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Diabetes & Metabolism Journal Jan 2024Novel strategies are required to reduce the risk of developing diabetes and/or clinical outcomes and complications of diabetes. In this regard, the role of the circadian... (Review)
Review
Novel strategies are required to reduce the risk of developing diabetes and/or clinical outcomes and complications of diabetes. In this regard, the role of the circadian system may be a potential candidate for the prevention of diabetes. We reviewed evidence from animal, clinical, and epidemiological studies linking the circadian system to various aspects of the pathophysiology and clinical outcomes of diabetes. The circadian clock governs genetic, metabolic, hormonal, and behavioral signals in anticipation of cyclic 24-hour events through interactions between a "central clock" in the suprachiasmatic nucleus and "peripheral clocks" in the whole body. Currently, circadian rhythmicity in humans can be subjectively or objectively assessed by measuring melatonin and glucocorticoid levels, core body temperature, peripheral blood, oral mucosa, hair follicles, rest-activity cycles, sleep diaries, and circadian chronotypes. In this review, we summarized various circadian misalignments, such as altered light-dark, sleep-wake, rest-activity, fasting-feeding, shift work, evening chronotype, and social jetlag, as well as mutations in clock genes that could contribute to the development of diabetes and poor glycemic status in patients with diabetes. Targeting critical components of the circadian system could deliver potential candidates for the treatment and prevention of type 2 diabetes mellitus in the future.
Topics: Animals; Humans; Diabetes Mellitus, Type 2; Circadian Rhythm; Circadian Clocks; Melatonin; Sleep
PubMed: 38173377
DOI: 10.4093/dmj.2023.0193 -
International Journal of Biological... 2024Rhythmicity of the circadian system is a 24-hour period, driven by transcription-translation feedback loops of circadian clock genes. The central circadian pacemaker in... (Review)
Review
Rhythmicity of the circadian system is a 24-hour period, driven by transcription-translation feedback loops of circadian clock genes. The central circadian pacemaker in mammals is located in the hypothalamic suprachiasmatic nucleus (SCN), which controls peripheral circadian clocks. In general, most physiological processes are regulated by the circadian system, which is modulated by environmental cues such as exposure to light and/or dark, temperature, and the timing of sleep/wake and food intake. The chronic circadian disruption caused by shift work, jetlag, and/or irregular sleep-wake cycles has long-term health consequences. Its dysregulation contributes to the risk of psychiatric disorders, sleep abnormalities, hypothyroidism and hyperthyroidism, cancer, and obesity. A number of neurological conditions may be worsened by changes in the circadian clock via the SCN pacemaker. For stroke, different physiological activities such as sleep/wake cycles are disrupted due to alterations in circadian rhythms. Moreover, the immunological processes that affect the evolution and recovery processes of stroke are regulated by the circadian clock or core-clock genes. Thus, disrupted circadian rhythms may increase the severity and consequences of stroke, while readjustment of circadian clock machinery may accelerate recovery from stroke. In this manuscript, we discuss the relationship between stroke and circadian rhythms, particularly on stroke development and its recovery process. We focus on immunological and/or molecular processes linking stroke and the circadian system and suggest the circadian rhythm as a target for designing effective therapeutic strategies in stroke.
Topics: Animals; Humans; Circadian Clocks; Circadian Rhythm; Suprachiasmatic Nucleus; Sleep; Mammals; Stroke
PubMed: 38169640
DOI: 10.7150/ijbs.88370 -
Journal of Biomedical Research Dec 2023In mammals, the timing of physiological, biochemical and behavioral processes over a 24-h period is controlled by circadian rhythms. To entrain the master clock located...
In mammals, the timing of physiological, biochemical and behavioral processes over a 24-h period is controlled by circadian rhythms. To entrain the master clock located in the suprachiasmatic nucleus of the hypothalamus to a precise 24-h rhythm, environmental zeitgebers are used by the circadian system. This is done primarily by signals from the retina the retinohypothalamic tract, but other cues like exercise, feeding, temperature, anxiety, and social events have also been shown to act as non-photic zeitgebers. The recently identified myokine irisin is proposed to serve as an entraining non-photic signal of exercise. Irisin is a product of cleavage and modification from its precursor membrane fibronectin type Ⅲ domain-containing protein 5 (FNDC5) in response to exercise. Apart from well-known peripheral effects, such as inducing the "browning" of white adipocytes, irisin can penetrate the blood-brain barrier and display the effects on the brain. Experimental data suggest that FNDC5/irisin mediates the positive effects of physical activity on brain functions. In several brain areas, irisin induces the production of brain-derived neurotrophic factor (BDNF). In the master clock, a significant role in gating photic stimuli in the retinohypothalamic synapse for BDNF is suggested. However, the brain receptor for irisin remains unknown. In the current review, the interactions of physical activity and the irisin/BDNF axis with the circadian system are reconceptualized.
