scholarly journals Flies, clocks and evolution

2001 ◽  
Vol 356 (1415) ◽  
pp. 1769-1778 ◽  
Author(s):  
Ezio Rosato ◽  
Charalambos P. Kyriacou
Keyword(s):  
Gene Regulation ◽  
Negative Feedback ◽  
Clock Gene ◽  
Circadian System ◽  
Gene Duplications ◽  
Closely Related Species ◽  
Feedback Model ◽  
Silk Moth ◽  
The Brain

The negative feedback model for gene regulation of the circadian mechanism is described for the fruitfly, Drosophila melanogaster . The conservation of function of clock molecules is illustrated by comparison with the mammalian circadian system, and the apparent swapping of roles between various canonical clock gene components is highlighted. The role of clock gene duplications and divergence of function is introduced via the timeless gene. The impressive similarities in clock gene regulation between flies and mammals could suggest that variation between more closely related species within insects might be minimal. However, this is not borne out because the expression of clock molecules in the brain of the giant silk moth, Antheraea pernyi , is not easy to reconcile with the negative feedback roles of the period and timeless genes. Variation in clock gene sequences between and within fly species is examined and the role of co-evolution between and within clock molecules is described, particularly with reference to adaptive functions of the circadian phenotype.

scholarly journals Neuroendocrine Impairments of Polycystic Ovary Syndrome

Endocrinology ◽  
2019 ◽  
Vol 160 (10) ◽  
pp. 2230-2242 ◽  
Author(s):  
Amy Ruddenklau ◽  
Rebecca E Campbell
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Neuronal Network ◽  
Negative Feedback ◽  
Polycystic Ovary ◽  
Steroid Hormone ◽  
Unknown Etiology ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
The Brain

Abstract Polycystic ovary syndrome (PCOS) is a prevalent and distressing disorder of largely unknown etiology. Although PCOS defined by ovarian dysfunction, accumulating evidence supports a critical role for the brain in the ontogeny and pathophysiology of PCOS. A critical pathological feature of PCOS is impaired gonadal steroid hormone negative feedback to the GnRH neuronal network in the brain that regulates fertility. This impairment is associated with androgen excess, a cardinal feature of PCOS. Impaired steroid hormone feedback to GnRH neurons is thought to drive hyperactivity of the neuroendocrine axis controlling fertility, leading to a vicious cycle of androgen excess and reproductive dysfunction. Decades of clinical research have been unable to uncover the mechanisms underlying this impairment, because of the extreme difficulty in studying the brain in humans. It is only recently, with the development of preclinical models of PCOS, that we have begun to unravel the role of the brain in the development and progression of PCOS. Here, we provide a succinct overview of what is known about alterations in the steroid hormone–sensitive GnRH neuronal network that may underlie the neuroendocrine defects in clinical PCOS, with a particular focus on those that may contribute to impaired progesterone negative feedback, and the likely role of androgens in driving this impairment.

Entrainment of circadian clocks in mammals by arousal and food

2011 ◽  
Vol 49 ◽  
pp. 119-136 ◽  
Author(s):  
Ralph E Mistlberger ◽  
Michael C Antle
Keyword(s):  
Clock Gene ◽  
Gene Mutations ◽  
Circadian System ◽  
Neural Pathways ◽  
Suprachiasmatic Nuclei ◽  
Social Stimuli ◽  
Clock Gene Expression ◽  
Circadian Oscillators ◽  
External Time ◽  
The Brain

