Biological Clocks &

Dr. Milagros Rabe, MD, MSc,

Rhythms

22 February
2016

PhD

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These cryptochrome and period gene products

provides a negative feedback for the transcription of
clock genes. This happens around approximately 24
hours.

BMAL-1 and Clock gene activate transcription of Per

& Cry genes to eventually produce proteins.

The cryptochrome and period proteins, when

produced, will now cause inactivation of the BMALclock heterodimer (negative feedback).
The time in which you accumulate the period and
cryptochrome gene products from the time of
synthesis and termination is approximately 24 hours.
SCN knows when its morning and evening even
without the presence of sunlight.
The body knows when to secrete melatonin when you
sleep and the body temp decreases during the night.

III. Regulation of Circadian Rhythm

A.

Circadian clock molecules

Work in pacemaking and phase regulation of the

circadian rhythm in all cells
1.
2.
3.
4.

Clock Gene crucial regulator of SCN

BMAL -1 protein gene
- brain muscle ARNT like 1
Per (period) &
Cry (cryptochrome) genes
Inactivate Bmal proteins
Clock + BMAL-1 + heterodimer
Positive regulator or transcriptoin of period
genes Cry 1 & 2 gene products
Negative regulator of clock gene
transcription

IV. Terms
1.

Clock gene and BMAL protein gene transcribe the

clock protein and BMAL protein respectively.
They form a dimer that direct the transcription of
period and cryptochrome genes.
When period and cryptochrome genes are transcribed
and translated, then it produces cryptochrome and
period gene products.

2.

ENTRAIN
Synchronization
Internal clock to the external clock
ENTTRAINING AGENT
that which synchronizes the internal clock to
environmental cues - temeprature, light and actvity
(work, feeding, etc)
If you are diurnal organism, you will have increased
activity during the daytime.

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Even if youre an evening person, the body

temp will always be cold at night.

environmental cues / Zeitgeber

3. CHRONOTYPE

Refers to behavioral manifestation of

underlying circadian rhythms of physical
processes
Children are normally morning individuals and
older people usually become evening
chronotype.
Take a quiz and it will tell you if youre a
morning or evening chronotype.

Chronotype shifts as we get older. Usually it

has to do with alertness during certain times of
the day.

Suprachiasmatic nucleus gets light through the

retina. This will lead to entraining of the
external clock to the internal clock.
When shifting time-zones, the Zeitberg cycle
also shifts. This entrains the internal clock to
the external clock.
However even blind people have intact
circadian rhythms.

Collect infromation from other preipheral

clocks in the body that tell the degree of activity
and tell the body when to be active.
Afferents to the SCN

Retinohypothalamic Tract

Geniculo-hypothalamic Tract

Raphe Nuclei (Serotonergic)

Basal Forebrain (Cholinergic)

Mamillary Hypothalamus (Histaminergic)

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