A Theory of Neuropeptides?

Dag Stenberg dag.stenberg at nospam.helsinki.fi.invalid
Wed Jan 7 10:14:02 EST 2004

k p  Collins <kpaulc@[----------]earthlink.net> wrote:
> "yan king yin" <y.k.y at lycos.com> wrote in message
> news:72de81ae.0401060226.67da0596 at posting.google.com...
>> Neuropeptides (when they're located at the pre-synapse) are usually
>> secreted after intense stimulation such as tetanic trains. ...
> There's an easy first-test with respect to this question - assay
> peptide concentrations before and after episodes of sleeping
> consciousness [because, if your hypothesis is valid, then the
> 'catching-up' would be most-easily handled during sleeping-
> consciousness. And, since it's easy to look at before-and-
> after-sleep peptide concentrations [well, relatively-easy, all
> things considered], checking that out would be a good first
> 'step' to take with respect to your hypothesis.

Ken, do you mean "sleep" by "sleeping consciousness"? Or do you mean
"REM sleep"? Or do you mean "across the sleep-wake cycle"? 

Anyway, there are publications since 1909 attempting to assay protein or
peptide concentrations after prolonged waking in comparison with the
well-slept state, or differences between sleep and waking. Of course, in
1909 they could not identify the peptides, but they found that a
protein-based substance accumulated in the brains of sleep-deprived
animals would induce sleep when infused into the cerebroventricular
system of other animals. About 1975, the accumulation of muramyl peptide
during prolonged waking was observed. It was later found to relate to
and cause the production of interleukin-1 during waking, and indeed it
has been found that prolonged waking induces the transcription by
the interleukine-1 gene.
  Several other genes are transcribed more intensely during waking than
during sleep. It follows that their gene products (proteins eventually
broken down to peptides, which may be directly involved in transmission or
more indirectly, by affecting the regulation of cellular functions) may also
vary with the sleep-wake state. Most of these genes are immediate early genes
or gene products related to synaptic plasticity or cellular metabolism. A
very few genes are transcribed more during sleep. 

Thoughts about peptides related to sleep homeostasis can be divided into
the depletion hypotheses and the accumulation hypotheses. Does waking
activity deplete something useful and necessary, or does it accumulated something
harmful (the hypnotoxin theory)?

If levels of a peptide increases during wakefulness, it might mean that its use
is diminished, or alternatively, that its production is increased. This
latter may be due to increased gene transctiption, and may be a
compensatory phenomenon because of increased use. If a peptide
decreases during wakefulness, it might mean that it is used more and it
is being depleted, or that its production has simply become decreased.
If one samples the level during a longer period of wakefulness, one might
see initial depletion followed by compensatorily increased production. A
single time point may produce misleading results. Furthermore, study
during spontaneously oscillating sleep-wake cycles may not reveal the
true dependence on wake and sleep, as there may be a delay between the
change in state and the concentration changes. If the delay is due to
changes secretion from stores in the presynaptic terminal, these
concentration changes are seen with short delay; if the change involves
gene transcription, the change occurs with a delay of hours to days, and
cannot be analyzed by studying spontaneous sleep-wake patterns (with a
cycle of 24h in humans and even less than an hour in most other vertebrates.

So when Ken writes "There's an easy first-test with respect to this
question" it is not all that easy. In fact, a great deal of peptide
assay has been done during the last few decades in relation to sleep and
wake, and there is still no easy answer.

Dag Stenberg 


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