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Fertility and Sterility Aug 2014To summarize the role of melatonin and circadian rhythms in determining optimal female reproductive physiology, especially at the peripheral level. (Review)
Review
OBJECTIVE
To summarize the role of melatonin and circadian rhythms in determining optimal female reproductive physiology, especially at the peripheral level.
DESIGN
Databases were searched for the related English-language literature published up to March 1, 2014. Only papers in peer-reviewed journals are cited.
SETTING
Not applicable.
PATIENT(S)
Not applicable.
INTERVENTION(S)
Melatonin treatment, alterations of the normal light:dark cycle and light exposure at night.
MAIN OUTCOME MEASURE(S)
Melatonin levels in the blood and in the ovarian follicular fluid and melatonin synthesis, oxidative damage and circadian rhythm disturbances in peripheral reproductive organs.
RESULT(S)
The central circadian regulatory system is located in the suprachiasmatic nucleus (SCN). The output of this master clock is synchronized to 24 hours by the prevailing light-dark cycle. The SCN regulates rhythms in peripheral cells via the autonomic nervous system and it sends a neural message to the pineal gland where it controls the cyclic production of melatonin; after its release, the melatonin rhythm strengthens peripheral oscillators. Melatonin is also produced in the peripheral reproductive organs, including granulosa cells, the cumulus oophorus, and the oocyte. These cells, along with the blood, may contribute melatonin to the follicular fluid, which has melatonin levels higher than those in the blood. Melatonin is a powerful free radical scavenger and protects the oocyte from oxidative stress, especially at the time of ovulation. The cyclic levels of melatonin in the blood pass through the placenta and aid in the organization of the fetal SCN. In the absence of this synchronizing effect, the offspring may exhibit neurobehavioral deficits. Also, melatonin protects the developing fetus from oxidative stress. Melatonin produced in the placenta likewise may preserve the optimal function of this organ.
CONCLUSION(S)
Both stable circadian rhythms and cyclic melatonin availability are critical for optimal ovarian physiology and placental function. Because light exposure after darkness onset at night disrupts the master circadian clock and suppresses elevated nocturnal melatonin levels, light at night should be avoided.
Topics: Animals; Chronobiology Disorders; Circadian Clocks; Circadian Rhythm; Female; Fetus; Humans; Light; Melatonin; Ovary; Photoperiod; Placenta; Pregnancy; Pregnancy Complications; Reproduction; Signal Transduction; Suprachiasmatic Nucleus; Time Factors
PubMed: 24996495
DOI: 10.1016/j.fertnstert.2014.06.014 -
Neuropharmacology 2009Diurnal and circadian rhythms are prominent in nearly all bodily functions. Chronic disruptions in normal sleep wake and social schedules can lead to serious health... (Review)
Review
Diurnal and circadian rhythms are prominent in nearly all bodily functions. Chronic disruptions in normal sleep wake and social schedules can lead to serious health problems such as those seen in shift worker's syndrome. Moreover, genetic disruptions in normal circadian gene functions have recently been linked to a variety of psychiatric conditions including depression, bipolar disorder, seasonal affective disorder and alcoholism. Recent studies are beginning to determine how these circadian genes and rhythms are involved in the development of drug addiction. Several of these studies suggest an important role for these genes in limbic regions of the brain, outside of the central circadian pacemaker in the suprachiasmatic nucleus (SCN). This review summarizes some of the basic research into the importance of circadian genes in drug addiction.
Topics: Animals; Circadian Rhythm; Humans; Illicit Drugs; Substance-Related Disorders; Suprachiasmatic Nucleus
PubMed: 18644396
DOI: 10.1016/j.neuropharm.2008.06.054 -
International Journal of Molecular... Dec 2021In mammals, the hypothalamic suprachiasmatic nucleus (SCN) functions as the central circadian pacemaker, orchestrating behavioral and physiological rhythms in alignment...
