scholarly journals Impact of Fkbp5 × Early Life Adversity × Sex in Humanized Mice on Multidimensional Stress Responses and Circadian Rhythmicity

2021 ◽  
Author(s):  
Verena Nold ◽  
Dolores Del Prete ◽  
Andrea Blasius ◽  
Isabella Harris ◽  
Eliza Koros ◽  
...  
Keyword(s):  
Stress Responses ◽  
Early Life ◽  
Maternal Separation ◽  
Disease Risk ◽  
Nucleotide Polymorphisms ◽  
Early Life Adversity ◽  
Expression Of Genes ◽  
Specific Outcome ◽  
Hpa Axis Functioning

The cumulative load of genetic predisposition, early life adversity (ELA) and lifestyle shapes the prevalence of psychiatric disorders. Single nucleotide polymorphisms (SNPs) in the human FKBP5 gene were shown to modulate disease risk. To enable investigation of disease-related SNPs in behaviorally relevant context, we generated humanized mouse lines carrying either the risk (AT) or the resiliency (CG) allele of the rs1360780 locus and exposed litters of these mice to maternal separation. Behavioral and physiological aspects of their adult stress responsiveness displayed interactions of genotype, early life condition and sex. In humanized females carrying the CG- but not the AT-allele, ELA led to altered HPA-axis functioning, exploratory behavior and sociability. These changes correlated with differential expression of genes in the hypothalamus, where synaptic transmission, metabolism, and circadian entrainment pathways were deregulated. Our data suggest an integrative role of FKBP5 in shaping the sex-specific outcome of ELA in adulthood.

scholarly journals Maternal separation in rodents: a journey from gut to brain and nutritional perspectives

2019 ◽  
Vol 79 (1) ◽  
pp. 113-132 ◽  
Author(s):  
Marion Rincel ◽  
Muriel Darnaudéry
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Human Subjects ◽  
Early Life Stress ◽  
Long Term Effects ◽  
Early Life Adversity ◽  
Critical Window ◽  
Beneficial Impact ◽  
The Impact

The developmental period constitutes a critical window of sensitivity to stress. Indeed, early-life adversity increases the risk to develop psychiatric diseases, but also gastrointestinal disorders such as the irritable bowel syndrome at adulthood. In the past decade, there has been huge interest in the gut–brain axis, especially as regards stress-related emotional behaviours. Animal models of early-life adversity, in particular, maternal separation (MS) in rodents, demonstrate lasting deleterious effects on both the gut and the brain. Here, we review the effects of MS on both systems with a focus on stress-related behaviours. In addition, we discuss more recent findings showing the impact of gut-directed interventions, including nutrition with pre- and probiotics, illustrating the role played by gut microbiota in mediating the long-term effects of MS. Overall, preclinical studies suggest that nutritional approaches with pro- and prebiotics may constitute safe and efficient strategies to attenuate the effects of early-life stress on the gut–brain axis. Further research is required to understand the complex mechanisms underlying gut–brain interaction dysfunctions after early-life stress as well as to determine the beneficial impact of gut-directed strategies in a context of early-life adversity in human subjects.

scholarly journals Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function

2014 ◽  
Vol 16 (3) ◽  
pp. 321-333 ◽  
Keyword(s):  
Stress Responses ◽  
Childhood Adversity ◽  
Adrenal Function ◽  
Early Life Adversity ◽  
Hypothalamic Pituitary Adrenal ◽  
Expression Of Genes ◽  
Epigenetic Programming ◽  
Social Adversity ◽  
Wide Range ◽  
Nonhuman Species

We review studies with human and nonhuman species that examine the hypothesis that epigenetic mechanisms, particularly those affecting the expression of genes implicated in stress responses, mediate the association between early childhood adversity and later risk of depression. The resulting studies provide evidence consistent with the idea that social adversity, particularly that involving parent-offspring interactions, alters the epigenetic state and expression of a wide range of genes, the products of which regulate hypothalamic-pituitary-adrenal function. We also address the challenges for future studies, including that of the translation of epigenetic studies towards improvements in treatments.

scholarly journals Thyroid Functioning and Fatigue in Women With Functional Somatic Syndromes – Role of Early Life Adversity

