cell death in Korsakoff syndrome

F. Frank LeFever flefever at ix.netcom.com
Thu Dec 3 22:49:24 EST 1998


There must be SOME STORY behind that mind-boggling switch!  Anyway,
thanks for your "old" info; it's new to me and will give me much to
think about--maybe send me to a different lit search.  For starters,
have you a source you could cite??

F. LeFever


In <747dlr$14e$1 at nnrp1.dejanews.com> pelorus at coastalnet.com writes: 
>
>I haven't kept up with the literature in these areas in several years,
having
>gotten away from the study of membrane energetics in model membranes
and more
>into geology and paleomagnetics.  Yeah, what a switch!
>
>I do know, however, that the membranes surrounding mast cell granules
contain
>thiamin-specific phosphatases.  Histologists utilize this integral
membrane
>protein to chelate lead used in labelling work for electron
microscopy.  This
>enzyme regulates the histamine specific transporter, a proton-pumping
ATPase
>that maintains the inner compartment of the granules at an acidic pH. 
It is
>this proton gradient that traps histimine and other molecules
(specifically
>large concentrations of thiamin) inside the granules.  Maybe they
aggregate in
>these regions to dump thiamin in these thiamin deficient areas.
>
>Robert D. Brown, MD
>
>
>
>
>In article <744r67$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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>>
>
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