Long-term Effects Of Prenatal Stress Research Articles

Long-term effects of prenatal stress on the development of prefrontal cortex in the adolescent offspring

Exposure to stress during pregnancy consequently prompts long-lasting effects on fetal brain development and predisposes the offspring to mental illnesses in later life. Adolescence is a vulnerable period of prefrontal cortex (PFC) development and coincident with the onset of neuropsychiatric symptoms. The medial PFC (mPFC) is the brain area that plays a significant role in emotional processing, and stress alters the function of this brain area leading to emotional disorders. Microglia not only play a role in neuroinflammatory responses but also play a crucial role in brain development, especially during synaptic development and pruning. Previous studies have revealed the long-term effects of prenatal stress (PS) on microglia activation and neuroinflammation in the hippocampus of the offspring. However, there is still a need to investigate how PS alters the mPFC development during adolescence. This study examines the effects of maternal stress during the last week of gestation on microglia activation and neuroimmune response in the mPFC of adolescent offspring. Morphological study demonstrated that PS increased the density of activated microglia in the prelimbic region of the mPFC of adolescent offspring. Besides, PS significantly increased the levels of microglia marker (Iba1), interleukin-6 (IL-6), and brain-derived neurotrophic factor (BDNF) in the mPFC of the adolescent offspring. In conclusion, PS-induced microglia activation and neuroinflammation in the mPFC might increase the risk for neuropsychiatric disorders in the offspring in later years.

Вплив перенесеного пренатального стресу на майбутнє репродуктивного здоров’я жінок

Prenatal stress is quite a common occurrence in a modern society and in return affects the development of violations of women’s` reproductive health. It is an obvious need to give an appropriate attention to the woman in the process of a diagnosis of an obstetric and gynecological pathology and also a use of anti-stress therapy and the correction of systemic stress-induced disorders in treatment regimes. The purpose of research was to analyze the literary tributes, dedicated to the problem of prenatal stress and this infusion on the reproductive health of women. Material and methods. We analyzed publication of national and foreign authors on the research topic. Methods of research: statistical and method of expert evaluations. Results and discussion. Psychological unavailability to motherhood of infertile women creates a situation of a prolonged emotional stress, which leads to the prenatal stress and provokes an activation of the modified adaptive response, launches a pathological range of reproductive disorders. We studied the problem of prenatal stress and the general mechanisms of its effects on the body of women in the reproductive period. We described the long-term effects of prenatal stress on emotional suffering, mental and physical health of women. The experienced prenatal stress is a predictor of disorders of the reproductive system in the future, associated with emotional states, the elimination of which restores reproductive function. Psychological unpreparedness for motherhood among women with infertility creates a situation of prolonged emotional stress, which leads to prenatal stress and provokes the activation of their inherent altered adaptive response. The mentioned factors are the triggers for pathological range of reproductive disorders. Prenatal stress is a common phenomenon in modern society, which effects on the development of disorders of women reproductive function. Conclusion. There is a necessity to pay appropriate attention to the patient within the diagnosis of obstetric and gynecological pathology, as well as the necessity for adequate therapy and correction of system stress-induced disorders in treatment regimens. There is a necessity for in-depth study of infertility associated with prenatal stress, development of a comprehensive differential approach to diagnosis and treatment, taking into account the patients' psycho-emotional state with further improvement of pre-pregnancy training and tactics for treatment of such women

Long-term effects of prenatal stress on chloride transporters and GABAA receptor subunits in the prefrontal cortex of periadolescent rats

Long-term effects of prenatal stress on chloride transporters and GABAA receptor subunits in the prefrontal cortex of periadolescent rats

Sex-Related Effects of Prenatal Stress on Region-Specific Expression of Monoamine Oxidase A and β Adrenergic Receptors in Rat Hearts.

