Long-lived αMUPA transgenic mice exhibit pronounced circadian rhythms

Robust biological rhythms have been shown to affect life span. Biological clocks can be entrained by two feeding regimens, restricted feeding (RF) and caloric restriction (CR). RF restricts the time of food availability, whereas CR restricts the amount of calories with temporal food consumption. CR is known to retard aging and extend life span of animals via yet-unknown pathways. We hypothesize that resetting the biological clock could be one possible mechanism by which CR extends life span. Because it is experimentally difficult to uncouple calorie reduction from temporal food consumption, we took advantage of the murine urokinase-like plasminogen activator (αMUPA) transgenic mice overexpressing a serine protease implicated in brain development and plasticity; they exhibit spontaneously reduced eating and increased life span. Quantitative real-time PCR analysis revealed that αMUPA mice exhibit robust expression of the clock genes mPer1, mPer2, mClock, and mCry1 but not mBmal1 in the liver. We also found changes in the circadian amplitude and/or phase of clock-controlled output systems, such as feeding behavior, body temperature, and enteric cryptdin expression. A change in the light-dark regimen led to modified clock gene expression and abrogated circadian patterns of food intake in wild-type (WT) and αMUPA mice. Consequently, food consumption of WT mice increased, whereas that of αMUPA mice remained the same, indicating that reduced food intake occurs upstream and independently of the biological clock. Thus we surmise that CR could lead to pronounced and synchronized biological rhythms. Because the biological clock controls mitochondrial, hormonal, and physiological parameters, system synchronicity could lead to extended life span.

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The Role of Endogenous Carbon Monoxide (CO) in the Functioning of Biological Clocks in Pig and Wild Boar Hybrids During Long- and Short-day Seasons

10.21203/rs.3.rs-870647/v1 ◽

2021 ◽

Author(s):

Przemysław GILUN ◽

Barbara Wąsowska ◽

Magdalena Sowa-Kućma ◽

Katarzyna Kozioł ◽

Maria Romerowicz-Misielak ◽

...

Keyword(s):

Gene Expression ◽

Wild Boar ◽

Clock Genes ◽

Autologous Blood ◽

Biological Clock ◽

Biological Clocks ◽

Light Emitting ◽

Short Day ◽

The Right ◽

Induced Changes

Abstract Mature males of a wild boar-pig crossbreed during long- and short-day seasons were used for the study, which demonstrated that the chemical light carrier CO regulates the expression of biological clock genes in the hypothalamus (preoptic area - POA and dorsal part of hypothalamus - DH) via humoral pathways. Autologous blood with experimentally elevated concentrations of endogenous CO (using lamps with white light-emitting diodes) was infused into the ophthalmic venous sinus via the right dorsal nasal vein.The results showed that elevated endogenous CO levels through blood irradiation induced changes in gene expression involved in the functioning of the main biological clock. Changes in the expression of the transcription factors Bmal1, Clock and Npas2 had a similar pattern in both structures, where a very large decrease in gene expression was shown after exposure to elevated endogenous CO levels. The changes in the gene expression of PER 1-2, CRY 1-2, REV-ERB α-β and ROR β are not the same for both POA and DH hypothalamic structures, indicating that both structures respond differently to the received humoral signal.The obtained results indicate that CO is a chemical light molecule whose production in organisms depends on the amount of light. An adequate amount of light is an essential factor for the proper functioning of the main biological clock.

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Rhythms during the polar night: evidence of clock-gene oscillations in the Arctic scallop Chlamys islandica

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2020.1001 ◽

2020 ◽

Vol 287 (1933) ◽

pp. 20201001

Author(s):

Mickael Perrigault ◽

Hector Andrade ◽

Laure Bellec ◽

Carl Ballantine ◽

Lionel Camus ◽

...

