Acute Stress In Adulthood Research Articles

Early-Life Milk αS1-Casein Allergy Induces the Activation of Astrocytes in Mice and Leads to Stress Vulnerability in Adulthood.

In recent years, the incidence of food allergies in children has been increasing annually, significantly affecting the quality of life for patients and their families. It has long been suspected that childhood allergies might potentially lead to behavioral and psychological issues in adulthood, but the specific connection remains unclear. In this study, we established a model of young mice allergic to milk αS1-casein, conducted behavioral tests, and employed transcriptomics, immunohistochemistry, Golgi staining, and fecal microbiota transplantation to explore the link between early life allergies and adult psychological problems. The results showed that early life milk protein allergy significantly increased intestinal epithelial permeability in mice, leading to the translocation of gut microbiota metabolites. This process subsequently activated astrocyte lysosomes via SLC15a3, making astrocytes more susceptible. This susceptibility caused mice with early life milk protein allergy to have more activated astrocytes and excessive dendritic spine phagocytosis (normal group: 5.4 ± 1.26 spines/10 μm, allergy group: 3.2 ± 0.92 spines/10 μm) under acute stress in adulthood, leading to anxiety and depressive behaviors.

Exposure to elevated glucocorticoid during development primes altered transcriptional responses to acute stress in adulthood

Early life stress (ELS) is a major risk factor for developing psychiatric disorders, with glucocorticoids (GCs) implicated in mediating its effects in shaping adult phenotypes. In this process, exposure to high levels of developmental GC (hdGC) is thought to induce molecular changes that prime differential adult responses. However, identities of molecules targeted by hdGC exposure are not completely known. Here, we describe lifelong molecular consequences of hdGC exposure using a newly developed zebrafish double-hit stress model, which shows altered behaviors and stress hypersensitivity in adulthood. We identify a set of primed genes displaying altered expression only upon acute stress in hdGC-exposed adult fish brains. Interestingly, this gene set is enriched in risk factors for psychiatric disorders in humans. Lastly, we identify altered epigenetic regulatory elements following hdGC exposure. Thus, our study provides comprehensive datasets delineating potential molecular targets mediating the impact of hdGC exposure on adult responses.

Sex-dependent effects of acute stress in adolescence or adulthood on appetitive motivation.

Intensely stressful experiences can lead to long-lasting changes in appetitive and aversive behaviors. In humans, post-traumatic stress disorder increases the risk of comorbid appetitive disorders including addiction and obesity. We have previously shown that an acute stressful experience in adult male rats suppresses motivation for natural reward. We examine the impact of sex and age on the effects of intense stress on action-based (instrumental) and stimulus-based (Pavlovian) motivation for natural reward (food). Rats received 15 unsignaled footshocks (stress) in a single session followed by appetitive training and testing in a distinct context. In Experiment 1, stress occurred in either adolescence (PN28) or adulthood (PN70) with appetitive training and testing beginning on PN71 for all rats. In Experiment 2, stress and appetitive training/testing occurred in adolescence. Acute stress in adolescent females suppressed instrumental motivation assessed with progressive ratio testing when testing occurred in late adolescence or in adulthood, whereas in males stress in adolescence did not suppress instrumental motivation. Acute stress in adulthood did not alter instrumental motivation. In contrast, Pavlovian motivation assessed with single-outcome Pavlovian-to-instrumental transfer (SO-PIT) was consistently enhanced in females following adolescent or adult stress. In males, however, stress in adolescence had no effect, whereas stress in adulthood attenuated SO-PIT. Acute stress in adolescence or adulthood altered instrumental motivation and stimulus-triggered Pavlovian motivation in a sex and developmentally specific manner. These findings suggest that the persistent effects of acute stress on Pavlovian and instrumental motivational processes differ in females and males, and that males may be less vulnerable to the deleterious effects of intense stress during adolescence on appetitive motivation.

The Effects of Prenatal Dexamethasone Exposure on Brain Metabolic Homeostasis in Adulthood: Implications for Depression.