PubMed: 38164079
DOI: 10.7555/JBR.37.20230133 -
Brain Research Mar 2024Adar2 mice are a widely used model for studying the physiological consequences of reduced RNA editing. These mice are viable only when the Q/R editing site of the Gria2...
Adar2 mice are a widely used model for studying the physiological consequences of reduced RNA editing. These mice are viable only when the Q/R editing site of the Gria2 subunit of the AMPA receptor is constitutively mutated to the codon for arginine, and Gria2 mice often serve as the sole control for Adar2 mice. Our study aimed to investigate whether ADAR2 inactivity and the Gria2 phenotype affect the rhythmicity of the circadian clock gene pattern and the expression of Gria1 and Gria2 subunits in the suprachiasmatic nucleus (SCN), hippocampus, parietal cortex and liver. Our data show that Gria2 mice completely lost circadian rhythmicity in the hippocampus compared to Adar2 mice. Compared to C57BL/6J mice, the expression profiles in the hippocampus and parietal cortex of Gria2 mice differ to the same extent as in Adar2. No alterations were detected in the circadian profiles in the livers. These data suggest that the natural gradual postnatal increase in the editing of the Q/R site of the Gria2 subunit may be important for the development of circadian clockwork in some brain structures, and the use of Gria2 mice as the only control to Adar2 mice in the experiments dependent on the hippocampus and parietal cortex should therefore be considered.
Topics: Animals; Mice; Adenosine Deaminase; Brain; Circadian Rhythm; Gene Expression; Hippocampus; Mice, Inbred C57BL; Suprachiasmatic Nucleus
PubMed: 38157956
DOI: 10.1016/j.brainres.2023.148739 -
Journal of Alzheimer's Disease : JAD 2024Chronic disruption of the circadian timing system, often reflected as a loss of restful sleep, also includes myriad other pathophysiological effects.
BACKGROUND
Chronic disruption of the circadian timing system, often reflected as a loss of restful sleep, also includes myriad other pathophysiological effects.
OBJECTIVE
The current study examined how chronic circadian disruption (CD) could contribute to pathology and rate of progression in the AβPP/PS1 mouse model of Alzheimer's disease (AD).
METHODS
A chronic CD was imposed until animals reached 6 or 12 months of age in AβPP/PS1 and C57BL/6J control mice. Home cage activity was monitored for a period of 3-4 weeks prior to the endpoint along with a single timepoint measure of glucose sensitivity. To assess long term effects of CD on the AD phenotype, animals were re-entrained to a no disruption (ND) schedule just prior to the endpoint, after which a Morris water maze (MWM) was used to assess spatial learning and memory.
RESULTS
Dampening of nighttime activity levels occurred in disrupted animals, and female animals demonstrated a greater adaptability to CD. Diminished arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) levels in the suprachiasmatic nucleus (SCN) of 12-month male AβPP/PS1 exposed to the CD paradigm were observed, potentially accounting for the diminished re-entrainment response. Similarly, CD worsened performance in the MWM in 12-month male AβPP/PS1 animals, whereas no effect was seen in females.
CONCLUSIONS
Collectively, these findings show that exposure to chronic CD impairs circadian behavioral patterns and cognitive phenotypes of AβPP/PS1 mouse model in a sex-dependent manner.
