scholarly journals Early acquisition of threat conditioning in a selectively-bred anxiety-like rat phenotype: regulation by maternal presence and FGF2

2021 ◽  
Author(s):  
Amanda M. White ◽  
Da-Jeong Chang ◽  
Joanna H. Hider ◽  
Elaine K. Hebda-Bauer ◽  
Cortney A. Turner ◽  
...  

AbstractTemperament is an innate, stable predisposition towards particular emotional and behavioral responses. In humans, certain temperaments are associated with a heightened risk of developing anxiety later in life. Non-human animals, including rodents, also exhibit innate, stable dispositions; these are referred to as behavioral phenotypes. The interaction between behavioral phenotype and early life adverse events is critical for the development of maladaptive anxiety. Rodent studies of typically developing animals have identified a number of mechanisms that protect against aversive experiences in early life. One such mechanism is an early life quiescence of threat learning, which protects against the effects of stress and facilitates safety and attachment learning. However, little is known about the factors that alleviate the effects of early life aversive events on phenotypes vulnerable to pathological anxiety. Here, we examined threat learning and the stress response in selectively-bred infant rats that show an anxiety-like phenotype relative to typically developing animals. We investigated the potential roles of maternal presence and the anxiolytic neurotrophic factor fibroblast growth factor 2 (FGF2) in regulating threat learning and the stress response in infant anxiety-like phenotype animals. We observed that rats selectively-bred for anxiety-like behaviors could acquire conditioned freezing earlier in life than typically developing animals. FGF2 administration on postnatal day 1 (PND 1) and maternal presence during threat conditioning were both capable of suppressing this early emergence of conditioned freezing. However, neither FGF2 nor maternal presence during threat conditioning were associated with reduced corticosterone levels during threat conditioning. Our results suggest that although an anxiety-like phenotype may be associated with early threat learning, environmental factors (such as maternal presence) and pharmacological intervention (such as modulation of the FGF2 system) may be capable of counteracting that early aversive learning. Interventions in vulnerable infants may thus decrease the impact of aversive events.

Author(s):  
Maria Mousikou ◽  
Andreas Kyriakou ◽  
Nicos Skordis

The infantile, childhood, and adolescent periods of growth and development represent times of increased vulnerability to stressors. The rate of growth in each period depends on the interplay of genetic, environmental, dietary, socioeconomic, developmental, behavioral, nutritional, metabolic, biochemical, and hormonal factors. A stressor may have an impact on growth directly through modulation of the growth hormone axis or indirectly through modulation of other factors. The adaptive response to stressors culminates in behavioral, physiological, and biochemical responses, which together support survival and conservation of energy. The process begins within seconds and involves activation of sympathetic nervous system and Hypothalamic-Pituitary-Adrenal axis. The time-limited stress response is at once anti-growth, anti-reproductive and catabolic with no lasting adverse consequences. However, chronic activation of the stress system and hypercortisolism have consequential negative impacts on growth, thyroid function, reproduction-puberty, and metabolism. They suppress Growth Hormone-Insulin like growth factor 1, Hypothalamic-Pituitary-Gonadal and Thyroid axes and can be responsible for an increase in visceral adiposity, a decrease in lean mass, suppression of osteoblastic activity with risk of osteoporosis, and induction of insulin resistance. Early life adversities, emotional or physical, have been associated with long-term negative physical and mental health outcomes. There are many models of chronic stress that corroborate that early life adversities affect optimal growth and have consequences throughout the lifespan. Targeted interventions to reduce stress during infancy, childhood and adolescence can have far reaching benefits to long-term health as well as attaining adequate growth. In this review we describe the neuroendocrinology of the stress response, the factors influencing growth, and the impact of chronic stress on growth during critical periods of infancy, childhood, and puberty with reference to each of growth, thyroid, and gonadal axis.


2015 ◽  
Vol 112 (18) ◽  
pp. 5637-5642 ◽  
Author(s):  
Katie A. McLaughlin ◽  
Margaret A. Sheridan ◽  
Florin Tibu ◽  
Nathan A. Fox ◽  
Charles H. Zeanah ◽  
...  

