Prenatal stress modifies hippocampal synaptic plasticity and spatial learning in young rat offspring

Clinical studies demonstrate that prenatal stress causes cognitive deficits and increases vulnerability to affective disorders in children and adolescents. The underlying mechanisms are not yet fully understood. Here, we reported that prenatal stress (10

Sex differences in the programming effects of prenatal stress on psychopathology and stress responses: an evolutionary perspective

There is strong evidence from animal studies that prenatal stress has different effects on male and female offspring. In general, although not always, prenatal stress increases anxiety, depression and stress responses, both hypothalamic–pituitary–adrenal and cardiovascular, in female offspring rather than in male. Males are more likely to show learning and memory deficits. There have been few studies so far in humans which differentiate effects of prenatal stress on male and female psychopathology. Some studies support the animal models, but the evidence is inconsistent. The mediating mechanisms for any sex specific effects are little understood, but there is evidence that placental function can differ depending on the sex of the fetus. We suggest that there may be an evolutionary reason for any sex differences in the long term effects of prenatal stress. In a stressful environment it may be adaptive for females, who are more likely to stay in one place and look after children, to be more vigilant, alert to danger and thus show more stress responsiveness. This can give rise to a more anxious or depressed phenotype. With males it may be more adaptive to go out and explore new environments, compete with other males, and be more aggressive. For this it may help to be less responsive to external stressors. More research is needed into sex differences in the effects of prenatal stress in humans, to test these ideas.

Could neonatal testosterone replacement prevent alterations induced by prenatal stress in male rats?

The present study was designed to examine whether testosterone replacement is able to prevent some effects of maternal restraint stress during the period of brain sexual differentiation - on endocrine system and sexual behavior in male rat descendants. Pregnant rats were exposed to restraint stress for 1 h/day from gestational days 18 to 22. At birth, some male pups from these stressed rats received testosterone propionate. The neonatal testosterone replacement was able to prevent the reduction in anogenital distance at 22 days of age observed in pups from stressed pregnant rats as well as prevents the decrease in testosterone levels during the adulthood of these animals. Testosterone replacement in these males also presented an improvement in sexual performance. In this way, testosterone replacement probably through increasing neonatal level of this hormone was able to prevent the later alterations caused by the prenatal stress during the period of brain sexual differentiation. (c) 2005 Published by Elsevier B.V.

Chronic mild prenatal stress exacerbates the allergen-induced airway inflammation in rats

The effects of chronic mild prenatal stress on leukocyte infiltration into the airways was investigated in rat offspring. The chronic prenatal stress consisted of transitory and variable changes in the rat's living conditions. Offspring at adult age were actively sensitized (day 0) and intratracheally challenged (day 14) with ovalbumin. Bronchoalveolar lavage was performed in the offspring at 48 h after intratracheal challenge with ovalbumin. A significant increase in total leukocyte infiltration was observed in the non-stressed offspring group and this was associated with a marked recruitment of eosinophils without a significant effect on the influx of neutrophils and mononuclear cells. In the prenatal stressed offspring, the counts of both total leukocyte and eosinophils, as well as mononuclear cells, was increased by 50% compared to the non-stressed offspring. We provide here the first experimental evidence that chronic mild unpredictable prenatal stress produces a marked increase in the allergen-induced airway inflammation in the rat offspring.

Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus

Early experiences such as prenatal stress significantly influence the development of the brain and the organization of behavior. In particular, prenatal stress impairs memory processes but the mechanism for this effect is not known. Hippocampal granule neurons are generated throughout life and are involved in hippocampal-dependent learning. Here, we report that prenatal stress in rats induced lifespan reduction of neurogenesis in the dentate gyrus and produced impairment in hippocampal-related spatial tasks. Prenatal stress blocked the increase of learning-induced neurogenesis. These data strengthen pathophysiological hypotheses that propose an early neurodevelopmental origin for psychopathological vulnerabilities in aging.

