circadian rhythms and neuroendocrine regulation Flashcards

1
Q

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

A

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

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2
Q

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

A

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

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3
Q

why is sst secretion not a circadian rhythm?

A

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

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4
Q

requirements for a rhythm to be considered circadian (2)

A
  1. ~ 24h
  2. endogenous
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5
Q

problems if want to assess endogenous circadian rhythms (2)

A
  1. entrainment by environmental cues
  2. masking (sleep, light, feeding, etc.)
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6
Q

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

A

(a) light
(b) sleep

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7
Q

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

A
  1. constant routine protocol
  2. forced desynchrony protocol
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8
Q

what does the constant routine protocol involve (5)

A
  1. sustained wakefulness
  2. semi-recumbant posture (45)
  3. limited activity
  4. dim light
  5. hourly snacks (no meals)
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9
Q

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

A

gets rid of anything that could mask endogenous CR

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10
Q

which rhythms are truly circadian (5)

A
  1. melatonin
  2. body temp (somewhat)
  3. cortisol (somewhat)
  4. urine volume (somewhat)
  5. tsh (somewhat)
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11
Q

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

A

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

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12
Q

what does the forced desynchrony protocol assess

A

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

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13
Q

what does the forced desynchrony protocol reveal

A

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

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14
Q

effect of DD cycle on rodent activity and why

A

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

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15
Q

what proved that scn dictates CR

A

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

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16
Q

conserved features of clock genes (2)

A
  1. oscillating mRNAs, proteins or activity
  2. autoregulatory feedback loops
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17
Q

mammalian clock genes (4)

A
  1. clock
  2. bmal1/2
  3. per1/2/3
  4. cry 1/2
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18
Q

feedback loop of molecular clockwork

A

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

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19
Q

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

A

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

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20
Q

how visualize per expression

A

per controls luciferase -> bioluminescence when gene expressed

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21
Q

effect of bmal1 ko (2)

A
  1. blunted per rna expression in scn
  2. arrhythmicity
22
Q

tau mutation (4)

A
  1. mutation of CKIe (kinase)
  2. less stable per proteins
  3. decreased duration of clock/bmal1 inhibition
  4. shorter period
23
Q

what does tau mutation prove

A

PTM of clock proteins essential for pace of CRs

24
Q

mutation in what genes results in faspd

A

per2 and CKId

25
Q

health problems associated with late shift work (7)

A
  1. reproductive effects
  2. CVD
  3. mental health
  4. CR disruptions
  5. brain effects
  6. GI disorders
  7. increased cancer
26
Q

what are clock-controlled genes + ex

A

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

27
Q

vasopressin in scn vs son

A

in scn = CCG
in son =/= CCG

28
Q

how is avp a ccg in the scn

A

clock/bmal1 bind to avp gene in scn

29
Q

ccgs in liver vs scn

A

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

30
Q

why does CR have an impact on hormones

A

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

31
Q

where is melatonin synthesized

A

pineal gland

32
Q

what conveys rhythmicity to melatonin secretion

A

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

33
Q

result of action of na on aa-nat

A

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

34
Q

effect of scn lesion on cort secretion

A

no rhythm

35
Q

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

A

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

36
Q

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

A

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

37
Q

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

A

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

38
Q

mechanisms that regulate feeding (2)

A
  1. homeostatic regulation (response to feeding/fasting)
  2. circadian regulation
39
Q

why does CR have an impact on feeding

A

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

40
Q

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

A

(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

41
Q

where is the food-entrainable oscillator

A

not restricted to a single region: several regions involved

42
Q

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

A

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

43
Q

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

A

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

44
Q

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

A

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

45
Q

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

A
  1. irregular estrous cycle
  2. affected pregnancies
46
Q

why is lh always secreted on evening of proestrus

A

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

47
Q

effect of constant estrogen (ovariectomized) administration on lh secretion

A

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)

48
Q

lh is controlled by

A

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

49
Q

where do scn neurons project to regulate hpg axis

A

on gnrh neurons and kisspeptin neurons (ERa)

50
Q

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

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