BackgroundPrenatal stress may increase risk of developing cardiovascular disorders in adulthood. The cardiotoxic effects of catecholamines are mediated via prolonged adrenergic receptor stimulation and increased oxidative stress upon their degradation by monoamine oxidase A (MAO-A).ObjectivesWe investigated long-term effects of prenatal stress on β (1, 2, 3) adrenergic receptors and MAO-A gene expression in the hearts of adult rat offspring.MethodsPregnant rats were exposed to unpredictable mild stress during the third week of gestation. RNA was isolated from left ventricular apex and base of adult offspring. Quantitative PCR was used to measure gene expression in collected ventricular tissue samples. The level of significance was set to p < 0.05.Resultsβ3 adrenergic receptor mRNA was undetectable in rat left ventricle. β1 adrenergic receptor was the predominantly expressed subtype at the apical and basal left ventricular myocardium in the control females. Male offspring from unstressed mothers displayed higher apical cardiac β1 than β2 adrenergic receptor mRNA levels. However, β1 and β2 adrenergic receptor mRNAs were similarly expressed at the ventricular basal myocardium in males. Unlike males, prenatally stressed females exhibited decreased β1 adrenergic receptor mRNA expression at the apical myocardium. Prenatal stress did not affect cardiac MAO-A gene expression.ConclusionsCollectively, our results show that prenatal stress may have exerted region- and sex-specific β1 and β2 adrenergic receptor expression patterns within the left ventricle.

Duloxetine prevents the effects of prenatal stress on depressive-like and anxiety-like behavior and hippocampal expression of pro-inflammatory cytokines in adult male offspring rats

Stress during pregnancy may cause neurodevelopmental and psychiatric disorders. However, the mechanisms are largely unknown. Currently, pro-inflammatory cytokines have been identified as a risk factor for depression and anxiety disorder. Unfortunately, there is very little research on the long-term effects of prenatal stress on the neuroinflammatory system of offspring. Moreover, the relationship between antidepressant treatment and cytokines in the central nervous system, especially in the hippocampus, an important emotion modulation center, is unclear. Therefore, the aim of this study was to determine the effects of prenatal chronic mild stress during development on affective-like behaviors and hippocampal cytokines in adult offspring, and to verify whether antidepressant (duloxetine) administration from early adulthood could prevent the harmful consequences. To do so, prenatally stressed and non-stressed Sprague-Dawley rats were treated with either duloxetine (10mg/kg/day) or vehicle from postnatal day 60 for 21days. Adult offspring were divided into four groups: 1) prenatal stress+duloxetine treatment, 2) prenatal stress+vehicle, 3) duloxetine treatment alone, and 4) vehicle alone. Adult offspring were assessed for anxiety-like behavior using the open field test and depression-like behavior using the forced swim test. Brains were analyzed for pro-inflammatory cytokine markers in the hippocampus via real-time PCR. Results demonstrate that prenatal stress-induced anxiety- and depression-like behaviors are associated with an increase in hippocampal inflammatory mediators, and duloxetine administration prevents the increased hippocampal pro-inflammatory cytokine interleukin-6 and anxiety- and depression-like behavior in prenatally stressed adult offspring. This research provides important evidence on the long-term effect of PNS exposure during development in a model of maternal adversity to study the pathogenesis of depression and its therapeutic interventions.

Animal research data on prenatal factors of functional neuroendocrine disorders

The term “prenatal stress” is widely used in the scientific literature, although the immediate effects of stressor exposed maternal organism. It is experimentally proved that in this case in fetus body neurohormonal imbalance occurs that typical for the stress state. In particular, in blood increased corticosteroid level of maternal origin. Opioids, catecholamines, and other neurotransmitters levels change in neuroendocrine brain structures. There is potential danger of the mother’s body stress for the fetus development, particularly for the formation of various forms of behavior, neuroendocrine reproduction regulation, metabolism, immunity and adaptive responses.The results of experimental research by author and co-workers regarding long-term effects of prenatal stress as far as neuroendocrine control of puberty and sex behavior concerned are summarized in the article.In the study of pregnant rats were stressed after prior administration of drugs with different mechanisms of action, capable of blocking the implementation of the pathogenic effects of prenatal stress. The stress in rats was reproduced by daily immobilization for 1 hour in the last week of pregnancy. 30 minutes before immobilization the rat was administered one of the study drugs: dexamethasone, naltrexone, nimodipine, methyldopa, phenibutum. The control group was formed from the same age intact animals.Experimental studies were carried out on the offspring of both sexes. Activity of aromatase steroids, catecholamines level and metabolism, distribution of proteins in neuroendocrine brain structures, timing of puberty, male and female sexual behavior, fertility, fecundity, estrous cycle and their phase structure were studied.It is demonstrated the potential of pharmacological prevention of the neuroendocrine disorders in the offspring that have been delivered by mothers exposed to stress during pregnancy using calcium channel blocker, nimodipine, or by diminishing cathecholaminergic activation of neuroendocrine mechanisms of stress with methyldopa, or by stimulation of GABA-ergic receptor with phenibutum. Contrary, methyldopa or phenibutum administration in non-stressed pregnant animals causes disorders of puberty and sex behavior.There is proposed the concept of dualistic drug effects on the fetus neuroendocrine function development.

