cell death in Korsakoff syndrome

pelorus at coastalnet.com pelorus at coastalnet.com
Thu Dec 3 20:25:17 EST 1998

I haven't kept up with the literature in these areas in several years, having
gotten away from the study of membrane energetics in model membranes and more
into geology and paleomagnetics.  Yeah, what a switch!

I do know, however, that the membranes surrounding mast cell granules contain
thiamin-specific phosphatases.  Histologists utilize this integral membrane
protein to chelate lead used in labelling work for electron microscopy.  This
enzyme regulates the histamine specific transporter, a proton-pumping ATPase
that maintains the inner compartment of the granules at an acidic pH.  It is
this proton gradient that traps histimine and other molecules (specifically
large concentrations of thiamin) inside the granules.  Maybe they aggregate in
these regions to dump thiamin in these thiamin deficient areas.

Robert D. Brown, MD

In article <744r67$i3u at sjx-ixn8.ix.netcom.com>,
  flefever at ix.netcom.com(F. Frank LeFever) wrote:
> I've had a special interest in mast cells since hearing Rae Silver
> describe them in an entirely new light at the NY Academy of Sciences
> about 5 yrs ago, and tend to forget that most people (including many
> neuroscientists I've polled at Society for Neuroscience meetings) think
> of them precisely the way you described them--histamine, allergic
> reactions, etc.
> Their phenotype can vary from location to location within the body, but
> besides histamine they can produce a wide variety of other substaances,
> including many cytokines, and can release them in a graded and
> selective fashion--not just the classic massive degranulation and
> release of histamine.
> Effective signals for activation include cytokines and neural impulses.
>  For ex., IL-1 can signal them to decrease PAF release and increase NO
> release.
> Rae Silver's initial work suggested a role in normal reproductive
> behavior in birds, mediating between peripheral factors and the
> habenula.  Her work preented at SFN last month showed that thalamic
> mast cells had migrated from the circulation.
> Although usually near blood vessels, they are on the other side of the
> BBB, squarely in the parenchyma.  They migrate and/or multiply in many
> pathological conditions, with MS getting the most attention in this
> regard--they may be agents of demyelination.
> Your point re breakdown in BBB in thiamine deficiency suggests a role
> for mast cells, in that they are adjacent to the brain/blood interface
> and are thought to have an effect on BBB.
> My references are all at work (email at home), but Medline search for
> Theoharides should turn up something re "new look" of mast cells...also
> Blalock??  And of course, Rae Silver, espec review article--Trends in
> Neuroscience?? c. 2 years ago??
> F. Frank LeFever, Ph.D.
> New York Neuropsychology Group
> In <742tvn$5hf$1 at nnrp1.dejanews.com> pelorus at coastalnet.com writes:
> >
> >
> >>
> >> However, I also cited a paper at the recent Society for Neuroscience
> >> meeting relating mast cell proliferation in the thalamus, preceding
> >> focal lesions in thiamine-deficient rats.  I read this as an
> argument
> >> for a gradual process, but it occurs to me now that although perhaps
> >> contributing to prodromal symptoms they could be activated in the
> rapid
> >> lesioning processes precipitated by a sudden demannd (e.g. glucose
> >> infusion).  What is your thinking on this?
> >>
> >The mast cell is a histamine-containing element of the immune system,
> and I
> >could only hazard a guess as to why mast cells should accumulate in
> the
> >thalamus during advanced thiamin deficiency in rats.
> >
> >There is a direct correlation between the thiamin content of a cell
> and its
> >level of metabilic activity.  As I noted before, thiamin's membrane
> functions
> >are intimately connected to solute transport reactions of a
> chemiosmotic
> >variety.  Brain vascular tissues maintain a "blood-brain" barrier that
> acts to
> >keep out of neural networks many compounds that are otherwise present
> in blood
> >and delivered to organs other than the brain.  Thiamin deficiency is
> known to
> >cause a breakdown in these barrier functions.  This would allow
> molecules that
> >do not normally appear in brain tissues to diffuse into the
> extracellular
> >matrix.  Perhaps in this location these molecules cause a mast cell
> mediated
> >form of "allergy".  It is just a guess.
> >
> >Robert D. Brown, MD
> >
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