Abstract Prenatal stress (PS) and early postnatal environment may alter maternal care. Infant rats learn to identify their mother through the association between maternal care and familiar odors. ...Female Wistar rats were exposed to restraint stress for 30 min, 4 sessions per day, in the last 7 days of pregnancy. At birth, pups were cross-fostered and assigned to the following groups: prenatal non-stressed mothers raising non-stressed pups (NS:NS), prenatal stressed mothers raising non-stressed pups (S:NS), prenatal non-stressed mothers raising stressed pups (NS:S), prenatal stressed mothers raising stressed pups (S:S). Maternal behaviors were assessed during 6 postpartum days. On postnatal day (PND) 7, the behavior of male and female pups was analyzed in the odor preference test; and noradrenaline (NA) activity in olfactory bulb (OB) was measured. The results showed that restraint stress increased plasma levels of corticosterone on gestational day 15. After parturition, PS reduced maternal care, decreasing licking the pups and increasing frequency outside the nest. Female pups from the NS:S, S:NS, S:S groups and male pups from the S:S group showed no nest odor preference. Thus, at day 7, female pups that were submitted to perinatal interventions showed more impairment in the nest odor preference test than male pups. No changes were detected in the NA activity in the OB. In conclusion, repeated restraint stress during the last week of gestation reduces maternal care and reduces preference for a familiar odor in rat pups in a sex-specific manner.
We studied the effect of chronic caffeine on parameters related to oxidative stress in different brain regions of stressed and non-stressed rats. Wistar rats were divided into three groups: control ...(receiving water), caffeine 0.3 g/L and caffeine 1.0 g/L (in the drinking water). These groups were subdivided into non-stressed and stressed (repeated restraint stress during 40 days). Lipid peroxide levels and the total radical-trapping potential were assessed, as well as antioxidant enzyme activities superoxide dismutase, gluthatione peroxidase, and catalase in hippocampus, striatum and cerebral cortex. Results showed interactions between stress and caffeine, especially in the cerebral cortex, since caffeine increased the activity of some antioxidant enzymes, but not in stressed animals. We concluded that chronic administration of caffeine led, in some cases, to increased activity of antioxidant enzymes. However, these effects were not observed in the stressed animals.
Caffeine is widely consumed in beverages and food, and its consumption in high doses is associated with anxiety increase. Stress situations are often associated to coffee consumption, and have a ...strong influence on oxidative DNA damage. As there are sex-specific differences in many metabolic, neurochemical and behavioral aspects, the aim of this study is to verify the interaction between chronic consumption of caffeine and chronic stress on anxiety and DNA breaks in the hippocampus on male and female rats. Wistar rats were submitted to restraint stress for at least 50 days. The diet consisted of standard rat chow and caffeine 0.3 or 1 g/L in drinking water “ad libitum” as the only drinking source
. Controls received tap water. Anxiety-like behavior and DNA breaks in the hippocampus were evaluated. Caffeine consumption and chronic stress increased anxiety-like behavior as well as DNA breaks in the hippocampus of male rats. No effect on these parameters was observed in females. These results may be related to the presence of estradiol, which may have anxiolytic and neuroprotective properties.
Abstract This study was undertaken to verify if repeated long-term separation from dams would affect the development of parameters related to post-traumatic stress disorder (PTSD) after animals are ...subjected to inescapable shock when adults. Wistar rats were subjected to repeated maternal separation during post-natal days 1–10. When adults, rats from both sexes were submitted to a PTSD model consisting of exposure to inescapable footshock, followed by situational reminders. We observed long-lasting effects of both interventions. Exposure to shock increased fear conditioning. Anxiety-like behavior was increased and exploratory activity decreased by both treatments, and these effects were more robust in males. Additionally, basal corticosterone in plasma was decreased, paralleling effects observed in PTSD patients. Levels of S100B protein in serum and cerebrospinal fluid (CSF) were measured. Levels in serum correlated with the effects observed in anxiety-like behavior, increasing in males exposed to shock, and presenting no effect in females. S100B in CSF was increased in females submitted to maternal separation during the neonatal period. These results suggest that, in rats, an early stress experience such as maternal separation may aggravate some effects of exposure to a stressor during adult age, and that this effect is sex-specific. Additionally, data suggest that the increased S100B levels, observed in serum, have an extracerebral origin, possibly mediated by an increase in the noradrenergic tonus. Increased S100B in brain could be related to its neurotrophic actions.
Early life events lead to behavioral and neurochemical changes in adulthood. The aim of this study is to verify the effects of neonatal handling on spatial memory, nitric oxide (NO) production, ...antioxidant enzymatic activities and DNA breaks in the hippocampus of male and female adult rats. Litters of rats were non-handled or handled (10 min/day, days 1–10 after birth). In adulthood they were subjected to a Morris water maze or used for biochemical evaluations. Female handled rats showed impairment in spatial learning. They also showed decreased NO production, while no effects were observed in these parameters in male rats. No effects were observed on the number of hippocampal NADPH diaphorase positive cells. In the Comet Assay, male handled rats showed increased DNA breaks index when compared to non-handled ones. We conclude that neonatal handling impairs learning performance in a sex-specific manner, what may be related to NO decreased levels.
