Suppression of Glutamate-Induced Neuronal Activity

[[Buddie]]

Found this interesting as we continue to look at different topics that tie in with glutamate expression....

https://www.frontiersin.org/articles/10.3389/fnint.2010.00018/full


Suppression of Glutamate-Induced Neuronal Activity
Lysine and arginine are positively charged amino acids, while glutamate is negatively charged. Both lysine and arginine completely blocked glutamate-evoked neuronal excitation in microiontophoresis experiments, suggesting that lysine and arginine suppress glutamatergic neuronal activity in vivo and dietary levels of these amino acids might modulate brain activity via glutamatergic inhibition. Glutamate activates ionotropic glutamate receptors, including NMDA receptor that behaves as a single-occupancy channel for small monovalent and divalent permeant cations (Zarei and Dani, 1994 ). Considering the rapid onset of the suppressive effects, lysine/arginine might block directly the ion channels (open channel block) via mechanisms similar to those associated with Zn2+ and Mg2+ (Mayer et al., 1984 ; Nowak et al., 1984 ). Another possibility relates to indirect actions of lysine/arginine via activation of non-glutamate receptors or via adjacent inhibitory interneurons. For example, lysine interacts directly with a variety of receptors and can act both as an partial antagonist of the serotonin receptor type 4 (Smriga and Torii, 2003a ) and as an agonist of benzodiazepine (Chang and Gao, 1995 ), calcium-sensing (Conigrave et al., 2000 ) and “GPRC6A” (G-protein-coupled receptor, family C, group 6, subtype A; Wellendorph et al., 2005 ) receptors. However, these mechanisms were less likely since microiontophoretically applied chemicals can act only within a very narrow area, possibly involving only the recorded neuron. Although it is premature to assign any particular function, our findings bring to light a functional interaction between basic amino acids and glutamate in the brain. Suppression of glutamatergic neurons by lysine and arginine might contribute to the suppression of cerebral ischemic damages. Further studies are needed to clarify the mechanisms of these inhibitory actions and potential therapeutic interventions.

[[Buddie]]

thanks. have you tried these?

[[Buddie]]

thanks. have you tried these?

Just in research mode at the moment... neither looks like they have any majore side effects out side of taking too much. Which holds true for most aminos. The warning label on the Arginine supplement is worth reading though.

[[Buddie]]

posted this on alternative  section

https://www.hindawi.com/journals/ecam/2017/6048936/

Glutamate is the primary excitatory neurotransmitter in the central nervous system.

 Excessive concentrations of glutamate in the brain can be excitotoxic and cause oxidative stress, which is associated with Alzheimer’s disease. In the present study, the effects of vitamin E in the form of tocotrienol-rich fraction (TRF) and alpha-tocopherol (α-TCP) in modulating the glutamate receptor and neuron injury markers in an in vitro model of oxidative stress in neural-derived embryonic stem (ES) cell cultures were elucidated.
 
A transgenic mouse ES cell line (46C) was differentiated into a neural lineage in vitro via induction with retinoic acid. These cells were then subjected to oxidative stress with a significantly high concentration of glutamate. Measurement of reactive oxygen species (ROS) was performed after inducing glutamate excitotoxicity, and recovery from this toxicity in response to vitamin E was determined.

The gene expression levels of glutamate receptors and neuron-specific enolase were elucidated using real-time PCR. The results reveal that neural cells derived from 46C cells and subjected to oxidative stress exhibit downregulation of NMDA, kainate receptor, and NSE after posttreatment with different concentrations of TRF and α-TCP, a sign of neurorecovery.
Treatment of either TRF or α-TCP reduced the levels of ROS in neural cells subjected to glutamate-induced oxidative stress; these results indicated that vitamin E is a potent antioxidant.


https://www.sciencedaily.com/releases/2019/10/191015140249.htm

this last one was in conjunction with the damage statins can cause.


As glutamate is a potent activator of muscle pain receptors,
this release was proposed to trigger the sensation of muscle pain.

Irena Rebalka, first author of the study
 and a research associate in the Hawke Lab added:

"We found that administering some well-known antioxidants, such as Vitamin E,
were successful in helping reduce glutamate release.

We are now expanding our studies to determine
further compounds which could be used in conjunction
 to reduce the burden of muscle pain resulting from this drug."

Both interesting in regards to glutamate problems

[[Buddie]]

thanks. have you tried these?

Just in research mode at the moment... neither looks like they have any majore side effects out side of taking too much. Which holds true for most aminos. The warning label on the Arginine supplement is worth reading though.

I'm experimenting with lysine atm, without arginine. Do you think i should add the latter for a better outcome? I agree that aminos must be used carefully to prevent "issues"; problem is we tend to think if something works at a relatively small dose, double should be better. Now we know, don't we?

[[Buddie]]

thanks. have you tried these?

Just in research mode at the moment... neither looks like they have any majore side effects out side of taking too much. Which holds true for most aminos. The warning label on the Arginine supplement is worth reading though.

I'm experimenting with lysine atm, without arginine. Do you think i should add the latter for a better outcome? I agree that aminos must be used carefully to prevent "issues"; problem is we tend to think if something works at a relatively small dose, double should be better. Now we know, don't we?

I'm not sure; that's something you would have to want to dive into yourself after you've done your due dilligence from a research perspective.

I am going to add this to my stack for the time being. Probably in the evening. I'm primarily doing this for muscle tissue recovery as I go to the gym 5-6 days per week and I'm sore all of the time. So I'm hoping there will be some benefit there and possibly some added benefit to my brain... but without a deep-dive into this, I'm not sure how relevant these Aminos could be to our situation. It was more food for thought as I came across this while researching post workout protocols.

There's a Tri-Amino made by NOW brand that has the 3 aminos I'm going to be taking below but I have all 3 so I'm going to simply take them together (1x/day).

L-Lysine 500mg
L-Arginine 500mg
L-Ornathine 500mg

[[Buddie]]

During last taper when excitotoxicity got very bad taking 5mgs Memantine stopped it and a set of symptoms eased and never returned.

[[Buddie]]

Do you think memantine can help PAWS?

[[Buddie]]

I want to bump this topic and ask if L-citrulline would help too, and if anyone else has experience using arginine, citrulline, lysine to help Benz withdrawal symptoms.