Vitamin B12 attenuates leukocyte inflammatory signature in COVID-19 via methyl-dependent changes in epigenetic markings.

COVID-19 induces chromatin remodeling in host immune cells, and it had previously been shown that vitamin B12 downregulates some inflammatory genes via methyl-dependent epigenetic mechanisms. In this work, whole blood cultures from moderate or severe COVID-19 patients were used to assess the potential of B12 as adjuvant drug. The vitamin normalized the expression of a panel of inflammatory genes still dysregulated in the leukocytes despite glucocorticoid therapy during hospitalization. B12 also increased the flux of the sulfur amino acid pathway, that regulates the bioavailability of methyl. Accordingly, B12-induced downregulation of CCL3 strongly and negatively correlated with the hypermethylation of CpGs in its regulatory regions. Transcriptome analysis revealed that B12 attenuates the effects of COVID-19 on most inflammation-related pathways affected by the disease. As far as we are aware, this is the first study to demonstrate that pharmacological modulation of epigenetic markings in leukocytes favorably regulates central components of COVID-19 physiopathology.

An Overview of the Methods Used to Measure the Impact of Mindfulness-Based Interventions in Sleep-Related Outcomes.

Introduction Systematic reviews and metanalyses have shown that mindfulness-based interventions can have positive effects on health, such as reducing anxiety, depression, and chronic pain. However, their effect on sleep-related outcomes is not yet well established. Sleep can be assessed subjectively (questionnaires, sleep logs, self-reporting) and/or objectively (actigraphy, polysomnography, biological markers), and outcomes may differ depending on which type of assessment is used. Objective In this study, we present a literature overview on mindfulness and sleep, innovatively presenting and discussing studies that address sleep subjectively and objectively. Methods The search was undertaken using four databases (Pubmed Medline, Scopus, Web of Science, Psychinfo) in September 2019, and repeated in May 2021. Studies were analyzed through a two-step process: (1) reading titles and abstracts, and (2) full text analysis that met the review's eligibility criteria, with the final sample comprising 193 articles. We observed a growth in the number of studies published, particularly since 2005. However, this was mostly due to an increase in studies based on subjective research. There is a moderate to nonexistent agreement between objective and subjective sleep measures, with results of subjective measures having higher variability and uncertainty.We identified 151 articles (78%) using an exclusively subjective sleep evaluation, which can cause a misperception about mindfulness effects on sleep. Conclusion Future studies should place greater emphasis on objective measurements to accurately investigate the effects of mindfulness practices on sleep, although subjective measures also have a role to play in respect of some aspects of this relationship.

Fostering emotional self-regulation in female teachers at the public teaching network: A mindfulness-based intervention improving psychological measures and inflammatory biomarkers.