This study evaluated the effects of chronic stress and lithium treatments on oxidative stress parameters in hippocampus, hypothalamus, and frontal cortex. Adult male Wistar rats were divided into two ...groups: control and submitted to chronic variate stress, and subdivided into treated or not with LiCl. After 40 days, rats were killed, and lipoperoxidation, production free radicals, total antioxidant reactivity (TAR) levels, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were evaluated. The results showed that stress increased lipoperoxidation and that lithium decreased free radicals production in hippocampus; both treatments increased TAR. In hypothalamus, lithium increased TAR and no effect was observed in the frontal cortex. Stress increased SOD activity in hippocampus; while lithium increased GPx in hippocampus and SOD in hypothalamus. We concluded that lithium presented antioxidant properties, but is not able to prevent oxidative damage induced by chronic variate stress.
•Long daily separations from pups changed the quality and pattern of maternal care.•Handling the pups induced a persistent increase in dams’ central oxytocin levels.•Maternal separation adult ...offspring showed differences in corticosterone secretion.•Qualitative analyses appear useful to study maternal care impact in early life.
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 10days 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.
Glutamate is an excitatory neurotransmitter involved in neuronal plasticity and neurotoxicity. Chronic stress produces several physiological changes on the spinal cord, many of them presenting ...sex-specific differences, which probably involve glutamatergic system alterations. The aim of the present study was to verify possible effects of exposure to chronic restraint stress and 17β-estradiol replacement on
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H-glutamate release and uptake in spinal cord synaptosomes of ovariectomized (OVX) rats. Female rats were subjected to OVX, and half of the animals received estradiol replacement. Animals were subdivided in controls and chronically stressed. Restraint stress or estradiol had no effect on
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H-glutamate release. The chronic restraint stress promoted a decrease and 17β-estradiol induced an increase on
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H-glutamate uptake, but the uptake observed in the restraint stress +17β-estradiol group was similar to control. Furthermore, 17β-estradiol treatment caused a significant increase in the immunocontent of the three glutamate transporters present in spinal cord. Restraint stress had no effect on the expression of these transporters, but prevented the 17β-estradiol effect. We suggest that changes in the glutamatergic system are likely to take part in the mechanisms involved in spinal cord plasticity following repeated stress exposure, and that 17β-estradiol levels may affect chronic stress effects in this structure.
Muitas evidências indicam que exposições a eventos adversos no início da vida, tais como abuso e negligência, aumentam a vulnerabilidade a psicopatologias na vida adulta. Tem sido relatado que ...psicopatologias podem levar a não apenas prejuízos cognitivos, emocionais e sociais, mas também a uma variedade de alterações neuroquímicas. Separações maternas periódicas no período neonatal têm sido usadas como um modelo animal de eventos adversos no início da vida, avaliando-se seus efeitos sobre aspectos comportamentais e fisiológicos observados na vida adulta. As primeiras duas semanas de vida representam um período crítico para o desenvolvimento neural em ratos. Sabe-se que períodos prolongados de separação materna (SM) podem modificar parâmetros neurobiológicos e comportamentais. Logo, o objetivo do presente estudo foi verificar os efeitos duradouros de SM repetida em diferentes parâmetros, incluindo comportamentos de medo, sociais, cognitivos e alimentar, assim como uma série de análises neuroquímicas. Ratos Wistar machos e fêmeas foram sujeitos a SM repetidas (incubadora a 32°C, 3h/dia) nos dia 1 ao 10 de vida. Na primeira parte deste trabalho, os animais foram expostos à tarefa de Medo Condicionado ao Contexto aos 60 dias de idade. Uma semana após, as atividades da Na+, K+-ATPase e de enzimas antioxidantes foram medidas na amígdala. Na segunda parte deste trabalho, os animais foram expostos ao teste de Interação Social por 15 min aos 70 dias de idade. Foram observadas as frequências e durações dos seguintes comportamentos: cheirar; ataque lateral; ataque frontal; boxing; e tempo gasto sem demonstrar comportamentos sociais. A ocitocina foi medida no líquor. Na terceira parte deste trabalho, ratos adultos foram expostos a tarefas de memória (Reconhecimento de Objetos e ao Labirinto Aquático de Morris). O Comportamento Alimentar também foi analisado. Dano celular, quebras do ADN, citocinas inflamatórias e fator neurotrófico derivado do encéfalo (BDNF) foram medidos no hipocampo. A SM aumentou o Medo Condicionado ao Contexto e a atividade da Na+, K+-ATPase na amígdala. Foi encontrado um efeito significativo da SM sobre a catalase apenas em fêmeas, aumentando sua atividade. A SM reduziu os comportamentos sociais (duração de cheirar; frequências de ataques lateral e frontal; frequência e duração de boxing). Houve uma tendência dos animais SM apresentarem redução na ocitocina no líquor. Animais SM apresentaram desempenho prejudicado nos testes de Reconhecimento de Objetos e Labirinto aquático de Morris. Não houve efeito sobre o Comportamento Alimentar. Os seguintes