Topics: Mice; Male; Female; Animals; Amyloid beta-Protein Precursor; Mice, Transgenic; Mice, Inbred C57BL; Alzheimer Disease; Disease Models, Animal; Presenilin-1
PubMed: 38143343
DOI: 10.3233/JAD-230089 -
International Journal of Molecular... Dec 2023The circadian rhythm is a 24 h internal clock within the body that regulates various factors, including sleep, body temperature, and hormone secretion. Circadian rhythm... (Review)
Review
The circadian rhythm is a 24 h internal clock within the body that regulates various factors, including sleep, body temperature, and hormone secretion. Circadian rhythm disruption is an important risk factor for many diseases including neurodegenerative illnesses. The central and peripheral oscillators' circadian clock network controls the circadian rhythm in mammals. The clock genes govern the central clock in the suprachiasmatic nucleus (SCN) of the brain. One function of the circadian clock is regulating lipid metabolism. However, investigations of the circadian regulation of lipid metabolism-associated apolipoprotein genes in the brain are lacking. This review summarizes the rhythmic expression of clock genes and lipid metabolism-associated apolipoprotein genes within the SCN in . Nine of the twenty apolipoprotein genes identified from searching the published database (SCNseq and CircaDB) are highly expressed in the SCN. Most apolipoprotein genes (ApoE, ApoC1, apoA1, ApoH, ApoM, and Cln) show rhythmic expression in the brain in mice and thus might be regulated by the master clock. Therefore, this review summarizes studies on lipid-associated apolipoprotein genes in the SCN and other brain locations, to understand how apolipoproteins associated with perturbed cerebral lipid metabolism cause multiple brain diseases and disorders. This review describes recent advancements in research, explores current questions, and identifies directions for future research.
Topics: Mice; Animals; Lipid Metabolism; Brain; Circadian Rhythm; Suprachiasmatic Nucleus; Circadian Clocks; Apolipoproteins; Mammals
PubMed: 38139244
DOI: 10.3390/ijms242417415 -
Scientific Reports Dec 2023Circadian (24-h) rhythms in the suprachiasmatic nucleus (SCN) are established in utero in rodents, but rhythmicity of peripheral circadian clocks appears later in...
Circadian (24-h) rhythms in the suprachiasmatic nucleus (SCN) are established in utero in rodents, but rhythmicity of peripheral circadian clocks appears later in postnatal development. Since peripheral oscillators can be influenced by maternal feeding and behavior, we investigated whether exposure to the adverse environmental conditions of limited bedding (LB) during postnatal life would alter rhythmicity in the SCN, adrenal gland and liver in neonatal (postnatal day PND10), juvenile (PND28) and adult rats. We also examined locomotor activity in adults. Limited bedding increased nursing time and slightly increased fragmentation of maternal behavior. Exposure to LB reduced the amplitude of Per2 in the SCN on PND10. Adrenal clock gene expression (Bmal1, Per2, Cry1, Rev-erbα, Dbp) and corticosterone secretion were rhythmic at all ages in NB offspring, whereas rhythmicity of Bmal1, Cry1 and corticosterone was abolished in neonatal LB pups. Circadian gene expression in the adrenal and liver was well established by PND28. In adults, liver expression of several circadian genes was increased at specific daytimes by LB and the microstructure of locomotor behavior was altered. Thus, changes in maternal care and behavior might provide important signals to the maturing peripheral oscillators and modify, in particular their output functions in the long-term.
Topics: Female; Rats; Animals; Circadian Rhythm; Corticosterone; ARNTL Transcription Factors; Circadian Clocks; Suprachiasmatic Nucleus
PubMed: 38129480
DOI: 10.1038/s41598-023-47968-y -
Endocrinology Nov 2023Repeated or chronic stress can change the phase of peripheral circadian rhythms. Melatonin (Mel) is thought to be a circadian clock-controlled signal that might play a...
Repeated or chronic stress can change the phase of peripheral circadian rhythms. Melatonin (Mel) is thought to be a circadian clock-controlled signal that might play a role in synchronizing peripheral rhythms, in addition to its direct suppressing effects on the stress axis. In this study we test whether Mel can reduce the social-defeat stress-induced phase shifts in peripheral rhythms, either by modulating circadian phase or by modulating the stress axis. Two experiments were performed with male Mel-deficient C57BL/6J mice carrying the circadian reporter gene construct (PER2::LUC). In the first experiment, mice received night-restricted (ZT11-21) Mel in their drinking water, resulting in physiological levels of plasma Mel peaking in the early dark phase. This treatment facilitated re-entrainment of the activity rhythm to a shifted light-dark cycle, but did not prevent the stress-induced (ZT21-22) reduction of activity during stress days. Also, this treatment did not attenuate the phase-delaying effects of stress in peripheral clocks in the pituitary, lung, and kidney. In a second experiment, pituitary, lung, and kidney collected from naive mice (ZT22-23), were treated with Mel, dexamethasone (Dex), or a combination of the two. Dex application affected PER2 rhythms in the pituitary, kidney, and lung by changing period, phase, or both. Administering Mel did not influence PER2 rhythms nor did it alleviate Dex-induced delays in PER2 rhythms in those tissues. We conclude that exogenous Mel is insufficient to affect peripheral PER2 rhythms and reduce stress effects on locomotor activity and phase changes in peripheral tissues.