OBJECTIVE: To examine the effect of a mindfulness-based program specifically designed for teachers in reducing perceived stress and improving the quality of experienced emotion in female active working teachers. A second outcome evaluated is the associated change in cellular inflammatory activity, measured by peripheral blood levels of cytokines. METHOD: Eighty-eight female active teachers from public schools from São Paulo Municipality were recruited, and randomly allocated to an eight-week Mindfulness-Based Health Program for Educators (MBHP-Educa) or to Neuroscience for Education Program (Neuro-Educa: active control group). The venue of both programs were several public school facilities, where many of the teachers actually worked. Both groups received activities during eight weeks in a 2 â€‹h/week regimen, totalizing 16 â€‹h. Sixty-five participants completed the program and pre- and post-interventions measures were taken from the following scales: Interpersonal Multidimensional Reactivity Scale (IRI), Positive-and-Negative Affects Scale (PANAS), Perceived Stress Scale (PSS), Connor-Davidson Resilience Scale (CD-RISC), and a primary outcome in Ryff's Psychological Well-Being Scale (PBWS). At pre-and post-intervention, blood samples were collected for the measurement of several important inflammatory biomarkers, Tumor Necrosis Factor - α (TNF-α), Interleukin 1ß (IL-1ß), Interleukin 6 (IL-6), Interleukin 8 (IL-8), Interleukin 10 (IL-10) and Interleukin 12p70 (IL-12P70) through flow cytometry assay. Intervention effects were analyzed via Generalized mixed models (GLMM). RESULTS: According to the GLMM, MBHP-Educa significantly reduced the scores of perceived stress (p â€‹< â€‹0.0001), and negative affect (p â€‹< â€‹0.0001) compared to active control group (Neuro-Educa). Conversely, an increase was observed on Psychological Well Being Scale in dimensions of Self-acceptance (p â€‹< â€‹0.0001), and Autonomy (p â€‹= â€‹0.001), as well as improvements in Resilience (p â€‹< â€‹0.0001), and Positive Affect (p â€‹< â€‹0.0001). MBHP-Educa also promoted a reduction in the levels of IL-6 (p â€‹= â€‹0.003), IL-8 (p â€‹= â€‹0.036), and increase in the levels of IL-10 (p â€‹< â€‹0.0001) and IL-12p70 (p â€‹< â€‹0.044). TNF-α, IL-1ß, and IL-10p70 showed results below theoretical limit of detection accepted for CBA kit. CONCLUSIONS: Our data suggest that mindfulness-based interventions introduced as a strategy for reducing stress, promoting well-being and improve immune function can be a useful asset in promoting psychological health among teachers in Basic Education.

Maternal methionine supplementation in mice affects long-term body weight and locomotor activity of adult female offspring.

Methionine is a precursor of s-adenosylmethionine, the main donor of methyl radicals for methylation of DNA and other compounds. Previous studies have shown that reduced availability of methyl radicals during pregnancy/lactation decreased offspring perigonadal white adipose tissue (PWAT) and body weight. Therefore, we aimed to evaluate the effects of methionine supplementation during early development, a time of great ontogenic plasticity, by assessing the biometric, biochemical and behavioural parameters of the offspring of adult Swiss female mice supplemented with 1 % methionine in water 1 month before pregnancy, during pregnancy or pregnancy/lactation. After birth, the offspring were distributed into three groups: control (CT), methionine supplementation during pregnancy (SP) and methionine supplementation during pregnancy and lactation (SPL), and were followed until postnatal day (PND) 300. No changes were observed in offspring birth weight in both sexes. At PND 5, 28 and 90, no differences in body weight were found in females; however, at PND 300, SP and SPL females showed an increase in body weight when compared with the control group. This increase in body weight was accompanied by a total and relative increase in PWAT, and a decrease in locomotor activity in these groups. No differences in the body and organ weights were found in male offspring. In conclusion, the increased availability of methyl radicals during pregnancy and lactation impacted long-term body composition and locomotor activity in female offspring.

Mindfulness meditation training effects on quality of life, immune function and glutathione metabolism in service healthy female teachers: A randomized pilot clinical trial.

BACKGROUND: Despite the crucial role of educators in encourage students' academic learning, addressing educator stress inside the classroom remains a significant challenge in the educational context. Mindfulness Meditation training (MM) has been recommended as an environmental enrichment strategy in schools to help teachers cope with stress and cultivating a state of awareness in daily life. Although studies have shown that MM can improve immune system dynamics the biological mechanism underlying glutathione metabolism in a healthy human is unclear. OBJECTIVE: The purpose of this study was to determine whether MM training benefits psychological and behavioral response, immunological functions and glutathione metabolism in service healthy female teachers from public schools. METHODS: We randomly assigned 76 teachers to an 8-week Mindfulness-Based Health Program for Educators (MBHPEduca) or Neuroscience for Education program (Neuro-Educa; active control group). Using the quality of life as our primary outcome, perceived stress, negative affectivity, and resilience as our secondary outcome, and pro-inflammatory cytokines and glutathione levels as our third outcome at baseline and post-intervention that occurred in public schools. Blood samples were collected for the measurement of three proinflammatory markers, including interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and interleukin-8 (IL-8) and three GSH metabolism, including Cysteine (Cys), Homocysteine (HCys) and GSH were conducted at pre-and post-intervention, with selfreported assessments over time. Treatment effects were analyzed using generalized estimating equations (GEE) with to intention to treat. RESULTS: We observed statistically significant improvements to the MBHP-Educa group compared to active control in perceived stress, resilience, positive and negative affect, and quality of life after 8-weeks MM (p â€‹< â€‹0.0001). Further, the MBHP-Educa group exhibited lower circulating IL-6 production accompanied by high circulating GSH, and Cys (p â€‹< â€‹0.0001). Additional analyses indicated that enhancing quality of life through mindfulness meditation training was mediated by reducing perceived stress and serum levels of IL- 6 and increasing resilience and teachers 'plasma GSH levels. CONCLUSIONS: The present study is a pilot trial with low-power and provides preliminary evidence that mindfulness meditation training help teachers to cope with stress in the school environment with an impact on the quality of life, immune function, and glutathione metabolism.

