Circadian clock in mammals
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The paired suprachiasmatic nuclei (SCN) of the hypothalamus is the primary biological clock regulating circadian rhythms in mammals. The SCN generates coherent circadian oscillations through internal coupling of individual neurons that each express self-sustained circadian rhythms. The circadian clock consists of a core oscillator, output pathways, and feedback loops that allow it to maintain roughly 24-hour periods across different temperatures, known as temperature compensation.
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Principal circadian oscillators in mammals.
Almost all species exhibit daily changes in their biological activity with respect to a 24 hour light-dark cycle known as the circadian rhythm. The synchrony of an organism with both its external and internal environments is critical for the organism’s well-being and survival.
The presentation focuses on the fundamentals of circadian rhythm, components, development, molecular mechanism, functional and clinical implications of this astonishing system.
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SCN ( supra chiasmatic nucleus)
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3) Disruptions to circadian rhythms can lead to sleep disorders like jet lag or shift work disorder. Melatonin supplements and medications targeting melatonin receptors or o
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awarded to Jeffrey C. Hall, Michael Rosbash and
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- It has both exocrine and endocrine functions. Exocrine cells secrete enzymes like trypsinogen and amylase. Endocrine cells are clustered in islets of Langerhans.
- Acute pancreatitis is commonly caused by gallstones or alcohol and results from premature enzyme activation within the pancreas. Chronic pancreatitis involves irreversible inflammation and fibrosis over many years.
Mechanism of action of hormones
Hormones can be classified into four groups based on their mechanism of action. Group 1 hormones bind to intracellular receptors and include androgens, calcitriol, estrogens, glucocorticoids, and progestins. Group 2 hormones bind to cell surface receptors and use either cyclic AMP or cyclic GMP as second messengers, such as ACTH, ADH, and atrial natriuretic factor. Group 3 hormones also bind to cell surface receptors but use calcium or phosphatidyl inositols as second messengers like GnRH and TRH. Group 4 hormones signal through a kinase or phosphatase cascade as a second messenger, including insulin, GH, and prolactin.
Hypophysis (Pituitary Gland)
The document discusses the pituitary gland (hypophysis), which regulates other endocrine glands. It is located below the hypothalamus and has an anterior lobe that secretes hormones like growth hormone. The hypothalamus controls the pituitary through releasing and inhibitory hormones. The pituitary's hormones target various tissues and have roles like stimulating growth, milk production, and controlling metabolism. The document provides detailed information on the anatomy, histology, development, and functions of the pituitary gland and its relationship to the hypothalamus.
Hypothalamus
The hypothalamus is a small structure located at the base of the brain that connects the nervous system to the endocrine system. It produces neurohormones that stimulate or inhibit the secretion of hormones from the pituitary gland. Some key neurohormones produced by the hypothalamus include thyrotrophin-releasing hormone, corticotrophin-releasing hormone, gonadotropin-releasing hormone, growth hormone-releasing hormone, and antidiuretic hormone. These neurohormones help regulate important bodily functions.
Pituitary Gland
The pituitary gland is a small gland located at the base of the brain that regulates several important bodily functions. It is divided into anterior and posterior lobes. The anterior lobe secretes hormones that control other endocrine glands and regulate processes like growth, metabolism, and reproduction. These include growth hormone, thyroid stimulating hormone, and adrenocorticotropic hormone. The posterior lobe stores and releases oxytocin and vasopressin, which are produced in the hypothalamus and help regulate water balance and milk release. Disorders of the pituitary can impact hormone levels and cause wide-ranging symptoms.
Mechanism & action hormone
1) Hormones are organic substances that regulate growth, metabolism and other functions by acting as biochemical messengers. They can be classified based on their chemical composition and target organs.
2) Hormone action involves processes like synergism, permissiveness, antagonism and feedback loops. Lipid-soluble hormones like steroids directly enter cells and activate genes, while water-soluble hormones trigger intracellular signaling cascades.
3) The document discusses the mechanisms and characteristics of hormone action, including the different classes of receptors, signal amplification pathways, and how lipid-soluble and water-soluble hormones elicit their effects on target cells and tissues. Negative and positive feedback loops help regulate hormone secretion.
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Similar to Circadian clock in mammals
The role of vasopressin in light-induced c-Fos expression in the SCN
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- A population of retinal projections to the SCN express the neuropeptide vasopressin (VP), but the physiological significance is unknown.
