Sa1405 How Can We Treat Patients With Early Life Stress? Social Interaction Attenuates Stress Responses of GI Tract Following Chronic Stress in Maternally Separated Rats

The developmental origins of stress-related mental illnesses are well-established, and early-life stress/adversity (ELA) is an important risk factor. However, it is unclear how ELA impacts the maturation of salient brain circuits, provoking enduring vulnerability to stress and stress-related disorders. Here we find that ELA increases the number and function of excitatory synapses onto stress-sensitive hypothalamic corticotropin-releasing hormone (CRH)-expressing neurons, and implicate disrupted synapse pruning by microglia as a key mechanism. Microglial process dynamics on live imaging, and engulfment of synaptic elements by microglia, were both attenuated in ELA mice, associated with deficient signaling of the microglial phagocytic receptor Mer. Accordingly, selective chemogenetic activation of ELA microglia increased microglial process dynamics and reduced excitatory synapse density to control levels. Selective early-life microglial activation also mitigated the adrenal hypertrophy and prolonged stress responses in adult ELA mice, establishing microglial actions during development as powerful contributors to experience-dependent sculpting of stress-related brain circuits.

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Early Life Stress Restricts Translational Reactivity in CA3 Neurons Associated With Altered Stress Responses in Adulthood

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2019.00157 ◽

2019 ◽

Vol 13 ◽

Cited By ~ 13

Author(s):

Jordan Marrocco ◽

Jason D. Gray ◽

Joshua F. Kogan ◽

Nathan R. Einhorn ◽

Emma M. O’Cinneide ◽

...

Keyword(s):

Stress Responses ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Ca3 Neurons

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The adaptive and maladaptive continuum of stress responses – a hippocampal perspective

Reviews in the Neurosciences ◽

10.1515/revneuro-2014-0083 ◽

2015 ◽

Vol 26 (4) ◽

Cited By ~ 17

Author(s):

Deepika Suri ◽

Vidita A. Vaidya

Keyword(s):

Stress Responses ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Negative Consequences ◽

Functional Responses ◽

Physiological Level ◽

Early Stress ◽

Wide Range ◽

Potential Factors

AbstractExposure to stressors elicits a spectrum of responses that span from potentially adaptive to maladaptive consequences at the structural, cellular and physiological level. These responses are particularly pronounced in the hippocampus where they also appear to influence hippocampal-dependent cognitive function and emotionality. The factors that influence the nature of stress-evoked consequences include the chronicity, severity, predictability and controllability of the stressors. In addition to adult-onset stress, early life stress also elicits a wide range of structural and functional responses, which often exhibit life-long persistence. However, the outcome of early stress exposure is often contingent on the environment experienced in adulthood, and could either aid in stress coping or could serve to enhance susceptibility to the negative consequences of adult stress. This review comprehensively examines the consequences of adult and early life stressors on the hippocampus, with a focus on their effects on neurogenesis, neuronal survival, structural and synaptic plasticity and hippocampal-dependent behaviors. Further, we discuss potential factors that may tip stress-evoked consequences from being potentially adaptive to largely maladaptive.

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Early Life Stress: Long-Term Physiological Impact in Rodents and Primates

Physiology ◽

10.1152/nips.01367.2001 ◽

2002 ◽

Vol 17 (4) ◽

pp. 150-155 ◽

Cited By ~ 15

Author(s):

Christopher R. Pryce ◽

Daniela Rüedi-Bettschen ◽

Andrea C. Dettling ◽

Joram Feldon

Keyword(s):

Life Span ◽

Stress Responses ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Human Infants ◽

Hypothalamic Pituitary Adrenal ◽

Physiological Impact ◽

Pituitary Adrenal Axis

Rat, monkey, and human infants have evolved to expect certain patterns of care. Spontaneous or experimental deviations of care from the norm result in infant stress responses. Hyperactivity of immature stress systems such as the limbic-hypothalamic-pituitary-adrenal axis and the limbic-sympatho-adrenomedullary axis can alter their subsequent reactivity across the life span.

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2341

Journal of Clinical and Translational Science ◽

10.1017/cts.2017.132 ◽

2017 ◽

Vol 1 (S1) ◽

pp. 36-36

Author(s):

Courtney Vaughan ◽

Bethany Stangl ◽

Rajita Sinha ◽

Vijay Ramchandani

Keyword(s):

Life Events ◽

Chronic Stress ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Stressful Events ◽

Computer Assisted ◽

Chronic Stressors ◽

Stress Interview ◽

The Impact

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.

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Early life stress followed by subsequent adult chronic stress potentiates anxiety and blunts hippocampal structural remodeling

Hippocampus ◽

10.1002/hipo.20862 ◽

2010 ◽

Vol 22 (1) ◽

pp. 82-91 ◽

Cited By ~ 98

Author(s):

Lisa Eiland ◽

Bruce S. McEwen

Keyword(s):

Chronic Stress ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Structural Remodeling

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Altered hypothalamic DNA methylation and stress-induced hyperactivity following early life stress

Epigenetics & Chromatin ◽

10.1186/s13072-021-00405-8 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Eamon Fitzgerald ◽

Matthew C. Sinton ◽

Sara Wernig-Zorc ◽

Nicholas M. Morton ◽

Megan C. Holmes ◽

...

Keyword(s):

Dna Methylation ◽

Brain Development ◽

Open Field ◽

Stress Responses ◽

Life Stress ◽

Early Life ◽

Maternal Separation ◽

Neonatal Period ◽

Early Life Stress ◽

Mediated Effects

AbstractExposure to early life stress (ELS) during childhood or prenatally increases the risk of future psychiatric disorders. The effect of stress exposure during the neonatal period is less well understood. In preterm infants, exposure to invasive procedures is associated with altered brain development and future stress responses suggesting that the neonatal period could be a key time for the programming of mental health. Previous studies suggest that ELS affects the hypothalamic epigenome, making it a good candidate to mediate these effects. In this study, we used a mouse model of early life stress (modified maternal separation; MMS). We hypothesised MMS would affect the hypothalamic transcriptome and DNA methylome, and impact on adult behaviour. MMS involved repeated stimulation of pups for 1.5 h/day, whilst separated from their mother, from postnatal day (P) 4–6. 3’mRNA sequencing and DNA methylation immunoprecipitation (meDIP) sequencing were performed on hypothalamic tissue at P6. Behaviour was assessed with the elevated plus, open field mazes and in-cage monitoring at 3–4 months of age. MMS was only associated with subtle changes in gene expression, but there were widespread alterations in DNA methylation. Notably, differentially methylated regions were enriched for synapse-associated loci. MMS resulted in hyperactivity in the elevated plus and open field mazes, but in-cage monitoring revealed that this was not representative of habitual hyperactivity. ELS has marked effects on DNA methylation in the hypothalamus in early life and results in stress-specific hyperactivity in young adulthood. These results have implications for the understanding of ELS-mediated effects on brain development.

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

10.1101/319285 ◽

2018 ◽

Author(s):

Tamsyn M. Uren Webster ◽

Deiene Rodriguez-Barreto ◽

Samuel A.M. Martin ◽

Cock van Oosterhout ◽

Pablo Orozco-terWengel ◽

...

Keyword(s):

Immune Response ◽

Atlantic Salmon ◽

Chronic Stress ◽

Life Stress ◽

Early Life ◽

Molecular Mechanisms ◽

Acute Stress ◽

Early Life Stress ◽

Altered Expression ◽

Acute And Chronic Stress

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.

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