Week 10 ELM 20: Rhythms and Sleep

Flashcards about sleep and circadian rhythms.

Biological rhythms

Organisms on Earth have adapted to the 24-h changes in their environment by developing these.

Importance of Clocks

This is wide-spread, impacting: Physiological Sleep/Wake, Body temperature, Cardiac output, Memory, Energy metabolism, Eating behaviour, Immune response, Detoxification… Cellular Cell cycle progression, DNA damage repair, Cellular energy metabolism, Cell detoxification, Neuronal excitability

Clock impact on disease

Affective disorders (Bipolar depression), Sleep disorders, Neurodegenerative disease (e.g. Alzheimer's), Obesity/metabolic syndrome, Inflammation (Asthma, COPD), Cancer… are associated with this.

Modern lifestyles

These oppose our natural rhythms leading to Chronic shift work, Sleep deprivation, Altered eating habits and Jet Lag.

Clock alterations

Jet lag, Shift work, Social jet lag, Road accidents, Industrial accidents, Health problems occur when this goes wrong

Shift work

Mental Health problems, Circadian rhythm disruptions, Brain effects, Cardiovascular disorders, Gastrointestinal disorders, Reproductive effects, and Increased cancer, are associated with this type of work schedule.

Ultradian Rhythms

These rhythms have a period of less than 20 hours.

Circadian Rhythms

These rhythms have a period between 20-28 hours.

Infradian Rhythms

These rhythms have a period of greater than 28 hours. Circalunar - monthly. Circannual - annual/ seasonal rhythms

Mammalian circadian system

A self-sustained oscillator with a period of 24 hours, entrained by environment (Light) and driving rhythmical outputs.

Suprachiasmatic Nucleus (SCN)

Master circadian pacemaker located in the hypothalamus. This receives input from eyes (RHT) from melanopsin-expressing retinal ganglion cells and sends output to other brain areas → VLPO, SPZ, PVN, DMH, LH, periphery. Influences melatonin and corticosteroid secretion

Molecular clock

This generates circadian rhythms in neuronal function through the circadian expression of clock genes within SCN neurons.

Chronopharmacology

Studies how biological rhythms affect medication kinetics and dynamics. Takes into account time of day to maximise drug efficiency and minimise side effects.

Sleep

Two systems regulate this and wakefulness: the homeostatic drive to sleep and the circadian drive for arousal.

Core SCNn , ventrolateral SCN

receives input from the eyes

Shell SCN, dorsomedial SCN

sends output to other brain areas

neuropeptides involved in SCN orginzation

VIP (vasointestinal polypeptide) ,AVP (arginine vasopressin)

Per and Cry genes

transcribed and translated, then form a complex that inhibits their own transcription

Bmal1 and Clock genes

promote the transcription of Per and Cry genes. Rev-Erba regulates Bmal1 expression

Pineal gland

Where melatonin is secreted from

Melatoning secretion

starts at 9 pm and stops at 7:30 am

Oxaliplatin

The first anticancer drug to undergo chronotherapeutic development. Constant application rate had 10x higher incidence of neutropenia & distal parasthesias, 55% higher vomitting. Circadian-rhythm modulated rate: mean does of oxaliplatin and its max tolerated does could be increased by 15%

Lithium

first-line treatment for bpd. affects the expression of numerous circadian genes. causes period lengthening and phase delay of the sleep-wake and body temp rhythms

Encephalitis lethargica

patients slept over 20 hours a day. only 1/3 of patients made full recovery