In mammals, the hypothalamic suprachiasmatic nucleus (SCN) functions as the central circadian pacemaker, orchestrating behavioral and physiological rhythms in alignment to the environmental light/dark cycle. The neurons that comprise the SCN are anatomically and functionally heterogeneous, but despite their physiological importance, little is known about the pathways that guide their specification and differentiation. Here, we report that the stem/progenitor cell transcription factor, (), is required in the embryonic SCN to control the expression of SCN-enriched neuropeptides and transcription factors. Ablation of in the developing SCN leads to downregulation of circadian neuropeptides as early as embryonic day (E) 15.5, followed by a decrease in the expression of two transcription factors involved in SCN development, and , in neonates. Thymidine analog-retention assays revealed that deficiency contributed to reduced survival of SCN neurons during the postnatal period of cell clearance, but did not affect progenitor cell proliferation or SCN specification. Our results identify SOX2 as an essential transcription factor for the proper differentiation and survival of neurons within the developing SCN.
Topics: Animals; Cell Differentiation; Circadian Rhythm; Embryonic Development; Mice; Neurons; SOXB1 Transcription Factors; Suprachiasmatic Nucleus
PubMed: 35008655
DOI: 10.3390/ijms23010229 -
PloS One 2018The circadian clock in the suprachiasmatic nucleus (SCN) regulates daily rhythms in physiology and behaviour and is an important part of the mammalian homeostatic...
The circadian clock in the suprachiasmatic nucleus (SCN) regulates daily rhythms in physiology and behaviour and is an important part of the mammalian homeostatic system. Previously, we have shown that systemic inflammatory stimulation with lipopolysaccharide (LPS) induced the daytime-dependent phosphorylation of STAT3 in the SCN. Here, we demonstrate the LPS-induced Stat3 mRNA expression in the SCN and show also the circadian rhythm in Stat3 expression in the SCN, with high levels during the day. Moreover, we examined the effects of LPS (1mg/kg), applied either during the day or the night, on the rhythm in locomotor activity of male Wistar rats. We observed that recovery of normal locomotor activity patterns took longer when the animals were injected during the night. The clock genes Per1, Per2 and Nr1d1, and phosphorylation of kinases ERK1/2 and GSK3β are sensitive to external cues and function as the molecular entry for external signals into the circadian clockwork. We also studied the immediate changes in these clock genes expressions and the phosphorylation of ERK1/2 and GSK3β in the suprachiasmatic nucleus in response to daytime or night-time inflammatory stimulation. We revealed mild and transient changes with respect to the controls. Our data stress the role of STAT3 in the circadian clock response to the LPS and provide further evidence of the interaction between the circadian clock and immune system.
Topics: Animals; Circadian Rhythm; Gene Expression Regulation; Lipopolysaccharides; Locomotion; MAP Kinase Signaling System; Male; Mitogen-Activated Protein Kinase 3; Rats; Rats, Wistar; STAT3 Transcription Factor; Suprachiasmatic Nucleus
PubMed: 30265676
DOI: 10.1371/journal.pone.0199405 -
Mathematical Biosciences and... Mar 2019Circadian rhythms have been observed in behavioral and physiological activities of living things exposed to the natural 24 h light-darkness cycle. Interestingly, even... (Review)
Review
Circadian rhythms have been observed in behavioral and physiological activities of living things exposed to the natural 24 h light-darkness cycle. Interestingly, even under constant darkness, living organisms maintain a robust endogenous circadian rhythm suggesting the existence of an endogenous clock. In mammals, the endogenous clock is located in the suprachiasmatic nucleus (SCN) which is composed of about 20,000 neuronal oscillators. These neuronal oscillators are heterogeneous in their properties, including the intrinsic period, intrinsic amplitude, light information sensitivity, cellular coupling strength, intrinsic amplitudes and the topological links. In this review, we introduce the influence of the heterogeneity of these properties on the two main functions of the SCN, i.e. the free running rhythm in constant darkness and entrainment to the external cycle, based on mathematical models where heterogeneous neuronal oscillators are coupled to form a network. Our findings show that the heterogeneities can alter the free running periods under constant darkness and the entrainment ability to the external cycle for the SCN by controlling a fine balance between flexibility and robustness of the clock. These findings can explain experimental observation, e.g., why the free running periods and entrainment abilities are different between species, and shed light on the heterogeneity of the SCN network.