Keyword(s):

Gene Expression ◽

Clock Gene ◽

Clock Genes ◽

Biological Rhythms ◽

The Arctic ◽

Polar Night ◽

Clock Gene Expression ◽

Chlamys Islandica ◽

Autumnal Equinox ◽

Cyclic Variations

Arctic regions are highly impacted by climate change and are characterized by drastic seasonal changes in light intensity and duration with extended periods of permanent light or darkness. Organisms use cyclic variations in light to synchronize daily and seasonal biological rhythms to anticipate cyclic variations in the environment, to control phenology and to maintain fitness. In this study, we investigated the diel biological rhythms of the Arctic scallop, Chlamys islandica , during the autumnal equinox and polar night. Putative circadian clock genes and putative light perception genes were identified in the Arctic scallop. Clock gene expression oscillated in the three tissues studied (gills, muscle, mantle edge). The oscillation of some genes in some tissues shifted from daily to tidal periodicity between the equinox and polar night periods and was associated with valve behaviour. These results are the first evidence of the persistence of clock gene expression oscillations during the polar night and might suggest that functional clockwork could entrain rhythmic behaviours in polar environments.

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Chronobiology and the design of marine biology experiments

ICES Journal of Marine Science ◽

10.1093/icesjms/fsy131 ◽

2018 ◽

Vol 76 (1) ◽

pp. 60-65 ◽

Cited By ~ 1

Author(s):

Audrey M Mat

Keyword(s):

Marine Biology ◽

Clock Genes ◽

Biological Rhythms ◽

Marine Species ◽

Temporal Organization ◽

Biological Clocks ◽

Solar Cycles ◽

Dark Cycle ◽

Marine Habitats ◽

Selection Of

AbstractMarine habitats are shaped by several geophysical cycles ranging from a few hours (tidal and solar cycles) to a year (seasons). These cycles have favoured the selection of endogenous biological clocks. Such a clock is a molecular time-keeping mechanism that consists of a set of core clock genes whose expression oscillates. The clocks produce biological rhythms and influence virtually all metabolic, physiological, and behavioural functions in organisms. This work highlights the importance to take chronobiology into account in experimental marine biology to avoid faulty results, misinterpretation of results, and/or to strengthen observations and conclusion. A literature survey, based on 150 articles, was conducted and showed that, despite the pervasive imprint of biological rhythms in marine species, environmental cycles such as the 24 h-light/dark cycle and the seasonality are rarely considered in experimental designs. This work emphasizes that better integrating the temporal organization and regulation of marine species within the marine biology community is essential for obtaining representative results.

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Depriving mice of sleep also deprives of food

10.1101/2021.12.21.473656 ◽

2021 ◽

Author(s):

Nina Đukanović ◽

Francesco La Spada ◽

Yann Emmenegger ◽

Guy Niederhäuser ◽

Frédéric Preitner ◽

...

Keyword(s):

Gene Expression ◽

Food Intake ◽

Food Deprivation ◽

Clock Gene ◽

Clock Genes ◽

Energy Deficit ◽

Clock Gene Expression ◽

Recovery Sleep ◽

Tightly Coupled ◽

Access To Food

Both sleep-wake behavior and circadian rhythms are tightly coupled to energy metabolism and food intake. Altered feeding times in mice are known to entrain clock-gene rhythms in brain and liver and sleep-deprived humans tend to eat more and gain weight. Previous observations in mice showing that sleep deprivation (SD) changes clock-gene expression might thus relate to altered food intake and not to the loss of sleep per se. Whether SD affects food intake in the mouse and how this might affect clock-gene expression is, however, unknown. We therefore quantified i) the cortical expression of the clock genes Per1, Per2, Dbp, and Cry1 in mice that had access to food or not during a 6h SD, and ii) food intake during baseline, SD, and recovery sleep. We found that food deprivation did not modify the SD-incurred clock-gene changes in the cortex. Moreover, we discovered that although food intake during SD did not differ from baseline, mice lost weight and increased food intake during subsequent recovery. We conclude that SD is associated with food deprivation and that the resulting energy deficit might contribute to the effects of SD that are commonly interpreted as a response to sleep loss.

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Maternal Obesity during Pregnancy Alters Daily Activity and Feeding Cycles, and Hypothalamic Clock Gene Expression in Adult Male Mouse Offspring

International Journal of Molecular Sciences ◽

10.3390/ijms20215408 ◽

2019 ◽

Vol 20 (21) ◽

pp. 5408

Author(s):

Jane K. Cleal ◽

Kimberley D. Bruce ◽

Jasmin L. Shearer ◽

Hugh Thomas ◽

Jack Plume ◽

...

