Zzzzzzzz We have to do it every night but nobody knows why

Nick Medford nick at hermit0.demon.co.uk
Thu Sep 30 12:20:11 EST 1999

Maybe this just reflects my ignorance, but I'm curious about some of the
assertions you make. Certainly it's well established that growth hormone
release is much higher during sleep. However I am unclear about the
relationship between neurotransmitter synthesis and sleep, also your
statements re. the immune system. Perhaps you could post some references
(eg the experiment involving sleep-deprived animals who apparently died
of overwhelming sepsis?)

FWIW, I include some references culled from Medline searches. These
would certainly imply a relationship between sleep and
neuroimmune/neuroendocrine processes, but they stop a long way short of
the very definite and direct relationships you describe. Some
clarification would be appreciated!

Nick Medford

[Neuropsychopharmacology 1999 Aug;21(2 Suppl):24S-27S 

Sleep and serotonin: an unfinished story.

Jouvet M
Claude Bernard University, Lyon, France. 

Serotonin (5-HT) was first believed to be a true neuromodulator of sleep
because the destruction of 5-HT neurons of the raphe system or the
inhibition of 5-HT synthesis with p-chlorophenylalanine induced a severe
insomnia which could be reversed by restoring 5-HT synthesis. However
the demonstration that the electrical activity of 5-HT perikarya and the
release of 5-HT are increased during waking and decreased during sleep
was in direct contradiction to this hypothesis. More recent experiments
suggest that the release of 5-HT during waking may initiate a cascade of
genomic events in some hypnogenic neurons located in the preoptic area.
Thus, when 5-HT is released during waking, it leads to an homeostatic
regulation of slow-wave sleep.] 

[J Clin Endocrinol Metab 1999 Jun;84(6):1979-85 

Effects of sleep and sleep deprivation on catecholamine and interleukin-
2 levels in humans: clinical implications.

Irwin M, Thompson J, Miller C, Gillin JC, Ziegler M
Department of Psychiatry, University of California, and San Diego
Veterans Affairs Medical Center, 92161, USA. 

The objective of this study was to evaluate the effects of nocturnal
sleep, partial night sleep deprivation, and sleep stages on
catecholamine and interleukin-2 (IL-2) levels in humans. Circulating
levels of catecholamines and IL-2 were sampled every 30 min during 2
nights: undisturbed, baseline sleep and partial sleep deprivation-late
night (PSD-L; awake from 0300-0600 h) in 17 healthy male volunteers.
Sleep was monitored somnopolygraphically. Sleep onset was associated
with a significant (P < 0.05) decline of circulating concentrations of
norepinephrine and epinephrine, with a nocturnal nadir that occurred 1 h
after nocturnal sleep. On the PSD-L night, levels of norepinephrine and
epinephrine significantly (P < 0.05) increased in association with
nocturnal awakening. During stage 3-4 sleep, levels of norepinephrine,
but not epinephrine, were significantly lower (P < 0.05) compared to
average levels during the awake period, stages 1-2 sleep, and rapid eye
movement sleep. Nocturnal levels of circulating IL-2 did not change with
sleep onset or in relation to PSD-L or the various sleep stages. We
conclude that sleep onset is associated with changes in levels of
circulating catecholamines. Loss of sleep and disordered sleep with
decreases in slow wave sleep may serve to elevate nocturnal
catecholamine levels and contribute to cardiovascular disease.] 

[Ann Med 1999 Apr;31(2):146-51 

Transcriptional activity in the brain during sleep deprivation.

Toppila J, Porkka-Heiskanen T
Institute of Biomedicine, Department of Physiology, University of
Helsinki, Finland. jussi.toppila at helsinki.fi 

Molecular biological techniques combined with experimental sleep
deprivation have revealed alterations in gene transcriptional activity
of several proteins which may mediate the effects of prolonged
wakefulness in the brain. During sleep deprivation gene transcription is
altered in neuronal systems known to participate in the regulation of
vigilance and sleep, ie the norardenergic and cholinergic systems, and
several neuropeptides and cytokines. The study of immediate early genes
during sleep deprivation has revealed increased transcriptional activity
in those brain areas that are active during wakefulness. Systemic search
for alterated levels of messenger RNA in sleep-deprived brain has
revealed signal transduction proteins and metabolic enzymes which may
mediate changes in neuronal function during prolonged wakefulness. The
purpose of this article is to give a short overview of those genes whose
transcription is affected by sleep deprivation according to the current
literature, and to characterize the possible role of these genes in
sleep regulation.]

