: In a sample of 4,831 women from the Biology, Affect, Stress, Imaging and Cognition cohort in Sweden, participants were asked about history of migraine prior to pregnancy. The participants completed the Edinburgh Postnatal Depression Scale (EPDS) at gestational weeks 17 and 32 and postpartum week 6. Multinomial logistic regression analyses were used to assess associations between migraine and symptoms of depression, anxiety or mixed depression and anxiety, while adjusting for potential confounders. RESULTS: In crude estimates, migraine was associated with separate and mixed symptoms of depression and anxiety at most time points. After adjustments, migraine was associated with anxiety at week 17 (adjusted odds ratio: 1.69; 95% confidence interval: 1.11-2.54) and with mixed depression and anxiety at week 32 (adjusted odds ratio: 1.45; 95% confidence interval: 1.06-1.99). None of the other associations remained statistically significant after adjustments. LIMITATIONS: Migraine history was self-reported. Symptoms of depression and anxiety were based on the screening tool EPDS and not on clinical diagnoses. CONCLUSIONS: The results demonstrate that migraine may be a risk factor for anxiety in mid- pregnancy and mixed symptoms of peripartum depression and anxiety in late pregnancy. Inflammatory and hormonal factors may underlie the association between migraine, depression and anxiety across the peripartum period.

Migraine and gastrointestinal disorders in middle and old age: A UK Biobank study.

INTRODUCTION: Migraine is a prevalent condition causing a substantial level of disability worldwide. Despite this, the pathophysiological mechanisms are not fully understood. Migraine often co-occurs with gastrointestinal disorders, but the direction of a potential causal link is unclear. The aim of this project was to investigate the associations between migraine and several gastrointestinal disorders in the same cohort in order to determine the relative strengths of these associations. METHODS: This cross-sectional study examined whether migraine is associated with irritable bowel syndrome (IBS), peptic ulcers, Helicobacter pylori (HP) infections, celiac disease, Crohn's disease and ulcerative colitis. Baseline data covering 489,753 UK Biobank participants (migraine group: n = 14,180) were analyzed using Pearson's chi-square tests and adjusted binary logistic regression models. RESULTS: Migraine was significantly associated with IBS (odds ratio [OR] 2.24, 95% confidence interval [CI] 2.08-2.40, p <.001) and peptic ulcers (OR 1.55, 95% CI 1.35-1.77, p <.001). Migraine was not associated with HP infection (OR 1.34, 95% CI 1.04-1.73, p = .024), celiac disease (OR 1.29, 95% CI 1.04-1.60, p = .023), Crohn's disease (OR 1.08, 95% CI 0.80-1.45, p = .617) or ulcerative colitis (OR 1.00, 95% CI 0.79-1.27, p = .979) after adjusting for multiple testing. CONCLUSIONS: Migraine was associated with IBS and peptic ulcers in this large population-based cohort. The associations with HP infection, celiac disease, Crohn's disease, and ulcerative colitis did not reach significance, suggesting a weaker link between migraine and autoimmune gastrointestinal conditions or HP infection.

Depression and Vegetarians: Association between Dietary Vitamin B6, B12 and Folate Intake and Global and Subcortical Brain Volumes.

Deficiency of vitamin B6 and vitamin B12, mostly in vegetarians, is found to be associated with depression and adverse neurological function. We investigated whether vitamin B6, B12, and folate have an effect on brain structure, especially among depressed people who follow a specific diet. The study sample comprised 9426 participants from the UK Biobank cohort with a mean age of 62.4 years. A generalized linear model controlling for age, sex, body mass index, ethnicity, town send deprivation index, educational qualification, smoking, and alcohol intake was used to test the association between study groups and structural brain volumes. Depression was more prevalent, and intake of vitamin B6 and B12 was lower among vegetarians, while non-vegetarians had a lower intake of folate. Overall, no significant association was observed between vitamin B6, B12, and folate intakes and both global and subcortical brain volumes among participants with depression. However, vitamin B12 intake was positively associated with right pallidum among non-depressed participants, and a significant interaction between vitamin B12 intake and depression status on the right pallidum was observed. Also, a significant interaction between folate intake and depression status on grey matter (GM) volume and left thalamus was observed. Upon diet stratification, folate intake is associated with total brain volume and GM volume among vegetarians with depression. Furthermore, no significant associations were observed for subcortical regions. Our findings suggest that dietary intake of vitamin B6 and B12 might have an effect on brain structure. Vegetarians, particularly those who suffer from depression may benefit from supplementing their diets with vitamins B6, B12, and folate to ensure brain health. Further studies, especially with a larger sample size and longitudinal design, are needed to confirm these findings.