- This study investigated whether VP released from retinal neurons mediates light-induced c-Fos expression in the SCN. Rats pre-treated with a VP antagonist before light exposure still showed c-Fos expression in the SCN, with no significant decrease. This suggests VP is not essential for generating light-induced c-Fos expression in the SCN.
Searching of membrane target for circadian clock
1. The suprachiasmatic nucleus (SCN) regulates circadian rhythms in mammals and individual SCN neurons express self-sustained circadian oscillations that generate a coherent output signal.
2. The study examines whether spike-associated currents are the primary target responsible for circadian modulation of firing rates in SCN neurons.
3. The results suggest that subthreshold, voltage-dependent cation channels, which are active at resting potential and increase opening probability with depolarization, may be the key target mediating effects of the circadian clock on electrical firing rates in SCN neurons.
Monitoring neural activities by optical imaging
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Allison Nash SURF proposal Melibe 2015
This study seeks to analyze the molecular basis of circadian rhythms and behavioral modulation by hormones in the nudibranch Melibe leonina. The goals are to localize circadian clock neurons in the central nervous system using immunohistochemistry, stain for the neurotransmitters conopressin and melatonin, and assess behavioral responses to injections of these hormones through video recordings. Understanding the relationship between clock neurons, hormones, and behavior can provide insights into circadian rhythm regulation applicable to fields like medicine.
CHRONOBIOLOGY.pptx
This document provides an overview of chronobiology, which is the study of biological time and circadian rhythms. Some key points:
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- At the molecular level, circadian rhythms are generated by transcriptional feedback loops involving clock genes such as Period and Cryptochrome.
- Disruptions to circadian rhythms are implicated in psychiatric
Allison Nash INBRE
The document reports on research investigating circadian rhythms in the nudibranch Melibe leonina. It was found that there are two circadian clocks: one in the brain controlling locomotion and one in the buccal ganglia controlling digestion/swallowing. Preliminary experiments showed neurons containing clock proteins CRY2 and CLK in the brain and buccal ganglia expressed independent daily activity rhythms. Future experiments aim to further characterize clock protein expression and activity of clock neurons in these regions.
Allison Nash INBRE
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Knsx13
WLIM1 is a candidate transcription factor downstream of the core circadian clock that may help extend circadian output in Arabidopsis thaliana. WLIM1 shows strong cycling under constant conditions and is anti-phasic to core clock proteins LHY and CCA1. However, ChIP-seq revealed only weak evening element binding, suggesting WLIM1 interacts with other proteins. Future experiments will characterize WLIM1's role and interactions with the core clock.
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and lifelong absence of FXR as occurs inthe FXR-null model, .docx
and lifelong absence of FXR as occurs in
the FXR-null model, can result in
abnormal metabolic effects that are quite
different from those caused by acute,
transient antagonism of this receptor.
Because the FXR-null mouse was
produced using Cre–loxP technology,
conditional disruption of this allele after
normal development has occurred can
now be used to help resolve this issue. An
alternative explanation is that the site(s)
of pharmacological action of
guggulsterone do not include all of the
tissues in which FXR is functional, such as
the liver and gut (i.e. although FXR
synthesis is uniformly absent from all
tissues of the FXR-null mouse model,
guggulsterone might antagonize FXR only
within a subset of these sites). In the
absence of in vivo data regarding the
modulation of FXR target gene expression
by guggulsterone, this is difficult to judge.
Thus, it remains a possibility that the
effects of orally-administered
guggulsterone occur primarily at the level
of the gut (i.e. versus gut and liver), for
instance, by affecting cholesterol
absorption and bile-acid reuptake
processes regulated by FXR, rather than
the hepatic biosynthesis and transport of
bile acids. Again, the conditional nature of
the strategy used to create the FXR-null
mouse model allows for tissue-specific
deletion of the FXR gene and might help
resolve this issue.
As reinforced by the recent work of
Urizar et al. [3], as well as by the present
therapeutic use of bile-acid binding
resins for hypercholesterolemia, there
exists an intimate linkage between bile
acid and cholesterol metabolism. Recent
demonstrations that FXR is also involved
in the regulation of genes (e.g. encoding
apolipoprotein A-I, apolipoprotein C-II
and phospholipids transfer protein) [4–6]
more closely linked with lipid rather
than bile-acid homeostasis, presents
additional avenues by which FXR
ligands could be beneficial for the
treatment of disorders of lipid
metabolism. As suggested by the work of
Urizar et al. [3] and others (e.g. [7]),
careful and comprehensive study of the
effects of natural products, such as
guggulsterone, on the function of nuclear
hormone receptors, is likely to yield
additional agents with desirable
therapeutic effects.
