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Endocrine Reviews Jun 2020The past decade has seen several critical advances in our understanding of hypothalamic-pituitary-adrenal (HPA) axis regulation. Homeostatic physiological circuits need... (Review)
Review
The past decade has seen several critical advances in our understanding of hypothalamic-pituitary-adrenal (HPA) axis regulation. Homeostatic physiological circuits need to integrate multiple internal and external stimuli and provide a dynamic output appropriate for the response parameters of their target tissues. The HPA axis is an example of such a homeostatic system. Recent studies have shown that circadian rhythmicity of the major output of this system-the adrenal glucocorticoid hormones corticosterone in rodent and predominately cortisol in man-comprises varying amplitude pulses that exist due to a subhypothalamic pulse generator. Oscillating endogenous glucocorticoid signals interact with regulatory systems within individual parts of the axis including the adrenal gland itself, where a regulatory network can further modify the pulsatile release of hormone. The HPA axis output is in the form of a dynamic oscillating glucocorticoid signal that needs to be decoded at the cellular level. If the pulsatile signal is abolished by the administration of a long-acting synthetic glucocorticoid, the resulting disruption in physiological regulation has the potential to negatively impact many glucocorticoid-dependent bodily systems. Even subtle alterations to the dynamics of the system, during chronic stress or certain disease states, can potentially result in changes in functional output of multiple cells and tissues throughout the body, altering metabolic processes, behavior, affective state, and cognitive function in susceptible individuals. The recent development of a novel chronotherapy, which can deliver both circadian and ultradian patterns, provides great promise for patients on glucocorticoid treatment.
Topics: Adrenocorticotropic Hormone; Animals; Bodily Secretions; Circadian Rhythm; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Secretory Pathway
PubMed: 32060528
DOI: 10.1210/endrev/bnaa002 -
Molecular and Cellular Endocrinology May 2020Many physiological systems rely on hormones to communicate and time cellular and tissue-level functions. Most endocrine systems are dynamic and governed by complex...
Many physiological systems rely on hormones to communicate and time cellular and tissue-level functions. Most endocrine systems are dynamic and governed by complex regulatory systems and/or feedback mechanisms to generate precise patterns and modes of hormone release in order to optimize control of physiological and cellular processes. This Special Issue focuses on hormone release patterns (ultradian, infradian, pulsatile, circadian), with a special emphasis on the hypothalamic-pituitary axis as well as melatonin release, and how these patterns of hormone secretion change during life stages and disease.
Topics: Animals; Circadian Rhythm; Hormones; Humans; Mammals; Melatonin; Secretory Pathway
PubMed: 32119896
DOI: 10.1016/j.mce.2020.110781 -
Trends in Neurosciences Jan 2024Among the central goals of stress neurobiology research is to understand the mechanisms by which stressors change neural circuit function to precipitate or exacerbate... (Review)
Review
Among the central goals of stress neurobiology research is to understand the mechanisms by which stressors change neural circuit function to precipitate or exacerbate psychiatric symptoms. Yet despite decades of effort, psychiatric medications that target the biological substrates of the stress response are largely lacking. We propose that the clinical advancement of stress response-based therapeutics for psychiatric disorders may be hindered by 'hidden variables' in stress research, including considerations of behavioral study design (stressors and outcome measures), individual variability, sex differences, and the interaction of the body's stress hormone system with endogenous circadian and ultradian rhythms. We highlight key issues and suggest ways forward in stress neurobiology research that may improve the ability to assess stress mechanisms and translate preclinical findings.
Topics: Humans; Male; Female; Circadian Rhythm; Neurobiology; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Sex Characteristics; Stress, Physiological; Stress, Psychological
PubMed: 37985263
DOI: 10.1016/j.tins.2023.10.006 -
The Journal of Neuroscience : the... Sep 2023The impedance is a fundamental electrical property of brain tissue, playing a crucial role in shaping the characteristics of local field potentials, the extent of...
The impedance is a fundamental electrical property of brain tissue, playing a crucial role in shaping the characteristics of local field potentials, the extent of ephaptic coupling, and the volume of tissue activated by externally applied electrical brain stimulation. We tracked brain impedance, sleep-wake behavioral state, and epileptiform activity in five people with epilepsy living in their natural environment using an investigational device. The study identified impedance oscillations that span hours to weeks in the amygdala, hippocampus, and anterior nucleus thalamus. The impedance in these limbic brain regions exhibit multiscale cycles with ultradian (∼1.5-1.7 h), circadian (∼21.6-26.4 h), and infradian (∼20-33 d) periods. The ultradian and circadian period cycles are driven by sleep-wake state transitions between wakefulness, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Limbic brain tissue impedance reaches a minimum value in NREM sleep, intermediate values in REM sleep, and rises through the day during wakefulness, reaching a maximum in the early evening before sleep onset. Infradian (∼20-33 d) impedance cycles were not associated with a distinct behavioral correlate. Brain tissue impedance is known to strongly depend on the extracellular space (ECS) volume, and the findings reported here are consistent with sleep-wake-dependent ECS volume changes recently observed in the rodent cortex related to the brain glymphatic system. We hypothesize that human limbic brain ECS changes during sleep-wake state transitions underlie the observed multiscale impedance cycles. Impedance is a simple electrophysiological biomarker that could prove useful for tracking ECS dynamics in human health, disease, and therapy. The electrical impedance in limbic brain structures (amygdala, hippocampus, anterior nucleus thalamus) is shown to exhibit oscillations over multiple timescales. We observe that impedance oscillations with ultradian and circadian periodicities are associated with transitions between wakefulness, NREM, and REM sleep states. There are also impedance oscillations spanning multiple weeks that do not have a clear behavioral correlate and whose origin remains unclear. These multiscale impedance oscillations will have an impact on extracellular ionic currents that give rise to local field potentials, ephaptic coupling, and the tissue activated by electrical brain stimulation. The approach for measuring tissue impedance using perturbational electrical currents is an established engineering technique that may be useful for tracking ECS volume.