Since depression produces a long-term negative impact on quality of life, understanding the pathophysiological changes implicated in this disorder is urgent. There is growing evidence that demonstrates a key role for dysfunctional energy metabolism in driving the onset of depression; thus, bioenergetic alterations should be extensively studied. Brain metabolism is known to be a glucocorticoid-sensitive process, but the long-lasting consequences in adulthood following high levels of glucocorticoids at the early stages of life are unclear. We examined a possible association between brain energetic changes induced by synthetic glucocorticoid-dexamethasone treatment in the prenatal period and depressive-like behavior. The results show a reduction in the oxidative phosphorylation process, Krebs cycle impairment, and a weakening of the connection between the Krebs cycle and glycolysis in the frontal cortex of animals receiving dexamethasone, which leads to ATP reduction. These changes appear to be mainly due to decreased expression of pyruvate dehydrogenase, impairment of lactate transport to neurons, and pyruvate to the mitochondria. Acute stress in adulthood only slightly modified the observed alterations in the frontal cortex, while in the case of the hippocampus, prenatal exposure to dexamethasone made this structure more sensitive to future adverse factors.

Chronic adolescent stress increases exploratory behavior but does not appear to change the acute stress response in adult male C57BL/6 mice

Chronic stress exposure in adolescence can lead to a lasting change in stress responsiveness later in life and is associated with increased mental health issues in adulthood. Here we investigate whether the Chronic Social Instability (CSI) paradigm influences the behavioral and molecular responses to novel acute stressors in mice, and whether it alters physiological responses influenced by the noradrenergic system. Using large cohorts of mice, we show that CSI mice display a persistent increase in exploratory behaviors in the open field test alongside small but widespread transcriptional changes in the ventral hippocampus. However, both the transcriptomic and behavioral responses to novel acute stressors are indistinguishable between groups. In addition, the pupillometric response to a tail shock, known to be mediated by the noradrenergic system, remains unaltered in CSI mice. Ultra-high performance liquid chromatography analysis of monoaminergic neurotransmitter levels in the ventral hippocampus also shows no differences between control or CSI mice at baseline or in response to acute stress. We conclude that CSI exposure during adolescence leads to persistent changes in exploratory behavior and gene expression in the hippocampus, but it does not alter the response to acute stress in adulthood and is unlikely to alter the function of the noradrenergic system.

Moderate Adolescent Ethanol Vapor Exposure and Acute Stress in Adulthood: Sex-Dependent Effects on Social Behavior and Ethanol Intake in Sprague-Dawley Rats.

Adolescent alcohol use can lead to numerous consequences, including altered stress reactivity and higher risk for later anxiety and alcohol use disorders. Many studies have examined the consequences of heavy ethanol exposure in adolescence, but far less is understood about lower levels of intoxication. The present study examined moderate adolescent ethanol exposure as a possible factor in increasing stress reactivity in adulthood, measured through general and social anxiety-like behaviors, as well voluntary ethanol intake. Male and female Sprague–Dawley rats underwent an adolescent chronic intermittent ethanol (aCIE) vapor exposure during early adolescence, reaching moderate blood ethanol concentrations. Animals then underwent two days of forced swim stress in adulthood. We found that ethanol-exposed males consumed more ethanol than their air counterparts and an interesting stress and ethanol exposure interaction in males. There were no significant effects on voluntary drinking in females. However, the social interaction test revealed increased play-fighting behavior in ethanol-exposed females and reduced social preference in females after two days of stress exposure. Overall, this work provides evidence for sex-specific, long-term effects of moderate aCIE and susceptibility to acute stress in adulthood.

Morphological Responses of Excitatory Prelimbic and Orbitofrontal Cortical Neurons to Excess Corticosterone in Adolescence and Acute Stress in Adulthood.