[Gynecol Endocrinol 1998 Dec;12(6):381-9

The impact of sleep on gonadotropin secretion.

Rossmanith WG
Department of Obstetrics-Gynecology, University of Ulm, Germany. 

Comparable to the period of pubertal transition, sleep also exerts
effects on episodic gonadotropin secretion in adult women. During the
follicular phase of the menstrual cycle, a sleep-induced slowing of
luteinizing hormone (LH) secretion occurs concurrently with a rise in LH
pulse amplitude. A selective increase in opioidergic, but not in
dopaminergic or serotoninergic activity may account for this decline in
pulsatility. In addition, sleep-reversal studies have confirmed that the
presence of sleep is essential for the expression of this neuroendocrine
function. Since pituitary gonadotropin responsiveness to
gonadotropin-releasing hormone (GnRH) is virtually unchanged during
the reasons for the enhanced LH pulse amplitude remain unresolved. This
sleep-associated increase in opioidergic activity may be restricted to a
hypothalamic site, since opiate blockade does not modify the
response to GnRH stimulation. In addition, circadian variability is
in terms of gonadotropin secretion in regularly cycling women; this may
again represent sleep-associated effects on gonadotropin release.
the physiological importance of sleep-associated neuroendocrine
remains basically unexplained, the observed changes in LH secretory
profiles during sleep in adult women suggest close functional links
the endocrine secretion and the rest-activity cycle of the brain.] 
[Psychiatry Clin Neurosci 1999 Apr;53(2):199-201 

Effects of sleep deprivation: the phosphorus metabolism in the human
measured by 31P-magnetic resonance spectroscopy.

Murashita J, Yamada N, Kato T, Tazaki M, Kato N
Department of Psychiatry, Shiga University of Medical Science, Otsu,

[Medline record in process]

Sleep deprivation (SD) has an antidepressant effect in some, but not
patients with depression, although its biological mechanisms have not
been characterized. We previously reported altered brain phosphorus
metabolism measured by phosphorus-31 magnetic resonance spectroscopy
(31P-MRS) in patients with bipolar depression. We preliminarily examined
effects of SD on phosphorus metabolism in the frontal lobes of 15 normal
subjects using 31P-MRS. No significant differences of membrane
metabolism, high-energy phosphate metabolism and intracellular pH were
found between before and after SD in these subjects. Further studies
be necessary to elucidate the physiological mechanism of SD for

In article <37EF56B6.6E7232D8 at access.net.au>, Graeme Whelan
<gwhelan at access.net.au> writes
>It's not that we don't know why we sleep, it's just that it is difficult to
>The slow wave sleep (SWS) referred to is the time that growth hormone is
>released at twice the normal rate and also the period during which
>neurotransmitters are synthesized in the brain at up to four times the rate done
>at any other time.  Ever wonder why we get a little fuzzy in our thinking when
>sleep deprived, have trouble with judgement and with co-ordination?  The immune
>system also gets a boost while we are experiencing SWS.
>The rapid eye movement (REM) sleep appears to have very little to do with
>consolidation of experience and more to do with establishing and repairing
>connections in the brain.  A foetus at 26 weeks gestation spends 100% of its
>time in REM sleep, having had almost no 'experiences' to deal with and no
>psychological dilemmas which Freud proposed as the function of dreaming.  A
>new-born baby spends 10 of its 20 sleeping hours a day in REM sleep, this amount
>diminishing as the brain approaches its adult size.
>Total sleep deprivation will kill.  There is a point of no return marked by
>hypothermia after which a person will die, no matter what sleep they are allowed
>and what care they are given after that point.  This is the result of a poorly
>functioning immune system.  True, the cause of these deaths was a mystery for
>many years, but it has been shown to be septicaemia.  The mammals tested min
>these experiments were simply overwhelmed by the sheer number of bacteria in
>their bodies, hence the increasing energy consumption but decreasing weight and
>body temperature.  Very difficult to detect when the responsible organisms are
>those that ordinarily inhabit the body and are totally benign.  It just goes to
>show you won't see what you're not looking for.
>I was disappointed to see that the article below was from New Scientist.  I
>would have expected more thorough research from such a journal.  Clearly they
>needed a filler piece in a hurry and thought that naming a few related
>disciplines and calling on the name of evolution - which we should remember is
>still a theory, not a fact - would create something to pass for a credible
>gwhelan at XXXaccess.net.au
>(remove the X's to reply)

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