scholarly journals Evolutionary conserved neural signature of early life stress affects animal social competence

2018 ◽  
Vol 285 (1871) ◽  
pp. 20172344 ◽  
Author(s):  
Cecilia Nyman ◽  
Stefan Fischer ◽  
Nadia Aubin-Horth ◽  
Barbara Taborsky
Keyword(s):  
Social Competence ◽  
Social Environment ◽  
Life Stress ◽  
Glucocorticoid Receptors ◽  
Molecular Mechanisms ◽  
Cichlid Fish ◽  
Early Life Stress ◽  
Later Life ◽  
Stress Axis ◽  
Molecular Pathway

In vertebrates, the early social environment can persistently influence behaviour and social competence later in life. However, the molecular mechanisms underlying variation in animal social competence are largely unknown. In rats, high-quality maternal care causes an upregulation of hippocampal glucocorticoid receptors ( gr ) and reduces offspring stress responsiveness. This identifies gr regulation as a candidate mechanism for maintaining variation in animal social competence. We tested this hypothesis in a highly social cichlid fish, Neolamprologus pulcher , reared with or without caring parents. We find that the molecular pathway translating early social experience into later-life alterations of the stress axis is homologous across vertebrates: fish reared with parents expressed the glucocorticoid receptor gr1 more in the telencephalon. Furthermore, expression levels of the transcription factor egr-1 (early growth response 1) were associated with gr1 expression in the telencephalon and hypothalamus. When blocking glucocorticoid receptors (GR) with an antagonist, mifepristone (RU486), parent-reared individuals showed more socially appropriate, submissive behaviour when intruding on a larger conspecific's territory. Remarkably, mifepristone-treated fish were less attacked by territory owners and had a higher likelihood of territory takeover. Our results indicate that early social-environment effects on stress axis programming are mediated by an evolutionary conserved molecular pathway, which is causally involved in environmentally induced variation of animal social competence.

scholarly journals Does epigenetic ‘memory’ of early-life stress predispose to chronic pain in later life? A potential role for the stress regulator FKBP5

2019 ◽  
Vol 374 (1785) ◽  
pp. 20190283 ◽  
Author(s):  
S. M. Géranton
Keyword(s):  
Chronic Pain ◽  
Life Stress ◽  
Early Life ◽  
Potential Role ◽  
Adult Life ◽  
Early Life Stress ◽  
Later Life ◽  
Stress Axis ◽  
Evolutionarily Conserved ◽  
Early Life Events

Animal behaviours are affected not only by inherited genes but also by environmental experiences. For example, in both rats and humans, stressful early-life events such as being reared by an inattentive mother can leave a lasting trace and affect later stress response in adult life. This is owing to a chemical trace left on the chromatin attributed to so-called epigenetic mechanisms. Such an epigenetic trace often has consequences, sometimes long-lasting, on the functioning of our genes, thereby allowing individuals to rapidly adapt to a new environment. One gene under such epigenetic control is FKBP5 , the gene that encodes the protein FKPB51, a crucial regulator of the stress axis and a significant driver of chronic pain states. In this article, we will discuss the possibility that exposure to stress could drive the susceptibly to chronic pain via epigenetic modifications of genes within the stress axis such as FKBP5 . The possibility that such modifications, and therefore, the susceptibility to chronic pain, could be transmitted across generations in mammals and whether such mechanisms may be evolutionarily conserved across phyla will also be debated. This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.

scholarly journals Active behaviour during early development shapes glucocorticoid reactivity

2019 ◽  
Author(s):  
Luis A. Castillo-Ramírez ◽  
Soojin Ryu ◽  
Rodrigo J. De Marco
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Developmental Stages ◽  
Early Life Stress ◽  
Later Life ◽  
Stress Axis ◽  
Glucocorticoid Response ◽  
The Central Nervous System ◽  
Response To Stress ◽  
Early Life Events

AbstractGlucocorticoids are the final effectors of the stress axis, with numerous targets in the central nervous system and the periphery. They are essential for adaptation, yet currently it is unclear how early life events program the glucocorticoid response to stress. Here we provide evidence that involuntary swimming at early developmental stages can reconfigure the cortisol response to homotypic and heterotypic stress in larval zebrafish (Danio rerio), also reducing startle reactivity and increasing spontaneous activity as well as energy efficiency during active behaviour. Collectively, these data identify a role of the genetically malleable zebrafish for linking early life stress with glucocorticoid function in later life.

scholarly journals Hormesis in Health and Disease: Molecular Mechanisms

2020 ◽  
Vol 12 (4) ◽  
pp. 288-303
Author(s):  
Anna Meiliana ◽  
Andi Wijaya
Keyword(s):  
Life Stress ◽  
Molecular Mechanisms ◽  
Genetic Manipulation ◽  
Early Life Stress ◽  
Later Life ◽  
Dietary Factors ◽  
Dose Effect ◽  
Beneficial Effects ◽  
Natural Event ◽  
Living Organisms