Preschoolers’ Executive Control and Diurnal Cortisol as Mediators of the Relations of Prenatal Stress to Child Adjustment

Thesis (Ph.D.)--University of Washington, 2016-08

Enriched environment treatment counteracts enhanced addictive and depressive-like behavior induced by prenatal chronic stress

Prenatal stress can cause many long-term behavior changes in offspring, but whether prenatal stress can alter addictive behavior in offspring and postnatal enriched environment treatment (EE) can restore these changes are unknown. We reported here that pr

Enriched environment treatment restores impaired hippocampal synaptic plasticity and cognitive deficits induced by prenatal chronic stress

Prenatal stress can cause long-term effects on cognitive functions in offspring. Hippocampal synaptic plasticity, believed to be the mechanism underlying certain types of learning and memory, and known to be sensitive to behavioral stress, can be changed

Frequency of infant stroking reported by mothers moderates the effect of prenatal depression on infant behavioural and physiological outcomes

Animal studies find that prenatal stress is associated with increased physiological and emotional reactivity later in life, mediated via fetal programming of the HPA axis through decreased glucocorticoid receptor (GR) gene expression. Post-natal behaviours, notably licking and grooming in rats, cause decreased behavioural indices of fear and reduced HPA axis reactivity mediated via increased GR gene expression. Post-natal maternal behaviours may therefore be expected to modify prenatal effects, but this has not previously been examined in humans. We examined whether, according to self-report, maternal stroking over the first weeks of life modified associations between prenatal depression and physiological and behavioral outcomes in infancy, hence mimicking effects of rodent licking and grooming. From a general population sample of 1233 first time mothers recruited at 20 weeks gestation we drew a stratified random sample of 316 for assessment at 32 weeks based on reported inter-partner psychological abuse, a risk to child development. Of these 271 provided data at 5, 9 and 29 weeks post delivery. Mothers reported how often they stroked their babies at 5 and 9 weeks. At 29 weeks vagal withdrawal to a stressor, a measure of physiological adaptability, and maternal reported negative emotionality were assessed. There was a significant interaction between prenatal depression and maternal stroking in the prediction of vagal reactivity to a stressor (p = .01), and maternal reports of infant anger proneness (p = .007) and fear (p = .043). Increasing maternal depression was associated with decreasing physiological adaptability, and with increasing negative emotionality, only in the presence of low maternal stroking. These initial findings in humans indicate that maternal stroking in infancy, as reported by mothers, has effects strongly resembling the effects of observed maternal behaviours in animals, pointing to future studies of the epigenetic, physiological and behavioral effects of maternal stroking.

Sexual behavior, neuroendocrine, and neurochemical aspects in male rats exposed prenatally to stress

The present study was designed to examine some short- and long-term effects of maternal restraint stress-during the period of sexual brain differentiation-on reproductive and endocrine systems, sexual behavior, and brain neurotransmitters in male rat descendants. Pregnant rats were exposed to restraint stress for 1 h/day from gestational days (GDs) 18 to 22. Prenatal stress did not influence the wet weight of sexual organs and the quantity of germ cells in adult male pups; however, these animals showed reduced testosterone levels, delayed latency to the first mount and first intromission, and also decreased number of ejaculations. Additionally, there was an increase in the dopamine and serotonin levels in the striatum. Our results indicate that prenatal stress had a long-term effect on neurotransmitter levels and sexual behavior. In this sense, reproductive problems caused by injuries during the fetal period can compromise the later success of mating as well as the capacity to generate descendants. (C) 2004 Elsevier B.V. All rights reserved.

Heat stress impairs performance and induces intestinal inflammation in broiler chickens infected with Salmonella Enteritidis

Stressful situations reduce the welfare, production indices and immune status of chickens. Salmonella spp. are a major zoonotic pathogens that annually cause over 1 billion infections worldwide. We therefore designed the current experiment to analyse the effects of 31 +/- 1 degrees C heat stress (HS) (from 35 to 41 days) on performance parameters, Salmonella invasion and small intestine integrity in broiler chickens infected with Salmonella Enteritidis. We observed that HS decreased body weight gain and feed intake. However, feed conversion was only increased when HS was combined with Salmonella Enteritidis infection. In addition, we observed an increase in serum corticosterone levels in all of the birds that were subjected to HS, showing a hypothalamus-pituitary-adrenal axis activation. Furthermore, mild acute multifocal lymphoplasmacytic enteritis, characterized by foci of heterophil infiltration in the duodenum, jejunum and ileum, was observed in the HS group. In contrast, similar but more evident enteritis was noted in the heat-stressed and Salmonella-infected group. In this group, moderate enteritis was observed in all parts of the small intestine. Lastly, we observed an increase in Salmonella counts in the spleens of the stressed and Salmonella-infected chickens. The combination of HS and Salmonella Enteritidis infection may therefore disrupt the intestinal barrier, which would allow pathogenic bacteria to migrate through the intestinal mucosa to the spleen and generate an inflammatory infiltrate in the gut, decreasing performance parameters.

