Got Rhythm? (melatonin)

[Supadupafly]

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Who could ask for anything more?

MS2 here... so our neuro prof goes on about how using melatonin can straighten out circadian rhythm. He didn't give any physiologic or pharmacologic reason though. Sure, pineal 5HT-N-Acetylase goes up at night, but is sleep an effect of this or is this an effect of sleep? What if it's not melatonin production that helps you sleep but serotonin deprivation? My minds telling me that exogenous melatonin might cause negative feedback- downregulation of endogenous melatonin production or 5HT pile-up, and screw your rhythm up even more.

So smartypants neuro residents... can anybody clear this up so I know what to say to my patients who ask if they should take melatonin?

 

[Supadupafly]

Wow, is there not a single gunner neuro resident who can answer a simple neurophys question?

iBUMP!

 

[Circadian Man]

Who could ask for anything more?

MS2 here... so our neuro prof goes on about how using melatonin can straighten out circadian rhythm. He didn't give any physiologic or pharmacologic reason though. Sure, pineal 5HT-N-Acetylase goes up at night, but is sleep an effect of this or is this an effect of sleep? What if it's not melatonin production that helps you sleep but serotonin deprivation? My minds telling me that exogenous melatonin might cause negative feedback- downregulation of endogenous melatonin production or 5HT pile-up, and screw your rhythm up even more.

So smartypants neuro residents... can anybody clear this up so I know what to say to my patients who ask if they should take melatonin?

I'm not a neuro resident, but I did undergraduate research on the circadian rhythm. I'm a little fuzzy on remembering all the details, but I think this will clear up the issue. The circadian rhythm in mammals is governed by a region of the hypothalamus called the suprachiasmatic nuclei (SCN). Neurons in this region of the brain fire action potentials in a daily sinusoidal pattern (i.e. firing more rapidly during midday and tapering off at night). The circadian pattern of action potential firing is endogenously driven by genetics, and projections from neurons in the SCN result in inhibitory or excitatory effects on many different physiological processes. However, it is important to remember that the SCN output does not control all physiological processes that follow a 24 hour rhythm; it is merely one of the major factors that influences them (in other words, the circadian rhythm does not independently make us sleep, nor does melatonin production or serotonin deprivation as you mentioned). The pineal gland receives input from the SCN, so the release of melatonin is partially controlled by the circadian rhythm. However, there is a feedback loop from the pineal gland to the SCN, so the nightly release of melatonin helps keep the circadian pacemaker on track. This is important because the circadian pacemaker is capable of resetting itself in response to various stimuli (such as light via the neurotransmitter glutamate or in some cases melatonin from the pineal). This is necessary because the circadian rhythm of most humans is approximately 24.3 hours, varying slightly from the solar cycle. Also, people are able to travel across many time zones in a day, so the pacemaker must be able to reset itself in order to coordinate with the "new" solar cycle. The time that it takes us to reset our pacemaker to a new time zone after traveling is the period during which we experience jet lag. By taking exogenous melatonin, we artifically stimulate the feedback loop from the pineal gland to the SCN during a time when the SCN isn't expecting to receive melatonin feedback based on its current rhythm. This signals to the SCN that its pattern has become out of sync and helps to jump start the resetting of the circadian clock. It by no means eliminates jet lag, but I seem to recall reading a few studies that found some beneficial effects of taking it when traveling.

I hope that makes sense and answers your question.