Epigenetic regulatory mechanisms of early life stress responses and memory

2013 ◽  
Author(s):  
N. Meiri ◽  
T. Kisliouk ◽  
M. Yossifoff ◽  
T. Cramer
2021 ◽  
Author(s):  
Jessica L Bolton ◽  
Annabel K Short ◽  
Shivashankar Othy ◽  
Cassandra L Kooiker ◽  
Manlin Shao ◽  
...  

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.


Author(s):  
Jordan Marrocco ◽  
Jason D. Gray ◽  
Joshua F. Kogan ◽  
Nathan R. Einhorn ◽  
Emma M. O’Cinneide ◽  
...  

2015 ◽  
Vol 26 (4) ◽  
Author(s):  
Deepika Suri ◽  
Vidita A. Vaidya

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.


Physiology ◽  
2002 ◽  
Vol 17 (4) ◽  
pp. 150-155 ◽  
Author(s):  
Christopher R. Pryce ◽  
Daniela Rüedi-Bettschen ◽  
Andrea C. Dettling ◽  
Joram Feldon

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.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Eamon Fitzgerald ◽  
Matthew C. Sinton ◽  
Sara Wernig-Zorc ◽  
Nicholas M. Morton ◽  
Megan C. Holmes ◽  
...  

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.


2016 ◽  
Vol 3 (10) ◽  
pp. 160382 ◽  
Author(s):  
Marco A. Vindas ◽  
Angelico Madaro ◽  
Thomas W. K. Fraser ◽  
Erik Höglund ◽  
Rolf E. Olsen ◽  
...  

Ongoing rapid domestication of Atlantic salmon implies that individuals are subjected to evolutionarily novel stressors encountered under conditions of artificial rearing, requiring new levels and directions of flexibility in physiological and behavioural coping mechanisms. Phenotypic plasticity to environmental changes is particularly evident at early life stages. We investigated the performance of salmon, previously subjected to an unpredictable chronic stress (UCS) treatment at an early age (10 month old parr), over several months and life stages. The UCS fish showed overall higher specific growth rates compared with unstressed controls after smoltification, a particularly challenging life stage, and after seawater transfer. Furthermore, subjecting fish to acute stress at the end of the experiment, we found that UCS groups had an overall lower hypothalamic catecholaminergic and brain stem serotonergic response to stress compared with control groups. In addition, serotonergic activity was negatively correlated with final growth rates, which implies that serotonin responsive individuals have growth disadvantages. Altogether, our results may imply that a subdued monoaminergic response in stressful farming environments may be beneficial, because in such situations individuals may be able to reallocate energy from stress responses into other life processes, such as growth.


2019 ◽  
Vol 133 (1) ◽  
pp. 50-58 ◽  
Author(s):  
Nathalie D. Elliott ◽  
Rick Richardson

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