NMDA again

Stephan Anagnostaras stephan at psych.ucla.edu
Tue Oct 24 12:07:21 EST 1995


In article <DGwAC3.CDv at uns.bris.ac.uk>, p.j.roberts at bristol.ac.uk wrote:

> Glutamate agonists may be neurotoxic via both NMDA and non-NMDA receptors
> if given i.c.v. The evidence that glutamate is neurotoxic following oral
> administration in man (including neonates) is lacking. This has been
> convinvingly demonstrated only in neonatal rodents. The August 1995 FASEB
> (FDA) report on all aspects of the safety of MSG concluded that orally
> administered glutamate was wholly safe, although there may be a very small
> subgroup of individuals who show some sensitivity and exhibit peripheral
> (not CNS effects). Furher research has been indicated in a small number of
> asthmatics who may show sensitivity. Glutamate basically does not enter
> the brain, or rather, there is no net accumulation. Compounds like domoic
> acid from contaminated mussels, do cross the bbb to activate kainate/AMPA
> receptors and produce neurotoxic sequelae.
> Peter Roberts


Sure, but under normal physiological conditions I don't think AMPA
receptors contribute much to neurotoxic damage, because they depotentiate
rapidly when rapidly overstimulated.  This is why the whole brain doesn't
die during hypoxia but just places where there are lots of NMDA receptors.
So the system overall is pretty conservative; NMDA receptors won't be
activated unless there are already lots of AMPA receptors activated
and these are usually going to depotentiate rapidly.

Cheers
> 
> Sandra L Wegert (sandraw at U.Arizona.EDU) wrote:
> : Right, agonists at this receptor can be neurotoxic.  Glutamate (ie, MSG) 
> : is suspected to be toxic to the brain because it overexcites these 
> : receptors.  As an aside, I personally doubt that (much) MSG crosses the 
> : blood-brain barrier in healthy adult humans (it does in babies, 
> : however) when given in the concentrations found in food.  Please, correct 
> : me on this, I'm playing devil's advocate a little here.
> 
> : On 20 Oct 1995, Jason Kennerly wrote:
> 
> : > LSCCLAB <lscclab at biovx1.biology.ucla.edu> writes:
> : > > What is NMDA receptor?
> : >  
> : > A receptor stimulated by NMDA.
> : > PCP and Ketamine block (antagonize) NMDA's effects at this receptor
> : > NMDA's neurotoxicity stems from its excitotoxic effect at this receptor 
> : > (this isnt the best way to explaine it is it?)

-- 
STEPHAN ANAGNOSTARAS                   UCLA BEHAVIORAL NEUROSCIENCE
STEPHAN at PSYCH.UCLA.EDU



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