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1.
J Biol Rhythms ; 37(3): 310-328, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35575430

RESUMO

Circadian rhythms are internal processes repeating approximately every 24 hours in living organisms. The dominant circadian pacemaker is synchronized to the environmental light-dark cycle. Other circadian pacemakers, which can have noncanonical circadian mechanisms, are revealed by arousing stimuli, such as scheduled feeding, palatable meals and running wheel access, or methamphetamine administration. Organisms also have ultradian rhythms, which have periods shorter than circadian rhythms. However, the biological mechanism, origin, and functional significance of ultradian rhythms are not well-elucidated. The dominant circadian rhythm often masks ultradian rhythms; therefore, we disabled the canonical circadian clock of mice by knocking out Per1/2/3 genes, where Per1 and Per2 are essential components of the mammalian light-sensitive circadian mechanism. Furthermore, we recorded wheel-running activity every minute under constant darkness for 272 days. We then investigated rhythmic components in the absence of external influences, applying unique multiscale time-resolved methods to analyze the oscillatory dynamics with time-varying frequencies. We found four rhythmic components with periods of ∼17 h, ∼8 h, ∼4 h, and ∼20 min. When the ∼17-h rhythm was prominent, the ∼8-h rhythm was of low amplitude. This phenomenon occurred periodically approximately every 2-3 weeks. We found that the ∼4-h and ∼20-min rhythms were harmonics of the ∼8-h rhythm. Coupling analysis of the ridge-extracted instantaneous frequencies revealed strong and stable phase coupling from the slower oscillations (∼17, ∼8, and ∼4 h) to the faster oscillations (∼20 min), and weak and less stable phase coupling in the reverse direction and between the slower oscillations. Together, this study elucidated the relationship between the oscillators in the absence of the canonical circadian clock, which is critical for understanding their functional significance. These studies are essential as disruption of circadian rhythms contributes to diseases, such as cancer and obesity, as well as mood disorders.


Assuntos
Relógios Circadianos , Ritmo Ultradiano , Animais , Ritmo Circadiano , Escuridão , Mamíferos , Camundongos , Fotoperíodo
2.
Chronobiol Int ; 39(4): 513-524, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983274

RESUMO

Circadian rhythms in core body temperature (CBT) have been widely studied, but fewer studies have explored higher-frequency (ultradian) rhythms in detail. We analyzed CBT recordings from young and middle-aged wild-type mice as well as from the Q175 model of Huntington's disease (HD), at sufficient temporal resolution to address the question of ultradian rhythms. We used model selection methods to show that the overall circadian pattern was better fit by a square wave than a sine wave. Then, using Fourier analysis of the CBT rhythms, we identified the spectral signature of an 8-hour oscillation that occurs in the night but not the day, an observation that can be confirmed by direct inspection of the rhythms. This diurnal amplitude modulation of the 8-hour rhythm was lost with aging as well as in the HD model. Thus, the impact of aging and disease is seen here in the loss of the ability to separate rhythms into a daytime phase and a nighttime phase. These findings raise the possibility that ultradian rhythms in CBT may be a useful biomarker for the pathology within the central nervous system.


Assuntos
Doença de Huntington , Ritmo Ultradiano , Animais , Ritmo Circadiano/fisiologia , Modelos Animais de Doenças , Camundongos
3.
Mol Cell Endocrinol ; 542: 111530, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34896241

