the older you are....

[Guest guest]

I may as well use this mailing list as a place to post rough drafts of

things I plan to post on my website.... that way people can comment if they

like to...

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The abstract below pertains to a study relevant to aging and glutamate

excitotoxicity.

Glutamate is potentially toxic to neurons that have NMDA receptors but not

because of the presence of any kainate receptors. NMDA and kainate receptors

are two common types of glutamate receptor.

It takes a tremendous amount of energy to control any increase in

extracellular glutamate, and so the toxicity of glutamate increases as one

ages and the brain becomes increasingly " energy-compromised " .

Glutamate comes in contact with the NMDA receptor on the dendrite or body of

the neuron, opening a calcium channel. Calcium then flows into the cell,

causing the neuron to " fire " . This entry of calcium into the neuron

initiates a sequence of events inside the neuron that requires energy in the

form of ATP and which also unleashes free-radicals inside the neuron. If too

much calcium enters the cell then the quantity of free-radicals released can

destroy the neuron.

Too much calcium can enter the cell if the exposure to glutamate is too

great even if the exposure is brief. In such cases the calcium channel can

" lock " in the open position and allow calcium to keep streaming into the

cell until the neuron dies. The actual cell death in such cases will occur

about two hours after the exposure to excess glutamate, even if there is no

longer any extra glutamate present.

It is known that increases in brain glutamine cause increases in

extracellular glutamate in the brain. If the magnitude of glutamate increase

is great enough and/or the brain is mature enough and thus

" energy-compromised " and/or the neurons are otherwise compromised as a

result of what might be just normal wear and tear from ordinary free-radical

damage from daily living (or perhaps from free-radical damage caused by

prior abuse from foolish chronic megadosing with glutamine), then the result

will be damage or death of those neurons. It might be subtle almost

undetectable damage that happens gradually over a long period of time in

response to chronic megadosing on glutamine for GH purposes, and that is of

course my primary concern. I believe such supplementation can make people

senile before their time.

Certainly the vast majority of mature people interested in anti-aging have

some significant number of neurons which would be vulnerable to glutamate.

How old does one have to be to be too old for glutamine GH supplementation?

I would say that's a judgement call, but that it would be smart and prudent

to err on the side of caution by taking glutamine with meals containing

complete proteins and using something else for GH purposes.

-gts

www.optexinc.com

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Title

Neurotoxicity at the N-methyl-D-aspartate receptor in energy-compromised

neurons. An hypothesis for cell death in aging and disease.

Author

Henneberry RC; Novelli A; JA; Lysko PG

Address

Molecular Neurobiology Section, National Institute of Neurological and

Communicative, Disorders & Stroke, National Institutes of Health, Bethesda,

land 20892.

Source

Ann N Y Acad Sci, 568():225-33 1989

Abstract

Our results demonstrated that the neurotoxicity of glutamate and closely

related agonists was mediated by the NMDA receptor in rat cerebellar granule

cells. Evidence was presented to support our hypothesis that the pivotal

event in the transition of these EAAs from neurotransmitters to neurotoxins

is relief of the voltage-dependent Mg++ block of the NMDA channel due to

changes in membrane potential which can be caused by depletion of highly

phosphorylated nucleotides or by other depolarizing stimuli. Persistent

stimulation of NMDA receptors whose channels are unblocked by Mg++ can

permit excessive influx of Na+ and Ca++ and neuronal death can follow by a

mechanism not yet understood. Glutamate is not toxic at kainate receptors

although they are present on these cells. These findings underline the

potential importance of perturbations in energy metabolism in a variety of

neurodegenerative disorders and in the normal process of aging which share

the common feature of the loss of neurons.

Language

Eng

Unique Identifier

90196809