Yogic meditation improves objective and subjective sleep quality of healthcare professionals.

OBJECTIVE: Our aim was to evaluate the impact of yogic meditation in sleep quality of healthy pediatric healthcare professionals. METHOD: Subjects were randomized into a meditation group (MG, n = 32), who attended a yogic meditation class held for eight weeks, or a control group (CG, n = 32). Polysomnography (PSG) and Pittsburgh Sleep Quality Index (PSQI) scores were determined at baseline and after eight weeks. RESULTS: The PSQI overall score was lower (p = 0.024) in the MG. Reported sleep latency (p = 0.046) and MG sleep latency (p = 0.028) were lower in the MG at eight weeks. PSG showed a time effect (p = 0.020) on decreasing minutes of wake after sleep onset in the MG. There were strong and significant correlations between PSG and PSQI variables. There was a significant time effect on heart rate (p = 0.001) in the MG. CONCLUSION: Yogic meditation may be used as an integrative health tool to foster improvements in the health-related aspects of healthcare professionals' lives. TRIAL REGISTRATION: CinicalTrials.gov identifier: NCT02947074; trial registry name: Meditation Practice in Pediatric Healthcare Professionals: A Randomized Controlled Clinical Trial.

Vitamin B12 is neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylation.

BACKGROUND: Bacterial meningitis (BM) causes apoptotic damage to the hippocampus and homocysteine (Hcy) accumulation to neurotoxic levels in the cerebrospinal fluid of children. The Hcy pathway controls bioavailability of methyl, and its homeostasis can be modulated by vitamin B12, a cofactor of the methionine synthase enzyme. Herein, the neuroprotective potential and the underlying mode of action of vitamin B12 adjuvant therapy were assessed in an infant rat model of BM. METHODS: Eleven-day old rats were intracysternally infected with Streptococcus pneumoniae serotype 3, or saline, treated with B12 or placebo, and, 24 h after infection, their hippocampi were analyzed for apoptosis in the dentate gyrus, sulfur amino acids content, global DNA methylation, transcription, and proximal promoter methylation of candidate genes. Differences between groups were compared using 2-way ANOVA followed by Bonferroni post hoc test. Correlations were tested with Spearman's test. RESULTS: B12 attenuated BM-induced hippocampal apoptosis in a Hcy-dependent manner (r = 0.80, P < 0.05). BM caused global DNA hypomethylation; however, B12 restored this parameter. Accordingly, B12 increased the methylation capacity of hippocampal cells from infected animals, as inferred from the ratio S-adenosylmethionine (SAM):S-adenosylhomocysteine (SAH) in infected animals. BM upregulated selected pro-inflammatory genes, and this effect was counteracted by B12, which also increased methylation of CpGs at the promoter of Ccl3 of infected animals. CONCLUSION: Hcy is likely to play a central role in hippocampal damage in the infant rat model of BM, and B12 shows an anti-inflammatory and neuroprotective action through methyl-dependent epigenetic mechanisms.