RESUMO

Kisspeptin is vital for the regulation of both fertility and metabolism. Kisspeptin receptor (Kiss1r) knockout (KO) mice exhibit increased adiposity and reduced energy expenditure in adulthood. Kiss1r mRNA is expressed in brown adipose tissue (BAT) and Kiss1r KO mice exhibit reduced Ucp1 mRNA in BAT and impaired thermogenesis. We hypothesised that mice with diminished kisspeptin signalling would exhibit reduced core body temperature (Tc) and altered dynamics of circadian and ultradian rhythms of Tc. Tc was recorded every 15-min over 14-days in gonadectomised wild-type (WT), Kiss1r KO, and also Kiss1-Cre (95% reduction in Kiss1 transcription) mice. Female Kiss1r KOs had higher adiposity and lower Ucp1 mRNA in BAT than WTs. No change was detected in Kiss1-Cre mice. Mean Tc during the dark phase was lower in female Kiss1r KOs versus WTs, but not Kiss1-Cre mice. Female Kiss1r KOs had a lower mesor and amplitude of the circadian rhythm of Tc than did WTs. In WT mice, there were more episodic ultradian events (EUEs) of Tc during the dark phase than the light phase, but this measure was similar between dark and light phases in Kiss1r KO and Kiss1-Cre mice. The amplitude of EUEs was higher in the dark phase in female Kiss1r KO and male Kiss1-Cre mice. Given the lack of clear metabolic phenotype in Kiss1-Cre mice, 5% of Kiss1 transcription may be sufficient for proper metabolic control, as was shown for fertility. Moreover, the observed alterations in Tc suggest that kisspeptin has a role in circadian and ultradian rhythm-driven pathways.


Assuntos
Kisspeptinas , Ritmo Ultradiano , Animais , Temperatura Corporal , Feminino , Kisspeptinas/genética , Kisspeptinas/metabolismo , Masculino , Camundongos , Camundongos Knockout , Obesidade/metabolismo , Receptores de Kisspeptina-1
4.
PLoS Biol ; 19(12): e3001492, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34968386

RESUMO

Rhythmicity of biological processes can be elicited either in response to environmental cycles or driven by endogenous oscillators. In mammals, the circadian clock drives about 24-hour rhythms of multitude metabolic and physiological processes in anticipation to environmental daily oscillations. Also at the intersection of environment and metabolism is the protein kinase-AKT. It conveys extracellular signals, primarily feeding-related signals, to regulate various key cellular functions. Previous studies in mice identified rhythmicity in AKT activation (pAKT) with elevated levels in the fed state. However, it is still unknown whether rhythmic AKT activation can be driven through intrinsic mechanisms. Here, we inspected temporal changes in pAKT levels both in cultured cells and animal models. In cultured cells, pAKT levels showed circadian oscillations similar to those observed in livers of wild-type mice under free-running conditions. Unexpectedly, in livers of Per1,2-/- but not of Bmal1-/- mice we detected ultradian (about 16 hours) oscillations of pAKT levels. Importantly, the liver transcriptome of Per1,2-/- mice also showed ultradian rhythms, corresponding to pAKT rhythmicity and consisting of AKT-related genes and regulators. Overall, our findings reveal ultradian rhythms in liver gene expression and AKT phosphorylation that emerge in the absence of environmental rhythms and Per1,2-/- genes.


Assuntos
Regulação da Expressão Gênica/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ritmo Ultradiano/genética , Animais , Células Cultivadas , Relógios Circadianos/genética , Expressão Gênica/genética , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Fatores de Transcrição/metabolismo , Transcriptoma/genética
5.
Riv Psichiatr ; 56(6): 314-320, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34927626

RESUMO

We aimed at investigating the gender and/or ultradian pattern of serum levels of the Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF). Blood samples were collected at the 8.00, 13.00 and 20.00 hours of the day in healthy men and women, and the neurotrophins concentration was measured in the serum by ELISA. A further aim of the study was to evaluate whether or not the NGF/BDNF variations might be related to specific physiological or psychological traits as mood, feeling good and feeling rested, sexual desire and energy. Heart rate and blood pressure were also monitored at the same hours in each enrolled subject. The anxiety (STAI-T and STAI-S score) and sleeping quality were once evaluated in the morning too. We found that serum BDNF increases in men and decreases in women from morning to evening, while NGF shows a similar ultradian profile between men and women, but with higher concentrations in women. Both neurotrophins also show gender-related associations with psychophysiological variables. High NGF levels correlated with a high score for all the psychological variables in men, but with a low score in women. An inverse correlation was found between BDNF and energy and sexual desire in women, while no correlations were found in men. These data disclose that the condition of well-being (or activity/arousal status) is featured by an increasing NGF profile in men and a negative BDNF/NGF trend in women. The clinical relevance of the present data is discussed.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Fator de Crescimento Neural , Fatores Sexuais , Ritmo Ultradiano , Afeto , Ansiedade , Fator Neurotrófico Derivado do Encéfalo/sangue , Feminino , Humanos , Libido , Masculino , Fator de Crescimento Neural/sangue , Descanso
6.
Front Endocrinol (Lausanne) ; 12: 754522, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721302

