circadian rhythms and neuroendocrine regulation

Question 1

what is an (a) ultradian rhythm, (b) circadian rhythm, (c) infradian rhythm

Answer 1

(a) cycle < 20h
(b) cycle around 24h
(c) cycle > 28h

Question 2

what is the (a) phase, (b) amplitude, (c) period

Answer 2

(a) timing of rhythm
(b) how big the difference is between peak and trough
(c) duration of 1 cycle

Question 3

why is sst secretion not a circadian rhythm?

Answer 3

rhythm isn’t endogenous: cycle only appears when go to sleep

Question 4

requirements for a rhythm to be considered circadian (2)

Answer 4

1. ~ 24h
2. endogenous

Question 5

problems if want to assess endogenous circadian rhythms (2)

Answer 5

1. entrainment by environmental cues
2. masking (sleep, light, feeding, etc.)

Question 6

what masks rhythm of (a) melatonin (b) body temperature

Answer 6

(a) light
(b) sleep

Question 7

time-isolation protocols to address problems of assessing endogenous circadian rhythms (2)

Answer 7

1. constant routine protocol
2. forced desynchrony protocol

Question 8

what does the constant routine protocol involve (5)

Answer 8

1. sustained wakefulness
2. semi-recumbant posture (45)
3. limited activity
4. dim light
5. hourly snacks (no meals)

Question 9

why does the constant routine protocol allow us to assess endogenous CR

Answer 9

gets rid of anything that could mask endogenous CR

Question 10

which rhythms are truly circadian (5)

Answer 10

1. melatonin
2. body temp (somewhat)
3. cortisol (somewhat)
4. urine volume (somewhat)
5. tsh (somewhat)

Question 11

peak of (a) melatonin, (b) cortisol, (c) body temp

Answer 11

(a) night
(b) wake up
(c) day (lowest at night)

Question 12

what does the forced desynchrony protocol assess

Answer 12

assess endogenous rhythms if put subject on forced LD cycle outside of range of entrainment (20 or 28h)

Question 13

what does the forced desynchrony protocol reveal

Answer 13

LD cycle desynchronizes from other CRs if LD cycle is > 28h or < 20h

Question 14

effect of DD cycle on rodent activity and why

Answer 14

CR altered -> becomes shorter because follows endogenous cycle instead of being entrained by light

Question 15

what proved that scn dictates CR

Answer 15

scn lesion -> loss of CR
scn transplantation -> CR of donor

Question 16

conserved features of clock genes (2)

Answer 16

1. oscillating mRNAs, proteins or activity
2. autoregulatory feedback loops

Question 17

mammalian clock genes (4)

Answer 17

1. clock
2. bmal1/2
3. per1/2/3
4. cry 1/2

Question 18

feedback loop of molecular clockwork

Answer 18

TFs clock and bmal1 associate together and bind DNA -> transcription of clock genes (per or cry) -> per and cry proteins accumulate form complexes when in enough amounts -> stop expression of TFs

Question 19

expression of per and cry rna and protein in the scn throughout a day

Answer 19

high rna/low protein during the day, low rna/high protein during the night

Question 20

how visualize per expression

Answer 20

per controls luciferase -> bioluminescence when gene expressed

Question 21

effect of bmal1 ko (2)

Answer 21

1. blunted per rna expression in scn
2. arrhythmicity

Question 22

tau mutation (4)

Answer 22

1. mutation of CKIe (kinase)
2. less stable per proteins
3. decreased duration of clock/bmal1 inhibition
4. shorter period

Question 23

what does tau mutation prove

Answer 23

PTM of clock proteins essential for pace of CRs

Question 24

mutation in what genes results in faspd

Answer 24

per2 and CKId

Question 25

health problems associated with late shift work (7)

Answer 25

1. reproductive effects 2. CVD 3. mental health 4. CR disruptions 5. brain effects 6. GI disorders 7. increased cancer

Question 26

what are clock-controlled genes + ex

Answer 26

not part of the clockwork, but regulated by clock (like AVP)

