Circadian Rhythm

actogram

measure circadian activity in mice by counting the number of wheel rotations (activity)

crepuscular

nocturnal but most active at dawn and dusk eg mice

Siffre’s cave, 1972

• effect of no sunlight, constant temp on circadian rhythm

• emerged after 179 days thinking 151 days

• circadian rhythm lengthened

6am to midday circadian rhythm

cortisol released → rapidest increase in blood pressure, high alertness

18 to 24 hours

body temp reaches peak → highest blood pressure → melatonin secretion

suprachiasmatic nucleus

• receives info directly from eye

• rhythm reset by amount of light entering the eye

effect of light on melatonin

inhibits melatonin release from pineal gland

photosensitive retinal ganglion cells (pRGCs)

Connect to optic nerve. Contain melanopsin receptor which detects blue light (450 to 480nm)

How does melatonin work?

Antioxidant which donates protons to free radicals. Indirectly synthesises antioxidants eg glutathiones, SOD and glucose-6-phosphatase dehydrogenase

two-component oscillators

circadian rhythm can affect animal behaviours through changes in gene expression in the SCN over the circadian day. Effects on predator/prey populations

D. Melanogaster study

• larvae usually emerge at night

• mutagenesis → eclosion mutants

• PERIOD gene isolated

• Per accumulates overnight inhibiting its own gene’s transcription

basic helix-loop-helix transcription factors eg Clock-Bmal1/Per-CRY

heterodimers which bind E-box motifs in target gene promoters

Per-Cry cycle (24 hours)

increased transcription via Clock, Bmal1 and Npas2 → Per and Cry accumulation → reduced transcription → degradation of repressors → cycle restarts

peripheral effects of circadian rhythms

• dip in blood pressure

• motility of GI tract, acid secretion and mucosa maintenance

• Clock-KO mice have kidney pathology

modulation of Clock-Bmal1 DNA binding activity

• NAD+:NADH ratio

• energy/redox state influences circadian rhythm?

Describe familial advanced sleep phase disorder (FASPD)

• sleep disorder w/ early habitual wake and sleep times

• tired in early afternoon

What causes FASPD?

autosomal dominant missense mutation in PER2 gene which prevents phosphorylation by casein kinases I-delta and I-epsilon

define circadian rhythms

physiological and behavioural oscillations regulated on a 24 hour cycle which persists in the absence of environmental cues

Parkinson’s disease and circadian rhythm

PD neurodegeneration → circadian dysfunctions inc Bmal and Per gene alterations and changes in secretion of melatonin and cortisol → insomnia and excessive daytime sleep

sleep-wake disorders in Alzheimers patients

in over 50% of patients, usually increased sleep latency, nocturnal awakening, excessive daytime naps