Circadian rhythms in mammals are regulated by a system of endogenous circadian oscillators (clock cells) in the brain and in most peripheral organs and tissues. One group of clock cells in the hypothalamic SCN (suprachiasmatic nuclei) functions as a pacemaker for co-ordinating the timing of oscillators elsewhere in the brain and body. This master clock can be reset and entrained by daily LD (light–dark) cycles and thereby also serves to interface internal with external time, ensuring an appropriate alignment of behavioural and physiological rhythms with the solar day. Two features of the mammalian circadian system provide flexibility in circadian programming to exploit temporal regularities of social stimuli or food availability. One feature is the sensitivity of the SCN pacemaker to behavioural arousal stimulated during the usual sleep period, which can reset its phase and modulate its response to LD stimuli. Neural pathways from the brainstem and thalamus mediate these effects by releasing neurochemicals that inhibit retinal inputs to the SCN clock or that alter clock-gene expression in SCN clock cells. A second feature is the sensitivity of circadian oscillators outside of the SCN to stimuli associated with food intake, which enables animals to uncouple rhythms of behaviour and physiology from LD cycles and align these with predictable daily mealtimes. The location of oscillators necessary for food-entrained behavioural rhythms is not yet certain. Persistence of these rhythms in mice with clock-gene mutations that disable the SCN pacemaker suggests diversity in the molecular basis of light- and food-entrainable clocks.

Neurobiology of Bipolar Disorder

2020 ◽  
pp. 141-154
Author(s):  
Francisco Romo-Nava ◽  
Susan L. McElroy
Keyword(s):  
Bipolar Disorder ◽  
Neuronal Network ◽  
Intracellular Signaling ◽  
Circadian System ◽  
Medical Comorbidities ◽  
Subcortical Regions ◽  
Spinal Afferents ◽  
New Evidence ◽  
The Brain

As frequently occurs in science, progress made on the neurobiology of bipolar disorder has followed a nonlinear course that often revisits deserted concepts. The neurobiological blueprint of bipolar disorder continues to unfold from a neurotransmitter-based hypothesis to include peptides and intracellular signaling pathways, and into a broader neuronal network perspective that involves cortical and subcortical regions in the brain. Moreover, new evidence makes it increasingly clear that the mechanisms of disease in bipolar disorder extend beyond the brain, providing plausible “missing links” between psychopathology and the elevated medical comorbidities. This is illustrated by the expanding role of the circadian system in bipolar disorder and the emerging evidence on the contribution of spinal afferents to the construct of mood, portraying that brain–body communication pathways are relevant to the pathophysiology of bipolar disorder. This chapter provides an overview of the current and emerging neurobiological frameworks for bipolar disorder.

scholarly journals Circadian Rhythms in Bacterial Sepsis Pathology: What We Know and What We Should Know

2021 ◽  
Vol 11 ◽  
Author(s):  
Malena Lis Mul Fedele ◽  
Camila Agustina Senna ◽  
Ignacio Aiello ◽  
Diego Andres Golombek ◽  
Natalia Paladino
Keyword(s):  
Circadian Rhythms ◽  
Animal Models ◽  
Clock Gene ◽  
Circadian System ◽  
Main Role ◽  
Bacterial Sepsis ◽  
Hypothermic Response ◽  
Sepsis Induction ◽  
Improve Patient

Sepsis is a syndrome caused by a deregulated host response to infection, representing the primary cause of death from infection. In animal models, the mortality rate is strongly dependent on the time of sepsis induction, suggesting a main role of the circadian system. In patients undergoing sepsis, deregulated circadian rhythms have also been reported. Here we review data related to the timing of sepsis induction to further understand the different outcomes observed both in patients and in animal models. The magnitude of immune activation as well as the hypothermic response correlated with the time of the worst prognosis. The different outcomes seem to be dependent on the expression of the clock gene Bmal1 in the liver and in myeloid immune cells. The understanding of the role of the circadian system in sepsis pathology could be an important tool to improve patient therapies.