References
1 Sinal, C.J. et al. (2000) Targeted disruption of the
nuclear receptor FXR/BAR impairs bile acid and
lipid homeostasis. Cell 102, 731–744
2 Singh, R.B. et al. (1994) Hypolipidemic and
antioxidant effects of Commiphora mukul as an
adjunct to dietary therapy in patients with
hypercholesterolemia. Cardiovasc. Drugs Ther. 8,
659–664
3 Urizar, N.L. et al. (2002) A natural product that
lowers cholesterol as an antagonist ligand for
FXR. Science 296, 1703–1706
4 Claudel, T. et al. (2002) Bile acid-activated nuclear
receptor FXR suppresses apolipoprotein A-I
transcription via a negative FXR response
element. J. Clin. Invest. 109, 961–971
5 Kast, H.R. et al. (2001) Farnesoid X-activated
receptor induces apolipoprotein C-II
transcription: a molecular mech.
Chronopharmacology- Biological and Circadian rhythms.pptx
This document discusses chronopharmacology and biological rhythms. It begins by defining chronobiology as the study of periodic phenomena in living organisms and their adaptation to solar and lunar rhythms. Chronopharmacology is the study of how drug effects and pharmacokinetics are influenced by biological rhythms. Biological rhythms include circadian rhythms which have a period of about 24 hours and regulate functions like sleep-wake cycles and hormone secretion. The suprachiasmatic nucleus located in the hypothalamus acts as the master circadian clock, receiving light input from the retina and coordinating circadian rhythms. Disruptions to circadian rhythms can occur from jet lag, shift work, and in various diseases.
Making Optical and Electrophysiological Measurements in the Brain of Head-Fix...
A growing number of researchers are moving from reduced preparations such as dissociated cultured neurons or brain slices, to experimentation in live animals - in vivo - using advanced methods such as two-photon microscopy or combined optogenetics and patch-clamp recordings. In order to immobilize the animal during these challenging applications general anesthesia is often administered; however, the use of anesthetics greatly distorts brain function.
Is there a better way?
In this exclusive webinar sponsored by Neurotar Ltd, leading experts in the technology will discuss methodology, best-practices and show attendees how to immobilize the rodent’s head without restraining its body using the Mobile HomeCage™. The result is a controlled research environment for studying brain function in awake, freely-moving subjects with no stress to the animal. Discussion around how this technique can be applied to the study of neuronal plasticity, neurodegeneration, addiction, brain trauma and other pathophysiological conditions in longitudinal experiments will be included. Furthermore, presenters will demonstrate how this methodology is best combined with microscopy and electrophysiology techniques – all in vivo.
Eeg seminar
The document discusses electrophysiology techniques used to study the electrical activity of neurons and other excitable cells. It begins by explaining that electrophysiology allows measurement of ionic currents across cell membranes and helps understand how cells and tissues function. Different techniques are then described, including intracellular recordings, patch clamp recordings, and extracellular recordings. The document outlines the historical development of the field and covers topics like resting membrane potentials, action potentials, ion channels, and how neurons encode and transmit information.
Eeg time series data analysis in focal cerebral ischemic rat model
The mammalian brain exists in a number of attractors. In order to characterize these attractors we have collected the time series data from the EEG recording of rat models. The time series was obtained by recording of the frontoparietal, occipital and temporal regions of the rat brain. Significant changes have
been observed in the dimensionalities of these brain attractors between the normal state, focal ischemic
state and the drug induced state. Thus, these three states were characterized by unique lyapunov exponents,
correlation dimensions and embedding dimensions. The inverse of the lyapunov exponent gave us the long
term coherence of the rat brain and was found to differ for the three states. The autocorrelation function
measured the mean similarity of the EEG signal with itself after a time t. The degree of decay was high indicating that there was maximum correlation in the time series. Thus, the autocorrelation functions clearly indicate the effect of focal cerebral ischemia and drugs induced on the rat brain.