Considerable evidence indicates that chronic stress and excess glucocorticoids induce neuronal remodeling in prefrontal cortical (PFC) regions. Adolescence is also characterized by a structural reorganization of PFC neurons, yet interactions between stress- and age-related structural plasticity are still being determined. We quantified dendritic spine densities on apical dendrites of excitatory neurons in the medial prefrontal cortex, prelimbic subregion (PL). Densities decreased across adolescent development, as expected, and spine volume increased. Unexpectedly, exposure to excess corticosterone (CORT) throughout adolescence did not cause additional dendritic spine loss detectable in adulthood. As a positive control dendrite population expected to be sensitive to CORT, we imaged neurons in the orbitofrontal cortex (OFC), confirming CORT-induced dendritic spine attrition on basal arbors of layer V neurons. We next assessed the effects of acute, mild stress in adulthood: On PL neurons, an acute stressor increased the density of mature, mushroom-shaped spines. Meanwhile, on OFC neurons, dendritic spine volumes and lengths were lower in mice exposed to both CORT and an acute stressor (also referred to as a “double hit”). In sum, prolonged exposure to excess glucocorticoids during adolescence can have morphological and also metaplastic consequences, but they are not global. Anatomical considerations are discussed.

Abstract P219: Mice Exposed To Early Life Stress Have Impaired Autonomic Activity At Baseline And In Response To Acute Stress In Adulthood

Early life stress (ELS) is an independent risk factor for the development of cardiovascular disease in adulthood in both humans and rodent models. Maternal separation and early weaning (MSEW), a model of ELS, produces mice with an increased risk of cardiovascular dysfunction in adulthood, despite resting blood pressures (BP), heart rates (HR), and body weights comparable to normally reared controls. Autonomic regulation of HR and BP is an important component of the homeostatic response to stress but has not been investigated in MSEW mice. We hypothesized that exposure to MSEW impairs autonomic function at baseline and in response to an acute psychosocial stressor in adult male mice. C57Bl/6J litters were randomly assigned to MSEW or normally reared control conditions. MSEW litters were separated from dams for 4 h on postnatal days (PDs) 2-5, 8 h on PDs 6-16, and weaned at PD 17. Control litters were undisturbed until weaning at PD 21. At 9 weeks old, telemeters were implanted in MSEW (n=16) and control mice (n=12). During cage switch stress (CSS), mice were moved to a soiled, unfamiliar cage for 4 h. HR, systolic BP (SBP), diastolic BP (DBP), and activity (monitored by telemetry) were similar between control and MSEW mice at baseline and during CSS (p>0.05, 2-way ANOVA). Spectral analysis of HR, SBP, and DBP indicated that HR variability (HRV) total power was lower in MSEW mice during the 12 h inactive period compared to controls (18.9±1.1 ms 2 vs. 27.5±3.1 ms 2 ; p=0.0033, 2-way ANOVA) at baseline. HRV low frequency (LF) power was also lower during the 12 h inactive period in MSEW mice (4.2±0.4 ms 2 vs.6.6±0.9 ms 2 ; p=0.009). At baseline, 12 h and 24 h DBP variability LF/high frequency (HF) ratio, normalized LF, and normalized HF power were lower in the MSEW group (p<0.05, all comparisons). During the final 90 minutes of CSS, MSEW mice had lower HRV total, LF, and HF power compared to controls (p<0.05); although HR, SBP, DBP, and activity remained similar between groups. These data suggest that MSEW mice have impaired autonomic control of HR and DBP and lack the ability to robustly respond and recover from an acute stressor. Reduced responsiveness of the autonomic nervous system may contribute to the increased risk of cardiovascular disease development in adult mice exposed to MSEW.