Topics: Algorithms; Animals; Circadian Clocks; Circadian Rhythm; Computer Simulation; Darkness; Hormones; Humans; Models, Neurological; Neurons; Oscillometry; Suprachiasmatic Nucleus
PubMed: 31137191
DOI: 10.3934/mbe.2019092 -
Pediatric Clinics of North America Apr 1997Increasing evidence indicates that the circadian timing system is a fundamental hemostatic system that potently influences human behavior and physiology throughout... (Review)
Review
Increasing evidence indicates that the circadian timing system is a fundamental hemostatic system that potently influences human behavior and physiology throughout development. Circadian clock function begins during fetal life, and photic regulation of circadian phase is present at birth in primates. After birth, there is progressive maturation of the circadian system, with day-night rhythms in activity and hormone secretion developing between 1 and 3 months of age. Several disorders of the circadian system are now recognized and include clock disorders and problems related to inadequate entrainment of circadian phase. Treatments for several circadian system disorders are now available and include light therapy and melatonin. With the continued elucidation of circadian system development and influences on human physiology and illness, it is anticipated that consideration of circadian biology will become an increasingly important component of clinical care.
Topics: Animals; Chronotherapy; Circadian Rhythm; Humans; Infant, Newborn; Melatonin; Phototherapy; Primates; Rodentia; Suprachiasmatic Nucleus
PubMed: 9130930
DOI: 10.1016/s0031-3955(05)70486-7 -
Analytical Chemistry Jan 2014Mammalian circadian rhythm is maintained by the suprachiasmatic nucleus (SCN) via an intricate set of neuropeptides and other signaling molecules. In this work,... (Comparative Study)
Comparative Study
Mammalian circadian rhythm is maintained by the suprachiasmatic nucleus (SCN) via an intricate set of neuropeptides and other signaling molecules. In this work, peptidomic analyses from two times of day were examined to characterize variation in SCN peptides using three different label-free quantitation approaches: spectral count, spectra index and SIEVE. Of the 448 identified peptides, 207 peptides were analyzed by two label-free methods, spectral count and spectral index. There were 24 peptides with significant (adjusted p-value < 0.01) differential peptide abundances between daytime and nighttime, including multiple peptides derived from secretogranin II, cocaine and amphetamine regulated transcript, and proprotein convertase subtilisin/kexin type 1 inhibitor. Interestingly, more peptides were analyzable and had significantly different abundances between the two time points using the spectral count and spectral index methods than with a prior analysis using the SIEVE method with the same data. The results of this study reveal the importance of using the appropriate data analysis approaches for label-free relative quantitation of peptides. The detection of significant changes in so rich a set of neuropeptides reflects the dynamic nature of the SCN and the number of influences such as feeding behavior on circadian rhythm. Using spectral count and spectral index, peptide level changes are correlated to time of day, suggesting their key role in circadian function.
Topics: Amino Acid Sequence; Animals; Circadian Rhythm; Male; Mass Spectrometry; Molecular Sequence Data; Neuropeptides; Rats; Rats, Long-Evans; Suprachiasmatic Nucleus
PubMed: 24313826
DOI: 10.1021/ac4023378 -
Cell Communication and Signaling : CCS Jun 2019The astroglial connexins Cx30 and Cx43 contribute to many important CNS functions including cognitive behaviour, motoric capacity and regulation of the sleep-wake cycle....
Connexin30 and Connexin43 show a time-of-day dependent expression in the mouse suprachiasmatic nucleus and modulate rhythmic locomotor activity in the context of chronodisruption.
BACKGROUND
The astroglial connexins Cx30 and Cx43 contribute to many important CNS functions including cognitive behaviour, motoric capacity and regulation of the sleep-wake cycle. The sleep wake cycle, is controlled by the circadian system. The central circadian rhythm generator resides in the suprachiasmatic nucleus (SCN). SCN neurons are tightly coupled in order to generate a coherent circadian rhythm. The SCN receives excitatory glutamatergic input from the retina which mediates entrainment of the circadian system to the environmental light-dark cycle. Connexins play an important role in electric coupling of SCN neurons and astrocytic-neuronal signalling that regulates rhythmic SCN neuronal activity. However, little is known about the regulation of Cx30 and Cx43 expression in the SCN, and the role of these connexins in light entrainment of the circadian system and in circadian rhythm generation.
METHODS
We analysed time-of-day dependent as well as circadian expression of Cx30 and Cx43 mRNA and protein in the mouse SCN by means of qPCR and immunohistochemistry. Moreover, we analysed rhythmic spontaneous locomotor activity in mice with a targeted deletion of Cx30 and astrocyte specific deletion of Cx43 (DKO) in different light regimes by means of on-cage infrared detectors.