RESUMO

Using preproghrelin-deficient mice (Ghrl-/-), we previously observed that preproghrelin modulates pulsatile growth hormone (GH) secretion in post-pubertal male mice. However, the role of ghrelin and its derived peptides in the regulation of growth parameters or feeding in females is unknown. We measured pulsatile GH secretion, growth, metabolic parameters and feeding behavior in adult Ghrl-/- and Ghrl+/+ male and female mice. We also assessed GH release from pituitary explants and hypothalamic growth hormone-releasing hormone (GHRH) expression and immunoreactivity. Body weight and body fat mass, linear growth, spontaneous food intake and food intake following a 48-h fast, GH pituitary contents and GH release from pituitary explants ex vivo, fasting glucose and glucose tolerance were not different among adult Ghrl-/- and Ghrl+/+ male or female mice. In vivo, pulsatile GH secretion was decreased, while approximate entropy, that quantified orderliness of secretion, was increased in adult Ghrl-/- females only, defining more irregular GH pattern. The number of neurons immunoreactive for GHRH visualized in the hypothalamic arcuate nucleus was increased in adult Ghrl-/- females, as compared to Ghrl+/+ females, whereas the expression of GHRH was not different amongst groups. Thus, these results point to sex-specific effects of preproghrelin gene deletion on pulsatile GH secretion, but not feeding, growth or metabolic parameters, in adult mice.


Assuntos
Grelina/fisiologia , Hormônio do Crescimento/metabolismo , Hipófise/metabolismo , Caracteres Sexuais , Ritmo Ultradiano , Animais , Núcleo Arqueado do Hipotálamo/citologia , Comportamento Alimentar , Feminino , Deleção de Genes , Masculino , Camundongos Endogâmicos C57BL
7.
Bull Exp Biol Med ; 172(1): 72-76, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34791558

RESUMO

The study examined the rhythmic oscillations of body temperature with the period ranging 100-400 min in three groups of laboratory mice maintained under persistent artificial illumination in Moscow and Ulyanovsk. The difference in the moments of sunrise or sunset in these towns is about 1 h. The greatest rhythmic oscillations of body temperature in examined mice had the periods of 100-400 min. The phase analysis of 100-200-min rhythms revealed their synchronicity with local but not universal time despite the mice had no photic signs indicating alternation of day and night. Of them, the most pronounced were the rhythms with the periods of 121, 143, 151, and 186 min. The present data suggest existence of an external environmental synchronizer of body temperature ultradian rhythms related to local solar time.


Assuntos
Relógios Biológicos/fisiologia , Temperatura Corporal/fisiologia , Iluminação/métodos , Ritmo Ultradiano/fisiologia , Animais , Ritmo Circadiano/fisiologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Masculino , Camundongos , Sono/fisiologia , Tempo
8.
Bull Exp Biol Med ; 172(1): 105-110, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34787780

RESUMO

The study examined association between oscillations of body temperature of laboratory Wistar rats maintained under constant illumination with the amplitude of fluctuations of secondary cosmic rays reported by neutron count rate provided by neutron monitors and geomagnetic undulations. In contrast to geomagnetic undulations, neutron count rate variations and body temperature oscillations in rats assessed by spectrum analysis of the corresponding step functions at 1-min intervals demonstrated almost permanent variations with the periods ranging from 100 to 400 min. Under conditions of constant illumination inducing changes in the period of circadian rhythm and predominance of the ultradian rhythms, an association between neutron count rate fluctuations and body temperature oscillations was observed perpetually during the day- and nighttime.