Bifidobacterium CECT 7765 modulates early stress-induced immune, neuroendocrine and behavioral alterations in mice

Emerging evidence suggests that there is a window of opportunity within the early developmental period, when microbiota-based interventions could play a major role in modulating the gut-brain axis and, thereby, in preventing mood disorders. This study aims at evaluating the effects and mode of action of Bifidobacterium pseudocatenulatum CECT 7765 in a murine model of chronic stress induced by maternal separation (MS). C57Bl/6J male breast-fed pups were divided into four groups, which were subjected or not to MS and supplemented with placebo or B. pseudocatenulatum CECT7765 until postnatal period (P) 21 and followed-up until P41. Behavioral tests were performed and neuroendocrine parameters were analyzed including corticosterone, cytokine/chemokine concentrations and neurotransmitters. Microbiota was also analyzed in stools by 16S rRNA gene sequencing. B. pseudocatenulatum CECT 7765 administration attenuated some aspects of the excessive MS-induced stress response of the hypothalamic–pituitary–adrenal (HPA) axis, particularly corticosterone production at baseline and in response to subsequent acute stress in adulthood. B. pseudocatenulatum CECT 7765 also down-regulated MS-induced intestinal inflammation (reducing interferon gamma [IFN-γ]) and intestinal hypercatecholaminergic activity (reducing dopamine [DA] and adrenaline [A] concentrations) at P21. These effects have a long-term impact on the central nervous system (CNS) of adult mice since MS mice fed B. pseudocatenulatum CECT 7765 showed lower anxiety levels than placebo-fed MS mice, as well as normal neurotransmitter levels in the hypothalamus. The anti-inflammatory effect of B. pseudocatenulatum CECT 7765 seemed to be related to an improvement in glucocorticoid sensitivity in mesenteric lymph node immunocompetent cells at P21. The administration of B. pseudocatenulatum CECT 7765 to MS animals also reversed intestinal dysbiosis affecting the proportions of ten Operational Taxonomic Units (OTUs) at P21, which could partly explain the restoration of immune, neuroendocrine and behavioral alterations caused by stress in early and later life. In summary, we show that B. pseudocatenulatum CECT 7765 is able to beneficially modulate the consequences of chronic stress on the HPA response produced by MS during infancy with long-lasting effects in adulthood, via modulation of the intestinal neurotransmitter and cytokine network with short and long-term consequences in brain biochemistry and behavior.

Individual differences in fear extinction and anxiety-like behavior

There is growing appreciation for the substantial individual differences in the acquisition and inhibition of aversive associations, and the insights this might give into identifying individuals particularly vulnerable to stress and psychopathology. We examined whether animals that differed in rate of extinction (i.e., Fast versus Slow) were different in their response to an acute stress in adulthood or following a chronic stress that occurred either early or later in life. We found that Slow Extinguishers had significantly poorer extinction retention than Fast Extinguishers, but an acute stressor did not differentially affect anxiety-like behavior in the two groups. Further, while exposure to chronic stress in adulthood did not impact on the extinction phenotypes or anxiety-like behavior, exposure to chronic stress early in life affected both extinction retention and anxiety-like behavior. These findings have implications for the development of a more nuanced approach to identifying those most at risk of anxiety disorders.

Microglia depletion in early life programs persistent changes in social, mood-related, and locomotor behavior in male and female rats

Microglia, the innate immune cells of the central nervous system, regulate brain development by promoting cell genesis, pruning synapses, and removing dying, newly-born or progenitor cells. However, the role of microglia in the early life programming of behavior under normal conditions is not well characterized. We used central infusion of liposomal clodronate to selectively deplete microglia from the neonatal rat brain and subsequently assessed the impact of microglial depletion on programming of juvenile and adult motivated behaviors. Liposomal clodronate treatment on postnatal days one and four led to greater than 70% loss of forebrain microglia by postnatal day 6 that lasted for approximately ten days. Neonatal microglia depletion led to reduced juvenile and adult anxiety behavior on the elevated plus maze and open field test, and increased locomotor activity. On a test of juvenile social play, microglial depletion led to decreased chase behaviors relative to control animals. There was no change in active social behavior in adults on a reciprocal social interaction test, but there was decreased passive interaction time and an increased number of social avoidance behaviors in clodronate treated rats relative to controls. There was an overall decrease in behavioral despair on the forced swim test in adult rats treated neonatally with clodronate. Females, but not males, treated neonatally with clodronate showed a blunted corticosterone response after acute stress in adulthood. These results show that microglia are important for the early life programming of juvenile and adult motivated behavior.