Long-term effects of prenatal stress and diazepam on D2 receptor expression in the nucleus accumbens of adult rats

Early life stress during the gestational period alters specific neuronal circuits leading to behavioral alterations later in life. In the present study, we assessed the effects of prenatal stress and repeated benzodiazepine administration on dopamine receptor 2 expression in the nucleus accumbens of adult offspring.Our results show elevated Drd2 expression levels in the nucleus accumbens (NAcc) of prenatally stressed rats compared to control subjects, while repeated diazepam administration in adulthood down-regulated Drd2 expression and prevented the effect of prenatal stress. These observations suggest that prenatal stress may induce permanent alterations in the corticolimbic pathway implicated in drug-seeking behavior.

Prenatal exposure to escitalopram and/or stress in rats produces limited effects on endocrine, behavioral, or gene expression measures in adult male rats

Stress and/or antidepressants during pregnancy have been implicated in a wide range of long-term effects in the offspring. We investigated the long-term effects of prenatal stress and/or clinically relevant antidepressant exposure on male adult offspring in a model of the pharmacotherapy of maternal depression. Female Sprague–Dawley rats were implanted with osmotic minipumps that delivered clinically relevant exposure to the antidepressant escitalopram throughout gestation. Subsequently, pregnant females were exposed on gestational days 10–20 to a chronic unpredictable mild stress paradigm. The male offspring were analyzed in adulthood. Baseline physiological measurements were largely unaltered by prenatal manipulations. Behavioral characterization of the male offspring, with or without pre-exposure to an acute stressor, did not reveal any group differences. Prenatal stress exposure resulted in a faster return towards baseline following the peak response to an acute restraint stressor, but not an airpuff startle stressor, in adulthood. Microarray analysis of the hippocampus and hypothalamus comparing all treatment groups revealed no significantly-altered transcripts. Real time PCR of the hippocampus confirmed that several transcripts in the CRFergic, serotonergic, and neural plasticity pathways were unaffected by prenatal exposures. This stress model of maternal depression and its treatment indicate that escitalopram use and/or stress during pregnancy produced no alterations in our measures of male adult behavior or the transcriptome, however prenatal stress exposure resulted in some evidence for increased glucocorticoid negative feedback following an acute restraint stress. Study design should be carefully considered before implications for human health are ascribed to prenatal exposure to stress or antidepressant medication.

Trans-generational effects of prenatal stress in quail

The prenatal environment is a source of phenotypic variability influencing the animal's characteristics. Prenatal stress affects not only the development of offspring, but also that of the following generation. Such effects have been best documented in mammals but can also be observed in birds, suggesting common processes across phylogenetic orders. We found previously that Japanese quail females stressed during laying produced offspring with higher fearfulness, probably related to modulation of testosterone levels in their eggs. Here, we evaluated long-term effects of prenatal stress by analysing reproductive traits of these F(1) offspring and, then, the development of their subsequent (F(2)) offspring. The sexual behaviour of F(1) prenatally stressed (F1PS) males was impaired. F1PS females' eggs contained less yolk and more albumen, and higher yolk testosterone and progesterone levels than did F(1) prenatal control females. The fearfulness of F(2) prenatally stressed quail was greater than that of F(2) prenatal control quail. These F(2) behavioural differences paralleled those evidenced by their parents, suggesting trans-generational transmission of prenatal stress effects, probably mediated by egg compositions of F1PS females.

Long-Term Effects of Prenatal Stress on the Characteristics of Hippocampal Neurons in Rats with Different Excitability of the Nervous Systems

We studied the effects of prenatal emotional painful stress on numerical density of neurons and characteristics of heterochromatin in developing and mature hippocampus of rats with different excitability of the nervous systems. It was shown that prenatal stress reduces the numerical density of neurons in hippocampal CA3 field in 24-day-old and adult (3 months) low excitable animals and chromocenter area in cells of developing hippocampus in embryos of both strains. The difference in chromocenter areas in offspring of stressed females was retained on postnatal day 24.

