RESUMO
OBJECTIVES: In this study, an in vivo model of Aß toxicity was used to investigate the effects of this peptide and the treatment with genistein on the lipid composition (gangliosides, phospholipids and cholesterol) in the frontal cortex of rats. METHODS: Male Wistar rats received bilateral intracerebroventricular infusions of Aß1-42 (2 nmol) and genistein 10 mg/kg orally for 10 days. Frontal cortex was homogenized with chloroform:methanol for lipid extraction and ganglioside, phospholipid and cholesterol levels were evaluated. RESULTS: The Aß-infused animals showed a significant decrease in ganglioside concentration and relative reduction of GD1b and GQ1b species. Treatment with genistein prevented the decrease in ganglioside levels. Phospholipid and cholesterol contents did not show significant differences. DISCUSSION: Considering the roles of gangliosides on neuronal function, findings described here can contribute to the knowledge of the potential neuroprotective mechanisms of genistein against Aß-induced alterations in the frontal cortex of rats and provide a novel view in the multifaceted scenario associated with its beneficial effects.
Assuntos
Peptídeos beta-Amiloides , Lobo Frontal , Gangliosídeos , Genisteína , Peptídeos beta-Amiloides/toxicidade , Animais , Colesterol/química , Lobo Frontal/química , Gangliosídeos/química , Genisteína/farmacologia , Masculino , Fragmentos de Peptídeos/toxicidade , Fosfolipídeos/química , Ratos , Ratos WistarRESUMO
INTRODUCTION: Polyphenols are compounds found in plants that have been extensively studied due to the health benefits of its consumption in adulthood. Meanwhile, recent evidence suggests that polyphenol consumption during pregnancy may not be safe for the fetus. OBJECTIVE: The goal of this study was to evaluate the effect of naringenin supplementation during pregnancy on brain redox homeostasis and mitochondrial activity of the newborn rat. METHODS: Adult female Wistar rats were divided into two groups: (1) vehicle (1â mL/Kg p.o.) or (2) naringenin (50â mg/Kg p.o.). Naringenin was administered once a day during pregnancy. The offspring were euthanized on postnatal day 7, as well the dams, and brain regions were dissected. RESULTS: The offspring cerebellum was the most affected region, presenting increased activity of the mitochondrial electron transport system, allied to increased reactive species levels, lipid peroxidation, and glutathione concentration. The nitric oxide levels suffered structure-dependent alteration, with decreased levels in the pups' cerebellum and increased in the hippocampus. The offspring parietal cortex was not affected, as well as the parameters evaluated in the dams' brains. CONCLUSION: Maternal consumption of naringenin alters offspring cerebellar redox homeostasis, which could be related to adverse effects on the motor and cognitive development in the descendants.
Assuntos
Polifenóis , Efeitos Tardios da Exposição Pré-Natal , Animais , Animais Recém-Nascidos , Cerebelo , Feminino , Glutationa , Homeostase , Humanos , Óxido Nítrico , Oxirredução , Gravidez , Ratos , Ratos WistarRESUMO
We aimed to evaluate the effects of the addition of oregano (Origanum vulgare) or green tea (Camellia sinensis L.) extracts (separately and associated) on feed intake, milk production, and hematological and antioxidant profiles of dairy cows. For that purpose, 16 Holstein and 16 Holstein-Gyr cows with 526.3±10.2 kg and within the first third of lactation were distributed according to a complete block design with measurements repeated in time. Treatments were control (CON), addition of 0.056% of oregano extract (OR), addition of 0.028% of green tea extract (GT), addition of a mixture of OR and GT extract (0.056% each) in the diet (MIX). Hematological and antioxidant profiles were monitored. Data were subjected to ANOVA, with block, treatment, days, and their interactions considered as fixed effects and animal and the residue as random effects. In Holstein cows, GT increased feed intake and milk yield compared with CON; in Holstein-Gyr crossbred cows, OR showed increased intake and GT increased milk yield compared with