By: Jeffery Jarmusik and Andrew McCurrach THE CYCLE Circadian Rhythms By: Jeffery Jarmusik and Andrew McCurrach

Definition Circadian Rhythms are responses to environmental factors that effect the physical, mental, and behavior of organisms The study of it is called chronobiology

Overview Biological clocks drive our circadian rhythms Source: http://www.nigms.nih.gov/Education/Factsheet_CircadianRhythms.htm Overview Biological clocks drive our circadian rhythms They are groups of interacting molecules that control circadian rhythms located throughout the body A “master clock” (central oscillator) is a group of nerve cells in the hypothalamus brain, called the suprachiasmatic nucleus (SCN), which has roughly 10,000-20,000 nerve cells DNA codes for circadian rhythms Light is a main factor, SCN is near optic nerve in the eyes Sleep cycles, hormone release, body temperature, and other functions are effected SCN controls production of melatonin (makes you sleepy)

We live on a “25” hour cycle Zeitgebers “time givers”- food availability, glucocorticoid (steroid hormone) level, temperature Feedback- NADH increases, NAD+ decreases (inhibits) Persists regardless of environmental factors (jet lag) Present in organism ranging from prokaryotic/eukaryotic microbes to plants, insects, and mammals

Three Main Components Entrainment Pathway- transmission of environmental signals to the timekeeping device Oscillator- timekeeping device, operates in the absence of environmental cues Output Pathway- activated by the oscillator

Mammals 5 structures: retina, RHT (retinohypothalmic tract), SCN, penile gland, peripheral oscillators SCN secretes factors that act in the hypothalamus Regulation of positive transcriptional elements in oscillator neurons These elements include two bLHL, PAS-domain containing transcription factors, Clk (clock) and BMAL1

The specifics are confusing… BMAL1 high at the beginning of a new day and Per and Cry are at low levels, throughout the day BMAL1 is reduced through metabolic pathways and transcriptions of various genes Positive and negative feedback cause levels to rise and fall CSNK-I-Epsilon phosphorylates Per2 to be degraded (FASPS, a sleeping disorder, caused by a mutation in CSNK) AMPK mediated phosphorylation- degrades CRY1

Sleep cycle problems hPer1 17p13.1 Gene Locus Associated circadian rhythm disorder hPer1 17p13.1 hPer2 2q37.3 Advanced sleep phase disorder (causative mutation) hPer3 1p36.2 Delayed sleep phase disorder (predisposition) hCry1 12q23.3 hCry2 11p11.2 hClock 4q12 Evening preference in sleep-wake behaviour hBmal1 11p15.2 hCKIδ 17q25.3 Advanced sleep phase disorder (causative mutation) hCKIε 22q13.1 Delayed sleep phase disorder (protection) hRev-Erbα 17q21.1 hRev-Erbβ 3p24.2 hRorα 15q22.2 hRorβ 9q21.13 hRorγ 1q21.3 hNpas2/Mop4 2q11.2 hArntl2/Mop9 12p11.23

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3104765/ http://www.signaling- gateway.org/update/updates/200912/nrm2806.html http://www.nigms.nih.gov/Education/Factsheet_CircadianRh ythms.htm http://www.acep.org/content.aspx?id=30560 http://www.sabiosciences.com/pathway.php?sn=Circadian_ Clock_in_Mammals http://www.annals.edu.sg/pdf/37VolNo8Aug2008/V 37N8p662.pdf https://www.boundless.com/biology/central- nervous-system/specialized-regions-vertebrate- brain/regulation-biological-clock/#.UQsZiGc1B8E