Assuntos
Temperatura Corporal/fisiologia , Radiação Cósmica/efeitos adversos , Nêutrons/efeitos adversos , Ritmo Ultradiano/fisiologia , Animais , Ritmo Circadiano , Iluminação , Masculino , Ratos , Ratos Wistar
9.
Bull Exp Biol Med ; 171(6): 783-788, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34709514

RESUMO

The study examined the effect of passive magnetic shielding on the magnitude of rhythmic oscillations of body temperature (BT) with 4-20 min periods in mice and their correlation with similar oscillations in unshielded control group. A magnetic permalloy screen that 35-fold attenuates the total geomagnetic field and decreased the undulations of magnetic field with the periods of few minutes by 5 times, produced no effect on the mean amplitude of BT oscillations within the same period range, their spectral power, and the cross-spectral density of examined rhythms in comparison with the control (unshielded) mice. Thus, either the mice possess a very sensitive magnetic sensory system or there exists an external non-magnetic factor affecting rhythmicity of BT. The study advanced intensity of thermal neutron radiation near the Earth's surface known to reflect the flow of accelerated particles generated by the secondary cosmic rays as the external factor, which strongly correlates with BT rhythms revealed by cross-spectrum analysis.


Assuntos
Temperatura Corporal/fisiologia , Ritmo Ultradiano/fisiologia , Animais , Campos Eletromagnéticos , Campos Magnéticos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteção Radiológica
10.
Dokl Biol Sci ; 499(1): 93-96, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34462833

RESUMO

Previously, in male Greenfinch, we have described ultradian rhythms of body temperature with periods of 3-6, 8-10, 12-20, and 40-60 min. There are individual variations in this rhythmicity. Rhythms with a period of 3-7 min are more characteristic of some males but not for the others. These males had small values of the ratio of the harmonic spectral density in the range of 12-20 min to the harmonic spectral density in the range of 3-7 min. In this study, we hypothesized that ultradian rhythmicity of body temperature fluctuations is related to the nervous system activity in general and to temperament in particular. We have conducted two sets of experiments for estimating the aggression level (n = 12 males) and reaction to novelty (n = 17). Individuals with predominant rhythms with a period of 3-7 min are less aggressive and more slowly adapt to new conditions. Thus, the ultradian body temperature rhythmicity in Greenfinch is related to their behavioral features and temperament.


Assuntos
Ritmo Ultradiano , Animais , Aves , Temperatura Corporal , Ritmo Circadiano , Humanos , Masculino , Temperamento
11.
Bull Exp Biol Med ; 171(3): 388-392, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34297296

RESUMO

The study examined the changes in intraperitoneal body temperature of laboratory mice, Jungar hamsters, European greenfinch Chloris chloris, and starlings. In a few minutes range, these changes significantly correlated not only between the animals of the same species, but also between the different classes such as birds and mammals, which were isolated from each other and maintained under different illumination regimen. This phenomenon indicates some external influence(s) on the central mechanisms of the thermal control system not related to illumination regiment. In 80% cases, the phases of most pronounced rhythms of body temperature oscillating with the periods of 8-9 and 12-13 min coincided with those of geomagnetic field within the accuracy of ±1 min. However, the amplitude of body temperature oscillations did not depend on the amplitude of geomagnetic field (GMF) oscillations. Synchronicity of the changes in body temperature and GMF was observed at the amplitude of GMF oscillation of 0.4 nT, which is extremely low value. In contrast, there was no reaction of body temperature to greater (6-10 nT) but irregular and abrupt perturbations of GMF.


Assuntos
Regulação da Temperatura Corporal/fisiologia , Temperatura Corporal/fisiologia , Tentilhões/fisiologia , Estorninhos/fisiologia , Ritmo Ultradiano/fisiologia , Animais , Cricetinae , Luz , Campos Magnéticos , Masculino , Camundongos , Especificidade da Espécie
12.
Comput Biol Med ; 135: 104580, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34166879

