Circadian clocks of the kidney: function, mechanism, and regulation

Physiological Reviews, Год журнала: 2022, Номер 102(4), С. 1669 - 1701

Опубликована: Май 16, 2022

An intrinsic cellular circadian clock is located in nearly every cell of the body. The peripheral clocks within cells kidney contribute to regulation a variety renal processes. In this review, we summarize what currently known regarding function, mechanism, and clocks. Additionally, effect extrarenal physiological processes, such as endocrine neuronal signals, on function also reviewed. Circadian rhythms are an integral part physiology, underscoring importance considering time day key biological variable. field physiology tremendous relevance, but with limited mechanistic information area need extensive investigation.

Язык: Английский

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Inputs and Outputs of the Mammalian Circadian Clock

Biology, Год журнала: 2023, Номер 12(4), С. 508 - 508

Опубликована: Март 28, 2023

Circadian rhythms in mammals are coordinated by the central circadian pacemaker, suprachiasmatic nucleus (SCN). Light and other environmental inputs change timing of SCN neural network oscillator, which, turn, sends output signals that entrain daily behavioral physiological rhythms. While much is known about molecular, neuronal, properties itself, circuits linking outside world to rhythmic outputs understudied. In this article, we review our current understanding synaptic non-synaptic onto from SCN. We propose a more complete description connectivity needed better explain how nearly all behaviors processes generated determine how, mechanistically, these disrupted disease or lifestyle.

Язык: Английский

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Seasonal changes in day length induce multisynaptic neurotransmitter switching to regulate hypothalamic network activity and behavior

Science Advances, Год журнала: 2022, Номер 8(35)

Опубликована: Сен. 2, 2022

Seasonal changes in day length (photoperiod) affect numerous physiological functions. The suprachiasmatic nucleus (SCN)–paraventricular (PVN) axis plays a key role processing photoperiod-related information. variations SCN and PVN neurotransmitter expression have been observed humans animal models. However, the molecular mechanisms by which SCN-PVN network responds to altered photoperiod is unknown. Here, we show mice that neuromedin S (NMS) vasoactive intestinal polypeptide (VIP) neurons display photoperiod-induced plasticity. In vivo recording of calcium dynamics revealed NMS alter activity response winter-like photoperiod. Chronic manipulation sufficient induce switching affects locomotor activity. Our findings reveal previously unidentified adaptations seasonality for adjusting hypothalamic function via coordinated multisynaptic affecting behavior.

Язык: Английский

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Potentials of Neuropeptides as Therapeutic Agents for Neurological Diseases

Biomedicines, Год журнала: 2022, Номер 10(2), С. 343 - 343

Опубликована: Фев. 1, 2022

Despite recent leaps in modern medicine, progress the treatment of neurological diseases remains slow. The near impermeable blood-brain barrier (BBB) that prevents entry therapeutics into brain, and complexity processes, limits specificity potential therapeutics. Moreover, a lack etiological understanding irreversible nature conditions have resulted low tolerability high failure rates towards existing small molecule-based treatments. Neuropeptides, which are proteinaceous molecules produced by body, either nervous system or peripheral organs, modulate function. Although peptide-based originated from metabolic 1920s, adoption development peptide drugs for relatively recent. In this review, we examine natural roles neuropeptides modulation function disorders. Furthermore, highlight these filling gaps current

Язык: Английский

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Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep

Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(34)

Опубликована: Авг. 15, 2022

The metronome-like circadian regulation of sleep timing must still adapt to an uncertain environment. Recent studies in Drosophila indicate that neuromodulation not only plays a key role clock neuron synchronization but also affects interactions between the network and brain centers. We show here targets neuromodulators, G Protein Coupled Receptors (GPCRs), are highly enriched fly network. Single-cell sequencing indicates they differentially expressed contribute identity. generated comprehensive guide library mutagenize individual GPCRs specific neurons verified strategy by introducing targeted approach. Combined with behavioral screen, mutagenesis revealed dopamine identifying two receptors subpopulation gate sleep.

