circadian rhythms and neuroendocrine regulation Flashcards
what is an (a) ultradian rhythm, (b) circadian rhythm, (c) infradian rhythm
(a) cycle < 20h
(b) cycle around 24h
(c) cycle > 28h
what is the (a) phase, (b) amplitude, (c) period
(a) timing of rhythm
(b) how big the difference is between peak and trough
(c) duration of 1 cycle
why is sst secretion not a circadian rhythm?
rhythm isn’t endogenous: cycle only appears when go to sleep
requirements for a rhythm to be considered circadian (2)
- ~ 24h
- endogenous
problems if want to assess endogenous circadian rhythms (2)
- entrainment by environmental cues
- masking (sleep, light, feeding, etc.)
what masks rhythm of (a) melatonin (b) body temperature
(a) light
(b) sleep
time-isolation protocols to address problems of assessing endogenous circadian rhythms (2)
- constant routine protocol
- forced desynchrony protocol
what does the constant routine protocol involve (5)
- sustained wakefulness
- semi-recumbant posture (45)
- limited activity
- dim light
- hourly snacks (no meals)
why does the constant routine protocol allow us to assess endogenous CR
gets rid of anything that could mask endogenous CR
which rhythms are truly circadian (5)
- melatonin
- body temp (somewhat)
- cortisol (somewhat)
- urine volume (somewhat)
- tsh (somewhat)
peak of (a) melatonin, (b) cortisol, (c) body temp
(a) night
(b) wake up
(c) day (lowest at night)
what does the forced desynchrony protocol assess
assess endogenous rhythms if put subject on forced LD cycle outside of range of entrainment (20 or 28h)
what does the forced desynchrony protocol reveal
LD cycle desynchronizes from other CRs if LD cycle is > 28h or < 20h
effect of DD cycle on rodent activity and why
CR altered -> becomes shorter because follows endogenous cycle instead of being entrained by light
what proved that scn dictates CR
scn lesion -> loss of CR
scn transplantation -> CR of donor
conserved features of clock genes (2)
- oscillating mRNAs, proteins or activity
- autoregulatory feedback loops
mammalian clock genes (4)
- clock
- bmal1/2
- per1/2/3
- cry 1/2
feedback loop of molecular clockwork
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
expression of per and cry rna and protein in the scn throughout a day
high rna/low protein during the day, low rna/high protein during the night
how visualize per expression
per controls luciferase -> bioluminescence when gene expressed
effect of bmal1 ko (2)
- blunted per rna expression in scn
- arrhythmicity
tau mutation (4)
- mutation of CKIe (kinase)
- less stable per proteins
- decreased duration of clock/bmal1 inhibition
- shorter period
what does tau mutation prove
PTM of clock proteins essential for pace of CRs
mutation in what genes results in faspd
per2 and CKId
health problems associated with late shift work (7)
- reproductive effects
- CVD
- mental health
- CR disruptions
- brain effects
- GI disorders
- increased cancer
what are clock-controlled genes + ex
not part of the clockwork, but regulated by clock (like AVP)
vasopressin in scn vs son
in scn = CCG
in son =/= CCG
how is avp a ccg in the scn
clock/bmal1 bind to avp gene in scn
ccgs in liver vs scn
many genes are either a ccg in liver or scn, a small fraction are a ccg in both
why does CR have an impact on hormones
scn has many connections with different areas in the brain that control hormone secretion
where is melatonin synthesized
pineal gland
what conveys rhythmicity to melatonin secretion
na is released in rhythmic fashion in the pineal gland and aa-nat (enzyme involved in synthesis of melatonin) is rhythmic
result of action of na on aa-nat
more transcription of gene and less degradation of protein (increase in melatonin)
effect of scn lesion on cort secretion
no rhythm
expression of clock genes in adrenal gland and what does it mean
different expression in night vs day, means local clock is present (independent of scn)
how discovered that adrenal tissue itself has role in variation of cort levels
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
why would there be different amounts of cort produced in response to same amount of acth
adrenal gland more sensitive to acth when time of day when supposed to be active (night for rodents)
mechanisms that regulate feeding (2)
- homeostatic regulation (response to feeding/fasting)
- circadian regulation
why does CR have an impact on feeding
scn projects to brain regions that regulate feeding (directly and indirectly)
FAA when (a) food restricted to 3h window (b) food deprivation (c) scn lesioned + DD (d) clock gene ko
(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
where is the food-entrainable oscillator
not restricted to a single region: several regions involved
metabolism mechanisms active during night for (a) fat (b) liver (c) pancreas
(a) lipid breakdown + leptin secretion
(b) processes to increase free glucose (like glycogenesis)
(c) increased glucagon secretion
metabolism mechanisms active during day for (a) muscle (b) fat (c) liver (d) pancreas
(a) glycolysis
(b) lipogenesis
(c) glycogen synthesis
(d) insulin secretion
effect of changing feeding time on (a) peripheral clocks (b) scn; + conclusion
(a) peripheral clocks adapt to feeding time
(b) scn doesn’t change even if feeding time does
-> peripheral clocks can be entrained (not scn)
effect of clock gene mutation on fertility of female mice (2)
- irregular estrous cycle
- affected pregnancies
why is lh always secreted on evening of proestrus
because estrogen is secreted during proestrus -> because timing of gnrh (affected by scn)
effect of constant estrogen (ovariectomized) administration on lh secretion
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)
lh is controlled by
integration of CR (scn) and infradian ryhthm of estrogen (ovarian rhythm)
where do scn neurons project to regulate hpg axis
on gnrh neurons and kisspeptin neurons (ERa)
effects of mutations of clock genes/lesioned scn on reproductive performance (3)
- smaller litter or infertile (decreased reproductive success)
- impaired estrous cycle
- impaired lh/fsh secretion