RESUMO

The hypothalamic-pituitary-adrenal (HPA) axis is a biological system in the human body that plays an important role in controlling stress and regulating various physiological elements, including the immune system, emotions, and moods in tense situations. Over the past two decades, several ordinary or delay differential equations models of the HPA axis have been proposed. In the majority of studies presented so far, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol are among the main variables employed to build the HPA axis models. In the present study, based on a previously introduced hypothesis which asserts that ultradian rhythms in the HPA axis are produced by the pituitary-adrenal network alone and these rhythms can endure in the absence of CRH secretion, a simple two-dimensional delayed dynamical model of the HPA axis based on only ACTH and cortisol is introduced. The model is shown to be able to capture the ultradian (low frequency) rhythms of ACTH and cortisol released into the bloodstream. By mathematical analysis of the model using the Hopf bifurcation theorem, it is also demonstrated how oscillating solutions can emerge. Also, the model employs physiologically reasonable parameter values to exhibit how in the absence of CRH secretion, a simple model of the pituitary-adrenal interaction can be used to produce ultradian rhythms of both cortisol and ACTH hormones.


Assuntos
Sistema Hipófise-Suprarrenal , Ritmo Ultradiano , Hormônio Adrenocorticotrópico/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Humanos , Hidrocortisona , Sistema Hipotálamo-Hipofisário
13.
Mol Syst Biol ; 17(5): e9902, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34031978

RESUMO

Ultradian oscillations of HES Transcription Factors (TFs) at the single-cell level enable cell state transitions. However, the tissue-level organisation of HES5 dynamics in neurogenesis is unknown. Here, we analyse the expression of HES5 ex vivo in the developing mouse ventral spinal cord and identify microclusters of 4-6 cells with positively correlated HES5 level and ultradian dynamics. These microclusters are spatially periodic along the dorsoventral axis and temporally dynamic, alternating between high and low expression with a supra-ultradian persistence time. We show that Notch signalling is required for temporal dynamics but not the spatial periodicity of HES5. Few Neurogenin 2 cells are observed per cluster, irrespective of high or low state, suggesting that the microcluster organisation of HES5 enables the stable selection of differentiating cells. Computational modelling predicts that different cell coupling strengths underlie the HES5 spatial patterns and rate of differentiation, which is consistent with comparison between the motoneuron and interneuron progenitor domains. Our work shows a previously unrecognised spatiotemporal organisation of neurogenesis, emergent at the tissue level from the synthesis of single-cell dynamics.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Repressoras/metabolismo , Análise de Célula Única/métodos , Medula Espinal/crescimento & desenvolvimento , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Comunicação Celular , Biologia Computacional , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Introdução de Genes , Camundongos , Neurogênese , Receptores Notch/metabolismo , Proteínas Repressoras/genética , Transdução de Sinais , Análise Espaço-Temporal , Medula Espinal/metabolismo , Ritmo Ultradiano
14.
J Biol Rhythms ; 36(4): 359-368, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33878968

RESUMO

Voles are small herbivorous rodents that can display both circadian activity rhythms (~24-h periodicity) and ultradian activity rhythms (~1- to 6-h periodicity). Ultradian rhythms are observed on an individual level, but also in synchronized populations. Ultradian rhythm period has been suggested to be influenced by energy balance, but the underlying mechanisms of ultradian rhythmicity are poorly understood. We manipulated energy balance by implementing the "work-for-food" paradigm, in which small rodents are exposed to increasing levels of food scarcity at different ambient temperatures in the laboratory. Photoperiodical spring-programmed voles on high workload changed their nocturnal circadian activity and body temperature rhythm to ultradian patterns, indicating that a negative energy balance induces ultradian rhythmicity. This interpretation was confirmed by the observation that ultradian patterns arose earlier at low temperatures. Interestingly, a positive relationship between ultradian period length and workload was observed in tundra voles. Spectral analysis revealed that the power of ultradian rhythmicity increased at high workload, whereas the circadian component of running wheel activity decreased. This study shows that the balance between circadian and ultradian rhythmicity is determined by energy balance, confirming flexible circadian and ultradian rhythms in females and males of 2 different vole species: the common vole (Microtus arvalis) and the tundra vole (Microtus oeconomus).