Protocol for a Nested Randomized Controlled Trial to Evaluate the Feasibility and Preliminary Efficacy of the Mindfulness Based Health Promotion Program on the Quality of Life of Older Adults Assisted in Primary Care-"The MBHP-Elderly Study".

Introduction: Population aging is a global phenomenon that has grown rapidly and progressively all over the world. Interventions that promote health must be studied and implemented to make the aging process be with quality of life. Depression and anxiety are the most common mental health conditions that compromise the quality of life on the elderly and it can cause damage to the autonomy and activities of daily life. Mindfulness training has been shown to improve psychological health and quality of life on adults. Studies involving Mindfulness-Based Interventions (MBIs) with older people are scarce in the literature, but they have been increasing in recent years showing promising results for healthy aging. This trial will investigate the feasibility and preliminary efficacy of an MBI on the quality of life of elderly assisted in the Primary Care. Materials and Methods: A cohort-nested randomized controlled trial with 3 assessment points (baseline, post-intervention and 1-year follow up) will be conducted to compare a MBI program (Mindfulness-Based Health Promotion) to a cognitive stimulation control-group in a Primary Care facility. One-hundred and two older adults will be recruited from a cohort of this facility and they will be randomized and allocated into an intervention group (N = 76) and the control group (N = 76). The primary outcome evaluated will be the improvement of quality of life assessed by the WHOQOL-BREF and WHOQOL-OLD. The secondary outcomes will be cognitive function, psychological health, sleep quality, self-compassion, and religiosity. Qualitative data will be assessed by focus group and the word free evocation technique. The feasibility of the program will also be evaluated by adherence and unwanted effects questionnaires. Discussion: This cohort-nested clinical trial will be the first mixed-methods study with 3 assessment points which will study the feasibility and preliminary efficacy of a mindfulness-based program for older people in Latin America population. If the findings of this study confirm the effectiveness of this program in this population it will be possible to consider it as intervention that might be implemented as public policy addressed to older people in healthcare systems. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03048708. Registered retrospectively on October 11th 2018.

Dietary sulfur amino acid restriction upregulates DICER to confer beneficial effects.

OBJECTIVE: Dietary restriction (DR) improves health and prolongs lifespan in part by upregulating type III endoribonuclease DICER in adipose tissue. In this study, we aimed to specifically test which missing dietary component was responsible for DICER upregulation. METHODS: We performed a nutrient screen in mouse preadipocytes and validated the results in vivo using different kinds of dietary interventions in wild type or genetically modified mice and worms, also testing the requirement of DICER on the effects of the diets. RESULTS: We found that sulfur amino acid restriction (i.e., methionine or cysteine) is sufficient to increase Dicer mRNA expression in preadipocytes. Consistently, while DR increases DICER expression in adipose tissue of mice, this effect is blunted by supplementation of the diet with methionine, cysteine, or casein, but not with a lipid or carbohydrate source. Accordingly, dietary methionine or protein restriction mirrors the effects of DR. These changes are associated with alterations in serum adiponectin. We also found that DICER controls and is controlled by adiponectin. In mice, DICER plays a role in methionine restriction-induced upregulation of Ucp1 in adipose tissue. In C. elegans, DR and a model of methionine restriction also promote DICER expression in the intestine (an analog of the adipose tissue) and prolong lifespan in a DICER-dependent manner. CONCLUSIONS: We propose an evolutionary conserved mechanism in which dietary sulfur amino acid restriction upregulates DICER levels in adipose tissue leading to beneficial health effects.

Oxidative stress assessment by glutathione peroxidase activity and glutathione levels in response to selenium supplementation in patients with Mucopolysaccharidosis I, II and VI.