Menegaz d sbbf 2019
- The study investigated the effects of in vivo hyperkalemia on neurons in the nucleus of the solitary tract (NTS) using brainstem slices from control rats, adrenalectomized rats, and rats pretreated with spironolactone.
- Results showed that hyperkalemia increased the firing rate of NTS neurons and depolarized their membrane potential. Neurons from adrenalectomized rats did not fire in response to hyperkalemia.
- Pretreatment with spironolactone partially prevented the effects of hyperkalemia on NTS neuronal excitability. This suggests that endogenous aldosterone increases the excitability of NTS neurons during hyperkalemia.
Gourov and Curran 2014
This document describes an in vitro model using mouse hippocampal brain slices to study the recovery of functional connectivity in neural tissue after damage. The study found that regularly stimulating severed hippocampal slices with low frequency electrical pulses promoted the recovery of synaptic connections between the slices over time. Specifically, they observed fiber volley potentials and excitatory postsynaptic potentials reemerging between 20-40 minutes and 1 hour after initiating stimulation, respectively, suggesting the restoration of neural connectivity. The authors hypothesize that electrical stimulation enhances recovery by maintaining neural membrane function and propose this model could help investigate strategies to promote recovery from brain injury.
Studying Epilepsy in Awake Head-Fixed Mice Using Microscopy, Electrophysiolog...
Epilepsy research employs sophisticated research methods such as fluorescence optical imaging and optogenetics, as well as novel electrophysiological techniques, to address unresolved questions about seizure generation and propagation on the cellular and circuitry levels. Since epilepsy research is most relevant when performed in non-anesthetized mice, it requires specialized tools that ensure stable head fixation during high-precision imaging and recordings.
In this webinar, Dr. Anthony Umpierre (Prof. LongJun Wu group, Mayo Clinic, USA) and Prof. Rob Wykes (UCL, UK) present their research on microglial calcium signaling and epileptic networks carried out in awake head-fixed mice. In addition to sharing exciting new findings, the presenters address the challenges of working with awake mice.
Key topics will include…
- Mesoscopic investigations of seizure dynamics and propagation using widefield calcium imaging
- Generating full-bandwidth electrophysiological recordings enabled by graphene micro-transistors to detect spreading depolarizations and seizures
- On-demand optogenetic induction of spreading depolarizations to investigate pharmacological suppression in the awake brain
- The impact of acute versus chronic window preparations on microglial calcium activity
- The use of genetically encoded calcium indicators to study calcium dynamics in microglia
- The effects of bi-directional shifts in neuronal activity caused by kainate-triggered status epilepticus and isoflurane anesthesia on microglial calcium
Gray et al. 2001 NatNeuro
Bilateral but not unilateral lesions of preBötzinger complex (preBötC) neurons that express neurokinin-1 receptors (NK1R neurons) in rats profoundly disrupted normal breathing patterns and responses to challenges. Rats with near complete bilateral destruction of preBötC NK1R neurons (preBötC- rats) showed an ataxic breathing pattern with irregular breathing periods and amplitude. They also exhibited abnormal blood gas levels and pathological responses to changes in oxygen and carbon dioxide levels, including fatal apneas with 100% oxygen. Thus, the approximately 600 preBötC NK1R neurons in rats appear critical for generating normal breathing rhythms and regulating responses to physiological challenges
04 nerve singnal processing
The document discusses nerve signal processing and transmission between neurons. It covers topics like the resting membrane potential, action potentials, propagation of action potentials, synaptic transmission both electrical and chemical, different neurotransmitter systems including acetylcholine, serotonin, dopamine, norepinephrine, glutamate, and GABA. It also mentions inhibitory versus excitatory postsynaptic potentials and currents.
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The role of vasopressin in light-induced c-Fos expression in the SCN
and lifelong absence of FXR as occurs inthe FXR-null model, .docx
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Certified as an ISO/IEC 27001: Information Security Management Systems (ISMS) Lead Implementer, Data Protection Officer, and Cyber Risks Analyst, Denis brings a heightened focus on data security, privacy, and cyber resilience to every endeavor.
His expertise extends across a diverse spectrum of reporting, database, and web development applications, underpinned by an exceptional grasp of data storage and virtualization technologies. His proficiency in application testing, database administration, and data cleansing ensures seamless execution of complex projects.
What sets Denis apart is his comprehensive understanding of Business and Systems Analysis technologies, honed through involvement in all phases of the Software Development Lifecycle (SDLC). From meticulous requirements gathering to precise analysis, innovative design, rigorous development, thorough testing, and successful implementation, he has consistently delivered exceptional results.
