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Circadian clock control of endocrine factors
Key Points
Various endocrine factors are known to exhibit time-of-day-dependent oscillations in both humans and animals
Endocrine factor rhythms are driven not only by environmental and behavioural influences, but also by intrinsic circadian clocks
Circadian dyssynchrony is associated with multiple pathologic states, including cardiometabolic diseases and cancer
Reinstatement of circadian synchrony through time-of-day-restricted feeding and pharmacologic strategies improves metabolic homeostasis
Adequate circadian oscillation of endocrine factors is essential in the maintenance of metabolic homeostasis. The authors of this Review explain the influence of extrinsic and intrinsic factors on endocrine circadian rhythms and how dysregulation of these rhythms can lead to disease in animals and humans. They also discuss therapeutic strategies to restore circadian rhythmicity and improve metabolism.
Organisms experience dramatic fluctuations in demands and stresses over the course of the day. In order to maintain biological processes within physiological boundaries, mechanisms have evolved for anticipation of, and adaptation to, these daily fluctuations. Endocrine factors have an integral role in homeostasis. Not only do circulating levels of various endocrine factors oscillate over the 24 h period, but so too does responsiveness of target tissues to these signals or stimuli. Emerging evidence suggests that these daily endocrine oscillations do not occur solely in response to behavioural fluctuations associated with sleep–wake and feeding–fasting cycles, but are orchestrated by an intrinsic timekeeping mechanism known as the circadian clock. Disruption of circadian clocks by genetic and/or environmental factors seems to precipitate numerous common disorders, including the metabolic syndrome and cancer. Collectively, these observations suggest that strategies designed to realign normal circadian rhythmicities hold potential for the treatment of various endocrine-related disorders.
Journal Article
20 fun facts about the digestive system
\"From the mouth and esophagus to the small and large intestine, re aders take a journey through the human body via the digestive tract, and enjoy learning about processes the digestive system does without us even knowing\"-- Provided by publisher.
Book
Technical Note: Modulation of fMRI brainstem responses by transcutaneous vagus nerve stimulation
•taVNS effects on brainstem activity are assessed during fMRI.•taVNS modulates activity in brainstem vagal afferent targets (including the NTS).•The signal dynamics over time indicates both acute, persistent and delayed effects of taVNS.
Our increasing knowledge about gut-brain interaction is revolutionising the understanding of the links between digestion, mood, health, and even decision making in our everyday lives. In support of this interaction, the vagus nerve is a crucial pathway transmitting diverse gut-derived signals to the brain to monitor of metabolic status, digestive processes, or immune control to adapt behavioural and autonomic responses. Hence, neuromodulation methods targeting the vagus nerve are currently explored as a treatment option in a number of clinical disorders, including diabetes, chronic pain, and depression. The non-invasive variant of vagus nerve stimulation (VNS), transcutaneous auricular VNS (taVNS), has been implicated in both acute and long-lasting effects by modulating afferent vagus nerve target areas in the brain. The physiology of neither of those effects is, however, well understood, and evidence for neuronal response upon taVNS in vagal afferent projection regions in the brainstem and its downstream targets remain to be established.
Therefore, to examine time-dependent effects of taVNS on brainstem neuronal responses in healthy human subjects, we applied taVNS during task-free fMRI in a single-blinded crossover design. During fMRI data acquisition, we either stimulated the left earlobe (sham), or the target zone of the auricular branch of the vagus nerve in the outer ear (cymba conchae, verum) for several minutes, both followed by a short ‘stimulation OFF’ period. Time-dependent effects were assessed by averaging the BOLD response for consecutive 1-minute periods in an ROI-based analysis of the brainstem.
We found a significant response to acute taVNS stimulation, relative to the control condition, in downstream targets of vagal afferents, including the nucleus of the solitary tract, the substantia nigra, and the subthalamic nucleus. Most of these brainstem regions remarkably showed increased activity in response to taVNS, and these effect sustained during the post-stimulation period. These data demonstrate that taVNS activates key brainstem regions, and highlight the potential of this approach to modulate vagal afferent signalling. Furthermore, we show that carry-over effects need to be considered when interpreting fMRI data in the context of general vagal neurophysiology and its modulation by taVNS.
