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BBS2051 Case 1 Camping
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Case 1 CampingLearning goals:
What is the circadian rhythm and what is its function?
The circadian rhythm is an internal biological clock which adapts to different times of the
day. It’s reset by Zeitgeber, environmental clues
Peripheral clock:
Infradian clock: Longer than circadian
Diurnal clock: Daytime period
Nocturnal clock: Darkness period, depends on seasons
Title rhythm: Depends on moon cycle, influences ocean
Cycle of moon and sun
Circadian: Period of 12 months
Hormonal levels
Melatonin: SCN directly interacts with the pineal gland though the sympathetic neurons of
the superior cervical ganglion; in turn, the rhythmic activity of the SCN determines the
release of melatonin, which directly correlated with day length. In both nocturnal and diurnal
animals, melatonin production peaks in the middle of the night, between 24:00 and 03:00,
inducing activity in the former and rest/ sleep the latter.
Melatonin plats several key roles, and can be considered the central ‘relayer’ which conveys
information about light-dark cycles. In mammals, melatonin is also essential in the regulation
of reproductive behaviour and sleep. In both primates and humans, melatonin modulates
adrenal glucocorticoid production, being able to supress cortisol production.
Cortisol : In humans cortisol production usually increases during the night and shows a peak
of secretion in the morning, around 7:00-8:00, in this wat setting the endocrine balance for
the stress associated with waking. Glucocorticoids and cortisol can modulate the expression
of clock controlled genes in the liver, kidney and adipose tissue.
The circadian rhythm of cortisol can be modified by environmental conditions, including
stressful events, light, and feeding.
o Acute stress leads to ACTH-induced release of cortisol that is not necessarily in phase
with the circadian pattern.
o Light exposure at night induces Per1 gene expression in the adrenal gland and
corticosterone release by activation of sympathetic fibers independently of the
hypothalamic-pituitary-adrenal axis.
o Restricted feeding triggers an anticipatory rise in circulating cortisol before food
access. This anticipatory peak is ACTH independent and distinct from the circadian
rhythm of cortisol controlled by the SCN clock
Body temperature:
In humans, the maximal body temperature is reached in the late afternoon and drops to a
minimum at the end of sleep phase. The circadian component in the body temperature is
under the control of the SCN, which project to the preoptic area. The SCN is continuously
entrained by light signals from the retinohypothalamic tract and, in turn, synchronizes
circadian body temperature cycles to environmental light-dark cycles
, How is the CR regulated by signals?
o PER, BMAL1, CRY1; CRY2, ARNTL
The molecular clock machinery involves 24-oscillations of core clock components known as
clock genes.
Clock genes: Genes whose protein products are necessary for generating circadian
rhythmicity within individual cells.
Transcription factors: CLOCK and BMAL1, dimerize and bind to E-box
sequences in the promotors of other clock genes
PER1/2/3, CRY1/2 are activated by the TF
The molecular clockwork relies on transcriptional-translational feedback loops. The main
loop involves BMAL1 stimulating the transcription of PER and CRY genes. In the auxiliary
loops, ROR and REVERB stimulate and inhibit the transcription of BMAL1
After reaching a given concentration in the cytoplasm, PERs and CRYs dimerize and
translocate into the nucleus to inhibit their own transcription mediated by CLOCK/BMAL1
dimers. Auxiliary loops are composed of the circadian nuclear receptors REV-ERBα-β and
RORα-β-γ, which modulate negatively and positively the circadian oscillations of Bmal1
expression
This cycle takes 24h
At night: much PER
During day: no PER1.
1. CLOCK and BMAL1 activate transcription of PER and CRY2.
2. PER and CRY to cytoplasm →dimerize →PER degraded to delay the cycle
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