Unstable Maternal Environment Affects Stress Response in Adult Mice in a Genotype-Dependent Manner.

Early postnatal events exert powerful effects on development, inducing persistent functional alterations in different brain network, such as the catecholamine prefrontal-accumbal system, and increasing the risk of developing psychiatric disorders later in life. However, a vast body of literature shows that the interaction between genetic factors and early environmental conditions is crucial for expression of psychopathologies in adulthood. We evaluated the long-lasting effects of a repeated cross-fostering (RCF) procedure in 2 inbred strains of mice (C57BL/6J, DBA/2), known to show a different susceptibility to the development and expression of stress-induced psychopathologies. Coping behavior (forced swimming test) and preference for a natural reinforcing stimulus (saccharine preference test) were assessed in adult female mice of both genotypes. Moreover, c-Fos stress-induced activity was assessed in different brain regions involved in stress response. In addition, we evaluated the enduring effects of RCF on catecholamine prefrontal-accumbal response to acute stress (restraint) using, for the first time, a new "dual probes" in vivo microdialysis procedure in mouse. RCF experience affects behavioral and neurochemical responses to acute stress in adulthood in opposite direction in the 2 genotypes, leading DBA mice toward an "anhedonic-like" phenotype and C57 mice toward an increased sensitivity for a natural reinforcing stimulus.

Acute stress in adulthood impoverishes social choices and triggers aggressiveness in preclinical models.

Adult C57BL/6J mice are known to exhibit high level of social flexibility while mice lacking the β2 subunit of nicotinic receptors (β2−/− mice) present social rigidity. We asked ourselves what would be the consequences of a restraint acute stress (45 min) on social interactions in adult mice of both genotypes, hence the contribution of neuronal nicotinic receptors in this process. We therefore dissected social interaction complexity of stressed and not stressed dyads of mice in a social interaction task. We also measured plasma corticosterone levels in our experimental conditions. We showed that a single stress exposure occurring in adulthood reduced and disorganized social interaction complexity in both C57BL/6J and β2−/− mice. These stress-induced maladaptive social interactions involved alteration of distinct social categories and strategies in both genotypes, suggesting a dissociable impact of stress depending on the functioning of the cholinergic nicotinic system. In both genotypes, social behaviors under stress were coupled to aggressive reactions with no plasma corticosterone changes. Thus, aggressiveness appeared a general response independent of nicotinic function. We demonstrate here that a single stress exposure occurring in adulthood is sufficient to impoverish social interactions: stress impaired social flexibility in C57BL/6J mice whereas it reinforced β2−/− mice behavioral rigidity.

258 Structural Plasticity of Gastric Glial Cells As Responses to Early Life Stress (Maternal Separation) and Acute Stress in Adulthood in Rats

258 Structural Plasticity of Gastric Glial Cells As Responses to Early Life Stress (Maternal Separation) and Acute Stress in Adulthood in Rats

Differential Effect of Prenatal Stress on the Expression of Cortiocotrophin-Releasing Hormone and its Receptors in the Hypothalamus and Amygdala in Male and Female Rats