BACKGROUND: Hormesis was initially defined as a phenomenon where a small dose of harmful agent exposure to living organisms gives beneficial effects. The dose and time of this ‘tress’ exposure has become the object of investigation across the broad range of biomedical studies.CONTENT: Hormesis characterized by the biphasic dose-effect or time-effect relationship for any substance. Some hormetic mechanisms performed biological plasticity, involve oxidative damage which instead induce antioxidant enzyme production in various cells. Early-life stress can increase resilience in later life and lack of stress can lead to vulnerability. Many stressors like dietary factors and natural environmental toxins can be occupied for healthy growth or homeostasis, which exemplifies how illness is the doorway to health.SUMMARY: Hormesis reconcile many paradoxical phenomena exert opposite effects of the same substance, either a xenobiotic or an endogenous substance, a hormone or a metabolite, a genetic manipulation or an epigenetic alteration, an experimental intervention or a natural event. Human bodies are highly adaptive. A resilient body would be resulted after the ‘training’. In this review, we will elucidate the hormesis’ definition, mechanisms and pathways, and also how hormesis impacts in human health and lifespan.KEYWORDS: biphasic, cell signaling, dose response, hormesis, preconditioning

scholarly journals Sexual dimorphic role of the glucocorticoid receptor in chronic muscle pain produced by early-life stress

2021 ◽  
Vol 17 ◽  
pp. 174480692110113
Author(s):  
Paul G Green ◽  
Pedro Alvarez ◽  
Jon D Levine
Keyword(s):  
Glucocorticoid Receptor ◽  
Adult Male ◽  
Life Stress ◽  
Early Life ◽  
Glucocorticoid Receptors ◽  
Early Life Stress ◽  
Nociceptive Threshold ◽  
Male And Female ◽  
Mechanical Nociceptive Threshold

Fibromyalgia and other chronic musculoskeletal pain syndromes are associated with stressful early life events, which can produce a persistent dysregulation in the hypothalamic-pituitary adrenal (HPA) stress axis function, associated with elevated plasm levels of corticosterone in adults. To determine the contribution of the HPA axis to persistent muscle hyperalgesia in adult rats that had experienced neonatal limited bedding (NLB), a form of early-life stress, we evaluated the role of glucocorticoid receptors on muscle nociceptors in adult NLB rats. In adult male and female NLB rats, mechanical nociceptive threshold in skeletal muscle was significantly lower than in adult control (neonatal standard bedding) rats. Furthermore, adult males and females that received exogenous corticosterone (via dams’ milk) during postnatal days 2–9, displayed a similar lowered mechanical nociceptive threshold. To test the hypothesis that persistent glucocorticoid receptor signaling in the adult contributes to muscle hyperalgesia in NLB rats, nociceptor expression of glucocorticoid receptor (GR) was attenuated by spinal intrathecal administration of an oligodeoxynucleotide (ODN) antisense to GR mRNA. In adult NLB rats, GR antisense markedly attenuated muscle hyperalgesia in males, but not in females. These findings indicate that increased corticosterone levels during a critical developmental period (postnatal days 2–9) produced by NLB stress induces chronic mechanical hyperalgesia in male and female rats that persists in adulthood, and that this chronic muscle hyperalgesia is mediated, at least in part, by persistent stimulation of glucocorticoid receptors on sensory neurons, in the adult male, but not female rat.

scholarly journals A Novel Mouse Model for Acute and Long-Lasting Consequences of Early Life Stress

Endocrinology ◽  
2008 ◽  
Vol 149 (10) ◽  
pp. 4892-4900 ◽  
Author(s):  
Courtney J. Rice ◽  
Curt A. Sandman ◽  
Mohammed R. Lenjavi ◽  
Tallie Z. Baram
Keyword(s):  
Mouse Model ◽  
Paraventricular Nucleus ◽  
Life Stress ◽  
Early Life ◽  
Molecular Mechanisms ◽  
Early Life Stress ◽  
Plasma Corticosterone ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Basal Plasma

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.

scholarly journals Early-life manipulation of cortisol and its receptor alters stress axis programming and social competence

2019 ◽  
Vol 374 (1770) ◽  
pp. 20180119 ◽  
Author(s):  
Maria Reyes-Contreras ◽  
Gaétan Glauser ◽  
Diana J. Rennison ◽  
Barbara Taborsky
Keyword(s):  
Social Competence ◽  
Early Life ◽  
Physiological Mechanism ◽  
Later Life ◽  
Evolutionary Medicine ◽  
Stress Axis ◽  
Long Term Effects ◽  
Coping With Stress ◽  
Expression Of Genes ◽  
Social Challenge

