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glutamic acid/NMDA question

Karsten Kueppenbender kueppenb at helix.mgh.harvard.edu
Thu Oct 2 16:04:47 EST 1997

Hello Martin,

NMDA is a synthetic component selectively activating a subclass of
ionotropic glutamate receptors (GluRs), i.e. GluRs which function as
ion-channels upon activation. Physiologically all GluRs are activated by
Glutamic Acid (=Glutamate). 

There won't be an excess of NMDA in a brain of any animal, if it is not
applied by anyone who did so deliberately. 

I don't quite understand, if you are talking about human beings (there has
been no NMDA in a human brain so far - it is used in laboratory only!) or
laboratory animals. Or are you talking about an excess of NMDA-RECEPTORS,
which would be another topic?

However, Glutamic acid levels in the plasma will not directly affect
neurons in the brain, regardless of NMDA there or not. The plasma is
seperated from the brain by the blood brain barrier and provided this
barrier is healthy and the Glu levels are not exorbitantly high, they will
have no effect on the neurons which sit safely behind this barrier.

Some Chinese food, potato chips and all that food which often contains
mono-sodium-glutamate to enhance tastiness won't hurt neurons directly.
Nevertheless, don't take too much of it or avoid it altogether. Who
knows - maybe there are other potential harmful effects, which we have
not thosught of. Fresh food is tasty without mono-sodium-glutamate.
Under experimental conditions (tissue cultures, intracranial injections)
Glutamic acid is neurotoxic, a phenomenon usually referred to as
exitoxicity. Its neurotoxic effects can be blocked by NMDA-receptor

You might be interested in the two following articles. Neither of them is
brand new, but both of them are very well written and provide 
comprehensive overview which is not outdated.

The first focuses more on the molecular pathophysiology, the second
extents to clinical aspects of excitoxicity.

Hope I could help you a little.



1. Choi DW (1988) Glutamate neurotoxicity and diseases of the central
nervous system. Neuron 1:623-634

2. Lipton SA, Rosenberg PA (1994) Excitatory amino acids as a final common
pathway for neurologic disorders. The New England Journal of Medicine

Karsten Kueppenbender             Phone (617) 726-3117
Neurology Research                FAX   (617) 724-1480
Warren 407
Massachusetts General Hospital
Fruit Street, Boston, MA 02114      

On Thu, 2 Oct 1997, drew martin wrote:

> Can anyone help me understand the relationship between increased
> plasma concentrations of glutamic acid and NMDA. Is it dangerous to
> increase glutamic acid if there is an excess of NMDA?
> thanks in advance
> drew

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