We assessed levels of plasma selenium (Se), selenoproteins and their change after Se supplementation in patients with mucopolysaccharidosis (MPS) types I, II and VI. This was done in a retrospective study of the medical records of 30 patients with MPS I (n=13), MPS II (n=9) and MPS VI (n=8) who were being treated with enzyme replacement therapy. As part of routine nutritional monitoring, Se levels were measured, revealing that 28 patients (93.3%) had values below the normal range. Therefore, they received supplementation for 12 months, and Se was measured after 6 and 12 months. Glutathione peroxidase (GPx) activity, total glutathione (GSHt), oxidized glutathione (GSSG) and reduced glutathione (GSH) were measured at baseline and 6 months after Se supplementation. The mean GSHt at baseline was 7.90 ± 2.36 µmol/g Hb, and after Se supplementation it was 5.76 ± 1.13 µmol/g Hb; GSH/GSSG was 2.3 ± 1.16 at baseline and 0.58 ± 0.38 after supplementation. GPx activity was 16.46 ± 3.31 U/g Hb at baseline and 4.53 ± 4.92 U/g Hb after Se supplementation. The difference was shown to be statistically significant by paired t-test. In conclusion, our study demonstrated that oxidative stress parameters were altered by Se supplementation in patients with MPS I, II and VI who were previously deficient in Se.

Mindfulness as a complementary intervention in the treatment of overweight and obesity in primary health care: study protocol for a randomised controlled trial.

BACKGROUND: Mindfulness has been applied in the United States and Europe to improve physical and psychological health; however, little is known about its feasibility and efficacy in a Brazilian population. Mindfulness may also be relevant in tackling obesity and eating disorders by decreasing binge eating episodes-partly responsible for weight regain for a large number of people-and increasing awareness of emotional and other triggers for overeating. The aim of the present study protocol is to evaluate and compare the feasibility and efficacy of two mindfulness-based interventions (MBIs) addressing overweight and obesity in primary care patients: a general programme called Mindfulness-Based Health Promotion and a targeted mindful eating protocol called Mindfulness-Based Eating Awareness Training. METHODS/DESIGN: A randomised controlled trial will be conducted to compare treatment as usual separately in primary care with both programmes (health promotion and mindful eating) added to treatment as usual. Two hundred forty adult women with overweight and obesity will be enrolled. The primary outcome will be an assessment of improvement in eating behaviour. Secondary outcomes will be (1) biochemical control; (2) anthropometric parameters, body composition, dietary intake and basal metabolism; and (3) levels of mindfulness, stress, depression, self-compassion and anxiety. At the end of each intervention, a focus group will be held to assess the programme's impact on the participants' lives, diet and health. A feasibility study on access to benefits from and importance of MBIs at primary care facilities will be conducted among primary care health care professionals and participants. Monthly maintenance sessions lasting at least 1 hour will be offered, according to each protocol, during the 3-month follow-up periods. DISCUSSION: This clinical trial will result in more effective mindfulness-based interventions as a complementary treatment in primary care for people with overweight and obesity. If the findings of this study confirm the effectiveness of mindfulness programmes in this population, it will be possible to improve quality of life and health while optimising public resources and reaching a greater number of people. In addition, on the basis of the evaluation of the feasibility of implementing this intervention in primary care facilities, we expect to be able to suggest the intervention for incorporation into public policy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02893150 . Registered retrospectively on 30 March 2017.

Tryptophan overloading activates brain regions involved with cognition, mood and anxiety

ABSTRACT Tryptophan is the only precursor of serotonin and mediates serotonergic activity in the brain. Previous studies have shown that the administration of tryptophan or tryptophan depletion significantly alters cognition, mood and anxiety. Nevertheless, the neurobiological alterations that follow these changes have not yet been fully investigated. The aim of this study was to verify the effects of a tryptophan-enriched diet on immunoreactivity to Fos-protein in the rat brain. Sixteen male Wistar rats were distributed into two groups that either received standard chow diet or a tryptophan-enriched diet for a period of thirty days. On the morning of the 31st day, animals were euthanized and subsequently analyzed for Fos-immunoreactivity (Fos-ir) in the dorsal and median raphe nuclei and in regions that receive serotonin innervation from these two brain areas. Treatment with a tryptophan-enriched diet increased Fos-ir in the prefrontal cortex, nucleus accumbens, paraventricular hypothalamus, arcuate and ventromedial hypothalamus, dorsolateral and dorsomedial periaqueductal grey and dorsal and median raphe nucleus. These observations suggest that the physiological and behavioral alterations that follow the administration of tryptophan are associated with the activation of brain regions that regulate cognition and mood/anxiety-related responses.

