scholarly journals Contrasting effects of acute and chronic stress on the transcriptome, epigenome, and immune response of Atlantic salmon

2018 ◽  
Author(s):  
Tamsyn M. Uren Webster ◽  
Deiene Rodriguez-Barreto ◽  
Samuel A.M. Martin ◽  
Cock van Oosterhout ◽  
Pablo Orozco-terWengel ◽  
...  

AbstractEarly-life stress can have long-lasting effects on immunity, but the underlying molecular mechanisms are unclear. We examined the effects of acute stress (cold-shock during embryogenesis) and chronic stress (absence of tank enrichment during larval-stage) on the gill transcriptome and methylome of Atlantic salmon four months after hatching. While only chronic stress induced pronounced transcriptional effects, both acute and chronic stress caused lasting, and contrasting, changes in the methylome. Crucially, we found that acute stress enhanced immune response to a pathogenic challenge (lipopolysaccharide), while chronic stress suppressed it. We identified stress-induced changes in promoter or gene-body methylation that were associated with altered expression for a small proportion of genes, and also evidence of wider epigenetic regulation within signalling pathways involved in immune response. Our study suggests that early-life stress can affect immuno-competence through epigenetic mechanisms, a finding that could open the way for improved stress and disease management of farmed fish.

Endocrinology ◽  
2008 ◽  
Vol 149 (10) ◽  
pp. 4892-4900 ◽  
Author(s):  
Courtney J. Rice ◽  
Curt A. Sandman ◽  
Mohammed R. Lenjavi ◽  
Tallie Z. Baram

Chronic early-life stress (ES) exerts profound acute and long-lasting effects on the hypothalamic-pituitary-adrenal system, with relevance to cognitive function and affective disorders. Our ability to determine the molecular mechanisms underlying these effects should benefit greatly from appropriate mouse models because these would enable use of powerful transgenic methods. Therefore, we have characterized a mouse model of chronic ES, which was provoked in mouse pups by abnormal, fragmented interactions with the dam. Dam-pup interaction was disrupted by limiting the nesting and bedding material in the cages, a manipulation that affected this parameter in a dose-dependent manner. At the end of their week-long rearing in the limited-nesting cages, mouse pups were stressed, as apparent from elevated basal plasma corticosterone levels. In addition, steady-state mRNA levels of CRH in the hypothalamic paraventricular nucleus of ES-experiencing pups were reduced, without significant change in mRNA levels of arginine vasopressin. Rearing mouse pups in this stress-provoking cage environment resulted in enduring effects: basal plasma corticosterone levels were still increased, and CRH mRNA levels in paraventricular nucleus remained reduced in adult ES mice, compared with those of controls. In addition, hippocampus-dependent learning and memory functions were impaired in 4- to 8-month-old ES mice. In summary, this novel, robust model of chronic early life stress in the mouse results in acute and enduring neuroendocrine and cognitive abnormalities. This model should facilitate the examination of the specific genes and molecules involved in the generation of this stress as well as in its consequences.


Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Carmen De Miguel ◽  
Dao H Ho ◽  
Analia S Loria ◽  
Ijeoma Obi ◽  
Jennifer S Pollock

We previously reported that maternal separation (MatSep), an animal model of early life stress, sensitizes rats to pro-hypertensive stimuli in adulthood. We hypothesized that MatSep induces a renal pro-inflammatory immune response. Immune cell populations and expression of cytokines were assessed by magnetic bead isolation, FACS analysis, ELISA and RT-PCR in adult male MatSep and normally-reared littermate control rats. Circulating and renal mononuclear or T cell numbers were similar between control and MatSep rats (n=4-11/group, p>0.05). Both groups presented similar percentages of circulating macrophages and T H , T C , and T reg cells (n=4, p>0.05). However, the percentage of circulating B cells was significantly decreased in MatSep rats (23.7±1.2% vs. 20.1±0.7%; n=4, p<0.05). Pro-inflammatory cytokine IL-1Beta was significantly elevated in kidneys from MatSep rats (4.4±0.5 vs. 7.9±1.0 pg/mg prot; n=7-8/group; p<0.05). However, IFN-gamma, IL-6, and IL-4 were not different between control and MatSep rats. To further assess the immune system in MatSep and control rats, we acutely challenged adult rats with lipopolysaccharide (LPS; 2 mg/kg; i.v., 14 h). LPS significantly elevated renal expression of pro-inflammatory chemokine receptors (CCR3, CCR4, CXCR4), cytokines (IFN-gamma, CCL3, CCL4, IL-16), and activation markers (CD40, CD40lg) in MatSep rats (4 to 6 fold increase; n=5/group, p<0.05), suggesting that MatSep induces an exaggerated pro-inflammatory renal immune response to LPS. In conclusion, early life stress induces a renal pro-inflammatory status in adulthood that leads to sensitization to further immune challenges. Funded by P01 HL 69999 to JSP, NIH T32 DK007545 to CDM, F32 HL 116145 to DHH and K99/R00 HL 111354 to ASL.


Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Megan K Rhoads ◽  
Kasi C McPherson ◽  
Keri M Kemp ◽  
Bryan Becker ◽  
Jackson Colson ◽  
...  

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.


2017 ◽  
Vol 1 (S1) ◽  
pp. 36-36
Author(s):  
Courtney Vaughan ◽  
Bethany Stangl ◽  
Rajita Sinha ◽  
Vijay Ramchandani

OBJECTIVES/SPECIFIC AIMS: The objective of this analysis was to characterize the impact of stress, both early life and chronic, on intravenous alcohol self-administration (IV-ASA) in healthy non-dependent drinkers using the Computer-Assisted Infusion System (CAIS). Personality measures also have shown to impact drinking behavior, particularly impulsivity. Few studies have assessed the impact of stress and impulsivity on drinking behaviors in a non-dependent population. METHODS/STUDY POPULATION: Healthy non-dependent drinkers (n=28) completed a CAIS session, where they push a button adlib to self-administer standardized IV alcohol infusions. Participants completed the Cumulative Chronic Stress interview and the Early Life Stress Questionnaire (ELSQ) for stress measures. The Cumulative Chronic Stress interview was broken up into 4 sections: major life events, life traumas, recent life events, and chronic stressors. The number of endorsed events was added up to create 4 separate scores. Subjective response and craving measures were collected serially using the Drug Effects Questionnaire (DEQ) and Alcohol Urge Questionnaire (AUQ). The Impaired Control Scale (ICS) assessed failed control over recent drinking in the past 6 months. Impulsivity was assessed using the NEO personality inventory, which included the N-impulsive sub-facet, as well as the UPPS-P Impulsive Behavior Scale. RESULTS/ANTICIPATED RESULTS: Results showed early life stress events (ELSQ) are related to more chronic stressors in the cumulative chronic stress interview (p=0.005). Participants with higher chronic stress scores showed lower subjective effects, as measured by the DEQ, following the priming exposure (p=0.036) but had more craving for alcohol as measured by the AUQ (p=0.009). A regression analysis showed the number of chronic stressful events predicted ICS failed attempts to control drinking (p=0.034), after covarying for sex. Participants with more chronic stressful events showed more impulsivity on the N-impulsivity measure (p=0.034) and the UPPS-P positive urgency measure (p=0.005). DISCUSSION/SIGNIFICANCE OF IMPACT: Non-dependent drinkers with more early life stress tend to have a higher number of chronic stressful events. More chronically stressful events were associated with feeling less effects of alcohol and higher craving for alcohol. Participants with more chronically stressful events also appear to have more failed attempts at controlling their drinking. Future analysis will assess for mediation and moderation of these factors. Chronically stressful events and impulsive behaviors could serve as important areas for intervention for better treatment outcomes for alcohol use disorders.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Olga L. Lopatina ◽  
Yulia A. Panina ◽  
Natalia A. Malinovskaya ◽  
Alla B. Salmina

AbstractEarly life stress (ELS) is one of the most critical factors that could modify brain plasticity, memory and learning abilities, behavioral reactions, and emotional response in adulthood leading to development of different mental disorders. Prenatal and early postnatal periods appear to be the most sensitive periods of brain development in mammals, thereby action of various factors at these stages of brain development might result in neurodegeneration, memory impairment, and mood disorders at later periods of life. Deciphering the processes underlying aberrant neurogenesis, synaptogenesis, and cerebral angiogenesis as well as deeper understanding the effects of ELS on brain development will provide novel approaches to prevent or to cure psychiatric and neurological deficits caused by stressful conditions at the earliest stages of ontogenesis. Neuropeptide oxytocin serves as an amnesic, anti-stress, pro-angiogenic, and neurogenesis-controlling molecule contributing to dramatic changes in brain plasticity in ELS. In the current review, we summarize recent data on molecular mechanisms of ELS-driven changes in brain plasticity with the particular focus on oxytocin-mediated effects on neurogenesis and angiogenesis, memory establishment, and forgetting.


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