Язык: Английский

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Disturbances of Hormonal Circadian Rhythms by Light Pollution

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(8), С. 7255 - 7255

Опубликована: Апрель 14, 2023

The circadian rhythms evolved to anticipate and cope with cyclic changes in environmental conditions. This adaptive function is currently compromised by increasing levels of artificial light at night (ALAN), which can represent a risk for the development diseases civilisation. causal links are not completely understood, this featured review focuses on chronodisruption neuroendocrine control physiology behaviour dim ALAN. published data indicate that low ALAN (2–5 lux) attenuate molecular mechanisms generating central oscillator, eliminate rhythmic dominant hormonal signals, such as melatonin, testosterone vasopressin, interfere rhythm glucocorticoid corticosterone rodents. These associated disturbed daily pattern metabolic behavioural activity food water intake. require identification pathways mediating possible negative consequences health design effective mitigation strategies or minimise effects pollution.

Язык: Английский

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SIK3–HDAC4 in the suprachiasmatic nucleus regulates the timing of arousal at the dark onset and circadian period in mice

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(11)

Опубликована: Март 6, 2023

Mammals exhibit circadian cycles of sleep and wakefulness under the control suprachiasmatic nucleus (SCN), such as strong arousal phase-locked to beginning dark phase in laboratory mice. Here, we demonstrate that salt-inducible kinase 3 (SIK3) deficiency gamma-aminobutyric acid (GABA)-ergic neurons or neuromedin S (NMS)-producing delayed peak lengthened behavioral cycle both 12-h light:12-h condition (LD) constant (DD) without changing daily amounts. In contrast, induction a gain-of-function mutant allele Sik3 GABAergic exhibited advanced activity onset shorter period. Loss SIK3 arginine vasopressin (AVP)-producing cycle, but was similar Heterozygous histone deacetylase (HDAC) 4, substrate, shortened whereas mice with HDAC4 S245A, which is resistant phosphorylation by SIK3, phase. Phase-delayed core clock gene expressions were detected liver lacking neurons. These results suggest SIK3-HDAC4 pathway regulates period length timing through NMS-positive SCN.

Язык: Английский

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Integrated multi-omics analysis reveals the molecular interplay between circadian clocks and cancer pathogenesis

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Авг. 30, 2023

Circadian rhythms (CRs) are fundamental biological processes that significantly impact human well-being. Disruption of these can trigger insufficient neurocognitive development, insomnia, mental disorders, cardiovascular diseases, metabolic dysfunctions, and cancer. The field chronobiology has increased our understanding how rhythm disturbances contribute to cancer pathogenesis, circadian timing influences the efficacy treatments. As clock steadily gains recognition as an emerging factor in tumorigenesis, a thorough comprehensive multi-omics analysis CR genes/proteins never been performed. To shed light on this, we performed, for first time, integrated data encompassing genomic/transcriptomic alterations across 32 types (n = 10,918 tumors) taken from PanCancer Atlas, unfavorable prognostic protein analysis, protein-protein interactomics, shortest distance score pathways hallmark phenotypes. This mining strategy allowed us unravel 31 essential CR-related proteins involved signaling crossroad between In context drugging clock, identified pharmacogenomic clinical annotations drugs currently late phase trials could be considered potential therapeutic strategies. These findings highlight diverse roles realm research therapy.

Язык: Английский

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Effects of the neonatal intensive care environment on circadian health and development of preterm infants

Frontiers in Physiology, Год журнала: 2023, Номер 14

Опубликована: Авг. 31, 2023

The circadian system in mammals ensures adaptation to the light-dark cycle on Earth and imposes 24-h rhythmicity metabolic, physiological behavioral processes. central pacemaker is located brain entrained by environmental signals called Zeitgebers. From here, neural, humoral systemic drive rhythms peripheral clocks nearly every mammalian tissue. During pregnancy, disruption of complex interplay between mother’s rhythmic fetal developing can lead long-term health consequences offspring. When an infant born very preterm, it loses temporal received from mother prematurely becomes totally dependent 24/7 care Neonatal Intensive Care Unit (NICU), where day/night usually blurred. In this literature review, we provide overview neonatal development system, short-term process as occurs NICU environment. Moreover, a theoretical molecular framework how could later-life disease. Finally, discuss studies that aim improve outcomes after preterm birth studying effects enhancing light noise exposure.

Язык: Английский

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A subclass of evening cells promotes the switch from arousal to sleep at dusk

Current Biology, Год журнала: 2024, Номер 34(10), С. 2186 - 2199.e3

Опубликована: Май 1, 2024

Язык: Английский

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