Charles Francisco Ferreira

Early life stress interacts with the diet deficiency of omega-3 fatty acids during the life course increasing the metabolic vulnerability in adult rats.

Early stress can cause metabolic disorders in adulthood. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) deficiency has also been linked to the development of metabolic disorders. The aim of this study was to assess whether an early stressful event such as maternal separation interacts with the nutritional availability of n-3 PUFAs during the life course on metabolic aspects. Litters were randomized into: maternal separated (MS) and non-handled (NH). The MS group was removed from their dam for 3 hours per day and put in an incubator at 32°C on days 1° to 10° postnatal (PND). On PND 35, males were subdivided into diets that were adequate or deficient in n-3 PUFAs, and this intervention was applied during the subsequent 15 weeks. Animals body weight and food consumption were measured weekly, and at the end of the treatment tissues were collected. MS was associated with increased food intake (p = 0.047) and weight gain (p = 0.012), but no differences were found in the NPY hypothalamic content between the groups. MS rats had also increased deposition of abdominal fat (p<0.001) and plasma triglycerides (p = 0.018) when compared to the NH group. Interactions between early life stress and n-3 PUFAs deficiency were found in plasma insulin (p = 0.033), HOMA index (p = 0.049), leptin (p = 0.010) and liver PEPCK expression (p = 0.050), in which the metabolic vulnerability in the MS group was aggravated by the n-3 PUFAs deficient diet exposure. This was associated with specific alterations in the peripheral fatty acid profile. Variations in the neonatal environment interact with nutritional aspects during the life course, such as n-3 PUFAs diet content, and persistently alter the metabolic vulnerability in adulthood.

Correlation between n-3 polyunsaturated fatty acids consumption and BDNF peripheral levels in adolescents

BackgroundAlthough several studies have reported an association between mental disorders and serum levels of brain-derived neurotrophic factor (BDNF), this association is still poorly understood. The study of factors associated with both BDNF levels and mental disorders, such as n-3 polyunsaturated fatty acids (n-3 PUFAs), may help to elucidate the mechanisms mediating the relationship between the two variables. Therefore, the present study aimed to evaluate whether the intake n-3 PUFAs correlates with serum levels of BDNF.FindingsThis study involved 137 adolescents drawn from a community sample, including a group with high levels of anxiety, assessed using the Screen for Children and Anxiety Related Emotional Disorders. Blood samples were collected and serum BDNF levels were measured. n-3 PUFAs were estimated using a food frequency questionnaire for adolescents. Correlations were performed to assess the association between n-3 PUFAs intake and BDNF levels. Effects of potential confounders (total fat consumption, age, gender and anxiety) were examined using linear regression models. There was a direct correlation between n-3 PUFAs consumption and serum BDNF levels, which remained significant even after accounting for potential confounders.ConclusionsWe were able to detect a correlation between n-3 PUFAs intake and peripheral BDNF levels. Our study was limited by its small sample size, and our external validity may be restricted by the oversampling of anxious adolescents. Our findings may help determine the nature of the association between mental disorders and serum levels of BDNF. However, more studies are needed to elucidate the possible mechanisms by which n-3 PUFAs intake affects BDNF levels, and how this may lead to an increased vulnerability to psychiatric disorders.

Impact of Perinatal Different Intrauterine Environments on Child Growth and Development in the First Six Months of Life--IVAPSA Birth Cohort: rationale, design, and methods.

BackgroundIn the last twenty years, retrospective studies have shown that perinatal events may impact the individual health in the medium and long term. However, only a few prospective studies were designed to address this phenomenon. This study aims to describe the design and methods of the Impact of Perinatal Environmental Variations in the First Six Months of Life - the IVAPSA Birth Cohort.Method/DesignThis is a clinical study and involves the recruitment of a birth cohort from hospitals in Porto Alegre, Rio Grande do Sul, Brazil. Mothers from different clinical backgrounds (hypertensive, diabetics, smokers, having an intrauterine growth restricted child for idiopathic reasons, and controls) will be invited to join the study twenty-four hours after the birth of their child. Data on economic, social, and maternal health care, feeding practices, anthropometric measures, physical activity, and neuropsychological evaluation will be obtained in interviews at postpartum, 7 and 15 days, 1, 3 and 6 months of life.DiscussionTo our knowledge, this is the first thematic cohort focused on the effects of intrauterine growth restriction to prospectively enroll mothers from different clinical backgrounds. The IVAPSA Birth Cohort is a promising research platform that can contribute to the knowledge on the relationship between perinatal events and their consequences on the childrens early life.