Personality, lifestyle and job satisfaction: causal association between neuroticism and job satisfaction using Mendelian randomisation in the UK biobank cohort.

Job-related stress has been associated with poor health outcomes but little is known about the causal nature of these findings. We employed Mendelian randomisation (MR) approach to investigate the causal effect of neuroticism, education, and physical activity on job satisfaction. Trait-specific genetic risk score (GRS) based on recent genome wide association studies were used as instrumental variables (IV) using the UK Biobank cohort (N = 315,536). Both single variable and multivariable MR analyses were used to determine the effect of each trait on job satisfaction. We observed a clear evidence of a causal association between neuroticism and job satisfaction. In single variable MR, one standard deviation (1 SD) higher genetically determined neuroticism score (4.07 units) was associated with -0.31 units lower job satisfaction (95% confidence interval (CI): -0.38 to -0.24; P = 9.5 × 10-20). The causal associations remained significant after performing sensitivity analyses by excluding invalid genetic variants from GRSNeuroticism (ß(95%CI): -0.28(-0.35 to -0.21); P = 3.4 x 10-15). Education (0.02; -0.08 to 0.12; 0.67) and physical activity (0.08; -0.34 to 0.50; 0.70) did not show any evidence for causal association with job satisfaction. When genetic instruments for neuroticism, education and physical activity were included together, the association of neuroticism score with job satisfaction was reduced by only -0.01 units, suggesting an independent inverse causal association between neuroticism score (P = 2.7 x 10-17) and job satisfaction. Our findings show an independent causal association between neuroticism score and job satisfaction. Physically active lifestyle may help to increase job satisfaction despite presence of high neuroticism scores. Our study highlights the importance of considering the confounding effect of negative personality traits for studies on job satisfaction.

Olesoxime in neurodegenerative diseases: Scrutinising a promising drug candidate.

Over the last years, the experimental compound olesoxime, a mitochondria-targeting cholesterol derivative, has emerged as a promising drug candidate for neurodegenerative diseases. Numerous preclinical studies have successfully proved olesoxime's neuroprotective properties in cell and animal models of clinical conditions such as amyotrophic lateral sclerosis, Huntington disease, Parkinson disease, peripheral neuropathy and spinal muscular atrophy. The beneficial effects were attributed to olesoxime's potential impact on oxidative stress, mitochondrial permeability transition or cholesterol homoeostasis. Although no significant benefits have been demonstrated in patients of amyotrophic lateral sclerosis, and only the first 12 months of a phase II/III clinical trial showed an improvement in motor symptoms of spinal muscular atrophy, this orphan drug may still offer undiscovered potential in the treatment of neurological diseases. In our earlier preclinical studies, we demonstrated that administration of olesoxime in mouse and rat models of Huntington disease improved psychiatric and molecular phenotypes. Aside from stabilising mitochondrial function, the drug reduced the overactivation of calpains, a class of calcium-dependent proteases entangled in neurodegenerative conditions. This observation may be credited to olesoxime's action on calcium dyshomeostasis, a further hallmark in neurodegeneration, and linked to its targets TSPO and VDAC, two proteins of the outer mitochondrial membrane associated with mitochondrial calcium handling. Further research into the mode of action of olesoxime under pathological conditions, including its effect on neuronal calcium homeostasis, may strengthen the untapped potential of olesoxime or other similar compounds as a therapeutic for neurodegenerative diseases.