CON. Compared with CON, GT and OR decreased eosinophils concentration; OR showed the highest neutrophils concentration and neutrophils to leukocyte ratio. Compared with CON, OR presented increased catalase (CAT) activity, while GT increased the reduced glutathione concentration. The MIX treatment reduced CAT activity compared with OR, presented the lowest concentration of oxidized dichlorofluorescein in the erythrocytes (DCFER) and plasma (DCFPLA), and increased eosinophils concentration compared with GT and OR. Extracts differently affected feed intake and milk yield depending on genetic group. Feeding green tea and oregano extracts separately or associated distinctly affects the antioxidant indicators of lactating dairy cows.(AU)
Assuntos
Animais , Feminino , Bovinos/fisiologia , Leite/fisiologia , Aditivos Alimentares/efeitos adversos , Antioxidantes/efeitos adversos , Chá/química , Extratos Vegetais/efeitos adversos , Origanum/químicaRESUMO
Research has shown the beneficial effects of naringin supplementation to adult rodents, which can ameliorate oxidative stress in disease models. However, evidence has demonstrated that polyphenol supplementation induced detrimental effects when consumed during sensitive periods of development, such as pregnancy. Therefore, we investigated the effect of maternal naringin supplementation during pregnancy on the offspring's cerebral redox status. Pregnant Wistar rats were divided into control and naringin groups and supplemented from gestational day 15 to gestational day 21. On postnatal days 1, 7, and 21, offspring were euthanized, and the prefrontal cortex, hippocampus, striatum, and cerebellum dissected. On postnatal day 1, maternal naringin supplementation positively modulated the pups' brain redox status. On postnatal day 7, a pro-oxidative milieu was observed in the offspring's striatum and cerebellum in a sex-dependent manner, even though the prefrontal cortex and hippocampus were not negatively affected. Besides, the alterations observed on postnatal day 7 did not persist up to weaning. Our findings demonstrated that the effect induced by naringin supplementation in the brain redox status differed according to the period of development in which naringin was consumed since the beneficial effects usually found in the adult rodents became detrimental when the supplementation was applied during pregnancy.
Assuntos
Encéfalo , Efeitos Tardios da Exposição Pré-Natal , Animais , Suplementos Nutricionais , Feminino , Flavanonas , Oxirredução , Gravidez , Ratos , Ratos WistarRESUMO
Sex differences in the brain of mammals range from neuroarchitecture through cognition to cellular metabolism. The hippocampus, a structure mostly associated with learning and memory, presents high vulnerability to neurodegeneration and aging. Therefore, we explored basal sex-related differences in the proteome of organotypic hippocampal slice culture, a major in vitro model for studying the cellular and molecular mechanisms related to neurodegenerative disorders. Results suggest a greater prevalence of astrocytic metabolism in females and significant neuronal metabolism in males. The preference for glucose use in glycolysis, pentose phosphate pathway and glycogen metabolism in females and high abundance of mitochondrial respiration subunits in males support this idea. An overall upregulation of lipid metabolism was observed in females. Upregulation of proteins responsible for neuronal glutamate and GABA synthesis, along with synaptic associated proteins, were observed in males. In general, the significant spectrum of pathways known to predominate in neurons or astrocytes, together with the well-known neuronal and glial markers observed, revealed sex-specific metabolic differences in the hippocampus. TEM qualitative analysis might indicate a greater presence of mitochondria at CA1 synapses in females. These findings are crucial to a better understanding of how sex chromosomes can influence the physiology of cultured hippocampal slices and allow us to gain insights into distinct responses of males and females on neurological diseases that present a sex-biased incidence.
