scholarly journals Early life trauma leads to violent behavior and its inheritance by impairing local thyroid hormone availability in brain

2021 ◽  
Author(s):  
Arpita Konar ◽  
Rohit Singh Rawat ◽  
Aksheev Bhambri ◽  
Muneesh Pal ◽  
Avishek Roy ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Early Life ◽  
Molecular Mechanisms ◽  
Violent Behavior ◽  
Epigenetic Programming ◽  
Gene Ablation ◽  
Aberrant Form ◽  
Early Life Trauma ◽  
Detrimental Impact

Violent behavior is an aberrant form of aggression that has detrimental impact on health and society. Early life trauma triggers adulthood violence and criminality, though molecular mechanisms remain elusive. Here, we provide brain region specific transcriptome profiles of peripubertal stress (PPS) exposed adult violent male and resilient female mice. We identify transthyretin (TTR) as a key regulator of PPS induced violent behavior and its intergenerational inheritance. TTR mediated long-term perturbation in hypothalamic thyroid hormone (TH) availability contributed to male violent behavior without affecting circulating hormone. Ttr gene ablation in hypothalamus impaired local TH signaling including levels of TH transporters (Mct8, Oatp1c1), deiodinase 2 (DIO2) and TH responsive genes (Nrgn, Trh and Hr). Violent behavior and impaired TTR-TH signaling was also inherited in F1 male progenies. Further, we deciphered Ttr promoter hyper methylation in hypothalamus of violent males across generations. Our findings reveal that trauma during puberty trigger lasting violent behavior by epigenetic programming of TTR and consequent impaired local thyroid availability in brain. TTR-TH signaling in hypothalamus can serve as potential target in reversal of violent behavior.

scholarly journals A Unique Mouse Model of Early Life Exercise Enables Hippocampal Memory and Synaptic Plasticity

2019 ◽  
Author(s):  
Autumn S. Ivy ◽  
Tim Yu ◽  
Enikö Kramár ◽  
Sonia Parievsky ◽  
Fred Sohn ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Early Life ◽  
Molecular Mechanisms ◽  
Memory Task ◽  
Long Term Potentiation ◽  
Long Term Memory ◽  
Critical Periods ◽  
Juvenile Period ◽  
Cognitive Benefits

AbstractAerobic exercise is a powerful modulator of learning and memory. Molecular mechanisms underlying the cognitive benefits of exercise are well documented in adult rodents. Animal models of exercise targeting specific postnatal periods of hippocampal development and plasticity are lacking. Here we characterize a model of early-life exercise (ELE) in male and female mice designed with the goal of identifying critical periods by which exercise may have a lasting impact on hippocampal memory and synaptic plasticity. Mice freely accessed a running wheel during three postnatal periods: the 4th postnatal week (juvenile ELE, P21-27), 6th postnatal week (adolescent ELE, P35-41), or 4th-6th postnatal weeks (juvenile-adolescent ELE, P21-41). All exercise groups significantly increased their running distances over time. When exposed to a weak learning stimulus, mice that had exercised during the juvenile period were able to form lasting long-term memory for a hippocampus-dependent spatial memory task. Electrophysiological experiments revealed enhanced long-term potentiation in hippocampal CA1 the juvenile-adolescent ELE group only. Furthermore, basal synaptic transmission was significantly increased in all mice that exercised during the juvenile period. Our results suggest early-life exercise can enable hippocampal memory, synaptic plasticity, and basal synaptic physiology when occurring during postnatal periods of hippocampal maturation.

Early life trauma is associated with decreased peripheral levels of thyroid‐hormone T3 in adolescents

2015 ◽  
Vol 47 (Part_B) ◽  
pp. 304-308 ◽  
Author(s):  
T.D. Machado ◽  
G.A. Salum ◽  
V.L. Bosa ◽  
M.Z. Goldani ◽  
M.J. Meaney ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Early Life ◽  
Early Life Trauma

Men’s experiences of early life trauma and pathways into long-term homelessness

2018 ◽  
Vol 80 ◽  
pp. 216-225 ◽  
Author(s):  
Julia Woodhall-Melnik ◽  
James R. Dunn ◽  
Stephen Svenson ◽  
Caroline Patterson ◽  
Flora I. Matheson
Keyword(s):  
Early Life ◽  
Early Life Trauma

scholarly journals Making headway towards understanding how epigenetic mechanisms contribute to early-life effects