Disruptions in stress response system functioning are thought to be a central mechanism by which exposure to adverse early-life environments influences human development. Although early-life adversity results in hyperreactivity of the sympathetic nervous system (SNS) and hypothalamic–pituitary–adrenal (HPA) axis in rodents, evidence from human studies is inconsistent. We present results from the Bucharest Early Intervention Project examining whether randomized placement into a family caregiving environment alters development of the autonomic nervous system and HPA axis in children exposed to early-life deprivation associated with institutional rearing. Electrocardiogram, impedance cardiograph, and neuroendocrine data were collected during laboratory-based challenge tasks from children (mean age = 12.9 y) raised in deprived institutional settings in Romania randomized to a high-quality foster care intervention (n = 48) or to remain in care as usual (n = 43) and a sample of typically developing Romanian children (n = 47). Children who remained in institutional care exhibited significantly blunted SNS and HPA axis responses to psychosocial stress compared with children randomized to foster care, whose stress responses approximated those of typically developing children. Intervention effects were evident for cortisol and parasympathetic nervous system reactivity only among children placed in foster care before age 24 and 18 months, respectively, providing experimental evidence of a sensitive period in humans during which the environment is particularly likely to alter stress response system development. We provide evidence for a causal link between the early caregiving environment and stress response system reactivity in humans with effects that differ markedly from those observed in rodent models.


2011 ◽  
Vol 13 (2) ◽  
pp. 177-185 ◽  
Author(s):  
Marcelo F. Mello ◽  
Paula M. Serafim ◽  
Maira L. Moraes ◽  
Agnes M. Miranda ◽  
Yusaku Soussumi ◽  
...  

2020 ◽  
Vol 63 (9) ◽  
pp. 3036-3050
Author(s):  
Elma Blom ◽  
Tessel Boerma

Purpose Many children with developmental language disorder (DLD) have weaknesses in executive functioning (EF), specifically in tasks testing interference control and working memory. It is unknown how EF develops in children with DLD, if EF abilities are related to DLD severity and persistence, and if EF weaknesses expand to selective attention. This study aimed to address these gaps. Method Data from 78 children with DLD and 39 typically developing (TD) children were collected at three times with 1-year intervals. At Time 1, the children were 5 or 6 years old. Flanker, Dot Matrix, and Sky Search tasks tested interference control, visuospatial working memory, and selective attention, respectively. DLD severity was based on children's language ability. DLD persistence was based on stability of the DLD diagnosis. Results Performance on all tasks improved in both groups. TD children outperformed children with DLD on interference control. No differences were found for visuospatial working memory and selective attention. An interference control gap between the DLD and TD groups emerged between Time 1 and Time 2. Severity and persistence of DLD were related to interference control and working memory; the impact on working memory was stronger. Selective attention was unrelated to DLD severity and persistence. Conclusions Age and DLD severity and persistence determine whether or not children with DLD show EF weaknesses. Interference control is most clearly impaired in children with DLD who are 6 years and older. Visuospatial working memory is impaired in children with severe and persistent DLD. Selective attention is spared.


Author(s):  
Misa Kayama ◽  
Wendy Haight ◽  
May-Lee Ku ◽  
Minhae Cho ◽  
Hee Yun Lee

Stigmatization is part of the everyday lives of children with disabilities, their families, and their friends. Negative social encounters, even with perfect strangers, can dampen joyful occasions, add stress to challenging situations, and lead to social isolation. This book describes a program of research spanning a decade that seeks to understand disabilities in their developmental and cultural contexts. The authors are especially interested in understanding adults’ socialization practices that promise to reduce stigmatization in the next generation. Guided by developmental cultural psychology, including the concept of “universalism without uniformity,” the authors focus on the understandings and responses to disability and associated stigmatization of elementary-school educators practicing in Japan, South Korea, Taiwan, and the U.S. Educators from all four cultural groups expressed strikingly similar concerns about the impact of stigmatization on the emerging cultural self, both of children with disabilities and their typically developing peers. Educators also described culturally nuanced socialization goals and practices pertaining to inclusive education. In Japan, for instance, educators emphasized the importance of peer group belonging and strategies to support the participation of children with disabilities. In the U.S., educators placed relatively more emphasis on individual development and discussed strategies for the equitable treatment of children with disabilities. Educators in South Korea and Taiwan emphasized the cultivation of compassion in typically developing children. The understanding gained through examination of how diverse individuals address common challenges using cultural resources available in their everyday lives provides important lessons for strengthening theory, policy, and programs.