Plasma stearoyl-CoA desaturase activity indices and bile acid concentrations after a low-fat meal: association with a genetic variant in the FTO gene.

PURPOSE: Dietary macronutrient composition, stearoyl-CoA desaturase (SCD) activity indices, and primary bile acid (BA) concentrations are among the factors that have been associated with lipid metabolism and contributed to obesity. We investigated the association between the polymorphic expression of the fat mass and obesity-associated (FTO) gene and its relationship with SCD activity indices and primary BA concentrations after a low-fat meal. SUBJECTS AND METHODS: Blood plasma samples were collected from 56 young (20-36 years) healthy subjects with different rs9939609 FTO genotypes. Fasting and post-meal (2 hours after a low-fat breakfast) blood samples were collected on the subsequent morning for the analysis of DNA methylation, SCD activity indices (product-to-precursor fatty acid ratios; 16:1n-7/16:0 and 18:1n-9/18:0), and chenodeoxycholic acid (CDCA) and cholic acid (CA) concentrations. Expression of lipogenic genes was investigated post-meal to assess the relationship between the CDCA and CA concentrations and mRNA levels of lipogenic genes. RESULTS: The FTO AA (obesity risk) genotype group (n=18) had higher (P<0.05) post-meal SCD-16 activity index than the FTO TT (wild type) genotype group (n=26). In both the FTO TT (n=16) and AA (n=8) genotype groups, the post-meal concentrations of CDCA and CA were lower (P<0.05) compared with the fasted state. No difference in BA concentrations between the FTO TT and AA genotype groups in both meal states was observed. After adjusting for the body mass index, the highest 50% post-meal concentrations of CA were inversely (P=0.010) correlated with the level of mRNA SCD expression. CONCLUSION: FTO AA carriers may be at a higher risk for obesity through higher SCD activity in a low-fat diet environment. This effect may be partly pronounced by very low CA concentrations.

One-night sleep deprivation induces changes in the DNA methylation and serum activity indices of stearoyl-CoA desaturase in young healthy men.

BACKGROUND: Sleep deprivation has been associated with obesity among adults, and accumulating data suggests that stearoyl-CoA desaturase 1 (SCD1) expression has a relevant impact on fatty acid (FA) composition of lipid pools and obesity. The aim of this study was to investigate the effect of one-night total sleep deprivation (TSD) on DNA methylation in the 5'-prime region of SCD1, and whether detected changes in DNA methylation are associated with SCD activity indices (product to precursor FA ratios; 16:1n-7/16:0 and 18:1n-9/18:0) derived from serum phospholipids (PL). METHODS: Sixteen young, normal-weight, healthy men completed two study sessions, one with one-night TSD and one with one-night normal sleep (NS). Sleep quality and length was assessed by polysomnography, and consisted of electroencephalography, electrooculography, and electromyography. Fasting whole blood samples were collected on the subsequent morning for analysis of DNA methylation and FAs in serum PL. Linear regression analyses were performed to assess the association between changes in DNA methylation and SCD activity indices. RESULTS: Three CpG sites close to the transcription start site (TSS) of SCD1 (cg00954566, cg24503796, cg14089512) were significantly differentially methylated in dependency of sleep duration (-log10 P-value > 1.3). Both SCD-16 and SCD-18 activity indices were significantly elevated (P < 0.05) following one-night TSD, and significantly associated with DNA methylation changes of the three mentioned probes in the 5' region of SCD1. CONCLUSION: Our results suggest a relevant link between TSD, hepatic SCD1 expression and de-novo fatty acid synthesis via epigenetically driven regulatory mechanisms.

Lifestyle determinants of the drive to eat: a meta-analysis.