Tryptophan overloading activates brain regions involved with cognition, mood and anxiety.

Tryptophan is the only precursor of serotonin and mediates serotonergic activity in the brain. Previous studies have shown that the administration of tryptophan or tryptophan depletion significantly alters cognition, mood and anxiety. Nevertheless, the neurobiological alterations that follow these changes have not yet been fully investigated. The aim of this study was to verify the effects of a tryptophan-enriched diet on immunoreactivity to Fos-protein in the rat brain. Sixteen male Wistar rats were distributed into two groups that either received standard chow diet or a tryptophan-enriched diet for a period of thirty days. On the morning of the 31st day, animals were euthanized and subsequently analyzed for Fos-immunoreactivity (Fos-ir) in the dorsal and median raphe nuclei and in regions that receive serotonin innervation from these two brain areas. Treatment with a tryptophan-enriched diet increased Fos-ir in the prefrontal cortex, nucleus accumbens, paraventricular hypothalamus, arcuate and ventromedial hypothalamus, dorsolateral and dorsomedial periaqueductal grey and dorsal and median raphe nucleus. These observations suggest that the physiological and behavioral alterations that follow the administration of tryptophan are associated with the activation of brain regions that regulate cognition and mood/anxiety-related responses.

Effects of isolated vitamin B6 supplementation on oxidative stress and heart function parameters in experimental hyperhomocysteinemia

Introduction: The purpose of this study was to investigate the effects of isolated vitamin B6 (VB6 ) supplementation on experimental hyperhomocysteinemia (Hhe) induced by homocysteine thiolactone (HcyT). Methods: Fifteen male Wistar rats were divided into three groups according to their treatment. Animals received water and food ad libitum and an intragastric probe was used to administer water for 60 days (groups: CB6, HcyT, and HB6 ). On the 30th day of treatment, two groups were supplemented with VB6 in the drinking water (groups: CB6 and HB6 ). After 60 days of treatment, homocysteine (Hcy), cysteine, and hydrogen peroxide concentration, nuclear factor (erythroid-derived 2)-like 2 (NRF2) and glutathione S-transferase (GST) immunocontent, and superoxide dismutase (SOD), catalase (CAT), and GST activities were measured. Results: The HcyT group showed an increase in Hcy concentration (62%) in relation to the CB6 group. Additionally, GST immunocontent was enhanced (51%) in the HB6 group compared to the HcyT group. Also, SOD activity was lower (17%) in the HB6 group compared to the CB6 group, and CAT activity was higher in the HcyT group (53%) compared to the CB6 group. Ejection fraction (EF) was improved in the HB6 group compared to the HcyT group. E/A ratio was enhanced in the HB6 group compared to the CB6 group. Correlations were found between CAT activity with myocardial performance index (MPI) (r = 0.71; P = 0.06) and E/A ratio (r = 0.6; P = 0.01), and between EF and GST activity (r = 0.62; P = 0.02). Conclusions: These findings indicate that isolated VB6 supplementation may lead to the reduction of Hcy concentration and promotes additional benefits to oxidative stress and heart function parameters (AU)

MCH levels in the CSF, brain preproMCH and MCHR1 gene expression during paradoxical sleep deprivation, sleep rebound and chronic sleep restriction.