In many vertebrate species, early social experience generates long-term effects on later life social behaviour. These effects are accompanied by persistent modifications in the expression of genes implicated in the stress axis. It is unknown, however, whether stress axis programming can affect the development of social competence, and if so, by which mechanism(s). Here, we used pharmacological manipulations to persistently reprogramme the hypothalamic–pituitary–interrenal axis of juvenile cooperatively breeding cichlids, Neolamprologus pulcher. During the first two months of life, juveniles were repeatedly treated with cortisol, mifepristone or control treatments. Three months after the last manipulation, we tested for treatment effects on (i) social competence, (ii) the expression of genes coding for corticotropin-releasing factor ( crf ), glucocorticoid receptor ( gr1 ) and mineralocorticoid receptor ( mr ) in the telencephalon and hypothalamus and (iii) cortisol levels. Social competence in a social challenge was reduced in cortisol-treated juveniles, which is in accordance with previous work applying early-life manipulations using different social experiences. During early life, both cortisol and mifepristone treatments induced a persistent downregulation of crf and upregulation of mr in the telencephalon. We suggest that these persistent changes in stress gene expression may represent an effective physiological mechanism for coping with stress. This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.

It Was Not Safe to Feel Angry: Disrupted Early Attachment and the Development of Chronic Pain in Later Life

2017 ◽  
Vol 11 (3) ◽  
pp. 223-241 ◽  
Author(s):  
Frances Sommer Anderson
Keyword(s):  
Chronic Pain ◽  
Life Stress ◽  
Psychological Treatment ◽  
Early Life Stress ◽  
Later Life ◽  
Secure Attachment ◽  
Somatic Pain ◽  
Treatment Techniques ◽  
Mind And Body

Using detailed clinical material from her treatment of three patients referred by physiatrist John E. Sarno, for psychological treatment of chronic pain, Dr Anderson illustrates a relationship between dissociated/repressed affect and the development of chronic musculoskeletal back pain. Sarno, conversant with the fundamentals of psychoanalysis, theorised that the somatic pain, which he termed tension myoneural syndrome (TMS), served as a distraction from emotions that were unbearable. That is, the pain served as a psychological defense or survival tactic. In treatment, the adverse impact of overwhelming physical and emotional experiences on attachment and emotion regulation are identified and discussed. Detailed clinical process, which includes the use of trauma treatment techniques, illuminate how psychological treatment can be used to help patients identify and tolerate feelings associated with early life stress, leading to relief from the somatic pain. Anderson, informed by the psychosomatic theories of Krystal and McDougall and by contemporary attachment theorists, advances the position that the physician as diagnostician functions symbolically as the "parent" who links mind and body, thereby reducing the patient's fear of pain and creating a secure attachment bond. In this secure attachment relationship, the physician "authorises" the patient to experience emotions that were previously disavowed. In the relationship with an empathic relational psychoanalyst, the patient's pain resolves as s/he builds a capacity to identify and tolerate emotions and learns how to use emotions, particularly anger, to enhance relationships and improve their quality of life.

scholarly journals Early-life stress and inflammation: A systematic review of a key experimental approach in rodents

2020 ◽  
Vol 4 ◽  
pp. 239821282097804
Author(s):  
Ethan G. Dutcher ◽  
E.A. Claudia Pama ◽  
Mary-Ellen Lynall ◽  
Shahid Khan ◽  
Menna R. Clatworthy ◽  
...  
Keyword(s):  
Systematic Review ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Later Life ◽  
Interleukin 10 ◽  
Brain Regions ◽  
Clinical Approach ◽  
Necrosis Factor Alpha

Repeated maternal separation is the most widely used pre-clinical approach to investigate the relationship between early-life chronic stress and its neuropsychiatric and physical consequences. In this systematic review, we identified 46 studies that conducted repeated maternal separation or single-episode maternal separation and reported measurements of interleukin-1b, interleukin-6, interleukin-10, tumour necrosis factor-alpha, or microglia activation and density. We report that in the short-term and in the context of later-life stress, repeated maternal separation has pro-inflammatory immune consequences in diverse tissues. Repeated maternal separation animals exhibit greater microglial activation and elevated pro-inflammatory cytokine signalling in key brain regions implicated in human psychiatric disorders. Notably, repeated maternal separation generally has no long-term effect on cytokine expression in any tissue in the absence of later-life stress. These observations suggest that the elevated inflammatory signalling that has been reported in humans with a history of early-life stress may be the joint consequence of ongoing stressor exposure together with potentiated neural and/or immune responsiveness to stressors. Finally, our findings provide detailed guidance for future studies interrogating the causal roles of early-life stress and inflammation in disorders such as major depression.

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