Question 27

vasopressin in scn vs son

Answer 27

in scn = CCG in son =/= CCG

Question 28

how is avp a ccg in the scn

Answer 28

clock/bmal1 bind to avp gene in scn

Question 29

ccgs in liver vs scn

Answer 29

many genes are either a ccg in liver or scn, a small fraction are a ccg in both

Question 30

why does CR have an impact on hormones

Answer 30

scn has many connections with different areas in the brain that control hormone secretion

Question 31

where is melatonin synthesized

Answer 31

pineal gland

Question 32

what conveys rhythmicity to melatonin secretion

Answer 32

na is released in rhythmic fashion in the pineal gland and aa-nat (enzyme involved in synthesis of melatonin) is rhythmic

Question 33

result of action of na on aa-nat

Answer 33

more transcription of gene and less degradation of protein (increase in melatonin)

Question 34

effect of scn lesion on cort secretion

Answer 34

no rhythm

Question 35

expression of clock genes in adrenal gland and what does it mean

Answer 35

different expression in night vs day, means local clock is present (independent of scn)

Question 36

how discovered that adrenal tissue itself has role in variation of cort levels

Answer 36

adrenal tissue of different times of day put into culture (but same conditions): resulted in different amount of cort secreted even if same initial concentration of acth from adrenal tissue

Question 37

why would there be different amounts of cort produced in response to same amount of acth

Answer 37

adrenal gland more sensitive to acth when time of day when supposed to be active (night for rodents)

Question 38

mechanisms that regulate feeding (2)

Answer 38

1. homeostatic regulation (response to feeding/fasting) 2. circadian regulation

Question 39

why does CR have an impact on feeding

Answer 39

scn projects to brain regions that regulate feeding (directly and indirectly)

Question 40

FAA when (a) food restricted to 3h window (b) food deprivation (c) scn lesioned + DD (d) clock gene ko

Answer 40

(a) becomes active right before food administration (b) sill active in anticipation (when was fed before) -> not dependent on having a meal (c) also active in anticipation -> scn not needed for ffa (d) ffa still present

Question 41

where is the food-entrainable oscillator

Answer 41

not restricted to a single region: several regions involved

Question 42

metabolism mechanisms active during night for (a) fat (b) liver (c) pancreas

Answer 42

(a) lipid breakdown + leptin secretion (b) processes to increase free glucose (like glycogenesis) (c) increased glucagon secretion

Question 43

metabolism mechanisms active during day for (a) muscle (b) fat (c) liver (d) pancreas

Answer 43

(a) glycolysis (b) lipogenesis (c) glycogen synthesis (d) insulin secretion

Question 44

effect of changing feeding time on (a) peripheral clocks (b) scn; + conclusion

Answer 44

(a) peripheral clocks adapt to feeding time (b) scn doesn't change even if feeding time does -> peripheral clocks can be entrained (not scn)

Question 45

effect of clock gene mutation on fertility of female mice (2)

Answer 45

1. irregular estrous cycle 2. affected pregnancies

Question 46

why is lh always secreted on evening of proestrus

Answer 46

because estrogen is secreted during proestrus -> because timing of gnrh (affected by scn)

Question 47

effect of constant estrogen (ovariectomized) administration on lh secretion

Answer 47

should secrete lh constantly if dependent on estrogen secretion, but not what is observed: peaks of lh secretion at ~20h interval (because endogenous CR from scn in rodents is a bit shorter than 24h)

Question 48

lh is controlled by

Answer 48

integration of CR (scn) and infradian ryhthm of estrogen (ovarian rhythm)

Question 49

where do scn neurons project to regulate hpg axis

Answer 49

on gnrh neurons and kisspeptin neurons (ERa)

Question 50

effects of mutations of clock genes/lesioned scn on reproductive performance (3)

Answer 50

1. smaller litter or infertile (decreased reproductive success) 2. impaired estrous cycle 3. impaired lh/fsh secretion