Neurons that utilize melanin-concentrating hormone (MCH) as neuromodulator are located in the lateral hypothalamus and incerto-hypothalamic area. These neurons project throughout the central nervous system and play a role in sleep regulation. With the hypothesis that the MCHergic system function would be modified by the time of the day as well as by disruptions of the sleep-wake cycle, we quantified in rats the concentration of MCH in the cerebrospinal fluid (CSF), the expression of the MCH precursor (Pmch) gene in the hypothalamus, and the expression of the MCH receptor 1 (Mchr1) gene in the frontal cortex and hippocampus. These analyses were performed during paradoxical sleep deprivation (by a modified multiple platform technique), paradoxical sleep rebound and chronic sleep restriction, both at the end of the active (dark) phase (lights were turned on at Zeitgeber time zero, ZT0) and during the inactive (light) phase (ZT8). We observed that in control condition (waking and sleep ad libitum), Mchr1 gene expression was larger at ZT8 (when sleep predominates) than at ZT0, both in frontal cortex and hippocampus. In addition, compared to control, disturbances of the sleep-wake cycle produced the following effects: paradoxical sleep deprivation for 96 and 120 h reduced the expression of Mchr1 gene in frontal cortex at ZT0. Sleep rebound that followed 96 h of paradoxical sleep deprivation increased the MCH concentration in the CSF also at ZT0. Twenty-one days of sleep restriction produced a significant increment in MCH CSF levels at ZT8. Finally, sleep disruptions unveiled day/night differences in MCH CSF levels and in Pmch gene expression that were not observed in control (undisturbed) conditions. In conclusion, the time of the day and sleep disruptions produced subtle modifications in the physiology of the MCHergic system.

Detraining in pregnancy and/or lactation modulates neuropeptidergic hypothalamic systems in offspring mice.

Manipulations in metabolic parameters during pregnancy/lactation can impact the development of short- and long-term energy control mechanisms, which are mainly modulated by neural and hormonal inputs to the hypothalamus. Thus, we tested how mice training and detraining during pregnancy and lactation affect hypothalamus gene expression and change biometric and metabolic profiles of the offspring. Three-month-old female Swiss mice were submitted to an 8-week exercise program (swimming 5 times/week, 1 h/day). Following this physical exercise protocol, these conditioned animals and the control group were submitted to matting. After pregnancy verification, the animals were distributed into four groups: training during pregnancy and lactation (T); detraining after pregnancy confirmation (DP); detraining during lactation (DL); and control (CT), without interventions. After weaning, the offspring of the four groups were derived into these as follows: TO, DPO, DLO, and CTO, respectively. The body weight was lower in conditioned females compared to control at weeks 4-8 of the exercise regimen. No statistical difference in dam's body weight was observed during pregnancy. Related to offspring, at post-natal day 90, the animals were euthanized and DPO and DLO showed decrease in Npy and Cart expression in hypothalamus, and DLO also had increased Lep gene expression in white adipose tissue. Additionally, DPO showed increase in plasma triglycerides levels, total liver weight, and decrease in brown adipose tissue compared to CTO. Together, these results support that detraining during critical periods of development leads to altered gene expression in hypothalamic neuropeptidergic systems.

Central and systemic responses to methionine-induced hyperhomocysteinemia in mice.

Hyperhomocysteinemia has been considered a risk factor for neuropsychiatric disorders, but the mechanisms involved in this process have not been completely elucidated. The aim of this study was to analyze the influence of hyperhomocysteinemia induction by methionine supplementation considering different levels and periods of exposure in mice. For this purpose, methionine supplementation at concentrations of 0.5 and 1% were administered in water to increase homocysteinemia in male C57BL/6 mice, and was maintained for 3 time periods (2, 4 and 6 months of treatment). The results from one-carbon metabolism parameters, brain-derived neurotrophic factor (BDNF) concentrations and behavioral evaluation were compared. The 0.5% supplementation was efficient in increasing plasma homocysteine levels after 2 and 6 months. The 1% supplementation, increased plasma homocysteine after 2, 4 and 6 months. Little influence was observed in cysteine and glutathione concentrations. Frontal cortex BDNF levels showed a lack of treatment influence in all periods; only the expected decrease due to increasing age was observed. Moreover, the only behavioral alteration observed using a novel object recognition task was that which was expected with increasing age. We found that responses to hyperhomocysteinemia varied based on how it was reached, and the length of toxicity. Moreover, hyperhomocysteinemia can affect the normal pattern of one carbon metabolism during age increase in mice. These findings allow the establishment of a reliable animal model for studies in this field.