2018 ◽  
Vol 9 ◽  
Author(s):  
Susanne Fischer ◽  
Charlotte Markert ◽  
Jana Strahler ◽  
Johanna M. Doerr ◽  
Nadine Skoluda ◽  
...  
Keyword(s):  
Early Life ◽  
Functional Somatic Syndromes ◽  
Early Life Adversity

scholarly journals Variations in Adipokine GenesAdipoQ,Lep, andLepRAre Associated with Risk for Obesity-Related Metabolic Disease: The Modulatory Role of Gene-Nutrient Interactions

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Jennifer Emily Enns ◽  
Carla G. Taylor ◽  
Peter Zahradka
Keyword(s):  
Metabolic Disease ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Disease Risk ◽  
Critical Role ◽  
Nucleotide Polymorphisms ◽  
Nutrient Interactions ◽  
The Metabolic Syndrome ◽  
Susceptible Populations

Obesity rates are rapidly increasing worldwide and facilitate the development of many related disease states, such as cardiovascular disease, the metabolic syndrome, type 2 diabetes mellitus, and various types of cancer. Variation in metabolically important genes can have a great impact on a population's susceptibility to becoming obese and/or developing related complications. The adipokines adiponectin and leptin, as well as the leptin receptor, are major players in the regulation of body energy homeostasis and fat storage. This paper summarizes the findings of single nucleotide polymorphisms in these three genes and their effect on obesity and metabolic disease risk. Additionally, studies of gene-nutrient interactions involving adiponectin, leptin, and the leptin receptor are highlighted to emphasize the critical role of diet in susceptible populations.

scholarly journals Repeated Three-Hour Maternal Separation Induces Depression-Like Behavior and Affects the Expression of Hippocampal Plasticity-Related Proteins in C57BL/6N Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Yaoyao Bian ◽  
Lili Yang ◽  
Zhongli Wang ◽  
Qing Wang ◽  
Li Zeng ◽  
...  
Keyword(s):  
Early Life ◽  
Maternal Separation ◽  
Forced Swimming Test ◽  
Life Experiences ◽  
Tail Suspension Test ◽  
Early Life Stages ◽  
Early Life Adversity ◽  
Swimming Test ◽  
Related Proteins ◽  
The Brain

Adverse early life experiences can negatively affect behaviors later in life. Maternal separation (MS) has been extensively investigated in animal models in the adult phase of MS. The study aimed to explore the mechanism by which MS negatively affects C57BL/6N mice, especially the effects caused by MS in the early phase. Early life adversity especially can alter plasticity functions. To determine whether adverse early life experiences induce changes in plasticity in the brain hippocampus, we established an MS paradigm. In this research, the mice were treated with mild (15 min, MS15) or prolonged (180 min, MS180) maternal separation from postnatal day 2 to postnatal day 21. The mice underwent a forced swimming test, a tail suspension test, and an open field test, respectively. Afterward, the mice were sacrificed on postnatal day 31 to determine the effects of MS on early life stages. Results implied that MS induces depression-like behavior and the effects may be mediated partly by interfering with the hippocampal GSK-3β-CREB signaling pathway and by reducing the levels of some plasticity-related proteins.

scholarly journals Early life adversity alters normal sex-dependent developmental dynamics of DNA methylation

2016 ◽  
Vol 28 (4pt2) ◽  
pp. 1259-1272 ◽  
Author(s):  
Renaud Massart ◽  
Zsofia Nemoda ◽  
Matthew J. Suderman ◽  
Sheila Sutti ◽  
Angela M. Ruggiero ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Early Life ◽  
Maternal Separation ◽  
Methylation Profile ◽  
Early Life Adversity ◽  
Developmental Evolution ◽  
Dna Methylation Profile ◽  
Males And Females ◽  
The Difference ◽  
The Impact

AbstractStudies in rodents, nonhuman primates, and humans suggest that epigenetic processes mediate between early life experiences and adult phenotype. However, the normal evolution of epigenetic programs during child development, the effect of sex, and the impact of early life adversity on these trajectories are not well understood. This study mapped the genome-wide DNA methylation changes in CD3+ T lymphocytes from rhesus monkeys from postnatal day 14 through 2 years of age in both males and females and determined the impact of maternal deprivation on the DNA methylation profile. We show here that DNA methylation profiles evolve from birth to adolescence and are sex dependent. DNA methylation changes accompany imposed weaning, attenuating the difference between males and females. Maternal separation at birth alters the normal evolution of DNA methylation profiles and targets genes that are also affected by a later stage maternal separation, that is, weaning. Our results suggest that early life events dynamically interfere with the normal developmental evolution of the DNA methylation profile and that these changes are highly effected by sex.