Assuntos
Hipocampo/metabolismo , Proteômica/métodos , Animais , Feminino , Citometria de Fluxo , Hipocampo/ultraestrutura , Humanos , Metabolismo dos Lipídeos/fisiologia , Masculino , Microscopia Eletrônica de Transmissão , Sistema Nervoso/metabolismo , Sistema Nervoso/ultraestrutura , Neuroglia/metabolismo , Neurotransmissores/metabolismo , Caracteres Sexuais , Transdução de Sinais/fisiologiaRESUMO
Introduction: Caloric restriction (CR) has been proven to promote a series of health benefits from yeast to primates. Nowadays, increasing rates of obesity certainly encourage researchers to evaluate CR effects and establish it as a therapeutic approach. Maternal obesity is also a concern, and studies in the developmental origins of health and disease (DOHaD) have shown the importance of interventions during pregnancy, especially those involving maternal nutrition. On the other hand, undernutrition during pregnancy leads to increased weight gain, disturbed feeding behavior and dysfunctional metabolism in adulthood.Methods: In this way, we utilized moderate CR (20% compared to control consumption) in pregnant Wistar rats as intervention, with malnutrition control by micronutrients supplementation. We assessed CR effects on offspring's developmental milestones, feeding behavior, exploratory behavior, and memory on adolescence (PND21) and adulthood (PND60).Results: We did not find alterations on litter size or birth weight, although CR pups were leaner at adult ages. Importantly, no delay in development was observed. Besides, female pups showed earlier suction reflex and male pups showed earlier response to the negative geotaxis. CR pups also showed less preference for palatable food (Froot Loops®) at adult age, which could be decisive on obesity tendency. Locomotor activity was increased by CR on PND60 and there was no effect on memory at all.Discussion: Our results on development and behavior demonstrate that gestational CR may be a helpful health strategy if malnutrition is well controlled, with potential clinical impact.
Assuntos
Restrição Calórica , Comportamento Alimentar , Adulto , Animais , Suplementos Nutricionais , Feminino , Humanos , Masculino , Micronutrientes , Gravidez , Ratos , Ratos WistarRESUMO
Mother-pup interactions are extremely important to offspring survival and growth. The goal of this study was to evaluate the influence of prenatal and neonatal interventions on maternal care, analyzing the effect of maternal exercise, as a healthy intervention, and also the litter size reduction, a model that has been widely used to study early overfeeding in rats. Female Wistar rats were divided into 1) sedentary, and 2) swimming exercise for four weeks, starting one week before mating (5 days/week, 30 min/session). One day after birth, the litter was culled to 8 pups (normal) or 3 pups (small) per dam, yielding control and overfed subgroups for each maternal group, respectively. From postnatal days 2-9 the litter was observed 5 periods a day, to evaluate maternal behavior. Litter reduction caused important alterations in maternal behavior, reducing the total time out of the nest and increasing the frequency of maternal care and lactation in several observation periods, justifying the increased pup's weight gain already demonstrated by this animal model. The practice of maternal exercise did not prevent, but cause the less intensive frequency of non-maternal behavior and lactation in arched-back position, induced by the reduction of litter size. These data demonstrated that small litter size altered maternal behavior, and gestational exercise does not influence significantly these changes.
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Comportamento Materno , Condicionamento Físico Animal , Animais , Feminino , Lactação , Tamanho da Ninhada de Vivíparos , Masculino , Gravidez , Ratos WistarRESUMO
Fibromyalgia is characterized by the amplification of central nervous system pain with concomitant fatigue, sleep, mood disorders, depression, and anxiety. It needs extensive pharmacological therapy. In the present study, Swiss mice were treated with reserpine (0.25 mg/kg, s.c.) over three consecutive days, in order to reproduce the pathogenic process of fibromyalgia. On day 4, the administrations of the Tx3-3 toxin produced significant antinociception in the mechanical allodynia (87.16% ±12.7%) and thermal hyperalgesia (49.46% ± 10.6%) tests when compared with the PBS group. The effects produced by the classical analgesics (duloxetine 30 mg/kg, pramipexole 1 mg/kg, and pregabalin 30 mg/kg, p.o., respectively) in both of the tests also demonstrated antinociception. The administrations were able to increase the levels of the biogenic amines (5-HTP and DE) in the brain. The treatments with pramipexole and pregabalin, but not duloxetine, decreased the immobility time in the FM-induced animals that were submitted to the forced swimming test; however, the Tx3-3 toxin (87.45% ± 4.3%) showed better results. Taken together, the data has provided novel evidence of the ability of the Tx3-3 toxin to reduce painful and depressive symptoms, indicating that it may have significant potential in the treatment of FM.