Topics: Humans; Electric Impedance; Sleep; Sleep, REM; Brain; Wakefulness; Hippocampus
PubMed: 37620157
DOI: 10.1523/JNEUROSCI.0241-23.2023 -
Clinical Endocrinology Sep 2019There is an increased mortality associated with adrenal insufficiency despite glucocorticoid replacement therapy with a standardized mortality ratio greater than two.... (Review)
Review
There is an increased mortality associated with adrenal insufficiency despite glucocorticoid replacement therapy with a standardized mortality ratio greater than two. The cause of the increased mortality is yet to be definitively elucidated, but may be due to excess steroid exposure, or replacement regimens that are uncoupled from the normal physiological cortisol profile. Cortisol secretion follows an ultradian pattern which is not possible to reproduce using oral replacement. With the advent of new pumps, it is now possible to mimic the pulsatility of the adrenal glands. While the cognitive and emotional benefits of reproducing the ultradian rhythm are known, the presence of long-term benefits is not yet clear. There is a dearth of evidence and high-quality studies to underline our current understanding of the pathophysiology of adrenal insufficiency and replacement therapy. There is a particular lack of research comparing objective outcomes between patients receiving hydrocortisone replacement (either standard therapy or new sustained release preparations), prednisolone replacement and ultradian pumps. Direct comparative studies are now warranted to understand the optimal approach.
Topics: Adrenal Insufficiency; Glucocorticoids; Hormone Replacement Therapy; Humans; Ultradian Rhythm
PubMed: 31017681
DOI: 10.1111/cen.13999 -
Journal of Neurology Jan 2022The etiology of transient global amnesia (TGA) is still a matter of debate. Based, among others, on the observation of a close temporal relation between certain events...
INTRODUCTION
The etiology of transient global amnesia (TGA) is still a matter of debate. Based, among others, on the observation of a close temporal relation between certain events and subsequent TGA episodes, recent proposals discuss the relevance of stress-associated processes impacting on hippocampal functioning. Circadian, infra- and ultradian rhythmicity has been found to play a relevant role in the multifactorial pathomechanisms of various disorders but has not been thoroughly studied in TGA.
METHODS
Data of patients with a final diagnosis of TGA were collected in Mannheim, Germany (06/1999-01/2018, n = 404), and in the Kansai district, Japan (04/2006-03/2018, n = 261). Chronological patterns of TGA occurrence were determined.
RESULTS
Significant circadian rhythmicity of TGA occurrence with bimodal peaks (mid-morning, late afternoon) was found for the entire population (p = 0.002) and for either sub-cohort (Mannheim: p = 0.003, Kansai: p = 0.007). This finding was confirmed for either sex (women: p = 0.004, men: p = 0.004) and different age groups (< 65 years: p = 0.0009, ≥ 65 years: p = 0.003). There was no variation according to day of the week, month or season, but the proportion of patients with a weekday episode was significantly higher in the Mannheim cohort (p = 0.002).
DISCUSSION
We identified a robust circadian rhythm in TGA occurrence which remarkably applied to either of the two study sites located on different continents and which was independent of sex and age. In light of abundant evidence of circadian rhythmicity of both, components of the human stress response system and memory, chronobiological analyses may provide an opportunity to further uncover the mechanisms underlying TGA.
Topics: Aged; Amnesia; Amnesia, Transient Global; Cohort Studies; Female; Germany; Hippocampus; Humans; Japan; Male
PubMed: 34104990
DOI: 10.1007/s00415-021-10639-x -
Physiology (Bethesda, Md.) Sep 2022The mammalian liver must cope with various metabolic and physiological changes that normally recur every day and result primarily from rest-activity and fasting-feeding... (Review)
Review
The mammalian liver must cope with various metabolic and physiological changes that normally recur every day and result primarily from rest-activity and fasting-feeding cycles. In this article, I present evidence supporting a temporal compartmentalization of rhythmic hepatic metabolic processes into four main clusters: regulation of energy homeostasis, maintenance of information integrity, immune response, and genetic information flow. I further review literatures and discuss how both the circadian and the newly discovered 12-h ultradian clock work together to regulate these four temporally separated processes in mouse liver, which, interestingly, is largely uncoupled from the liver zonation regulation.