The present study examined the effect of prenatal stress in rats from days 13-20 of gestation on anxiogenic behaviour in the elevated plus maze (EPM) together with changes in the gene expression of corticotrophin-releasing hormone (CRH), its receptors, CRHR1 and CRHR2, as well as CRH binding protein (CRH-BP) in the paraventricular nucleus (PVN) and amygdala of their male and female offspring. Both prenatally-stressed (PS) males and females showed heightened anxiety in the EPM. Prenatal stress did not alter the gene expression of CRH or its receptors in the male PVN, although it decreased CRH-BP mRNA, which could augment the activity of free CRH. In the PVN of PS females, there was an increase in the expression of CRH, coupled with a decrease in that of CRHR2 and CRH-BP. These changes are compatible with the greater activation of the hypothalamic pituitary adrenal axis to stress in females. Anxiogenic behaviour of PS rats was associated with a reduction of CRHR2 mRNA and of CRH-BP mRNA in the amygdala of males and an increase in CRH mRNA and decrease in CRHR2 mRNA in females. Two hours after acute stress of exposure to the elevated plus maze in which heightened anxiety was manifested, increases were seen only in the amygdala of females in CRH and CRHR1 signalling, whereas CRHR2 mRNA was reduced in both sexes. The data show that both prenatal stress and acute stress in adulthood have a differential sex-dependent effect on the expression of CRH its receptors and binding protein in the PVN and amygdala of rats.

Neonatal lipopolysaccharide exposure alters central cytokine responses to stress in adulthood in Wistar rats

“Perinatal programming” is a phenomenon describing how early life environmental conditions can produce long-term physiological alterations that either enhance or inhibit adaptive functioning. Previously, we have demonstrated that neonatal exposure to lipopolysaccharide (LPS) predisposes to anxiety-like behaviour in later life, which was associated with changes to the neuroendocrine response to stress. Given the known interactions between the neuroendocrine and neuroimmune systems, here we investigated whether neonatal exposure to a bacterial mimetic alters neuroimmune responses to acute stress in adulthood. Male and female Wistar rats were administered LPS (0.05 mg/kg, i.p.), or saline vehicle (equivolume) on days 3 and 5 post-partum. One group of rats was euthanised following early life treatment to assess immediate hypothalamic–pituitary–adrenal axis and central cytokine responses to treatment. A second group was assessed in adulthood (85 days) following exposure to either a “stress” (30-min restraint) or “no stress” condition. Blood was collected from all rats at baseline, 30, 60 and 90 min after “stress”, “no stress” treatment to assess peripheral corticosterone responses, and brains were collected 180 min following baseline to assess hippocampal content of interleukin-1β (IL-1β), tumour necrosis factor-α (TNFα) and IL-6 protein. Radioimmunoassay revealed that neonatal LPS treatment resulted in a prolonged corticosterone response to stress in adulthood compared to controls (p < 0.05). Enzyme-linked-immunosorbent assays revealed no group differences in hippocampal IL-6 content. However, brain IL-1β and TNFα protein concentrations were significantly greater in rats neonatally exposed to LPS and then exposed to stress in adulthood when compared to all other groups (p < 0.05). These findings suggest that early life bacterial toxin exposure results in a prolonged neuroendocrine response to acute stress in adulthood, which may be a consequence of increased release of IL-1β and TNFα in the brain.

Oxytocin response to an experimental psychosocial challenge in adults exposed to traumatic experiences during childhood or adolescence

Long-term implications of the exposure to traumatizing experiences during childhood or adolescence, such as sexual abuse, or cancer, have been documented, namely the subjects' response to an acute stress in adulthood. Several indicators of the stress response have been considered (e.g. cortisol, heart rate). Oxytocin (OT) response to an acute stress of individuals exposed to trauma has not been documented. Eighty subjects ( n=26 women who had experienced episodes of child abuse, n=25 men and women healthy survivors of cancer in childhood or adolescence, and 29 controls) have been submitted to a laboratory session involving an experimental stress challenge, the Trier social stress test. Overall, there was a clear OT response to the psychosocial challenge. Subjects having experienced a childhood/adolescence life-threatening illness had higher mean levels of OT than both abused and control subjects. There was a moderate negative relationship between OT and salivary cortisol. It is suggested that an acute stress stimulates OT secretion, and that the exposure to enduring life-threatening experiences in childhood/adolescence has long-lasting consequences regarding the stress system and connected functions, namely the activation of OT secretion. Better knowledge of such long-term implications is important so that to prevent dysregulations of the stress responses, which have been shown to be associated to the individual's mental health.