Throughout his career, he has taken on multifaceted roles, from leading technical project management teams to owning solutions that drive operational excellence. His conscientious and proactive approach is unwavering, whether he is working independently or collaboratively within a team. His ability to connect with colleagues on a personal level underscores his commitment to fostering a harmonious and productive workplace environment.
Date: May 29, 2024
Tags: Information Security, ISO/IEC 27001, ISO/IEC 42001, Artificial Intelligence, GDPR
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Circadian clock in mammals
- 1. Circadian Clock in Mammals Nikolai I. Kononenko Department of General Physiology of Nervous System, Bogomoletz Institute of Physiology, Kiev, Ukraine
- 2. INTRODUCTION As a consequence of the Earth’s rotation about its axis approximately every 24 hours, most organisms on our planet are subjected to fluctuations of light and temperature. A diverse range of species, from cyanobacteria to humans, developed endogenous biological clocks that allow for the anticipation of these daily variations. Thus, our internal physiology and function are fundamentally intertwined with this geophysical cycle.
- 3. The mammalian circadian timing system Hypothalamus The paired suprachiasmatic nuclei (SCN) of the hypothalamus is the primary biological clock regulating circadian rhythms in mammals. It has been show by lesion of these nuclei, destroying circadian behavior, with subsequent its restoration by implantation of SCN from donor animal. Retino-hypothalamic tract
- 4. Coronal and horizontal slices of suprachiasmatic nuclei Retino-hypothalamic glutamate tract ~ 700
- 5. Suprachiasmatic nuclei of the mouse 1 mm
- 6. SCN neurons of the mouse at infrared differential interference contrast microscopy 100 m
- 7. Multiple-unit activity (MUA) from the rat SCN in vitro . from ~100 SCN neurons
- 8. 1. The paired suprachiasmatic nuclei (SCN) of the hypothalamus is the primary biological clock regulating circadian rhythms in mammals
- 9. Multielectrode array dish (MED) Hz 0 1 2 3 4 5 (Days) 1 min 1 mm
- 10. Activity of dispersed SCN neurons in MED and MUA of SCN in slice preparation Firing rate (Hz)
- 11. Individual SCN neurons express self-sustained circadian oscillations. As a result of internal coupling, the SCN generates a coherent output signal
- 12. Three main components of clock: a) oscillator, b) gear, and c) hands or digitals
- 13. Circadian-clock core Messenger Membrane target Hz
- 14. Minimal mammalian circadian clockwork model (circadian oscillator) From Scheper et al., J Neurosci 1999 The delay and nonlinearity in the protein production and the cooperativity in the negative feedback were found to be necessary and sufficient to generate robust circadian oscillations Period Period Period*
- 15. Temperature compensation The effect of changes in temperature on the rate of most biochemical reactions is measured by a Q 10 value, which is defined as the ratio of the rate of a given process at one temperature to the rate at a temperature 10°C lower. Q 10 = V t /V t-10 o C for known biochemical reaction 2 < Q 10 < 3 , for period of circadian rhythms Q 10 ~1
- 16. Light production in fireflies is due to a type of chemical reaction called bioluminescence . This process occurs in specialised light-emitting organs , usually on a firefly's lower abdomen. The enzyme luciferase acts on the luciferin , in the presence of magnesium ions, ATP , and oxygen to produce light. Genes coding for these substances have been inserted into many different organisms Firefly
- 17. Circadian rhythms of PER2::LUC bioluminescence recorded from knock-in mouse SCN neurons in dispersed culture From D.K.Welsh et al., Annu. Rev. Physiol. , 2010
- 18. Activity of dispersed SCN neurons in MED and MUA of SCN in slice preparation Firing rate (Hz)
- 19. Circadian rhythms of PER2::LUC bioluminescence recorded from mouse SCN neurons in slice preparation
- 20. 1. Nothing is known about messenger(s) between circadian-clock core and membrane target(s) responsible for circadian peaks of firing rate 2. Nature of membrane target(s) responsible for circadian peaks of firing rate enigmatic and contradictory
- 21. Nature, 2002, 16 , 286-290
- 23. Nature Neuroscience, 2005, 8 , 650-656
- 24. Nature Neuroscience, 2006, 9 , 1041-1049