Psicobiología del estrés prenatal:implicaciones en el eje hipotálamo-hipofisiario-adrenal de los bebés

The womb is the first developmental environment. After developmental psychobiologists started to investigate intrauterine evolution of infant and its long-term impact, they found that prenatal and postnatal development is influenced by mother’s psychological health. Specifically, scientific research evidence indicates that prenatal stress is a possible cause of subsequent psychopathological vulnerability. This vulnerability comes from stress sensitivity and is the basis of many childhood disorders. In the last decade, there are evidences for a fetal origin of stress sensitivity in the context of the fetal programming theory (Entringer et al., 2009, Grant et al., 2009, Gutteling et al., 2004, Huizink et al., 2004, O’Connor et al., 2005). According to fetal programming hypothesis, babies that have been exposed to high levels of prenatal stress would develop elevated HPA axis reactivity and thus increased stress sensitivity in the postnatal period. In the field of animal psychobiology, several studies have shown that prenatal stress could play some role on fetal programming of neurodevelopment and HPA axis (Glover, 2010, Weinstock, 2005, 2008). In human psychobiology, evidences are less clear (Glover, 2010). Although research in this regard has been growing during the last few years, more studies are warranted to investigate the relationship between maternal stress and fetal programming of neurodevelopment and the HPA axis in humans, to confirm the findings which are evident from animal psychobiology...

The impact of maternal inflammation and maternal stress in the regulation of neurodevelopment and physiological function

The mechanisms governing fetal development follow a tightly regulated pattern of progression such that interference at any one particular stage is likely to have consequences for all other stages of development in the physiological system that has been affected thereafter. These disturbances can take the form of many different events but two of the most common and widely implicated in causing detrimental effects to the developing fetus are maternal immune activation (MIA) and maternal stress. MIA has been shown to cause an increase in circulating proinflammatory cytokines in both the maternal and fetal circulation. This increase in proinflammatory mediators in the fetus is thought to occur by fetal production rather than through exchange between the maternal-fetal interface. In the case of maternal stress it is increased levels of stress related hormones such as cortisol/corticosterone which is thought to elicit the detrimental effects on fetal development. In the case of both maternal infection and stress the timing and nature of the insult generally dictates the severity and type of effects seen in affected offspring. We investigated the effect of a proinflammatory environment on neural precursor cells of which exposure resulted in a significant decrease in the normal rate of proliferation of NPCs in culture but did not have any effect on cell survival. These effects were seen to be age dependent. Using a restraint stress model we investigated the effects of prenatal stress on the development of a number of different physiological systems in the same cohort of animals. PNS animals exhibited a number of aberrant changes in cardiovascular function with altered responses to stress and hypertension, modifications in respiratory responses to hypercapnic and hypoxic challenges and discrepancies in gastrointestinal innervation. Taken together these findings suggest that both maternal infection and maternal stress are detrimental to the normal development of the fetus.

Birth Weight, Working Memory and Epigenetic Signatures in IGF2 and Related Genes: A MZ Twin Study

Neurodevelopmental disruptions caused by obstetric complications play a role in the etiology of several phenotypes associated with neuropsychiatric diseases and cognitive dysfunctions. Importantly, it has been noticed that epigenetic processes occurring early in life may mediate these associations. Here, DNA methylation signatures at IGF2 (insulin-like growth factor 2) and IGF2BP1-3 (IGF2-binding proteins 1-3) were examined in a sample consisting of 34 adult monozygotic (MZ) twins informative for obstetric complications and cognitive performance. Multivariate linear regression analysis of twin data was implemented to test for associations between methylation levels and both birth weight (BW) and adult working memory (WM) performance. Familial and unique environmental factors underlying these potential relationships were evaluated. A link was detected between DNA methylation levels of two CpG sites in the IGF2BP1 gene and both BW and adult WM performance. The BW-IGF2BP1 methylation association seemed due to non-shared environmental factors influencing BW, whereas the WM-IGF2BP1 methylation relationship seemed mediated by both genes and environment. Our data is in agreement with previous evidence indicating that DNA methylation status may be related to prenatal stress and later neurocognitive phenotypes. While former reports independently detected associations between DNA methylation and either BW or WM, current results suggest that these relationships are not confounded by each other.