Vulnerability to dietary n-3 polyunsaturated fatty acid deficiency after exposure to early stress in rats

The exposure to adverse events early in life may affect brain development. Omega-3 polyunsaturated fatty acid (n-3 PUFA) deficiency has been linked to the development of mood and anxiety disorders. The aim of this study was to examine the interaction between variations in the early environment (handling or maternal separation) and the chronic exposure to a nutritional n-3 PUFA deficiency on locomotor activity, sucrose preference, forced swimming test and on serum and hippocampal brain-derived neurotrophic factor (BDNF) levels. Rats were randomized into Non-handled (NH), Neonatal Handled (H) and Maternal Separated (MS) groups. Pups were removed from their dams (incubator at 32°C on postnatal days (PND) 1-10) during 10 min/day (H) or 3h/day (MS). On PND 35, males were subdivided into diets adequate or deficient in n-3 PUFA for 15 weeks. H and MS gained weight differently, and animals receiving the n-3 PUFA deficient diet gained less weight. MS displayed a higher food consumption and higher consumption of sucrose solution during the second hour of exposure to the sucrose preference test. No differences were observed in the swimming test. H group had increased locomotion and showed a higher response to amfepramone. No significant effect was observed on serum BDNF levels. BDNF protein levels were decreased in animals receiving the n-3 PUFA deficient diet. We observed that early life environment and a mild n-3 PUFA deficiency are able to affect several behavioral aspects (food and sucrose consumption and locomotor response), and lead to a differential hippocampal BDNF metabolism in adult life.

Neonatal interventions differently affect maternal care quality and have sexually dimorphic developmental effects on corticosterone secretion.

Neonatal handling (H) and maternal separation (MS) both induce changes in maternal care, but the contribution of these changes to the behavioral and neurochemical outcomes of the offspring remains unclear, as studies often find opposite results concerning the frequency of maternal behaviors, particularly in the MS paradigm. In this study, behavior displayed by H, MS and non‐handled (NH) Wistar rat dams were observed during the first 10 days after birth. A tentative assessment of the quality of maternal care was made, using a previously reported score that reflects behavior fragmentation and inconsistency. Central oxytocin levels and hippocampal synaptic plasticity markers were also evaluated in dams, immediately after litter weaning. In adulthood, male and female offspring were subjected to a contextual stress‐induced corticosterone challenge to provide further information on the impact of early interventions on neuroendocrine parameters. We found that while both H and MS interventions induced an increase in the amount of pup‐directed behavior, MS dams displayed a more fragmented and inconsistent pattern of care, reflecting poorer maternal care quality. Interestingly, an increase in oxytocin levels was observed only in H dams. While H offspring did not differ from NH, MS males and females showed marked differences in corticosterone secretion compared to controls. Our results suggest that briefly removing the pups from the nest alters maternal care quantity but not quality and increases central oxytocin, while long separations appear to increase low quality maternal care and change neuroendocrine responses in adult offspring in a sex‐specific manner.

Mitochondrial and Oxidative Stress Aspects in Hippocampus of Rats Submitted to Dietary n-3 Polyunsaturated Fatty Acid Deficiency After Exposure to Early Stress.

Chronic dietary long-chain polyunsaturated fatty acids (PUFAs) deficiency may lead to changes in cortex and hippocampus neuronal membrane phospholipids, and may be linked to impaired central nervous system function. Particularly docosahexaenoic acid deficiency appears to be involved in neuropsychiatric disorders. On the other hand, adverse events early in life may also profoundly affect brain development, leading to long-lasting effects on neurophysiology, neurobiology and behavior. This research assessed if neonatal stress and a dietary n-3 PUFAs deficiency could interact to produce hippocampal alterations related to mitochondrial functions in adult rats. There were no effects of diet, neonatal intervention or interactions on superoxide dismutase or catalase enzymatic activities, mitochondrial membrane potential and respiratory chain complexes. Rats fed n-3 PUFAs deficient diet displayed higher levels of glutathione peroxidase and catalase activity, higher free radicals production and higher thiol content compared to rats fed n-3 PUFAs adequate diet. There were interactions among diets and neonatal stress, since glutathione peroxidase, free radicals production and thiol content were increased in groups that were subjected to neonatal interventions fed n-3 PUFAs deficient diet. Additionally, reduced mitochondrial potential was observed in handled animals. Total thiol revealed a neonatal stress effect, since animals subjected to neonatal interventions displayed lower thiol content. In conclusion, we observed that a chronic treatment with deficient n-3 PUFAs diet, from the puberty period on, increased free radicals production and imbalanced antioxidant enzymes activities, and these increases were higher in animals subjected to neonatal interventions.

