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Advances in Experimental Medicine and... 2013Female reproductive functioning requires the precise temporal -organization of numerous neuroendocrine events by a master circadian brain clock located in the... (Review)
Review
Female reproductive functioning requires the precise temporal -organization of numerous neuroendocrine events by a master circadian brain clock located in the suprachiasmatic nucleus. Across species, including humans, disruptions to circadian timing result in pronounced deficits in ovulation and fecundity. The present chapter provides an overview of the circadian control of female reproduction, underscoring the significance of kisspeptin as a key locus of integration for circadian and steroidal signaling necessary for the initiation of ovulation.
Topics: Animals; Circadian Rhythm; Female; Fertility; Humans; Kisspeptins; Ovulation; Signal Transduction; Suprachiasmatic Nucleus
PubMed: 23550016
DOI: 10.1007/978-1-4614-6199-9_18 -
The Anatomical Record Apr 1996The present paper describes the immunocytochemical and morphometric characteristics of two major cell groups of the suprachiasmatic nucleus (SCN) in the human...
BACKGROUND
The present paper describes the immunocytochemical and morphometric characteristics of two major cell groups of the suprachiasmatic nucleus (SCN) in the human hypothalamus: the vasopressin (VP) and vasoactive intestinal polypeptide (VIP) neuronal subdivisions. The dimensions (volume and length) and the number of neurons expressing each peptide in the two subdivisions were obtained, as well as the mean diameter of the cell nuclei. All morphometric parameters were studied in relation to sex and age.
METHODS
Brains of 42 human subjects (22 males and 20 females) ranging in age from 10 to 92 years were obtained at autopsy. The hypothalamic area containing the SCN was dissected from each brain, dehydrated, and embedded in paraffin. Serial sections of 6 microns were cut in a coronal plane and stained with thionin for general orientation. To determine the architectonic boundaries of the VP- and VIP-expressing cell populations every 25th section was immunocytochemically stained by means of antibodies against arginine VP or VIP using the peroxidase-antiperoxidase method. The VP- and VIP-expressing cell numbers in the SCN of each subject were estimated by unilaterally counting the number of nuclear profiles with the aid of a Zeiss microscope under x 500 magnification, using a deconvolution procedure and a correction for section thickness.
RESULTS
The main portion of the VP positive neurons is located in the dorsomedial part of the SCN and is rostrocaudally longer in females than in males (1.76 +/- 0.12 mm and 1.40 +/- 0.10 mm, respectively). The volume of the VP subdivision is 0.244 +/- 0.017 mm3 and contains 6,890 +/- 520 VP-immunoreactive neurons, with a mean density of about 29,000 neurons/mm3. No significant sexual dimorphism or age-related alterations in the population of VP neurons is found. The VIP positive neurons are mainly located in the ventral and central part of the SCN and extend rostrocaudally in a similar way in females and males (1.07 +/- 0.08 mm and 1.02 +/- 0.11 mm, respectively). The volume of the VIP subdivision is 0.034 +/- 0.004 mm3 and contains 1,700 +/- 140 VIP-immunoreactive neurons, with a mean density of about 63,000 neurons/mm3. An age-dependent sexual dimorphism is observed in the number of VIP-expressing neurons in the SCN: young males have about twice as many VIP neurons as females of the same age, whereas in middle-aged subjects this sexual difference is reversed, and less robust, with females now having about 1.7 times as many VIP neurons as males. In old subjects the difference in VIP cell number between men and women disappears.
CONCLUSIONS
The present study clearly shows that the population of VP neurons in the human SCN is considerably larger than the population of VIP neurons. Furthermore, the age-related sexual differences in the VIP cell number reinforces the idea that the SCN is not only involved in the timing of circadian rhythms but also in the temporal organization of reproductive functions.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Analysis of Variance; Cell Count; Child; Female; Humans; Immunohistochemistry; Male; Middle Aged; Neurons; Sex Characteristics; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide; Vasopressins
PubMed: 8694290
DOI: 10.1002/(SICI)1097-0185(199604)244:4<552::AID-AR13>3.0.CO;2-O -
Physiological Research Jul 2016The circadian rhythms of many behavioral and physiological functions are regulated by the major circadian pacemaker in the suprachiasmatic nucleus. Long-term opiate...