scholarly journals Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure

2017 ◽  
Vol 66 ◽  
pp. 210-220 ◽  
Author(s):  
Charlis Raineki ◽  
Tamara S. Bodnar ◽  
Parker J. Holman ◽  
Samantha L. Baglot ◽  
Ni Lan ◽  
...  
Keyword(s):  
Immune Function ◽  
Early Life ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Early Life Adversity ◽  
Prenatal Environment ◽  
Prenatal Alcohol

scholarly journals Early-life adversity and adolescent depression: mechanisms involving the ventral striatum

CNS Spectrums ◽  
2014 ◽  
Vol 20 (4) ◽  
pp. 337-345 ◽  
Author(s):  
Bonnie Goff ◽  
Nim Tottenham
Keyword(s):  
Neural Development ◽  
Early Life ◽  
Adolescent Depression ◽  
Ventral Striatum ◽  
Reward Processing ◽  
Limbic Structure ◽  
Early Life Adversity ◽  
Reward Circuitry ◽  
Established Risk Factor

Early-life adversity is a well-established risk factor for the development of depression later in life. Here we discuss the relationship between early-life adversity and depression, focusing specifically on effects of early-life caregiver deprivation on alterations in the neural and behavioral substrates of reward-processing. We also examine vulnerability to depression within the context of sensitive periods of neural development and the timing of adverse exposure. We further review the development of the ventral striatum, a limbic structure implicated in reward processing, and its role in depressive outcomes following early-life adversity. Finally, we suggest a potential neurobiological mechanism linking early-life adversity and altered ventral striatal development. Together these findings may help provide further insight into the role of reward circuitry dysfunction in psychopathological outcomes in both clinical and developmental populations.

scholarly journals Trajectories of Mother-Infant Communication: An Experiential Measure of the Impacts of Early Life Adversity

2021 ◽  
Vol 15 ◽  
Author(s):  
Lauren Granata ◽  
Alissa Valentine ◽  
Jason L. Hirsch ◽  
Jennifer Honeycutt ◽  
Heather Brenhouse
Keyword(s):  
Maternal Care ◽  
Early Life ◽  
Maternal Separation ◽  
Developmental Trajectories ◽  
Later Life ◽  
Developmental Trajectory ◽  
Acoustic Properties ◽  
Emission Rates ◽  
Acoustic Parameters ◽  
Early Life Adversity

Caretaking stability in the early life environment supports neurobehavioral development, while instability and neglect constitute adverse environments that can alter maturational processes. Research in humans suggests that different types of early life adversity (ELA) can have differential effects on caretaker relationships and later cognitive and social development; however, identifying mechanistic underpinnings will require animal models with translational validity. Two common rodent models, maternal separation (MS) and limited bedding (LB), influence the mother-infant relationship during a critical window of development. We hypothesized that these paradigms may affect the development of communication strategies on the part of the pup. Ultrasonic vocalizations (USVs) are a care-eliciting mechanism and ethologically relevant response to stressors in the rat pup. USV emission rates and acoustic parameters change throughout early development, presenting the opportunity to define developmental milestones in USVs that would reflect neurobehavioral aberrations if disrupted. This study investigated the effects of MS or LB on the dam-pup relationship by quantifying pup USVs, maternal behavior, and the relationship between the two. First, we used a generalized additive model approach to establish typical developmental trajectories of USV acoustic properties and determine windows of change in MS or LB rearing. Additionally, we quantified maternal behaviors and the predictability of maternal care sequences using an entropy rate calculation. MS and LB each shifted the developmental trajectories of USV acoustic parameters and call types in a sex-specific manner. MS more often impacted male USVs, while LB impacted female USVs. MS dams spent more time passive nursing, and LB dams spent more time on the nest. The predictability of maternal care was associated with the rate of USV emissions exclusively in females. Taken together, findings demonstrate sex- and model-specific effects of rearing environments on a novel developmental trajectory involving the mother-infant relationship, facilitating the translation of animal ELA paradigms to assess later-life consequences.

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