RESULTS
Fluctuation of Cx30 protein expression is strongly dependent on the light-dark cycle whereas fluctuation of Cx43 protein expression persisted in constant darkness. DKO mice entrained to the light-dark cycle. However, re-entrainment after a phase delay was slightly impaired in DKO mice. Surprisingly, DKO mice were more resilient to chronodisruption.
CONCLUSION
Circadian fluctuation of Cx30 and Cx43 protein expression in the SCN is differently regulated. Cx30 and astroglial Cx43 play a role in rhythm stability and re-entrainment under challenging conditions.
Topics: Animals; Circadian Rhythm; Connexin 30; Connexin 43; Locomotion; Male; Mice; Mice, Inbred C57BL; Suprachiasmatic Nucleus
PubMed: 31186021
DOI: 10.1186/s12964-019-0370-2 -
Scientific Reports Jun 2022For many animal species, knowing when to look for food may be as important as knowing where to look. Rats and other species use a feeding-responsive circadian timing...
For many animal species, knowing when to look for food may be as important as knowing where to look. Rats and other species use a feeding-responsive circadian timing mechanism to anticipate, behaviorally and physiologically, a predictable daily feeding opportunity. How this mechanism for anticipating a daily meal accommodates more than one predictable mealtime is unclear. Rats were trained to press a lever for food, and then limited to one or more daily meals at fixed or systematically varying times of day. The rats were able to anticipate up to 4 of 4 daily meals at fixed times of day and two 'daily' meals recurring at 24 h and 26 h intervals. When deprived of food, in constant dark, lever pressing recurred for multiple cycles at expected mealtimes, consistent with the periodicity of the prior feeding schedule. Anticipation did not require the suprachiasmatic nucleus circadian pacemaker. The anticipation rhythms could be simulated using a Kuramoto model in which clusters of coupled oscillators entrain to specific mealtimes based on initial phase and intrinsic circadian periodicity. A flexibly coupled system of food-entrainable circadian oscillators endows rats with adaptive plasticity in daily programming of foraging activity.
Topics: Animals; Circadian Rhythm; Feeding Behavior; Food; Food Deprivation; Rats; Suprachiasmatic Nucleus
PubMed: 35661783
DOI: 10.1038/s41598-022-13242-w -
The Journal of Physiology Nov 19961. Intracellular sharp electrode and whole-cell patch-clamp recording from characterized paraventricular nucleus (PVN) neurones in rat hypothalamic slices were used to...
1. Intracellular sharp electrode and whole-cell patch-clamp recording from characterized paraventricular nucleus (PVN) neurones in rat hypothalamic slices were used to study the synaptic mechanism and associated neurotransmitters that mediate their response to suprachiasmatic nucleus (SCN) stimulation. 2. Electrical stimulation restricted to SCN evoked short-latency inhibitory postsynaptic potentials (IPSPs) or combinations of IPSPs and excitatory postsynaptic potentials (EPSPs) in all (n = 59) PVN neurones tested. Type I neurones (n = 18) were magnocellular and a majority (13/18) demonstrated monosynaptic IPSPs that reversed polarity at the chloride equilibrium potential and were sensitive to bicuculline. 3. Type II (n = 10) and III parvocellular (n = 13), and unclassifiable neurones (n = 18) displayed combinations of IPSPs and EPSPs following similar stimuli applied to SCN. IPSP blockade with bicuculline uncovered SCN-evoked monosynaptic dual-component EPSPs that were sensitive to N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists. In addition, chemical microstimulation within SCN was associated with transient increases in spontaneous EPSPs recorded from these PVN neurones. 4. These data imply that the amino acids GABA and glutamate are important mediators of fast monosynaptic transmission from SCN to defined neurones in PVN, and are candidates for conveying circadian rhythmicity to PVN regulation of neuroendocrine and autonomic processes.
Topics: Animals; Bicuculline; Electric Stimulation; Evoked Potentials; Glutamic Acid; In Vitro Techniques; Male; Neurons; Paraventricular Hypothalamic Nucleus; Patch-Clamp Techniques; Rats; Suprachiasmatic Nucleus; Synaptic Transmission; Time Factors; gamma-Aminobutyric Acid
PubMed: 8930841
DOI: 10.1113/jphysiol.1996.sp021724