Maternal deprivation affects the neuromuscular protein profile of the rat colon in response to an acute stressor later in life

Early life stress as neonatal maternal deprivation (MD) predisposes rats to alter gut functions in response to acute psychological stressors in adulthood, mimicking features of irritable bowel syndrome (IBS). We applied proteomics to investigate whether MD permanently changes the protein profile of the external colonic neuromuscular layer that may condition the molecular response to an acute stressor later in life. Male rat pups were separated 3 h/day from their mothers during the perinatal period and further submitted to water avoidance (WA) stress during adulthood. Proteins were extracted from the myenteric plexus-longitudinal muscle of control (C), WA and MD+WA rat colon, separated on 2D gels, and identified by mass spectrometry. MD amplified the WA-induced protein changes involved in muscle contractile function, suggesting that stress accumulation along life imbalances the muscle tone towards hypercontractility. Our results also propose a stress dependent regulation of gluconeogenesis. Secretogranin II - the secretoneurin precursor - was induced by MD. The presence of secretoneurin in myenteric ganglia may partially explain the stress-mediated modulation of gastrointestinal motility and/or mucosal inflammation previously described in MD rats. In conclusion, our findings suggest that neonatal stress alters the responses to acute stress in adulthood in intestinal smooth muscle and enteric neurons.

Augmented Hypothalamic Corticotrophin‐Releasing Hormone mRNA and Corticosterone Responses to Stress in Adult Rats Exposed to Perinatal Hypoxia

Stressful events before or just after parturition alter the subsequent phenotypical response to stress in a general process termed programming. Hypoxia during the period before and during parturition, and in the postnatal period, is one of the most common causes of perinatal distress, morbidity, and mortality. We have found that perinatal hypoxia (prenatal day 19 to postnatal day 14) augmented the corticosterone response to stress and increased basal corticotrophin-releasing hormone (CRH) mRNA levels in the parvocellular portion of the paraventricular nucleus (PVN) in 6-month-old rats. There was no effect on the levels of hypothalamic parvocellular PVN vasopressin mRNA, anterior pituitary pro-opiomelanocortin or CRH receptor-1 mRNA, or hippocampus glucocorticoid receptor mRNA. We conclude that hypoxia spanning the period just before and for several weeks after parturition programmes the hypothalamic-pituitary-adrenal axis to hyper-respond to acute stress in adulthood, probably as a result of drive from the parvocellular CRH neurones.

Early life stress results in an exaggerated pressor response to acute air jet stress in adult male, but not female rats

Clinical studies have associated adverse childhood experiences with increased risk for cardiovascular events in adulthood, but the mechanism(s) are unknown. In animal studies, repeated separation from the mother (maternal separation, MS) during the first two weeks of life results in an exaggerated behavioral response to aversive environmental stimuli in male but not female rats. Therefore, we hypothesized that MS would influence the hypertensive response to acute stress in adulthood. Wild-type (wt) and endothelin B receptor deficient (sl/sl) rats were separated from their mothers for 3 hr/day on days 2–14 after birth (n=4–9/group). Un-separated littermates served as controls (C). At 10 weeks of age, 24 hr mean arterial pressure (MAP; telemetry) in wt rats was not different between MS and C rats. Similarly, MS had no effect on 24 hr MAP in sl/sl rats. Rats were then placed in a restraining cage and subjected to a 3 min period of air jet pulses. The total pressor response to air jet stress (area under the curve) in male rats was significantly elevated in MS compared to C groups (49±3 vs 35±5 mmHgx3min, respectively, P<0.05). In contrast, the response to air jet stress in female wt rats was similar between MS and C (43±5 vs 48±5 mmHgx3min, respectively). The exaggerated response to air jet stress was not evident in male sl/sl rats (42±10 mmHg in MS vs 44±10 mmHgx3min in C). These results are the first to demonstrate that early life stressors result in exaggerated cardiovascular responses in adulthood.