Biological Clocks & RhythmsDr. Milagros Rabe, MD, MSc, PhD

22 February 2016

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III. Regulation of Circadian Rhythm

A. Circadian clock molecules

Work in pacemaking and phase regulation of the circadian rhythm in all cells

1. Clock Gene – crucial regulator of SCN2. BMAL -1 protein gene –

- brain muscle ARNT like 13. Per (period) &4. 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

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.

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 BMAL-clock 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 it’s 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.

IV. Terms

1. ENTRAIN Synchronization Internal clock to the external clock

2. 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.

Even if you’re an evening person, the body temp will always be cold at night.

environmental cues / ZeitgeberTranscribers: Last Name, Last Name, Last Name, Last Name, Last Name, Last NameEditors: Last Name, Last Name, Last Name, Last Name, Last Name, Last Name [Subject][Title of Lecture]

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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 you’re 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)

Transcribers: Last Name, Last Name, Last Name, Last Name, Last Name, Last NameEditors: Last Name, Last Name, Last Name, Last Name, Last Name, Last Name [Subject][Title of Lecture]

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Transcribers: Last Name, Last Name, Last Name, Last Name, Last Name, Last NameEditors: Last Name, Last Name, Last Name, Last Name, Last Name, Last Name [Subject][Title of Lecture]

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