The circadian rhythms of many behavioral and physiological functions are regulated by the major circadian pacemaker in the suprachiasmatic nucleus. Long-term opiate addiction and drug withdrawal may affect circadian rhythmicity of various hormones or the sleep/activity pattern of many experimental subjects; however, limited research has been done on the long-term effects of sustained opiate administration on the intrinsic rhythmicity in the suprachiasmatic nucleus and pineal gland. Here we compared the effects of repeated daily treatment of rats with morphine or methadone and subsequent naloxone-precipitated withdrawal on the expression of the Per1, Per2, and Avp mRNAs in the suprachiasmatic nucleus and on arylalkylamine N-acetyltransferase activity in the pineal gland. We revealed that 10-day administration and withdrawal of both these drugs failed to affect clock genes and Avp expression in the SCN. Our results indicate that opioid-induced changes in behavioral and physiological rhythms originate in brain structures downstream of the suprachiasmatic nucleus regulatory output pathway. Furthermore, we observed that acute withdrawal from methadone markedly extended the period of high night AA-NAT activity in the pineal gland. This suggests that withdrawal from methadone, a widely used drug for the treatment of opioid dependence, may have stronger impact on melatonin synthesis than withdrawal from morphine.
Topics: Animals; Arginine Vasopressin; Circadian Rhythm; In Situ Hybridization; Male; Methadone; Morphine; Narcotics; Period Circadian Proteins; Rats, Wistar; Substance Withdrawal Syndrome; Suprachiasmatic Nucleus
PubMed: 27070740
DOI: 10.33549/physiolres.933183 -
The Journal of General Physiology Sep 2023JGP study (Hermanstyne et al. 2023. J. Gen. Physiol.https://doi.org/10.1085/jgp.202213310) shows that Kv12-encoded K+ currents reduce the repetitive firing rates of SCN...
JGP study (Hermanstyne et al. 2023. J. Gen. Physiol.https://doi.org/10.1085/jgp.202213310) shows that Kv12-encoded K+ currents reduce the repetitive firing rates of SCN neurons at night, thereby regulating daily oscillations in the master circadian pacemaker.
Topics: Circadian Rhythm; Suprachiasmatic Nucleus; Neurons
PubMed: 37584659
DOI: 10.1085/jgp.202313459 -
Proceedings of the National Academy of... Apr 2011Food anticipatory behavior (FAA) is induced by limiting access to food for a few hours daily. Animals anticipate this scheduled meal event even without the...
Food anticipatory behavior (FAA) is induced by limiting access to food for a few hours daily. Animals anticipate this scheduled meal event even without the suprachiasmatic nucleus (SCN), the biological clock. Consequently, a food-entrained oscillator has been proposed to be responsible for meal time estimation. Recent studies suggested the dorsomedial hypothalamus (DMH) as the site for this food-entrained oscillator, which has led to considerable controversy in the literature. Herein we demonstrate by means of c-Fos immunohistochemistry that the neuronal activity of the suprachiasmatic nucleus (SCN), which signals the rest phase in nocturnal animals, is reduced when animals anticipate the scheduled food and, simultaneously, neuronal activity within the DMH increases. Using retrograde tracing and confocal analysis, we show that inhibition of SCN neuronal activity is the consequence of activation of GABA-containing neurons in the DMH that project to the SCN. Next, we show that DMH lesions result in a loss or diminution of FAA, simultaneous with increased activity in the SCN. A subsequent lesion of the SCN restored FAA. We conclude that in intact animals, FAA may only occur when the DMH inhibits the activity of the SCN, thus permitting locomotor activity. As a result, FAA originates from a neuronal network comprising an interaction between the DMH and SCN. Moreover, this study shows that the DMH-SCN interaction may serve as an intrahypothalamic system to gate activity instead of rest overriding circadian predetermined temporal patterns.