Author(s):  
Audrey L. Michal ◽  
Yiwen Zhong ◽  
Priti Shah

AbstractToday’s citizens are expected to use evidence, frequently presented in the media, to inform decisions about health, behavior, and public policy. However, science misinformation is ubiquitous in the media, making it difficult to apply research appropriately. Across two experiments, we addressed how anecdotes and prior beliefs impact readers’ ability to both identify flawed science and make appropriate decisions based on flawed science in media articles. Each article described the results of flawed research on one of four educational interventions to improve learning (Experiment 1 included articles about having a tidy classroom and exercising while learning; Experiment 2 included articles about using virtual/augmented reality and napping at school). Experiment 1 tested the impact of a single anecdote and found no significant effect on either participants’ evidence evaluations or decisions to implement the learning interventions. However, participants were more likely to adopt the more plausible intervention (tidy classroom) despite identifying that it was unsupported by the evidence, suggesting effects of prior beliefs. In Experiment 2, we tested whether this intervention effect was driven by differences in beliefs about intervention plausibility and included two additional interventions (virtual reality = high plausible, napping = low plausible). We again found that participants were more likely to implement high plausible than low plausible interventions, and that evidence quality was underweighed as a factor in these decisions. Together, these studies suggest that evidence-based decisions are more strongly determined by prior beliefs than beliefs about the quality of evidence itself.


Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 605
Author(s):  
Jana Jandova ◽  
Anh B. Hua ◽  
Jocelyn Fimbres ◽  
Georg T. Wondrak

There are two stable isotopes of hydrogen, protium (1H) and deuterium (2H; D). Cellular stress response dysregulation in cancer represents both a major pathological driving force and a promising therapeutic target, but the molecular consequences and potential therapeutic impact of deuterium (2H)-stress on cancer cells remain largely unexplored. We have examined the anti-proliferative and apoptogenic effects of deuterium oxide (D2O; ‘heavy water’) together with stress response gene expression profiling in panels of malignant melanoma (A375V600E, A375NRAS, G361, LOX-IMVI), and pancreatic ductal adenocarcinoma (PANC-1, Capan-2, or MIA PaCa-2) cells with inclusion of human diploid Hs27 skin fibroblasts. Moreover, we have examined the efficacy of D2O-based pharmacological intervention in murine models of human melanoma tumor growth and metastasis. D2O-induction of apoptosis was substantiated by AV-PI flow cytometry, immunodetection of PARP-1, and pro-caspase 3 cleavage, and rescue by pan-caspase inhibition. Differential array analysis revealed early modulation of stress response gene expression in both A375 melanoma and PANC-1 adenocarcinoma cells elicited by D2O (90%; ≤6 h) (upregulated: CDKN1A, DDIT3, EGR1, GADD45A, HMOX1, NFKBIA, or SOD2 (up to 9-fold; p < 0.01)) confirmed by independent RT-qPCR analysis. Immunoblot analysis revealed rapid onset of D2O-induced stress response phospho-protein activation (p-ERK, p-JNK, p-eIF2α, or p-H2AX) or attenuation (p-AKT). Feasibility of D2O-based chemotherapeutic intervention (drinking water (30% w/w)) was demonstrated in a severe combined immunodeficiency (SCID) mouse melanoma metastasis model using luciferase-expressing A375-Luc2 cells. Lung tumor burden (visualized by bioluminescence imaging) was attenuated by D2O, and inhibition of invasiveness was also confirmed in an in vitro Matrigel transwell invasion assay. D2O supplementation also suppressed tumor growth in a murine xenograft model of human melanoma, and median survival was significantly increased without causing adverse effects. These data demonstrate for the first time that systemic D2O administration impairs growth and metastasis of malignant melanoma through the pharmacological induction of deuterium (2H)-stress.


Author(s):  
Éva Leiter ◽  
Tamás Emri ◽  
Klaudia Pákozdi ◽  
László Hornok ◽  
István Pócsi

Abstract Regulation of signal transduction pathways is crucial for the maintenance of cellular homeostasis and organismal development in fungi. Transcription factors are key elements of this regulatory network. The basic-region leucine zipper (bZIP) domain of the bZIP-type transcription factors is responsible for DNA binding while their leucine zipper structural motifs are suitable for dimerization with each other facilitiating the formation of homodimeric or heterodimeric bZIP proteins. This review highlights recent knowledge on the function of fungal orthologs of the Schizosaccharomyces pombe Atf1, Aspergillus nidulans AtfA, and Fusarium verticillioides FvAtfA, bZIP-type transcription factors with a special focus on pathogenic species. We demonstrate that fungal Atf1-AtfA-FvAtfA orthologs play an important role in vegetative growth, sexual and asexual development, stress response, secondary metabolite production, and virulence both in human pathogens, including Aspergillus fumigatus, Mucor circinelloides, Penicillium marneffei, and Cryptococcus neoformans and plant pathogens, like Fusarium ssp., Magnaporthe oryzae, Claviceps purpurea, Botrytis cinerea, and Verticillium dahliae. Key points • Atf1 orthologs play crucial role in the growth and development of fungi. • Atf1 orthologs orchestrate environmental stress response of fungi. • Secondary metabolite production and virulence are coordinated by Atf1 orthologs.


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