The weight gain response to stress during adulthood is conditioned by both sex and prenatal stress exposure

Food intake and weight gain are known to be affected by stress. However, the type and duration of the stress may have variable effects, with males and females responding differently. We report the short-term and long-term effects of prenatal and adult immobilization stress, as well as the combination of these two stresses, on weight gain and food intake in male and female rats and the role of post-pubertal gonadal hormones in this process. No long-term effect of prenatal stress on food intake or weight gain was found in either sex. However, during the period of adult stress [at postnatal day (P) 90; 10 days duration] stressed male rats gained significantly less weight than controls and previous exposure to prenatal stress attenuated this effect (control: 31.2+/-2.1g; prenatal stress: 24.6+/-3.8g; adult stress: 8.1+/-3.4g; prenatal and adult stress: 18.2+/-3.3g; p<0.0001). There was no change in food intake in response to either prenatal or adult stress. Adult stress increased circulating corticosterone levels during the initial part of the stress period, in both male and female rats with this rise being greater in male rats. No effect on corticosterone levels was observed on the last day of stress in either sex. No effect on weight gain or food intake was observed in female rats. Following adult stress, male rats increased their weight gain, with no change in food intake, such that 1 month later they reached control levels. At the time of sacrifice (P180), there were no differences in weight or circulating metabolic hormone levels between any of the male groups. Although castration alone modulated body weight in both male and female rats, it did not affect their weight gain response to adult stress. These results indicate that the weight gain response to adult stress is sexually dimorphic and that this is not dependent on post-pubertal gonadal steroids. Furthermore, the outcome of this response closely depends on the time at which the change in weight is analyzed, which could help to explain different results reported in the literature. Indeed, weight and metabolic hormone levels were normalized by the end of the study.

Effets du stress pendant la grossesse sur le développement du bébé et de l’enfant

The effects of prenatal stress on pregnancy and birth outcomes (prematurity, birthweight) have often been described. More recently, studies have reported the effects of prenatal stress on fetal behavior, leading to the hypothesis that there is a relationship between prenatal maternal mood and fetal behavior. Today, research is focusing on the long-term effects of stress during pregnancy. This article reviews long-term effects of prenatal stress on cognitive and behavioral development in children. In addition, the relationship between prenatal stress and the occurrence of psychopathological disorders is described. Finally, conclusions are drawn on the possible implications and perspectives of research conducted on prenatal stress.

Long-term effects of prenatal stress on dopamine and glutamate receptors in adult rat brain.

Prenatal stress greatly influences the ability of an individual to manage stressful events in adulthood. Such vulnerability may result from abnormalities in the development and integration of forebrain dopaminergic and glutamatergic projections during the prenatal period. In this study, we assessed the effects of prenatal stress on the expression of selective dopamine and glutamate receptor subtypes in the adult offsprings of rats subjected to repeated restraint stress during the last week of pregnancy. Dopamine D2-like receptors increased in dorsal frontal cortex (DFC), medial prefrontal cortex (MPC), hippocampal CA1 region and core region of nucleus accumbens (NAc) of prenatally stressed rats compared to control subjects. Glutamate NMDA receptors increased in MPC, DFC, hippocampal CA1, medial caudate-putamen, as well as in shell and core regions of NAc. Group III metabotropic glutamate receptors increased in MPC and DFC of prenatally stressed rats, but remained unchanged in all other regions examined. These results indicate that stress suffered during the gestational period has long lasting effects that extend into the adulthood of prenatally stressed offsprings. Changes in dopamine and glutamate receptor subtype levels in different forebrain regions of adult rats suggest that the development and formation of the corticostriatal and corticolimbic pathways may be permanently altered as a result of stress suffered prenatally. Maldevelopment of these pathways may provide a neurobiological substrate for the development of schizophrenia and other idiopathic psychotic disorders.

Early and long-term neuroendocrine effects of prenatal stress in male and female rats.

