Circadian Rhythms

What is Circadian Rhythms?

Circadian Rhythms are our natural biological processes that follow a 24-hour cycle. For something to follow a Circadian Rhythm it must follow three rules:

1) Endogenous, or exists without any external cues causing it, and lasts 24 hours
2) Entrainable by zeitgebers (cues), or can be modified by external cues such as light or nonphotic cues
3) Temperature compensation, or our body can adjust our circadian rhythms based on the temperatures

What is a Free-running period?

Free-running period is the natural cycle length for a person’s circadian rhythm when it is placed in an environment without external time cues such as light or temperature changes

1) Free-running period is how our body determines a biological day without cues
→ in humans it is a little longer than 24 hours

Why do we have circadian rhythms

All mammalian cells keep time using clock genes which are a group of four genes that establish a molecular clock
→ CLOCK, BMAL1, Per, Cry

These genes form a feedback loop with a positive and a negative arm
1) CLOCK and BMAL1 will dimerize and activate the negative arm: PER and CRY
2) PER and CRY are translated and dimerize
3) PER is phosphorylated, and then the new pPER:CRY dimer will move back into the nucleus
4) This new complex inhibits CLOCK+BMAL1 from further transcribing PER and CRY before being degraded

This process occurs over 24 hours, with CLOCK;BMAL1 affecting other clock controlled genes, creating rhythmic expression of genes

Why is Light the major zeitgeber? What is the master pacemaker?

Light is the strongest zeitgeber and entrainer of the circadian rhythm and works with the suprachiasmatic nucleus

1) The suprachiasmatic nucleus in the brain is the master pacemaker of the body

2) The suprachiasmatic nucleus gets input from the retinohypothalamic tract by integrating light sensitive melanopsin in the retina to the SCN
→ this is nonvisual light sensation and helps to entrain circadian rhythm

3) Light works as a zeitgeber when our body experiences light when it does not expect it
→ ie: shining a bright light at night will adjust our Circadian Rhythm during those periods (Phase delay)
→ shining a bright light earlier in the morning will shift our Circadian Rhythm earlier (phase advance)
→ if you shine light in the day when our body expects it, there is no effect or a dead zone

What is encephalitis lethargica?

1) encephalitis lethargica is a mysterious neurological illness where patients have long periods of sleep leading to death
→ this allowed us to discover that lesions to the posterior hypothalamus led to hypersomnia as seen in the disease

2) lesions in the anterior hypothalamus lead to insomnia

What is circadian medicine?

Circadian medicine is a method of using the circadian rhythm to improve treatment
1) Clocking the Drug
→ optimize the timing of drugs to improve efficacy and reduce side effects

2) Drugging the Clock
→ develop drugs that target clock-related genes

3) Training the Clock
→ be intentional with behavior to maintain a steady circadian rhythm