Topics: Mice; Male; Animals; Melatonin; Light; Suprachiasmatic Nucleus; Mice, Inbred C57BL; Circadian Rhythm; Circadian Clocks
PubMed: 38128120
DOI: 10.1210/endocr/bqad183 -
Frontiers in Physiology 2023Emerging evidence has highlighted that the gut microbiota plays a critical role in the regulation of various aspects of mammalian physiology and behavior, including...
Emerging evidence has highlighted that the gut microbiota plays a critical role in the regulation of various aspects of mammalian physiology and behavior, including circadian rhythms. Circadian rhythms are fundamental behavioral and physiological processes that are governed by circadian pacemakers in the brain. Since mice are nocturnal, voluntary wheel running activity mostly occurs at night. This nocturnal wheel-running activity is driven by the primary circadian pacemaker located in the suprachiasmatic nucleus (SCN). Food anticipatory activity (FAA) is the increased bout of locomotor activity that precedes the scheduled short duration of a daily meal. FAA is controlled by the food-entrainable oscillator (FEO) located outside of the SCN. Several studies have shown that germ-free mice and mice with gut microbiota depletion altered those circadian behavioral rhythms. Therefore, this study was designed to test if the gut microbiota is involved in voluntary wheel running activity and FAA expression. To deplete gut microbiota, C57BL/6J wildtype mice were administered an antibiotic cocktail via their drinking water throughout the experiment. The effect of antibiotic cocktail treatment on wheel running activity rhythm in both female and male mice was not detectable with the sample size in our current study. Then mice were exposed to timed restricted feeding during the day. Both female and male mice treated with antibiotics exhibited normal FAA which was comparable with the FAA observed in the control group. Those results suggest that gut microbiota depletion has minimum effect on both circadian behavioral rhythms controlled by the SCN and FEO respectively. Our result contradicts recently published studies that reported significantly higher FAA levels in germ-free mice compared to their control counterparts and gut microbiota depletion significantly reduced voluntary activity by 50%.
PubMed: 38107475
DOI: 10.3389/fphys.2023.1299474 -
Schizophrenia Research Feb 2024A molecular clock in the suprachiasmatic nucleus of the anterior hypothalamus, which is entrained by the dark-light cycle and controls the sleep-wake cycle, regulates... (Review)
Review
A molecular clock in the suprachiasmatic nucleus of the anterior hypothalamus, which is entrained by the dark-light cycle and controls the sleep-wake cycle, regulates circadian rhythms. The risk of developing mental disorders, such as schizophrenia, has long been linked to sleep abnormalities. Additionally, a common aspect of mental disorders is sleep disturbance, which has a direct impact on the intensity of the symptoms and the quality of life of the patient. This relationship can be explained by gene alterations such as CLOCK in schizophrenia which are also important components of the physiological circadian rhythm. The function of dopamine and adenosine in circadian rhythm should also be noted, as these hypotheses are considered to be the most popular theories explaining schizophrenia pathogenesis. Therefore, determining the presence of a causal link between the two can be key to identifying new potential targets in schizophrenia therapy, which can open new avenues for clinical research as well as psychiatric care. We review circadian disruption in schizophrenia at the genetic, metabolic, and clinical levels. We summarize data about clock and clock-controlled genes' alterations, neurotransmitter systems' impairments, and association with chronotype in schizophrenia patients. Our findings demonstrate that in schizophrenia either homeostatic or circadian processes of sleep regulation are disturbed. Also, we found an insufficient number of studies aimed at studying the relationship between known biological phenomena of circadian disorders and clinical signs of schizophrenia.
Topics: Humans; Schizophrenia; Quality of Life; Circadian Rhythm; Sleep; Photoperiod
PubMed: 38101179
DOI: 10.1016/j.schres.2023.12.002