2019 ◽  
Vol 374 (1770) ◽  
pp. 20180126 ◽  
Author(s):  
Maja Vukic ◽  
Haoyu Wu ◽  
Lucia Daxinger
Keyword(s):  
Early Life ◽  
Molecular Mechanisms ◽  
Evolutionary Medicine ◽  
Current Evidence ◽  
Long Term Effects ◽  
Environmental Signals ◽  
Technological Advances ◽  
Health And Disease ◽  
Scientific Fields

It has become clear that in addition to the DNA sequence there is another layer of information, termed epigenetic modifications, that can influence phenotypes and traits. In particular, environmental epigenomics, which addresses the effect of the environment on the epigenome and human health, is becoming an area of great interest for many researchers working in different scientific fields. In this review, we will consider the current evidence that early-life environmental signals can have long-term effects on the epigenome. We will further evaluate how recent technological advances may enable us to unravel the molecular mechanisms underlying these phenomena, which will be crucial for understanding heritability in health and disease. This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine'.

scholarly journals Early Life Stage Thyroid Hormone Disruption Causes Long-Term Impacts On Immune Cell Function And Transcriptional Responses To Pathogen In The Fathead Minnow (Pimephales Promelas)

2021 ◽  
Author(s):  
Leah M. Thornton Hampton ◽  
Miranda G. Finch ◽  
Christopher J. Martyniuk ◽  
Barney J. Venables ◽  
Marlo K. Sellin Jeffries
Keyword(s):  
Immune System ◽  
Thyroid Hormone ◽  
Immune Function ◽  
Early Life ◽  
Cell Function ◽  
Immune Cell ◽  
Life Stage ◽  
Bacterial Load ◽  
Early Life Stage

Abstract Current evidence suggests thyroid hormones (THs) impact development of the immune system, but few studies have explored the connection between the thyroid and immune systems, especially in fish. This is important as some environmental contaminants disrupt TH homeostasis and may thus have negative impacts on the immune system. To determine the long-term consequences of early life stage (ELS) hypothyroidism on immune function, fathead minnows were exposed to the model thyroid hormone suppressant propylthiouracil (PTU) from <1 to 30 days post hatch. Fish were transferred to clean water and raised to adulthood at which time, several aspects of immune function were evaluated. Ex vivo assessment of immune cell function revealed significant decreases in the phagocytic cell activity of PTU-treated fish relative to the controls. Fish were also injected with Yersinia ruckeri to evaluate their in vivo immune responses across a suite of endpoints (i.e., transcriptomic analysis, leukocyte counts, spleen index, hematocrit, bacterial load and pathogen resistance). The transcriptomic response to infection was significantly different between control and PTU-treated fish, though no differences in bacterial load nor pathogen resistance were noted. Overall, these results suggest that early life stage thyroid hormone suppression causes long-term impacts on immune function at the molecular and cellular levels suggesting a key role for TH signaling in normal immune system development. This study lays the foundation for further exploration into thyroid-immune crosstalk in fish. This is noteworthy as disruption of the thyroid system during development may have lasting effects on immune function in adulthood.

scholarly journals Epigenetic studies in Developmental Origins of Health and Disease: pitfalls and key considerations for study design and interpretation

2016 ◽  
Vol 8 (1) ◽  
pp. 30-43 ◽  
Author(s):  
L. Yamada ◽  
S. Chong
Keyword(s):  
Early Life ◽  
Molecular Mechanisms ◽  
Developmental Origins ◽  
Epigenetic Changes ◽  
Number Of Factors ◽  
Functional Consequences ◽  
Health And Disease ◽  
The Stability ◽  
The Impact

The field of Developmental Origins of Health and Disease (DOHaD) seeks to understand the relationships between early-life environmental exposures and long-term health and disease. Until recently, the molecular mechanisms underlying these phenomena were poorly understood; however, epigenetics has been proposed to bridge the gap between the environment and phenotype. Epigenetics involves the study of heritable changes in gene expression, which occur without changes to the underlying DNA sequence. Different types of epigenetic modifications include DNA methylation, post-translational histone modifications and non-coding RNAs. Increasingly, changes to the epigenome have been associated with early-life exposures in both humans and animal models, offering both an explanation for how the environment may programme long-term health, as well as molecular changes that could be developed as biomarkers of exposure and/or future disease. As such, epigenetic studies in DOHaD hold much promise; however, there are a number of factors which should be considered when designing and interpreting such studies. These include the impact of the genome on the epigenome, the tissue-specificity of epigenetic marks, the stability (or lack thereof) of epigenetic changes over time and the importance of associating epigenetic changes with changes in transcription or translation to demonstrate functional consequences. In this review, we discuss each of these key concepts and provide practical strategies to mitigate some common pitfalls with the aim of providing a useful guide for future epigenetic studies in DOHaD.

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