Keyword(s):

Gene Expression ◽

Food Intake ◽

Molecular Clock ◽

Daily Activity ◽

Maternal Obesity ◽

Clock Genes ◽

Expression Patterns ◽

Altered Expression ◽

Clock Gene Expression ◽

Feeding Rhythms

An obesogenic diet adversely affects the endogenous mammalian circadian clock, altering daily activity and metabolism, and resulting in obesity. We investigated whether an obese pregnancy can alter the molecular clock in the offspring hypothalamus, resulting in changes to their activity and feeding rhythms. Female mice were fed a control (C, 7% kcal fat) or high fat diet (HF, 45% kcal fat) before mating and throughout pregnancy. Male offspring were fed the C or HF diet postweaning, resulting in four offspring groups: C/C, C/HF, HF/C, and HF/HF. Daily activity and food intake were monitored, and at 15 weeks of age were killed at six time-points over 24 h. The clock genes Clock, Bmal1, Per2, and Cry2 in the suprachiasmatic nucleus (SCN) and appetite genes Npy and Pomc in the arcuate nucleus (ARC) were measured. Daily activity and feeding cycles in the HF/C, C/HF, and HF/HF offspring were altered, with increased feeding bouts and activity during the day and increased food intake but reduced activity at night. Gene expression patterns and levels of Clock, Bmal1, Per2, and Cry2 in the SCN and Npy and Pomc in the ARC were altered in HF diet-exposed offspring. The altered expression of hypothalamic molecular clock components and appetite genes, together with changes in activity and feeding rhythms, could be contributing to offspring obesity.

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Diurnal regulation of hypothalamic kisspeptin is disrupted during mouse pregnancy

Journal of Endocrinology ◽

10.1530/joe-16-0086 ◽

2016 ◽

Vol 229 (3) ◽

pp. 307-318 ◽

Cited By ~ 5

Author(s):

Cassandra C Yap ◽

Michaela D Wharfe ◽

Peter J Mark ◽

Brendan J Waddell ◽

Jeremy T Smith

Keyword(s):

Gene Expression ◽

Diurnal Variation ◽

Mrna Expression ◽

Clock Genes ◽

Pcr Analysis ◽

Clock Gene Expression ◽

Circadian Control ◽

Pregnant Mice ◽

Luteinizing Hormone Surge ◽

Diurnal Regulation

Kisspeptin, the neuropeptide product of the Kiss1 gene, is critical in driving the hypothalamic–pituitary–gonadal (HPG) axis. Kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (Arc) of the hypothalamus mediate differential effects, with the Arc regulating negative feedback of sex steroids and the AVPV regulating positive feedback, vital for the preovulatory surge and gated under circadian control. We aimed to characterize hypothalamic Kiss1 and Kiss1r mRNA expression in nonpregnant and pregnant mice, and investigate potential circadian regulation. Anterior and posterior hypothalami were collected from C57BL/6J mice at diestrus, proestrus, and days 6, 10, 14, and 18 of pregnancy, at six time points across 24h, for real-time PCR analysis of gene expression. Analysis confirmed that Kiss1 mRNA expression in the AVPV increased at ZT13 during proestrus, with a luteinizing hormone surge observed thereafter. No diurnal regulation was seen at diestrus or at any stage of pregnancy. Anterior hypothalamic Avp mRNA expression exhibited no diurnal variation, but Avpr1a peaked at 12:00h during proestrus, possibly reflecting the circadian input from the suprachiasmatic nucleus to AVPV Kiss1 neurons. Rfrp (Npvf) expression in the posterior hypothalamus did not demonstrate diurnal variation at any stage. Clock genes Bmal1 and Rev-erbα were strongly diurnal, but there was little change between diestrus/proestrus and pregnancy. Our data indicate the absence of the circadian input to Kiss1 in pregnancy, despite high gestational estradiol levels and normal clock gene expression, and may suggest a disruption of a kisspeptin-specific diurnal rhythm that operates in the nonpregnant state.