Topics: Animals; Anticipation, Psychological; Dorsomedial Hypothalamic Nucleus; Food; Immunohistochemistry; Kainic Acid; Models, Neurological; Proto-Oncogene Proteins c-fos; Rats; Suprachiasmatic Nucleus
PubMed: 21402951
DOI: 10.1073/pnas.1015551108 -
Scientific Reports Dec 2022Visual information processing in the retina requires the rhythmic expression of clock genes. The intrinsic retinal circadian clock is independent of the master clock...
Visual information processing in the retina requires the rhythmic expression of clock genes. The intrinsic retinal circadian clock is independent of the master clock located in the hypothalamic suprachiasmatic nucleus and emerges from retinal cells, including glia. Less clear is how glial oscillators influence the daily regulation of visual information processing in the mouse retina. Here, we demonstrate that the adult conditional deletion of the gene Bmal1 in GLAST-positive glial cells alters retinal physiology. Specifically, such deletion was sufficient to lower the amplitude of the electroretinogram b-wave recorded under light-adapted conditions. Furthermore, recordings from > 20,000 retinal ganglion cells (RGCs), the retina output, showed a non-uniform effect on RGCs activity in response to light across different cell types and over a 24-h period. Overall, our results suggest a new role of a glial circadian gene in adjusting mammalian retinal output throughout the night-day cycle.
Topics: Animals; Mice; Circadian Clocks; Circadian Rhythm; Mammals; Neuroglia; Retina; Suprachiasmatic Nucleus
PubMed: 36513717
DOI: 10.1038/s41598-022-25783-1 -
European Neuropsychopharmacology : the... Sep 2011Affective disorders such as major depression, bipolar disorder, and seasonal affective disorder are associated with major disruptions in circadian rhythms. Indeed,... (Review)
Review
Affective disorders such as major depression, bipolar disorder, and seasonal affective disorder are associated with major disruptions in circadian rhythms. Indeed, altered sleep/wake cycles are a critical feature for diagnosis in the DSM IV and several of the therapies used to treat these disorders have profound effects on rhythm length and stabilization in human populations. Furthermore, multiple human genetic studies have identified polymorphisms in specific circadian genes associated with these disorders. Thus, there appears to be a strong association between the circadian system and mood regulation, although the mechanisms that underlie this association are unclear. Recently, a number of studies in animal models have begun to shed light on the complex interactions between circadian genes and mood-related neurotransmitter systems, the effects of light manipulation on brain circuitry, the impact of chronic stress on rhythms, and the ways in which antidepressant and mood-stabilizing drugs alter the clock. This review will focus on the recent advances that have been gleaned from the use of pre-clinical models to further our understanding of how the circadian system regulates mood.
Topics: Affect; Animals; Circadian Rhythm; Cricetinae; Drug Evaluation, Preclinical; Humans; Mice; Models, Animal; Mood Disorders; Rats; Stress, Psychological; Suprachiasmatic Nucleus
PubMed: 21835596
DOI: 10.1016/j.euroneuro.2011.07.008 -
Journal of Neurochemistry Apr 2021The daily temporal order of physiological processes and behavior contribute to the wellbeing of many organisms including humans. The central circadian clock, which... (Review)
Review
The daily temporal order of physiological processes and behavior contribute to the wellbeing of many organisms including humans. The central circadian clock, which coordinates the timing within our body, is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Like in other parts of the brain, aging impairs the SCN function, which in turn promotes the development and progression of aging-related diseases. We here review the impact of aging on the different levels of the circadian clock machinery-from molecules to organs-with a focus on the role of the SCN. We find that the molecular clock is less effected by aging compared to other cellular components of the clock. Proper rhythmic regulation of intracellular signaling, ion channels and neuronal excitability of SCN neurons are greatly disturbed in aging. This suggests a disconnection between the molecular clock and the electrophysiology of these cells. The neuronal network of the SCN is able to compensate for some of these cellular deficits. However, it still results in a clear reduction in the amplitude of the SCN electrical rhythm, suggesting a weakening of the output timing signal. Consequently, other brain areas and organs not only show aging-related deficits in their own local clocks, but also receive a weaker systemic timing signal. The negative spiral completes with the weakening of positive feedback from the periphery to the SCN. Consequently, chronotherapeutic interventions should aim at strengthening overall synchrony in the circadian system using life-style and/or pharmacological approaches.