Journal Article
Circadian and Homeostatic Modulation of Functional Connectivity and Regional Cerebral Blood Flow in Humans under Normal Entrained Conditions
Diurnal rhythms have been observed in human behaviors as diverse as sleep, olfaction, and learning. Despite its potential impact, time of day is rarely considered when brain responses are studied by neuroimaging techniques. To address this issue, we explicitly examined the effects of circadian and homeostatic regulation on functional connectivity (FC) and regional cerebral blood flow (rCBF) in healthy human volunteers, using whole-brain resting-state functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL). In common with many circadian studies, we collected salivary cortisol to represent the normal circadian activity and functioning of the hypothalamic–pituitary–adrenal (HPA) axis. Intriguingly, the changes in FC and rCBF we observed indicated fundamental decreases in the functional integration of the default mode network (DMN) moving from morning to afternoon. Within the anterior cingulate cortex (ACC), our results indicate that morning cortisol levels are negatively correlated with rCBF. We hypothesize that the homeostatic mechanisms of the HPA axis has a role in modulating the functional integrity of the DMN (specifically, the ACC), and for the purposes of using fMRI as a tool to measure changes in disease processes or in response to treatment, we demonstrate that time of the day is important when interpreting resting-state data.
Journal Article
Neural regulation of endocrine and autonomic stress responses
Key Points
The response of mammals to external or internal challenge involves engagement of multiple physiological systems, prominently including the hypothalamic-pituitary-adrenocortical (HPA) axis and the autonomic nervous system (ANS).
Autonomic and HPA axis responses to systemic stressors are initiated by brainstem and hypothalamic structures that receive direct and indirect homeostatic feedback.
Psychological stress responses are activated and inhibited by limbic system structures, such as the medial prefrontal cortex, the hippocampus and the amygdala, which send multisynaptic input to brainstem and hypothalamic activators of the HPA axis and the ANS.
'Psychological' information and homeostatic information are integrated by telencephalic and diencephalic relays prior to the elaboration of HPA axis or ANS responses.
HPA axis and ANS components of the stress response are probably encoded in distinct yet highly interconnected limbic subregions.
Chronic stress induces neuroplasticity in central stress-processing networks, causing sensitization as well as habituation of HPA axis and ANS responses.
Limbic stress response networks overlap extensively with memory and reward circuitry, allowing stress responses to be coloured by prior experience and expected outcomes.
The physiological response to stress is regulated by a complex neurocircuitry that integrates and interprets stress-related and homeostatic information. Ulrich-Lai and Herman describe this circuitry, including its adaptation to chronic stress and its overlap with circuits that underlie memory and reward.
The survival and well-being of all species requires appropriate physiological responses to environmental and homeostatic challenges. The re-establishment and maintenance of homeostasis entails the coordinated activation and control of neuroendocrine and autonomic stress systems. These collective stress responses are mediated by largely overlapping circuits in the limbic forebrain, the hypothalamus and the brainstem, so that the respective contributions of the neuroendocrine and autonomic systems are tuned in accordance with stressor modality and intensity. Limbic regions that are responsible for regulating stress responses intersect with circuits that are responsible for memory and reward, providing a means to tailor the stress response with respect to prior experience and anticipated outcomes.
Journal Article
Why do I bleed?
\"Want to know how arteries carry oxygen-rich blood throughout our bodies and what blood type means? Fun illustrations and entertaining text help give kids a clear understanding of the blood and circulatory system\"-- Provided by publisher.
Book
Causal effects of the early caregiving environment on development of stress response systems in children
Significance 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 rodent models support this possibility, results from human studies have been decidedly mixed. Using data from an experimental study examining whether random assignment to a caregiving environment alters development of the autonomic nervous system and hypothalamic–pituitary–adrenal axis in humans, we provide causal evidence for persistent effects of the early caregiving environment on stress response system functioning in humans with effects that differ markedly from those observed in rodent models. We also provide evidence of a sensitive period in human development during which the environment is particularly likely to alter stress response system development.
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.
Journal Article