resultados foram encontrados nas avaliações neuroquímicas: SM aumentou as quebras de ADN no hipocampo, apresentou uma tendência a diminuir o TNF-α hipocampal em ratos machos e aumentou significativamente o TNF-α hipocampal em fêmeas. Nossos resultados sugerem um papel do ambiente precoce na programação das respostas de medo, sociais e cognitivas na vida adulta, assim como em suas neuroquímicas subjacentes. Observamos que um evento aversivo no início da vida, tal como a SM, pode levar a prejuízos em parâmetros comportamentais e neuroquímicos. Encontramos uma atividade aumentada na amígdala (indicada pela Na+, K+-ATPase) causada pela SM, afetando comportamentos relacionados ao medo, com melhor desempenho na tarefa de medo condicionado em adultos, e esse efeito pode ser tarefa-específico (os efeitos sobre a memória espacial e de reconhecimento de objetos são opostos). Ademais, a SM reduziu comportamentos agressivos e sociais. Esse resultado pode ser relacionado à tendência da SM reduzir os níveis de ocitocina no líquor, a qual é um hormônio envolvido em comportamentos afiliativos e sociais. As diferenças de sexo nos comportamentos sociais estão de acordo com estudos anteriores. Os prejuízos de memória em animais SM podem ser relacionados às mudanças neuroquímicas encontradas no hipocampo, tais como índices aumentados de quebras de ADN. Ademais, nosso trabalho encontrou diferenças de sexo nas atividades neuroquímicas, tais como atividade da CAT na amígdala em fêmeas SM e um efeito contrário entre machos e fêmeas SM nos níveis de TNF-α. Esses achados demonstram que um estresse no início da vida pode levar a efeitos neuroquímicos sexo-específicos.
A large body of evidences indicates that exposure to early adverse life events such as childhood neglect and abuse can increase vulnerability to psychopathology in adult life. It has been reported that psychopathologies may lead not only to cognitive, emotional and social impairments, but also to a variety of neurochemical alterations. Periodic neonatal maternal separation (MS) in the rat has been used as a rodent model of the effects of early adverse life events on adult physiology and behavior. The first two weeks of life are a critical period for neural development in rats. The purpose of the present study was to verify the long-term effects of repeated MS in different parameters, including conditioned fear, social, cognitive and feeding behaviors, as well as a series of neurochemical analysis. Female and male Wistar rats were subjected to repeated MS (incubator at 32°C, 3h/day, during postnatal days 1-10). In the first part of this work, the subjects were exposed to a Contextual Fear Conditioning task at 60 days of age, and Na+, K+ -ATPase and antioxidant enzymes activitieswere evaluated in the amygdala. In the second part of this work, the animals were exposed to 15-min Social Interaction test at 70 days of age in order to analyze social behaviors (frequencies and durations of sniffing; lateral attack; frontal attack; boxing; and time spent in non-social behavior). Oxytocin was measured in cerebral spinal fluid (CSF). In the third part of the present work, adult rats were exposed to Object Recognition and Morris Water Maze memory tasks. Feeding behavior was analyzed as well. Cell damage, mitochondrial viability, DNA breaks, inflammatory cytokines, and brain-derived neurotrophic factor (BDNF) were measured in the hippocampus. MS effects were observed, with increased Contextual Fear Conditioning and increased Na+, K+-ATPase in amygdala, without differences groups on the antioxidant enzymes activities (SOD, GPx, CAT) in male rats. Nevertheless, we found a significant MS effect in females, with an increase of CAT activity. MS decreased social behaviors (sniffing duration; frequencies of lateral and frontal attacks; frequency and duration of boxing). Two way ANOVA indicated a tendency of MS animals towards decreased CSF oxytocin levels. MS animals also shoed impairments on performances of object recognition and Morris water maze tasks, and no differences on feeding behavior. The following results were found on neurochemical assessments: MS increased DNA breaks in hippocampus; additionally, a tendency for MS decreasing hippocampal TNF-α in male rats was observed, while MS significantly increased hippocampal TNF-α in females. Our results suggest a role of early rearing environment in programming fear, social and cognitive responses in adulthood, as well as their underlying neurochemistry. We found that an aversive early-life event, such as MS, may lead to impairments in behavioral and neurochemical parameters. We found that MS increased activity in the amygdala (as indicated by the increased activity of Na+, K+-ATPase), affecting behaviors related to fear in adulthood, and this effect could be task-specific. Moreover, MS decreased aggressive and social behaviors. This result may be related to the marginally reduced CSF oxytocin levels in MS subjects, which is a hormone involved in affiliative and social behaviors. Sex differences on social behaviors are in accordance to previous studies. MS also impaired short- and long-term memories as observed on Object Recognition and Morris Water Maze tasks. These memory impairments on MS animals may be associated to neurochemical changes found in hippocampus, such as increased DNA breaks. Moreover, our work found sex differences on neurochemical activities, such as amygdalar CAT activity in MS females and an opposing effect of hippocampal TNF-α in MS females compared to males. These findings reveal that early stress may lead to sex-specific neurochemical effects.