Grape juice concentrate protects reproductive parameters of male rats against cadmium-induced damage: a chronic assay.

The aim of the present study was to investigate the effects of long-term grape juice concentrate (GJC) consumption, in two dosages, on the reproductive parameters of cadmium-exposed male rats. The effects of the concentrate on body mass gain, plasma testosterone levels, reproductive organ weights, daily sperm production, sperm morphology, testis histopathological and histomorphometrical parameters, and testicular antioxidant markers were investigated. Wistar rats (n 54) were distributed into six groups: CdCl2; cadmium and grape juice I (1·18 g/kg per d); cadmium and grape juice II (2·36 g/kg per d); grape juice I (1·18 g/kg per d); grape juice II (2·36 g/kg per d); control. A single dose of CdCl2 (1·2 mg/kg body weight (BW)) was injected intraperitoneally and the grape juice was administered orally for 56 d. The results indicated that cadmium changed all reproductive and antioxidant parameters. At dosage I (1·18 g/kg BW), GJC consumption did not show the effects against cadmium-induced damages. In contrast, at dosage II (2·36 g/kg BW), the GJC improved the gonadosomatic index (P= 0·003), serum testosterone levels (P= 0·001), the relative weight of epididymis (P= 0·013) and ventral prostate (P= 0·052), the percentage of normal sperm (P= 0·001), and histopathological and histomorphometrical parameters. In addition, at this dosage, normalisation of the enzymatic activity of superoxide dismutase (P= 0·001) and of testicular levels of glutathione (P= 0·03) were observed. The parameters of the non-exposed rats did not depict significant alterations. In conclusion, the product was able to act as a protector of reproductive function against cadmium-induced damage. Such a property was expressed in a dose-dependent manner as the more effective dose was dosage II. The GJC acted possibly by antioxidant mechanisms.

Effects of polyunsaturated fatty acids on cocaine-conditioned place preference in mice.

OBJECTIVE: The objective of the present study was to assess whether the administration of polyunsaturated fatty acids (PUFAs) would lead to alterations in cocaine-conditioned place preference by correlating behavioral data and plasma levels of PUFAs. METHODS: Five groups of C57Bl/6J mice received a linseed oil supplement or a control solution for 19 days and were conditioned to cocaine. RESULTS: PUFAs did not exert a protective effect against cocaine-conditioned place-preference behavior, although there were significant differences in the levels of eicosapentaenoic acid (EPA) and linoleic acid among the groups tested. Higher doses of PUFAs might be necessary to induce a change in the plasma level of EPA in cocaine-conditioned mice. DISCUSSION: PUFAs had no effect on cocaine-conditioned place preference.

Neonatal arthritis disturbs sleep and behaviour of adult rat offspring and their dams.

This study aims to evaluate the impact of neonatal arthritis on adult pain threshold, sleep and general behaviours in rats and their lactating dams. Male pups were injected in the hind paw with complete Freund's adjuvant or saline on postnatal day (PN) 1. After weaning, dams were tested for anxiety, sleep recording or hormone profiling (ACTH, corticosterone and prolactin) and brain sampling (pineal melatonin and hippocampus serotonin). At adulthood (PN90), distinct subgroups of neonatal arthritic (AR) and control rats (CR) were also assessed for anxiety and pain thresholds, sleep recording, and blood/brain sampling. Compared to their respective controls at PN12, dams of arthritic rats (DAR) showed a longer latency in expressing pup retrieval and dam-pup interaction. DAR and AR showed a lower pain threshold, anxiety-like behaviour, and sleep fragmentation. Compared to controls, DAR displayed longer sleep latency, reduced paradoxical sleep latency and sleep efficiency, a decrease in prolactin and serotonin levels and increased melatonin levels. This model of unilateral hindpaw inflammation has a wide range of long-term effects in both lactating dams and their adult offspring.