BACKGROUND: Obesity is emerging as the most significant health concern of the 21st century. Although this is attributable in part to changes in our environment-including the increased prevalence of energy-dense food-it also appears that several lifestyle factors may increase our vulnerability to this calorie-rich landscape. Epidemiologic studies have begun to show links between adiposity and behaviors such as television watching, alcohol intake, and sleep deprivation. However, these studies leave unclear the direction of this association. In addition, studies that investigated the acute impact of these factors on food intake have reported a wide variety of effect sizes, from highly positive to slightly negative. OBJECTIVE: The purpose of this article was to provide a meta-analysis of the relation between lifestyle choices and increases in acute food intake. DESIGN: An initial search was performed on PubMed to collect articles relating television watching, sleep deprivation, and alcohol consumption to food intake. Only articles published before February 2012 were considered. Studies that took place in a controlled, laboratory setting with healthy individuals were included. Studies were analyzed by using 3 meta-analyses with random-effects models. In addition, a 1-factor ANOVA was run to discover any main effect of lifestyle. RESULTS: The 3 most prominent lifestyle factors-television watching, alcohol intake, and sleep deprivation-had significant short-term effects on food intake, with alcohol being more significant (Cohen's d = 1.03) than sleep deprivation (Cohen's d = 0.49) and television watching (Cohen's d = 0.2). CONCLUSIONS: Our results suggest that television watching, alcohol intake, and sleep deprivation are not merely correlated with obesity but likely contribute to it by encouraging excessive eating. Because these behaviors are all known to affect cognitive functions involved in reward saliency and inhibitory control, it may be that they represent common mechanisms through which this eating is facilitated.

A debate on current eating disorder diagnoses in light of neurobiological findings: is it time for a spectrum model?

BACKGROUND: Sixty percent of eating disorders do not meet criteria for anorexia- or bulimia nervosa, as defined by the Diagnostic and Statistical Manual version 4 (DSM-IV). Instead they are diagnosed as 'eating disorders not otherwise specified' (EDNOS). Discrepancies between criteria and clinical reality currently hampering eating disorder diagnoses in the DSM-IV will be addressed by the forthcoming DSM-V. However, future diagnoses for eating disorders will rely on current advances in the fields of neuroimaging and genetics for classification of symptoms that will ultimately improve treatment. DISCUSSION: Here we debate the classification issues, and discuss how brain imaging and genetic discoveries might be interwoven into a model of eating disorders to provide better classification and treatment. The debate concerns: a) current issues in the classification of eating disorders in the DSM-IV, b) changes proposed for DSM-V, c) neuroimaging eating disorder research and d) genetic eating disorder research. SUMMARY: We outline a novel evidence-based 'impulse control' spectrum model of eating disorders. A model of eating disorders is proposed that will aid future diagnosis of symptoms, coinciding with contemporary suggestions by clinicians and the proposed changes due to be published in the DSM-V.

Acute sleep deprivation has no lasting effects on the human antibody titer response following a novel influenza A H1N1 virus vaccination.

BACKGROUND: Experimental studies in humans have yielded evidence that adaptive immune function, including the production of antigen-specific antibodies, is distinctly impaired when sleep is deprived at the time of first antigen exposure. Here we examined the effects of a regular 24-hour sleep-wake cycle (including 8 hours of nocturnal sleep) and a 24-hour period of continuous wakefulness on the 7-week antibody production in 11 males and 13 females in response to the H1N1 (swine flu) virus vaccination. The specific antibody titer in serum was assayed by the hemagglutination inhibition test on the days 5, 10, 17, and 52 following vaccination. RESULTS: In comparison to the sleep group, sleep-deprived males but not females had reduced serum concentration of H1N1-specific antibodies five days after vaccination, whereas antibody titers at later time points did not differ between the conditions. CONCLUSIONS: These findings concur with the notion that sleep is a supportive influence in the very early stage of an adaptive immune response to a viral antigen. However, our results do not support the view that acute sleep deprivation has lasting effects on the human antibody titer response to influenza vaccination.

Acute sleep deprivation reduces energy expenditure in healthy men.