Effect of Paullinia cupana Mart. Commercial Extract During the Aging of Middle Age Wistar Rats: Differential Effects on the Hippocampus and Striatum

During aging, there is a marked decline in the antioxidant capacity of brain tissue, leading to a gradual loss of the antioxidant/oxidant balance, which causes oxidative damage. The effects of Paullinia cupana Mart. extract, which is described as being rich in caffeine and many polyphenol compounds, on the central nervous system have not been extensively investigated. The aim of this study was to therefore investigate the effect of a commercial guarana extract (CGE) on cognitive function, oxidative stress, and brain homeostasis proteins related to cognitive injury and senescence in middle age, male Wistar rats. Animals were randomly assigned to a group according to their treatment (saline, CGE, or caffeine). Solutions were administered daily by oral gavage for 6 months. Open field and novel object recognition tasks were performed before and after treatment. Biochemical analyses were carried out on the hippocampus and striatum. Our open field data showed an increase in exploratory activity and a decrease in anxiety-like behavior with caffeine but not with the CGE treatment. In the CGE-treated group, catalase activity decreased in the hippocampus and increased in the striatum. Analyses of the hippocampus and striatum indicate that CGE and/or caffeine altered some of the analyzed parameters in a tissue-specific manner. Our data suggest that CGE intake does not improve cognitive development, but modifies the oxidative stress machinery and neurodegenerative-signaling pathway, inhibiting pro-survival pathway molecules in the hippocampus and striatum. This may contribute to the development of unfavorable microenvironments in the brain and neurodegenerative disorders.

Transcranial direct current stimulation effects on menopausal vasomotor symptoms

Objective: To assess the effects of transcranial direct current stimulation (tDCS) compared with tDCS-sham on vasomotor symptoms of postmenopausal women. Methods: Postmenopausal women (N = 30), aged between 45 and 68 years, with at least four episodes of vasomotor symptoms per day, were recruited from a specialized outpatient clinic at a tertiary hospital in the south of Brazil and through a media call after inclusion and exclusion criteria were ensured. Active and tDCS-sham were administered over the motor cortex position (anode electrode) and contralateral supraorbital region (cathode electrode) for 10 consecutive days, except weekends. The number and intensity records of hot flashes were evaluated for 7 days before and along 30 days after the intervention. The Womens Health Questionnaire and the Hamilton Depression Rating Scale were applied to assess the quality of life and the depressive symptoms, respectively. Results: The frequencies of hot flashes per day happened in a similar way in both groups, with a reduction in the first 3 weeks after the intervention. There was a return in hot flash frequencies to baseline in the fourth week (week 0: 79.0 ± 6.2 and 75.8 ± 6.0, week 1: 61.6 ± 9.6 and 57.0 ± 7.8, week 2: 56.8 ± 8.9 and 55.9 ± 7.1, week 3: 56.8 ± 8.9 and 54.2 ± 7.2, week 4: 64.9 ± 10.7, 70.1 ± 8.9; tDCS-sham and tDCS groups, respectively). In the tDCS group, a trend towards a conversion of intensive hot flashes into mild ones was observed. Conclusions: Our results suggest that the tDCS technique showed small trends on postmenopausal vasomotor symptoms, justifying searches for more effective methods by which tDCS could reduce hot flashes.

Feeding practices in the first 6 months after delivery: Effects of gestational hypertension

OBJECTIVE To identify the effects of gestational hypertension on feeding practices in the first 6 months after delivery. STUDY DESIGN A prospective cohort study enrolling 168 mother-newborn pairs (Gestational hypertension group n = 42, Normotensive group n = 124). The gestational hypertension diagnosis criteria was established as a systolic pressure of ≥140 mmHg or a diastolic pressure of ≥90 mmHg after 20 weeks of gestation, while its severity was categorized according to blood pressure, proteinuria, clinical and laboratory analysis. Demographic, clinical and social information were collected from the patients medical records. In order to collect information about the newborns feeding practices and possible difficulties in breastfeeding the mothers were interviewed via telephone 30, 60, 120 and 180 days after delivery. MAIN OUTCOME MEASURES Feeding practices (eg. exclusive breastfeeding, predominant breastfeeding, complementary breastfeeding and bottle-feeding) within the first 6 months after delivery. RESULTS The mothers with Gestational hypertension displayed greater difficulties in maintaining exclusive breastfeeding over time, when compared to normotensive mothers. There was a greater introduction of milk formulas in the group of women with gestational hypertension, and they presented greater difficulties in maintaining exclusive breastfeeding over time when compared to the group of normotensive mothers at hospital admission (p ≤ 0,0001). The group with gestational hypertension reported higher frequencies of predominant breastfeeding practices and presented shorter durations of breastfeeding after 6 months after delivery. CONCLUSIONS Women with gestational hypertension are at risk of using complementary breastfeeding and breastfeeding for shorter durations.

Associations between postpartum depression and hypertensive disorders of pregnancy

To identify possible relationships between postpartum depression and hypertensive disorders of pregnancy (HDP), as well as the associated risk factors for developing postpartum depression.