Monday, April 2, 2012

Circadian rhythms and neuroendocrine regulation

1Characteristics and classification¶

• rhythm: if you could draw a sinusoidal wave for it
• types
  • ultradian rhythm : <20hrs (ex: heart beat, neuron firing)
  • circaidan rhythm: between 20 and 28 hrs (ex: ~ a day) <-- our focus
  • infradian rhythm : >28hrs (ex: change of fertility, migration, etc)
• example: Three different hormonal rhythms in sheep##
  • prolactin rhythm is in infradian rhythms (measure of weeks)
  • melatonin is in circadian : high at night
  • LH is ultradian
• example: in human
  • body temp is high in day and low at night
  • cortisol is high in early day and decrease throughout the day.
    • somatostatin is the opposite since it downregulate cortisol (high when cortisol level is low.. like around sleeping time)
• time isolation experiment in caves and Jurgen Aschoff's bunker:
  • Michel Siffre, a French speleologist, isolate himself in the caves to evade environmental clues
  • both cases show that though circadian rhythms are a bit off from 24hr, we still have endogenous rhythms.
  • even w/o light, we still have rhythms cuz we're structure that way (that binds us to our mother earth!)

2Masking¶

• melatonin levels can be masked by light
  • exposing sheep with bright light in their dark cycle induce a sharp dive of melatonin level.
• core body temp. can be masked by sleep
  • napping during the day induces a drop in core body temperature, which is supposed to be high during the day and low at night.
• cortisol rhythm can be masked by stress
• conclusion: rhythmic physiological phenomena can be masked and can be entrained by environmental clues.
  • Therefore, to assess circadian rhythm, we must remove factors that can mask rhythms
    • i.e. constant routine protocol (see next). everyday is the same. no stress, etc
  • also forced desyncrhony protocols
    • no window, no clock, subjects are told to sleep and wake up at certain time.

2.1Constant routine protocol¶

• constant routine protocol : a way to keep environment constant
  • sustained wakefullness (ex: for 40 hrs straight)
  • semi-recumbent posture + limited activity (subjects are told to not completely lie down nor standing)
  • dim light : to avoid masking melatonin level.
  • hourly snacks (constantly feeding) : to avoid masking by food-intake schedule.
  • some effects that are seen:
    • cortisol and melatonin amp and period remain almost the same --> so their circadian rhythms are very endogenous
    • growth hormone and prolactin amp flattens, since both of these have a lot to do with waking/sleeping cycle.
    • TSH changes phases.
  • when a subject is forced to live on a LD(light-dark) cycle of 28 hours
    • circadian cycle becomes uncoupled from sleep-wake cycle cuz human circadian cycle cannot go over 26 hr.

2.2Autograms¶

• Human's endogenous rhythm is about 24 hr and 14 minutes (no wonder that extra 10 min in the morning matters so much...)
• for rodents, their cycle is about 22 hr. they're also nocturnal.
• Rodents' motor activity is recorded by turns of wheels.
  • each horizontal line is one day of recording.
  • We can see that in LD cycle, rodents start running when it's dark.
  • when environmental clue is removed (when it's DD, 24 hour darkness), rodents start running ~2 hrs earlier each day.
  • this help us determine the period of the endogenous cycle of rodents.
  • autograms are also useful tool to see how mutations in certain genes (esp clock genes, clock-controlled gene) affect endogenous rhythm.