Lecture 20 - Circadian rhythms

Question 1

what are some examples of cellular daily rhythms

Answer 1

cell cylce progression
dna damage repair
cellular energy metabolism
cell detoxification
neuronal excitability

Question 2

what diseases are associated with insuffiecient clocks

Answer 2

bipolar, depression
sleep disorders
neurdegenerative
obesity/metabolic syndrome
cardiovascular
reproductive effects
inflammation
cancer

Question 3

what is ultradian rhythm

Answer 3

several times in a day
e.g. heart beat
less than 20hrs

Question 4

what is infradian rhythm

Answer 4

more than 28hrs between its occurence
e.g. period
(e.g. circalunar)

Question 5

what are some requirements of the mammalian circadian rhythm

Answer 5

• a self sustained oscillator
• entrained by environemnt
• period of 24hrs
• drives rhythmical outputs

Question 6

what connects the eyes to SCN

Answer 6

retinohypothalamic tract

Question 7

what are the 2 components of SCN

Answer 7

core (ventrolateral SCN)
shell (dorsomedial SCN)

Question 8

what neuropeptide does ventrolateral sCN contain

Answer 8

VIP
vasointestinal polypeptide

Question 9

what neuropeptide does dorsomedial SCN contain

Answer 9

AVP
arginine vasopressin

Question 10

what function does vasolateral SCN have

Answer 10

recieves input from eyes

Question 11

what function does dorsomedial SCN contain

Answer 11

send output to other brain areas

Question 12

what genes are expressed in SCN neurons to generate circadian rhythm

Answer 12

clock genes
(also found throughout body, but SCN synchs the others)

Question 13

what releases melatonin

Answer 13

pineal gland

Question 14

what would clock genes in liver regulate

Answer 14

regulates food absorption and metabolism

Question 15

what time of day do cardiovascular diseases usually spike

Answer 15

in AM

Question 16

what time does chronic pain tend to spike

Answer 16

in afternoon

Question 17

what 2 things do chronopharmacology study

Answer 17

how med affec circ rhythm
how circ rhythms affect med

Question 18

what does conventional chemotherapy assume about chemo effectiveniess

Answer 18

the worse the toxicity/symptoms, the better the overall survival

Question 19

what did chronotherapy find w/ cancer drugs

Answer 19

drugs are most efficient at same time it’s best tolerated in the day

Question 20

what is oxaliplatin

Answer 20

first cancer chronodrug
was too toxic and failed clinical trial
but chronotherapeutic development meant it got approved

Question 21

what did oxaliplatin chronotherapeutic trials find

Answer 21

at constant rate : 10xhigher neutropenia and distal paraesthesias
55% higher vomiting
and dose could be 15% increased in a circadian rhtym modulated rate

Question 22

what drug is first in line for bipola rdisorder

Answer 22

lithium

Question 23

how does lithium affect circ rhythm

Answer 23

• causes period lengthening and phase delay
• affects expression of circadian genes, and clock transcription

Question 24

what can bright light therapy treat

Answer 24

mood disorders
jet lag, insomnia
cause improved mood and sleep efficiency

Question 25

hwo many nrem rem sleep cycles per night

Answer 25

4-5

Question 26

what are the 4 stages of sleep

Answer 26

NREM (N1) = light sleep NREM (N2) = deeper sleep NREM (N3) = deepest REM = dreamin

Question 27

normal length of all NREM and REM stages

Answer 27

1-7 mins 10-25 mins 20-40 mins REM = 10-60mins

Question 28

what virus in 20th century indicated the brain controls sleep

Answer 28

encephalitis lethargica

Question 29

what area did encaphalitis lethargica effect

Answer 29

midbrain and diencephalon

Question 30

what are the 3 stuctures in hypothalamus that control circ rythm

Answer 30

suprachiasmatic nuc (SCN) subparaventricular (SPZ) dorsomedial (DMH)

Question 31

what main structure in hypothalamus produces onset of sleep

Answer 31

ventrolateral preoptic nucleus (VLPO)

Question 32

what 4 structures control awakeness in the pons

Answer 32

laterodorsal tegmental (LDT)* pedunculopontine Raphe* locus coeruleus *important ones

Question 33

what structure in hypothalamus controls awakeness

Answer 33

lateral hypothalamic area LHA

Question 34

what neuropeptide is important in flipflop switch model

Answer 34

orexin

Question 35

what structure that controls body temp does the SPZ pass its signal to

Answer 35

the MPO

Question 36

where does dorsomedial hypothalamic nuc pass its signal to

Answer 36

VLPO PVH - corticosteroid release LHA - wakefulnesss

Question 37

what 2 things control sleep drive

Answer 37

- homeostatic sleep drive -circadian drive for arousal

Question 38

how is narcolepsy caused in humans

Answer 38

autoimmune attack on the neurons in the hypothal that produce orexin = usually orexin would act on Hcrtr2 (a GPCR) but cant anymore

Question 39

how is narcolepsy produced in dogs

Answer 39

premature stop codin in Hcrtr2 receptor