Assuntos
Arvicolinae , Ritmo Ultradiano , Ciclos de Atividade , Animais , Ritmo Circadiano , Feminino , Masculino , Estações do Ano
15.
Nat Chem Biol ; 17(4): 373-374, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33686295
16.
Nat Chem Biol ; 17(4): 477-484, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33574615

RESUMO

Redox cycles have been reported in ultradian, circadian and cell cycle-synchronized systems. Redox cycles persist in the absence of transcription and cyclin-CDK activity, indicating that cells harbor multiple coupled oscillators. Nonetheless, the causal relationships and molecular mechanisms by which redox cycles are embedded within ultradian, circadian or cell division cycles remain largely elusive. Yeast harbor an ultradian oscillator, the yeast metabolic cycle (YMC), which comprises metabolic/redox cycles, transcriptional cycles and synchronized cell division. Here, we reveal the existence of robust cycling of H2O2 and peroxiredoxin oxidation during the YMC and show that peroxiredoxin inactivation disrupts metabolic cycling and abolishes coupling with cell division. We find that thiol-disulfide oxidants and reductants predictably modulate the switching between different YMC metabolic states, which in turn predictably perturbs cell cycle entry and exit. We propose that oscillatory H2O2-dependent protein thiol oxidation is a key regulator of metabolic cycling and its coordination with cell division.


Assuntos
Divisão Celular/fisiologia , Peroxirredoxinas/metabolismo , Ritmo Ultradiano/fisiologia , Ciclo Celular/fisiologia , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Modelos Biológicos , Oxirredução , Peroxirredoxinas/fisiologia , Fosforilação , Saccharomyces/genética , Saccharomyces/metabolismo , Leveduras/metabolismo
17.
Cell Mol Life Sci ; 78(7): 3127-3140, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33449146

RESUMO

Biological oscillations often cycle at different harmonics of the 24-h circadian rhythms, a phenomenon we coined "Musica Universalis" in 2017. Like the circadian rhythm, the 12-h oscillation is also evolutionarily conserved, robust, and has recently gained new traction in the field of chronobiology. Originally thought to be regulated by the circadian clock and/or environmental cues, recent new evidences support the notion that the majority of 12-h rhythms are regulated by a distinct and cell-autonomous pacemaker that includes the unfolded protein response (UPR) transcription factor spliced form of XBP1 (XBP1s). 12-h cycle of XBP1s level in turn transcriptionally generates robust 12-h rhythms of gene expression enriched in the central dogma information flow (CEDIF) pathway. Given the regulatory and functional separation of the 12-h and circadian clocks, in this review, we will focus our attention on the mammalian 12-h pacemaker, and discuss our current understanding of its prevalence, evolutionary origin, regulation, and functional roles in both physiological and pathological processes.


Assuntos
Fenômenos Fisiológicos Celulares , Regulação da Expressão Gênica , Ritmo Ultradiano , Resposta a Proteínas não Dobradas , Animais , Homeostase , Humanos , Mamíferos
18.
Sci Rep ; 11(1): 1290, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446678

RESUMO

We have discovered a new 4 h ultradian rhythm that occurs during the interphase of the cell cycle in a wide range of individual mammalian cells, including both primary and transformed cells. The rhythm was detected by holographic lens-free microscopy that follows the histories of the dry mass of thousands of single live cells simultaneously, each at a resolution of five minutes. It was vital that the rhythm was observed in inherently heterogeneous cell populations, thus eliminating synchronization and labeling bias. The rhythm is independent of circadian rhythm, and is temperature-compensated. We show that the amplitude of the fundamental frequency provides a way to quantify the effects of, chemical reagents on cells, thus shedding light on its mechanism. The rhythm is suppressed by proteostasis disruptors and is detected only in proliferating cells, suggesting that it represents a massive degradation and re-synthesis of protein every 4 h in growing cells.