BACKGROUND: Epidemiologic evidence indicates that chronic sleep curtailment increases risk of developing obesity, but the mechanisms behind this relation are largely unknown. OBJECTIVE: We examined the influence of a single night of total sleep deprivation on morning energy expenditures and food intakes in healthy humans. DESIGN: According to a balanced crossover design, we examined 14 normal-weight male subjects on 2 occasions during a regular 24-h sleep-wake cycle (including 8 h of nocturnal sleep) and a 24-h period of continuous wakefulness. On the morning after regular sleep and total sleep deprivation, resting and postprandial energy expenditures were assessed by indirect calorimetry, and the free-choice food intake from an opulent buffet was tested in the late afternoon at the end of the experiment. Circulating concentrations of ghrelin, leptin, norepinephrine, cortisol, thyreotropin, glucose, and insulin were repeatedly measured over the entire 24-h session. RESULTS: In comparison with normal sleep, resting and postprandial energy expenditures assessed on the subsequent morning were significantly reduced after sleep deprivation by ≈5% and 20%, respectively (P < 0.05 and P < 0.0001). Nocturnal wakefulness increased morning plasma ghrelin concentrations (P < 0.02) and nocturnal and daytime circulating concentrations of thyreotropin, cortisol, and norepinephrine (P < 0.05) as well as morning postprandial plasma glucose concentrations (P < 0.05). Changes in food intakes were variable, and no differences between wake and sleep conditions were detected. CONCLUSION: Our findings show that one night of sleep deprivation acutely reduces energy expenditure in healthy men, which suggests that sleep contributes to the acute regulation of daytime energy expenditure in humans.

α-Melanocyte-stimulating hormone (α-MSH) reverses impairment of memory reconsolidation induced by interleukin-1 beta (IL-1 beta) hippocampal infusions.

Interleukin-1 beta (IL-1ß) significantly influences cognitive processes. Treatments which raise the level of IL-1ß in the brain impair memory consolidation in contextual fear conditioning. However, the effect of IL-1ß on memory reconsolidation has not yet been established. The melanocortin α-melanocyte-stimulating hormone (α-MSH) exerts potent anti-inflammatory actions by antagonizing the effect of proinflammatory cytokines. Five subtypes of melanocortin receptors (MC1R-MC5R) have been identified, of which MC3R and MC4R are predominant in the central nervous system. The present experiments show that the injection of IL-1ß (5 ng/0.25 µl) in dorsal hippocampus up to 30 min after re-exposition to the context decreases freezing during the contextual fear test. Impairment of memory reconsolidation was reversed by treatment with α-MSH (0.05 µg/0.25 µl). Administration of the MC4 receptor antagonist HS014 (0.5 µg/0.25 µl) blocked the effect of α-MSH. These results suggest that IL-1ß may influence memory reconsolidation and that activation of central MC4R could lead to improve cognitive performance.

Memory impairment induced by IL-1beta is reversed by alpha-MSH through central melanocortin-4 receptors.

Interleukin-1beta (IL-1beta) significantly influences memory consolidation. Treatments that raise the level of IL-1beta in the brain, given after training, impair contextual fear conditioning. The melanocortin alpha-MSH exerts potent anti-inflammatory actions by physiologically antagonizing the effect of pro-inflammatory cytokines. Five subtypes of melanocortin receptors (MC1R-MC5R) have been identified, with MC3R and MC4R predominating in the central nervous system. The present experiments show that injection of IL-1beta (5 ng/0.25 microl) in dorsal hippocampus up to 15 min after training decreased freezing during the contextual fear test. The treatment with IL-1beta (5 ng/0.25 microl) 12h after conditioning cause amnesia when animals were tested 7 days post training. Thus, our results also demonstrated that IL-1beta can influence persistence of long-term memory. We determined that animals previously injected with IL-1beta can acquire a new contextual fear memory, demonstrating that the hippocampus was not damaged. Treatment with alpha-MSH (0.05 microg/0.25 microl) blocked the effect of IL-1beta on contextual fear memory. Administration of the MC4 receptor antagonist HS014 (0.5 microg/0.25 microl) reversed the effect of alpha-MSH. However, treatment with gamma-MSH (0.5 microg/0.25 microl), an MC3 agonist, did not affect IL-1beta-induced impairment of memory consolidation. These results suggest that alpha-MSH, through central MC4R can inhibit the effect of IL-1beta on memory consolidation.