Topics: Aging; Animals; Circadian Clocks; Circadian Rhythm; Humans; Hypothalamus; Neurons; Suprachiasmatic Nucleus
PubMed: 33370457
DOI: 10.1111/jnc.15286 -
F1000Research 2022Meal timing resets circadian clocks in peripheral tissues, such as the liver, in seven days without affecting the phase of the central clock located in the...
Meal timing resets circadian clocks in peripheral tissues, such as the liver, in seven days without affecting the phase of the central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Anterior hypothalamus plays an essential role in energy metabolism, circadian rhythm, and stress response. However, it remains to be elucidated whether and how anterior hypothalamus adapts its circadian rhythms to meal timing. Here, we applied transcriptomics to profile rhythmic transcripts in the anterior hypothalamus of nocturnal female mice subjected to day- (DRF) or night (NRF)-time restricted feeding for seven days. This global profiling identified 128 and 3,518 rhythmic transcripts in DRF and NRF, respectively. NRF entrained diurnal rhythms among 990 biological processes, including 'Electron transport chain' and 'Hippo signaling' that reached peak time in the late sleep and late active phase, respectively. By contrast, DRF entrained only 20 rhythmic pathways, including 'Cellular amino acid catabolic process', all of which were restricted to the late active phase. The rhythmic transcripts found in both DRF and NRF tissues were largely resistant to phase entrainment by meal timing, which were matched to the action of the circadian clock. Remarkably, DRF for 36 days partially reversed the circadian clock compared to NRF. Collectively, our work generates a useful dataset to explore anterior hypothalamic circadian biology and sheds light on potential rhythmic processes influenced by meal timing in the brain (www.circametdb.org.cn).
Topics: Female; Animals; Mice; Suprachiasmatic Nucleus; Circadian Clocks; Circadian Rhythm; Hypothalamus; Liver
PubMed: 36531263
DOI: 10.12688/f1000research.125368.1 -
BioMed Research International 2018Cells expressing proteins characteristic of stem cells and progenitor cells are present in the suprachiasmatic nucleus (SCN) of the adult mammalian hypothalamus. Any... (Meta-Analysis)
Meta-Analysis
Cells expressing proteins characteristic of stem cells and progenitor cells are present in the suprachiasmatic nucleus (SCN) of the adult mammalian hypothalamus. Any relationship between this distinctive feature and the master circadian clock of the SCN is unclear. Considering the lack of obvious neurogenesis in the adult SCN relative to the hippocampus and other structures that provide neurons and glia, it is possible that the SCN has partially differentiated cells that can provide neural circuit plasticity rather than ongoing neurogenesis. To test this possibility, available databases and publications were explored to identify highly expressed genes in the mouse SCN that also have known or suspected roles in cell differentiation, maintenance of stem-like states, or cell-cell interactions found in adult and embryonic stem cells and cancer stem cells. The SCN was found to have numerous genes associated with stem cell maintenance and increased motility from which we selected 25 of the most relevant genes. Over ninety percent of these stem-like genes were expressed at higher levels in the SCN than in other brain areas. Further analysis of this gene set could provide a greater understanding of how adjustments in cell contacts alter period and phase relationships of circadian rhythms. Circadian timing and its role in cancer, sleep, and metabolic disorders are likely influenced by genes selected in this study.
Topics: Animals; Circadian Clocks; Circadian Rhythm; Gene Expression; Humans; Hypothalamus; Mice; Period Circadian Proteins; Suprachiasmatic Nucleus
PubMed: 30046594
DOI: 10.1155/2018/3610603