Assuntos
Analgésicos/administração & dosagem , Fibromialgia/tratamento farmacológico , Neuropeptídeos/administração & dosagem , Anestésicos/administração & dosagem , Animais , Modelos Animais de Doenças , Fibromialgia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Masculino , Camundongos , Reserpina/administração & dosagemRESUMO
Exposure to environmental factors can program the metabolism, conferring resistance or increasing the risk to chronic disease development in childhood and adulthood. In this sense, lactation is an important period in this window of development. Herein, we investigated the effect of early weaning on neurochemical and behavioral changes in offspring at weaning and adulthood. Female and male pups were divided into four groups: (1) Control weaning (weaning on the PND21, pups were kept with the biological mother); (2) Early Weaning Bromocriptine group (EWB) (pharmacological weaning on PND16); (3) Early Weaning Cross-Fostering group (EWCF) (pups housed with a foster mother on PND16 up to PND21); (4) Early Weaning Without Care group (EWWC) (weaning on PND16, maternal separation). Weight control of pups was recorded from postnatal Day 16 to 59. On the 21st day, part of the pups was euthanized and the hippocampus and hypothalamus were removed for biochemical evaluation. The remaining pups were submitted to behavioral tests on the 60th postnatal day. Early weaning reduced the pups' body weight, in a sex-dependent way. At 60 days of age, male pups of EWCF and EWWC groups have lower body weight compared to control male, and female body weight was lower than male pups. In relation to biochemical changes in the brain, weaning altered the levels of oxidants, increased the enzymatic activity of superoxide dismutase (SOD), and glutathione peroxidase (GPx), as well as induced lipid peroxidation. Weaning was also able to alter long-term memory and induce anxious behavior in pups. Our results demonstrate that the different types of early weaning changed the parameters of redox status in the hippocampus and hypothalamus of pups (21 days old), suggesting a prooxidative profile, in addition, to alter learning/memory and inducing an anxious behavior in male offspring (60 days old).
Assuntos
Hipocampo/metabolismo , Hipotálamo/metabolismo , Privação Materna , Desmame , Fatores Etários , Animais , Animais Recém-Nascidos , Feminino , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/fisiologia , Masculino , Atividade Motora/fisiologia , Oxirredução , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
The Developmental Origins of Health and Disease (DOHaD) states that intrauterine maternal environment influences postnatal life by programming offspring's metabolism. Intrauterine milieu induced by exercise during pregnancy promotes long-lasting benefits to the offspring's health and seems to offer some resistance against chronic diseases in adult life. Alzheimer's disease is a public health concern with limited treatment options. In the present study, we assessed the potential of maternal exercise during pregnancy in long-term programming of young adult male rat offspring's cerebellar metabolism in conferring neuroprotection against amyloid-ß (Aß) neurotoxicity. Female Wistar rats were submitted to a swimming protocol 1 week prior mating and throughout pregnancy (five sessions/a week lasting 30 min). Aß oligomers were infused bilaterally in the brain ventricles of 60-day-old male offspring. Fourteen days after surgery, we measured parameters related to redox state, mitochondrial function, and the immunocontent of proteins related to synaptic function. We found that maternal exercise during pregnancy attenuated several parameters in the offspring's male rat cerebellum, such as the reactive species rise, the increase of inducible nitric oxide synthase immunocontent and tau phosphorylation induced by Aß oligomers, increased mitochondrial fission indicated by dynamin-related protein 1 (DRP1), and protein oxidation identified by carbonylation. Strikingly, we find that maternal exercise promotes changes in the rat offspring's cerebellum that are still evident in young adult life. These favorable neurochemical changes in offspring's cerebellum induced by maternal exercise may contribute to a protective phenotype against Aß-induced neurotoxicity in young adult male rat offspring.