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The Tibetan medicineZuotaiinfluences clock gene expression in the liver of mice

PeerJ ◽

10.7717/peerj.1632 ◽

2016 ◽

Vol 4 ◽

pp. e1632 ◽

Cited By ~ 8

Author(s):

Huan Li ◽

Wen-Kai Li ◽

Yuan-Fu Lu ◽

Li-Xin Wei ◽

Jie Liu

Keyword(s):

Gene Expression ◽

Circadian Clock ◽

Nuclear Receptor ◽

Clock Gene ◽

Target Genes ◽

Oscillation Amplitude ◽

Biological Clock ◽

Tibetan Medicine ◽

Pcr Analysis ◽

Clock Gene Expression

Background.The circadian clock is involved in drug metabolism, efficacy and toxicity. Drugs could in turn affect the biological clock as a mechanism of their actions. Zuotai is an essential component of many popular Tibetan medicines for sedation, tranquil and “detoxification,” and is mainly composed of metacinnabar (β-HgS). The pharmacological and/or toxicological basis of its action is unknown. This study aimed to examine the effect of Zuotai on biological clock gene expression in the liver of mice.Materials and methods.Mice were orally given Zuotai (10 mg/kg, 1.5-fold of clinical dose) daily for 7 days, and livers were collected every 4 h during the 24 h period. Total RNA was extracted and subjected to real-time RT-PCR analysis of circadian clock gene expression.Results.Zuotai decreased the oscillation amplitude of the clock core gene Clock, neuronal PAS domain protein 2 (Npas2), Brain and muscle Arnt-like protein-1 (Bmal1) at 10:00. For the clock feedback negative control genes, Zuotai had no effect on the oscillation of the clock gene Cryptochrome (Cry1) and Period genes (Per1–3). For the clock-driven target genes, Zuotai increased the oscillation amplitude of the PAR-bZip family member D-box-binding protein (Dbp), decreased nuclear factor interleukin 3 (Nfil3) at 10:00, but had no effect on thyrotroph embryonic factor (Tef); Zuotai increased the expression of nuclear receptor Rev-Erbα (Nr1d1) at 18:00, but had little influence on the nuclear receptor Rev-Erbβ (Nr1d2) and RORα.Conclusion.The Tibetan medicine Zuotai could influence the expression of clock genes, which could contribute to pharmacological and/or toxicological effects of Zuotai.

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Melatonin alleviated the immune response and improved the salivary gland function in primary Sjögren’s syndrome

10.21203/rs.3.rs-46098/v1 ◽

2020 ◽

Author(s):

Yi Liu ◽

Xiuhong Weng ◽

Shaoling Yu ◽

Yumei Ding ◽

Bo Cheng

Keyword(s):

Gene Expression ◽

Salivary Gland ◽

Salivary Glands ◽

Clock Gene ◽

Clock Genes ◽

Biological Clock ◽

Lymphocyte Infiltration ◽

Clock Gene Expression ◽

Melatonin Administration ◽

Gland Function

Abstract Background Excessive inflammatory reactions participate in primary Sjögren’s syndrome (pSS) progression. In addition, biological clock genes have been detected in the salivary glands, which indicates that clock genes regulate the growth and development of the salivary glands as well as the quality and quantity of saliva secretion. Melatonin is an amine hormone secreted by the pineal gland that has many physiological functions, such as regulating immunity and correcting disorder in the biological clock rhythm. The purpose of this study was to clarify the correlation between pSS and the biological clock rhythm and explore the possibility of applying melatonin to treat pSS. Methods Melatonin (10 mg/kg/d or 15 mg/kg/d) or vehicle was administered to NOD/Ltj mice by intraperitoneal injection for 4 weeks. Clock gene expression levels in labial gland biopsy specimens from pSS patients and submandibular gland specimens from mice were measured by Western blotting (WB) and RT-PCR. The salivary flow rate of mice was measured at 12, 14, and 16 weeks. The severity of lymphocyte infiltration in the salivary glands was analysed by haematoxylin and eosin (H&E) staining. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining were used to detect the expression levels of related inflammatory factors in mice. The percentages of Th17, Th2, and Treg cells were analysed by flow cytometry. Results There was a distinct expression profile for clock genes in pSS patients compared with controls. Continuous melatonin administration improved salivary gland function in NOD/Ltj mice, with decreased lymphocyte infiltration in the submandibular glands and reduced related inflammatory factor expression in the serum and salivary glands. Melatonin treatment skewed T cells towards the Treg and Th2 subsets while suppressing Th17 responses. Additionally, melatonin administration regulated clock gene expression in NOD/Ltj mice. Conclusion pSS pathogenesis and progression are correlated with abnormal circadian gene expression. Melatonin improves the hypofunction of the salivary glands and inhibits the inflammatory development of pSS in NOD/Ltj mice. This study provides a theoretical basis and potential approach for the clinical prevention and treatment of pSS.

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