Lecture 20 - Circadian rhythms Flashcards
what are some examples of cellular daily rhythms
cell cylce progression
dna damage repair
cellular energy metabolism
cell detoxification
neuronal excitability
what diseases are associated with insuffiecient clocks
bipolar, depression
sleep disorders
neurdegenerative
obesity/metabolic syndrome
cardiovascular
reproductive effects
inflammation
cancer
what is ultradian rhythm
several times in a day
e.g. heart beat
less than 20hrs
what is infradian rhythm
more than 28hrs between its occurence
e.g. period
(e.g. circalunar)
what are some requirements of the mammalian circadian rhythm
- a self sustained oscillator
- entrained by environemnt
- period of 24hrs
- drives rhythmical outputs
what connects the eyes to SCN
retinohypothalamic tract
what are the 2 components of SCN
core (ventrolateral SCN)
shell (dorsomedial SCN)
what neuropeptide does ventrolateral sCN contain
VIP
vasointestinal polypeptide
what neuropeptide does dorsomedial SCN contain
AVP
arginine vasopressin
what function does vasolateral SCN have
recieves input from eyes
what function does dorsomedial SCN contain
send output to other brain areas
what genes are expressed in SCN neurons to generate circadian rhythm
clock genes
(also found throughout body, but SCN synchs the others)
what releases melatonin
pineal gland
what would clock genes in liver regulate
regulates food absorption and metabolism
what time of day do cardiovascular diseases usually spike
in AM
what time does chronic pain tend to spike
in afternoon
what 2 things do chronopharmacology study
how med affec circ rhythm
how circ rhythms affect med
what does conventional chemotherapy assume about chemo effectiveniess
the worse the toxicity/symptoms, the better the overall survival
what did chronotherapy find w/ cancer drugs
drugs are most efficient at same time it’s best tolerated in the day
what is oxaliplatin
first cancer chronodrug
was too toxic and failed clinical trial
but chronotherapeutic development meant it got approved
what did oxaliplatin chronotherapeutic trials find
at constant rate : 10xhigher neutropenia and distal paraesthesias
55% higher vomiting
and dose could be 15% increased in a circadian rhtym modulated rate
what drug is first in line for bipola rdisorder
lithium
how does lithium affect circ rhythm
- causes period lengthening and phase delay
- affects expression of circadian genes, and clock transcription
what can bright light therapy treat
mood disorders
jet lag, insomnia
cause improved mood and sleep efficiency
hwo many nrem rem sleep cycles per night
4-5
what are the 4 stages of sleep
NREM (N1) = light sleep
NREM (N2) = deeper sleep
NREM (N3) = deepest
REM = dreamin
normal length of all NREM and REM stages
1-7 mins
10-25 mins
20-40 mins
REM = 10-60mins
what virus in 20th century indicated the brain controls sleep
encephalitis lethargica
what area did encaphalitis lethargica effect
midbrain and diencephalon
what are the 3 stuctures in hypothalamus that control circ rythm
suprachiasmatic nuc (SCN)
subparaventricular (SPZ)
dorsomedial (DMH)
what main structure in hypothalamus produces onset of sleep
ventrolateral preoptic nucleus (VLPO)
what 4 structures control awakeness in the pons
laterodorsal tegmental (LDT)*
pedunculopontine
Raphe*
locus coeruleus
*important ones
what structure in hypothalamus controls awakeness
lateral hypothalamic area
LHA
what neuropeptide is important in flipflop switch model
orexin
what structure that controls body temp does the SPZ pass its signal to
the MPO
where does dorsomedial hypothalamic nuc pass its signal to
VLPO
PVH - corticosteroid release
LHA - wakefulnesss
what 2 things control sleep drive
- homeostatic sleep drive
-circadian drive for arousal
how is narcolepsy caused in humans
autoimmune attack on the neurons in the hypothal that produce orexin
= usually orexin would act on Hcrtr2 (a GPCR) but cant anymore
how is narcolepsy produced in dogs
premature stop codin in Hcrtr2 receptor