The effects of maternal stress, termed prenatal stress (PNS) on the neuroendocrine regulation of reproduction and the stress reactivity of offspring were studied in rats. PNS prevented the formation of sexual dimorphism in catecholamine levels, aromatase activity, and androgen 5alpha-reductase activity in the preoptic area of the brain and the mediobasal hypothalamus in 10-day-old rats. The morphological correlate of the functional lesions induced by PNS consisted of the elimination of gender-related differences in the volumes of neuron nuclei in the suprachiasmatic nucleus. Prenatal stress altered the stress and adrenergic reactivities of the hypothalamo-hypophyseal-adrenal system in mature males and females. The long-term effects of PNS were regarded as a consequence of the disruption of the hormone-neurotransmitter imprinting of the neuroendocrine system.

Long-term effects of prenatal stress and postnatal handling on age-related glucocorticoid secretion and cognitive performance: a longitudinal study in the rat.

There is growing evidence that stress during prenatal and postnatal periods of life can modify adaptive capacities in adulthood. The hypothalamo-pituitary-adrenal axis may mediate an animal's responses to perinatal stressful events and thus serve as a neurobiological substrate of the behavioural consequences of these early events. However, little is known about the long-term effects of prenatal stressors throughout the entire life of the animals. The focus of the present study was to examine the long-term influences of a prenatal and postnatal stress on glucocorticoid secretion and cognitive performance. Prenatal stress of rat dams during the last week of pregnancy and postnatal daily handling of rat pups during the first 3 weeks of life were used as stressors. The long-term effects of these manipulations were analysed using a longitudinal approach throughout the entire life of the animals, and were repeatedly tested in adulthood (4-7 months), middle age (13-16 months) and in later life (20-24 months). The study demonstrated that prenatal stress and postnatal handling induced opposite effects on both glucocorticoid secretion and cognitive performance. Prenatal stress accelerated the age-related hypothalamo-pituitary-adrenal axis dysfunctions; indeed, circulating glucocorticoids levels of prenatally stressed middle-aged animals are similar to old control ones, and also induced cognitive impairments. In contrast, postnatal handling protected from the age-related neuroendocrine and behavioural alterations. These results show that the altered glucocorticoid secretion induced by early environmental manipulations is primary to the cognitive alterations observed only later in life and could be one cause of age-related memory deficits.

Differential Effects of Prenatal Stress in Two Inbred Strains of Rats

STÖHR, T., D. SCHULTE WERMELING, T. SZURAN, V. PLISKA, A. DOMENEY, H. WELZL, I. WEINERAND J. FELDON. Differential effects of prenatal stress in two inbred strains of rats. 〈Default ¶ Font>PHARMACOL BIOCHEM BEHAV 59(4) 799–805, 1998.—The long-term effects of prenatal stress (three times daily restraint stress during the last week of gestation) on the behavioral response to stress, as assessed by novelty-induced locomotion, performance in the forced swim test, and the acquisition of a two-way active avoidance, were investigated in two inbred strains of rats, Fischer 344 (F344/NHsd/Zur) and Lewis (LEW/SsNHsd/Zur). Additional measures included birth weights, pain threshold on the hot plate, and basal and stress-induced corticosterone secretion. In all of the behavioral paradigms strain differences were found: LEW rats showed poorer acquisition of avoidance conditioning, displayed higher levels of activity on the open plate, less immobility time in the forced swim test, and lower pain thresholds in the hot-plate test compared with F344 rats. LEW rats had higher birth weights after prenatal stress, whereas F344 rats were lighter. Following prenatal stress the pattern of behavioral effects obtained in LEW rats in stress-related tests could be interpreted as improved coping abilities with stress, i.e., improved acquisition of active avoidance, less immobility in the forced swim test, and reduced novelty-induced locomotion. Prenatal stress was much less effective in inducing long-term behavioral changes in F344 rats, yielding only one effect, namely, enhanced novelty-induced locomotion in female F344 rats. Pain thresholds were increased as a consequence of prenatal stress, irrespective of strain and gender. Basal and stress-induced corticosterone release differed in the two strains, with LEW rats showing less stress-induced corticosterone release. Prenatal stress did not, however, affect basal or stress-induced corticosterone release. The results suggest that prenatal stress exerts long-term effects on behavior, which depend on the genetic background.

