A Theory of Neuropeptides?

Dag Stenberg dag.stenberg at nospam.helsinki.fi.invalid
Fri Jan 9 03:51:00 EST 2004


k p  Collins <kpaulc@[----------]earthlink.net> wrote:
> Hi Dag,
> ...
> As I've discussed in the past, it's my position that a lot of this sort
> of thing does happen during sleep - with respect to "experiential total"
> cross-correlation, which is absolutely-necessary with respect to
> maintaining 'normal', unified waking-consciousness - simply be-
> cause, during waking-consciousness, one's neural activation is
> necessarily [more or less] specifically-correlated to one's then-
> occurring experience, but cross-experiential-total cross-correlation
> of each 'day's new experience is =absolutely-necessary= if a
> unified consciousness is, in fact, to be maintained.

I used to think that my text was difficult to understand (although I
like to think that I make sense), but I see now, Ken, that your writing is a
whole lot more complicated.

> As you can imagine, because I've been at this for so long, I've become
> aware that there are several 'sub-processes' within sleeping-consciousness.
> They are recognizable because they go in and out of sync, stereotypically,
> as I allow my sleep cycle to rotate 'around the clock'.

There is much published literature about free-running rhythms and the
desynchronization of internal rhythms. It is, as you mention,
complicated to sort out the various rhythms forom each other. To couple that
to chemistry, though, is NOT easy. 

> So I can say, with Certainty, that if you find a subject who will endure
> an analogous waking-sleeping discipline, you'll see periodic fluctuations
> that correlate to these sleep sub-processes - and because they sort of
> 'slide-over' one another [they each 'go their own way'], the correlations
> will be 'easy' to identify in pharmocological assays. [Whoops! I =don't=
> know if such studies can be done in Humans - probably not, eh? Or do
> the substances you monitor occur, say, in bodily fluids? 

The discussion was about synaptically active neuropeptides. There is no
sense in measuring them other than in the immediate vicinity of the
synapses involved in each function. There is no sense in measuring them
even in the cerebrospinal fluid. Consequently, present technique does not
allow very much of intracerebral measurement in humans. Yes, some
invasive measurements can be done, monoamines (e.g. Ronne-Engstrom et
al., J Cereb Blood Flow Metab. 1992 Sep;12(5):873-6, Broderick et al.,
Brain Res. 2000 Sep 29;878(1-2):48-63) and metabolites (e.g.
Reinstrup et al., Neurosurgery. 2000 Sep;47(3):701-9, Nordstrom et al.,
Anesthesiology 2003 Apr;98(4):809-14) or noninvasive measurements of metabolites
(Urrila et al., J Cereb Blood Flow Metab. 2003 Aug;23(8):942-8). Obviously,
invasive procedures are ethically acceptable only in certain patients (whose
diagnosis or treatment may benefit from the measurement).

The invasive techniques used in the studies I cited above involve either
intracerebral microdialysis (artificial capillary) or microvoltammetry,
and the noninvasive technique is proton spectroscopy. Microdialysis
could lend itself to the measurement of small neuropeptides that pass
the membrane of the probe, but no big ones. Still, the actual measurement
would be exceedingly tricky because of the extremely small concentrations
occurring. For these reasons, animal studies will yield much more
relevant results, although conducting such experiments is in no way
trivial. 

To conclude, I agree that the question of depletion and replenishement
of neuropeptides across the sleep-wake cycle is interesting. To crudely
outline an experiment might be straightforward. To make it work in order
to produce relevant biological data (I mean relevant, actual, factual
data, not a hyopthesis) is extremely difficult, even for specialists involved
in such work during decades. Otherwise this would already have been done.

Dag Stenberg




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