Adiposity signals and food reward: expanding the CNS roles of insulin and leptin

2003 ◽  
Vol 284 (4) ◽  
pp. R882-R892 ◽  
Author(s):  
Dianne P. Figlewicz
Keyword(s):  
Energy Balance ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Mental Illnesses ◽  
Therapeutic Approaches ◽  
Reward Circuitry ◽  
Feedback Model ◽  
Adiposity Signals ◽  
The Central Nervous System ◽  
The Brain

The hormones insulin and leptin have been proposed to act in the central nervous system (CNS) as adiposity signals as part of a theoretical negative feedback loop that senses the caloric stores of an animal and orchestrates adjustments in energy balance and food intake. Much research has provided support for both the existence of such a feedback loop and the specific roles that insulin and leptin may play. Most studies have focused on hypothalamic sites, which historically are implicated in the regulation of energy balance, and on the brain stem, which is a target for neural and humoral signals relating to ingestive acts. More recent lines of research, including studies from our lab, suggest that in addition to these CNS sites, brain reward circuitry may be a target for insulin and leptin action. These studies are reviewed together here with the goals of providing a historical overview of the findings that have substantiated the originally hypothesized negative feedback model and of opening up new lines of investigation that will build on these findings and allow further refinement of the model of adiposity signal/CNS feedback loop. The understanding of how motivational circuitry and its endocrine or neuroendocrine modulation contributes to normal energy balance regulation should expand possibilities for future therapeutic approaches to obesity and may lead to important insights into mental illnesses such as substance abuse or eating disorders.

The evolving role of Hox genes in arthropods

Development ◽  
1994 ◽  
Vol 1994 (Supplement) ◽  
pp. 209-215
Author(s):  
Michael Akam ◽  
Michalis Averof ◽  
James Castelli-Gair ◽  
Rachel Dawes ◽  
Francesco Falciani ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Early Development ◽  
Hox Genes ◽  
Homeotic Gene ◽  
Homeotic Genes ◽  
Gene Duplications ◽  
Fushi Tarazu ◽  
Hox Gene ◽  
Hox Cluster

Comparisons between Hox genes in different arthropods suggest that the diversity of Antennapedia-class homeotic genes present in modern insects had already arisen before the divergence of insects and crustaceans, probably during the Cambrian. Hox gene duplications are therefore unlikely to have occurred concomitantly with trunk segment diversification in the lineage leading to insects. Available data suggest that domains of homeotic gene expression are also generally conserved among insects, but changes in Hox gene regulation may have played a significant role in segment diversification. Differences that have been documented alter specific aspects of Hox gene regulation within segments and correlate with alterations in segment morphology rather than overt homeotic transformations. The Drosophila Hox cluster contains several homeobox genes that are not homeotic genes – bicoid, fushi-tarazu and zen. The role of these genes during early development has been studied in some detail. It appears to be without parallel among the vertebrate Hox genes. No well conserved homologues of these genes have been found in other taxa, suggesting that they are evolving faster than the homeotic genes. Relatively divergent Antp-class genes isolated from other insects are probably homologues of fushi-tarazu, but these are almost unrecognisable outside of their homeodomains, and have accumulated approximately 10 times as many changes in their homeodomains as have homeotic genes in the same comparisons. They show conserved patterns of expression in the nervous system, but not during early development.

scholarly journals Negative Feedback Role of Astrocytes in Shaping Excitation in Brain Cell Co-cultures

2021 ◽  
Vol 15 ◽  
Author(s):  
Elnaz Khezerlou ◽  
Neela Prajapati ◽  
Mark A. DeCoster
Keyword(s):  
Glial Cells ◽  
Negative Feedback ◽  
Inflammatory Responses ◽  
Potential Effect ◽  
Brain Cell ◽  
No Production ◽  
Neuronal Synapses ◽  
The Individual ◽  
The Brain