Assuntos
Ritmo Ultradiano , Proliferação de Células , Células HeLa , Holografia , Humanos , Interfase , Análise de Célula Única , Temperatura
19.
Psychoneuroendocrinology ; 124: 105096, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33296841

RESUMO

Adrenal glucocorticoid secretion into the systematic circulation is characterised by a complex rhythm, composed of the diurnal variation, formed by changes in pulse amplitude of an underlying ultradian rhythm of short duration hormonal pulses. To elucidate the potential neurobiological significance of glucocorticoid pulsatility in man, we have conducted a randomised, double-blind, placebo-controlled, three-way crossover clinical trial on 15 healthy volunteers, investigating the impact of different glucocorticoid rhythms on measures of mood and neural activity under resting conditions by recruiting functional neuroimaging, computerised behavioural tests and ecological momentary assessments. Endogenous glucocorticoid biosynthesis was pharmacologically suppressed, and plasma levels of corticosteroid restored by hydrocortisone replacement in three different regimes, either mimicking the normal ultradian and circadian profile of the hormone, or retaining the normal circadian but abolishing the ultradian rhythm of the hormone, or by our current best oral replacement regime which results in a suboptimal circadian and ultradian rhythm. Our results indicate that changes in the temporal mode of glucocorticoid replacement impact (i) the morning levels of self-perceived vigour, fatigue and concentration, (ii) the diurnal pattern of mood variation, (iii) the within-network functional connectivity of various large-scale resting state networks of the human brain, (iv) the functional connectivity of the default-mode, salience and executive control networks with glucocorticoid-sensitive nodes of the corticolimbic system, and (v) the functional relationship between mood variation and underlying neural networks. The findings indicate that the pattern of the ultradian glucocorticoid rhythm could affect cognitive psychophysiology under non-stressful conditions and opens new pathways for our understanding on the neuropsychological effects of cortisol pulsatility with relevance to the goal of optimising glucocorticoid replacement strategies.


Assuntos
Glucocorticoides , Ritmo Ultradiano , Encéfalo , Ritmo Circadiano , Humanos , Hidrocortisona
20.
Clin Endocrinol (Oxf) ; 94(4): 636-644, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33369760

RESUMO

OBJECTIVE: To determine whether early (4-8h) post-operative ACTH after trans-sphenoidal surgery (TSS) predicts long-term hypothalamic-pituitary-adrenal (HPA) axis function and to investigate early morning day 1 ACTH/cortisol variability using rapid sampling. DESIGN: Prospective observational study. METHODS: Participants undergoing TSS were included; those treated with glucocorticoids pre-operatively received 100 mg intravenous hydrocortisone on anaesthetic induction. ACTH and cortisol were measured post-operatively at + 4h and + 8h after induction and on day 1 every 10 minutes between 0700h and 0900h. PRIMARY OUTCOME: glucocorticoid requirement at 6 months. RESULTS: Nineteen participants (10F, 9M): 6/19 (32%) were treated with replacement glucocorticoids pre-operatively; 4 had ceased by 6 weeks post-operatively. One patient developed new hypopituitarism post-operatively meaning 3/19 (16%) required glucocorticoids at 6 months. Post-operative + 4h ACTH < 14.3 pmol/L (65 ng/L) predicted secondary adrenal insufficiency (SAI) (sensitivity 100%, specificity 75%), whilst no participant with a post-operative + 4h ACTH ≥ 14.3 pmol/L (65 ng/L) required glucocorticoids at 6 months. Day 1 ACTH and cortisol showed a significant circadian fall between 0700h-0900h; ACTH 4.2 pmol/L (IQR 2.9-5.9) to 3.7 pmol/L (IQR 2.9-5.1) P = .006 and cortisol 549 nmol/L (IQR 337-618) to 439 nmol/L (IQR 315-606) P < .001, with clinically insignificant ultradian secretory pulses. CONCLUSIONS: No participant with a post-operative + 4h ACTH ≥ 14.3 pmol/L (65 ng/L) required glucocorticoids at 6 months; however, given only 3/19 participants had the primary outcome of interest, this must be confirmed in a larger cohort. The timing of a day 1 morning cortisol between 0700h and 0900h influences the accuracy of a single cut-off to diagnose SAI after pituitary surgery.


Assuntos
Hormônio Adrenocorticotrópico , Hidrocortisona , Hipófise , Ritmo Ultradiano , Glucocorticoides , Humanos , Sistema Hipotálamo-Hipofisário , Procedimentos Neurocirúrgicos , Hipófise/cirurgia , Sistema Hipófise-Suprarrenal
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