Topics: Animals; Circadian Clocks; Circadian Rhythm; Fasting; Homeostasis; Liver; Logic; Mammals; Mice
PubMed: 35658626
DOI: 10.1152/physiol.00003.2022 -
Proceedings of the National Academy of... Nov 2022Ultradian rhythms in metabolism and physiology have been described previously in mammals. However, the underlying mechanisms for these rhythms are still elusive. Here,...
Ultradian rhythms in metabolism and physiology have been described previously in mammals. However, the underlying mechanisms for these rhythms are still elusive. Here, we report the discovery of temperature-sensitive ultradian rhythms in mammalian fibroblasts that are independent of both the cell cycle and the circadian clock. The period in each culture is stable over time but varies in different cultures (ranging from 3 to 24 h). We show that transient, single-cell metabolic pulses are synchronized into stable ultradian rhythms across contacting cells in culture by gap junction-mediated coupling. Coordinated rhythms are also apparent for other metabolic and physiological measures, including plasma membrane potential (Δψ), intracellular glutamine, α-ketoglutarate, intracellular adenosine triphosphate (ATP), cytosolic pH, and intracellular calcium. Moreover, these ultradian rhythms require extracellular glutamine, several different ion channels, and the suppression of mitochondrial ATP synthase by α-ketoglutarate, which provides a key feedback mechanism. We hypothesize that cellular coupling and metabolic feedback can be used by cells to balance energy demands for survival.
Topics: Animals; Ultradian Rhythm; Ketoglutaric Acids; Glutamine; Circadian Clocks; Cell Cycle; Circadian Rhythm; Mammals
PubMed: 36322771
DOI: 10.1073/pnas.2211142119 -
Frontiers in Integrative Neuroscience 2022Circadian systems are composed of multiple oscillatory elements that contain both circadian and ultradian oscillations. The relationships between these components...
Circadian systems are composed of multiple oscillatory elements that contain both circadian and ultradian oscillations. The relationships between these components maintain a stable temporal function in organisms. They provide a suitable phase to recurrent environmental changes and ensure a suitable temporal sequence of their own functions. Therefore, it is necessary to identify these interactions. Because a circadian rhythm of activity can be recorded in each crayfish cheliped, this paired organ system was used to address the possibility that two quasi-autonomous oscillators exhibiting both circadian and ultradian oscillations underlie these rhythms. The presence of both oscillations was found, both under entrainment and under freerunning. The following features of interactions between these circadian and ultradian oscillations were also observed: (a) circadian modal periods could be a feature of circadian oscillations under entrainment and freerunning; (b) the average period of the rhythm is a function of the proportions between the circadian and ultradian oscillations; (c) the release of both populations of oscillations of Zeitgeber effect results in the maintenance or an increase in their number and frequency under freerunning conditions. These circadian rhythms of activity can be described as mixed probability distributions containing circadian oscillations, individual ultradian oscillations, and ultradian oscillations of Gaussian components. Relationships among these elements can be structured in one of the following six probability distributions: Inverse Gaussian, gamma, Birnbaum-Saunders, Weibull, smallest extreme value, or Laplace. It should be noted that at one end of this order, the inverse Gaussian distribution most often fits the freerunning rhythm segments and at the other end, the Laplace distribution fits only the segments under entrainment. The possible relationships between the circadian and ultradian oscillations of crayfish motor activity rhythms and between the probability distributions of their periodograms are discussed. Also listed are some oscillators that could interact with cheliped rhythms.
PubMed: 36339967
DOI: 10.3389/fnint.2022.876137 -
Journal of Biological Rhythms Feb 2022Work in recent years has provided strong evidence for the modulation of memory function and neuroplasticity mechanisms across circadian (daily), ultradian... (Review)
Review
Work in recent years has provided strong evidence for the modulation of memory function and neuroplasticity mechanisms across circadian (daily), ultradian (shorter-than-daily), and infradian (longer-than-daily) timescales. Despite rapid progress, however, the field has yet to adopt a general framework to describe the overarching role of biological rhythms in memory. To this end, Iyer and colleagues introduced the term iterative metaplasticity, which they define as the "gating of receptivity to subsequent signals that repeats on a cyclic timebase." The central concept is that the cyclic regulation of molecules involved in neuroplasticity may produce cycles in neuroplastic capacity-that is, the ability of neural cells to undergo activity-dependent change. Although Iyer and colleagues focus on the circadian timescale, we think their framework may be useful for understanding how biological rhythms influence memory more broadly. In this review, we provide examples and terminology to explain how the idea of iterative metaplasticity can be readily applied across circadian, ultradian, and infradian timescales. We suggest that iterative metaplasticity may not only support the temporal niching of neuroplasticity processes but also serve an essential role in the maintenance of memory function.
Topics: Circadian Rhythm; Infradian Rhythm; Neuronal Plasticity
PubMed: 34781753
DOI: 10.1177/07487304211058256