Glial cells play an important role in maintaining neuronal homeostasis and may thus influence excitability in epileptogenesis. These cells in the brain have glutamate (Glu) transporters, which remove this neurotransmitter from the extracellular space. Lack of negative (−) feedback makes local neuronal circuits more excitable and potentially contributing to epileptogenic phenomena. In this study, the role of glial cells in providing (−) feedback is shown through different models of brain cells in culture imaged for intracellular calcium concentration [(Ca2+)i]. Moreover, here we study the individual cells by putting them in categories. Neuronal networks with high and low (−) feedback were established by using anti-mitotics to deplete glial cells. Separate stimuli with very low subthreshold concentrations of Glu (250–750 nM) were added to cultures to test if the order of stimulations matter in regard to calcium dynamics outcomes. Additionally, KCl and ATP were used to stimulate glial cells. We found that for cultures high in (−) feedback, order of the stimulus was not important in predicting cellular responses and because of the complexity of networks in low (−) feedback cultures the order of stimulus matters. As an additional method for analysis, comparison of high (−) feedback cultures, and pure astrocytes was also considered. Glial cells in pure astrocyte cultures tend to be larger in size than glial cells in high (−) feedback cultures. The potential effect of (−) feedback at the blood brain barrier (BBB) was also considered for the inflammatory responses of nitric oxide (NO) production and [Ca2+]i regulation using brain microvascular endothelial cells (BMVECs). The inflammatory and calcium signaling pathways both indicate the negative feedback role of astrocytes, poised between the BBB and structures deeper within the brain, where neuronal synapses are homeostatically maintained by glial uptake of neurotransmitters.

scholarly journals Role of GABA-A and GABA-B receptors of the brain in the hypothalamo-pituitary-testicular regulation by the negative feedback mechanism

1995 ◽  
Vol 41 (4) ◽  
pp. 36-38
Author(s):  
Ye. V. V. Naumenko ◽  
A. V. Amikishiyeva ◽  
L. I. Serova
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Negative Feedback ◽  
Feedback Mechanism ◽  
Gaba A ◽  
Negative Feedback Mechanism ◽  
The Central Nervous System ◽  
The Brain ◽  
Stimulation Of

The role of gamma-aminobutyric acid (GABA) of the brain and its receptors in the hypothalamo-pituitary-testicular (HPT) regulation by the negative feedback mechanism was for the first time studied in sham-operated and unilaterally castrated adult Wister rats. Increased level of GABA in the central nervous system following an injection of GABA transaminase inhibitor, aminoacetic acid, into the lateral ventricle of the brain was associated with activation of a compensatory increase of testosterone level in the blood, caused by unilateral castration. GABA effect is mediated through the receptors. Muscimol stimulation of GABA-A receptors of the central nervous system activated and their blocking with bicucullin inhibited a compensatory increase of testosterone level in the blood caused by hemicastration. Baclofen stimulation of cerebral GABA-B receptors was associated with an inhibition and their saclofen blocking with stimulation of the level of male sex steroid hormone in the blood following unilateral castration. A conclusion is made about participation of GABAergic mechanisms of the brain in the regulation of HPT function via the negative feedback mechanism

scholarly journals The Role of Mammalian Glial Cells in Circadian Rhythm Regulation

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Donají Chi-Castañeda ◽  
Arturo Ortega
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Glial Cells ◽  
Clock Gene ◽  
Clock Genes ◽  
Time Pattern ◽  
Clock Gene Expression ◽  
Genetically Determined ◽  
The Brain ◽  
Clock Protein

Circadian rhythms are biological oscillations with a period of about 24 hours. These rhythms are maintained by an innate genetically determined time-keeping system called the circadian clock. A large number of the proteins involved in the regulation of this clock are transcription factors controlling rhythmic transcription ofso-calledclock-controlled genes, which participate in a plethora of physiological functions in the organism. In the brain, several areas, besides the suprachiasmatic nucleus, harbor functional clocks characterized by a well-defined time pattern of clock gene expression. This expression rhythm is not restricted to neurons but is also present in glia, suggesting that these cells are involved in circadian rhythmicity. However, only certain glial cells fulfill the criteria to be called glial clocks, namely, to display molecular oscillators based on the canonical clock protein PERIOD, which depends on the suprachiasmatic nucleus for their synchronization. In this contribution, we summarize the current information about activity of the clock genes in glial cells, their potential role as oscillators as well as clinical implications.

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