Prenatal manipulations reduce the proinflammatory response to a cytokine challenge in juvenile monkeys

Two studies were conducted to assess the potential long-term effects of prenatal stress on the cytokine-related inflammatory response in juvenile rhesus monkeys. Subjects were derived from two different pregnancy conditions. Study 1 involved endocrine activation of the pregnant female by daily adrenocorticotropic hormone (ACTH) injection across a 2-week period (days 120–133 post-conception). Pregnant females in Study 2 experienced a psychological stressor, 10 minutes per day, for a 6-week period (days 106–147 post-conception). When the offspring from these pregnancies were 1.5–2 years of age, they were administered recombinant human interleukin-1 β (rhIL-1 β) to stimulate the release of endogenous cytokines, elicit fever, and activate the hypothalamic–pituitary–adrenal (HPA) axis. Cerebrospinal fluid (CSF) and blood levels of interleukin-6 (IL-6) were measured, as well as cortisol levels and body temperature. The prenatal ACTH treatment altered the postnatal response to IL-1 β in juvenile offspring. These monkeys showed a significantly blunted response to the IL-1 β, with smaller increments in blood and CSF levels of IL-6 and diminished temperature responses to the IL-1 β. In contrast, the prenatal psychological stressor was not as potent and did not have lasting effects on this physiological response in juvenile monkeys. IL-1 β also induced significant increases in cortisol secretion, but this adrenal response was comparable in all monkeys. These data suggest that differences in the prenatal environment could have a selective effect on cytokine physiology accounting for individual differences in the inflammatory response.

Long-term effects of prenatal stress and handling on metabolic parameters: relationship to corticosterone secretion response

The prenatal and postnatal environment exerts a long-term influence on the stress-response of the hypothalamic-pituitary-adrenal (HPA) axis. In this study, the long-term effects of prenatal and postnatal manipulations and their related changes on glucocorticoid secretion were examined on metabolic parameters in adult rats. Plasma glucose levels, body weight and basal feeding behavior were measured. We show that modifications of the prenatal and postnatal environment have opposite long-term effects on these parameters, except for blood glucose, which was increased in prenatally stressed animals. Although the mechanisms underlying these phenomena remain to be elucidated, the observations show that perinatal manipulations have long-term effects on metabolic functions related to HPA activity.

Sexual differentiation of social play and copulatory behavior in prenatally stressed male and female offspring of the rat: the influence of simultaneous treatment by tyrosine during exposure to prenatal stress

The environmental stress in the late gestational life has been reported to induce impairments of androgen-dependent sex differentiation of the rat brain. This study was performed to investigate the effects of prenatal stress on the features of gender role behavior and copulatory behavior which are masculinized by perinatal androgens. Further, a possible counteraction of tyrosine to the long-term effects of prenatal stress was examined, because the supplementation of amino-acid precursor of catecholamines during the stress is known to maintain the content of catecholamines in the brain, which is considered to contribute to the differentiation of the brain. Time-mated pregnant females were subjected to the forced immobilization stress daily from day 15 of pregnancy to the day of delivery, and they received simultaneous i.p. injections of either tyrosine methylester HCl (200 mg/kg) or saline, less than 60 minutes before stress. Social play in the peripubescent period was observed in the male and female offspring. After maturation, they were castrated and male copulatory behavior under androgen-substitution was tested in the male offspring, and female copulatory behavior under estrogen-substitution was tested in the female offspring. In the male offspring, prenatal stress caused a significant depletion of social play as well as male copulatory behavior, showing the demasculinization of gender role centers and mating centers. In the female offspring exposed to the prenatal stress, a significant increase of social play was observed. And their lordosis quotient did not alter, but a reduced attractivity against male partner was found. These results in the female offspring suggest some extent of masculinization occurred in both centers, probably due to the increase of androgens derived from the adrenal glands when stressed. Tyrosine seemed to reduce the engagement of social play in both sexes, independently of the prenatal stress. On the other hand, tyrosine prevented, at least partially, the long-term effects of prenatal stress in copulatory behavior which were observed in this study. Tyrosine itself had no effect on copulatory behavior. The apparent counteraction of tyrosine in copulatory behavior suggests a positive involvement of catecholamines, especially norepinephrine, in the process of masculinization of the mating centers. The different action of tyrosine to these behaviors may reflect the fact that the different regions of the brain and separate mechanisms are responsible for the sexual differentiation of social play and copulatory behavior.