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Roles of Oxytocin in Stress Responses, Allostasis and Resilience.

ABSTRACT: Oxytocin has been revealed to work for anxiety suppression and anti-stress as well as for psychosocial behavior and reproductive functions. Oxytocin neurons are activated by various stressful stimuli. The oxytocin receptor is widely distributed within the brain, and oxytocin that is released or diffused affects behavioral and neuroendocrine stress responses. On the other hand, there has been an increasing number of reports on the role of oxytocin in allostasis and resilience. It has been shown that oxytocin maintains homeostasis, shifts the set point for adaptation to a changing environment (allostasis) and contributes to recovery from the shifted set point by inducing active coping responses to stressful stimuli (resilience). Recent studies have suggested that oxytocin is also involved in stress-related disorders, and it has been shown in clinical trials that oxytocin provides therapeutic benefits for patients diagnosed with stress-related disorders. This review includes the latest information on the role of oxytocin in stress responses and adaptation.

SUBMITTER: Takayanagi Y

PROVIDER: S-EPMC8745417 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Roles of Oxytocin in Stress Responses, Allostasis and Resilience.

Takayanagi Yuki Y Onaka Tatsushi T

International journal of molecular sciences 20211223 1

Oxytocin has been revealed to work for anxiety suppression and anti-stress as well as for psychosocial behavior and reproductive functions. Oxytocin neurons are activated by various stressful stimuli. The oxytocin receptor is widely distributed within the brain, and oxytocin that is released or diffused affects behavioral and neuroendocrine stress responses. On the other hand, there has been an increasing number of reports on the role of oxytocin in allostasis and resilience. It has been shown t ...[more]

PMID: 35008574

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Project description:BackgroundSubstantial empirical evidence has demonstrated that individuals who are socially isolated or have few positive social connections seem to age at a faster rate and have more chronic diseases. Oxytocin is a neurohypophyseal hormone hypothesized to coordinate both the causes and effects of positive social interactions, and may be involved in positive physiological adaptations such as buffering the deleterious effects of stress and promoting resilience. The proposed research will examine whether and how oxytocin influences responses to stress in humans and will consider effects in relation to those of social support.Methods/designExperimental research will be used to determine whether exogenously administered oxytocin (intranasal) influences psychological and physiological outcomes under conditions of stress across gender and age in adulthood. Hypotheses to be tested are: 1) Oxytocin ameliorates the deleterious neuroendocrine, cardiovascular, and subjective effects of stress; 2) Oxytocin and social support have similar and additive stress-buffering effects; 3) Oxytocin effects are stronger in women versus men; and 4) Oxytocin effects are similar across a range of adult ages. Hypotheses will be tested with a placebo-controlled, double-blind study using a sample of healthy men and women recruited from the community. Participants are randomly assigned to receive either oxytocin or placebo. They undergo a social stress manipulation with and without social support (randomly assigned), and outcome measures are obtained at multiple times during the procedure.DiscussionUnderstanding the determinants of healthy aging is a major public health priority and identifying effective measures to prevent or delay the onset of chronic diseases is an important goal. Experimental research on oxytocin, social relationships, and health in adulthood will contribute to the scientific knowledge base for maximizing active life and health expectancy. At conclusion of the study we will have solid evidence concerning the effects of oxytocin on stress response and whether it has similar effects across age and gender groups. A neurobiological understanding of resilience can inform efforts for both prevention and intervention of diseases or problems common in later life.

Project description:ObjectivePancreatic β cells play a key role in maintaining glucose homeostasis; dysfunction of this critical cell type causes type 2 diabetes (T2D). Emerging evidence points to sex differences in β cells, but few studies have examined male-female differences in β cell stress responses and resilience across multiple contexts, including diabetes. Here, we address the need for high-quality information on sex differences in β cell and islet gene expression and function using both human and rodent samples.MethodsIn humans, we compared β cell gene expression and insulin secretion in donors with T2D to non-diabetic donors in both males and females. In mice, we generated a well-powered islet RNAseq dataset from 20-week-old male and female siblings with similar insulin sensitivity. Our unbiased gene expression analysis pointed to a sex difference in the endoplasmic reticulum (ER) stress response. Based on this analysis, we hypothesized female islets would be more resilient to ER stress than male islets. To test this, we subjected islets isolated from age-matched male and female mice to thapsigargin treatment and monitored protein synthesis, cell death, and β cell insulin production and secretion. Transcriptomic and proteomic analyses were used to characterize sex differences in islet responses to ER stress.ResultsOur single-cell analysis of human β cells revealed sex-specific changes to gene expression and function in T2D, correlating with more robust insulin secretion in human islets isolated from female donors with T2D compared to male donors with T2D. In mice, RNA sequencing revealed differential enrichment of unfolded protein response pathway-associated genes, where female islets showed higher expression of genes linked with protein synthesis, folding, and processing. This differential expression was physiologically significant, as islets isolated from female mice were more resilient to ER stress induction with thapsigargin. Specifically, female islets showed a greater ability to maintain glucose-stimulated insulin production and secretion during ER stress compared with males.ConclusionsOur data demonstrate sex differences in β cell gene expression in both humans and mice, and that female β cells show a greater ability to maintain glucose-stimulated insulin secretion across multiple physiological and pathological contexts.

Dataset Information

Roles of Oxytocin in Stress Responses, Allostasis and Resilience.

Publications

Roles of Oxytocin in Stress Responses, Allostasis and Resilience.

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