Glutamate and the NMDA Receptor

Glutamate and the NMDA Receptor

If you have meandered throughout our site, you should have stumbled upon glutamate, calcium, and action potentials. Glutamate is the brain’s number one excitatory chemical in terms of quantity; however, when its natural balance becomes compromised, the brain becomes extremely electrified.  An excitatory chemical, by nature, is a chemical that increases electricity throughout the brain and body.  As we continue to invest much time and effort in the science behind the mysteries of medicine, we are continually brought back to glutamate and its role in the brain. Below is a figure demonstrating the vast abundance of glutamate compared to other neurotransmitters.

By delving into more detail on glutamate and its role in the brain and body, we can cover two teaching points as well.  First, you will understand more clearly the emphasis put on this mechanism, which will help you better comprehend the material throughout the site.  Secondly, you will understand the meaning of a biochemical mechanism and how it relates to nearly all of the concepts outlined on our site. This information on glutamate will educate you about the science behind this mechanism, which will help you understand how this concept is applied to all 100+ biomarkers utilized in the UCDTM protocol.  Moreover, glutamate’s link to toxin exposure confirms its critical and vital importance associating it to nearly all medical issues discussed throughout this site.

Glutamate and the Brain

As aforementioned, glutamate is an excitatory chemical – meaning, it increases electricity in the brain, but there is a precise mechanism at which this occurs. When the brain and body are exposed to toxins, specifically mycotoxins, the amount of glutamate increases (1).  In precise quantities, when exposed to mycotoxins (mold toxins), glutamate was measured to increase by 213% (1). As discussed on various pages, glutamate is in balance with its primary inhibitory (calming) counterpart, GABA. Moreover, it has been discussed further that as excitatory chemicals increase due to toxin exposure, inhibitory (calming) chemicals will increase in attempts to balance the increase in voltage.

In attempts to remain in balance, as glutamate increased by 213%, GABA rose by an astounding 455% (1). This shows how hard the brain is working to correct its imbalances. However, if this toxin exposure continues, GABA and other inhibitory chemical production will become exhausted from these excess efforts to balance the increase in electricity. This inhibitory exhaustion will cause the brain’s electricity to stay continually elevated, and this elevation can cause neuronal apoptosis (brain cell death).

But how does glutamate cause neuronal death exactly? There are two brain receptors of primary interest when it comes to glutamate – the N-methyl-D-Aspartate (NMDA) receptors and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors. These receptors work together in terms of electricity. Additionally, the NMDA receptors require co-factors to fire (see Brain Chemistry Treatment for more details on co-factors) (2). Some of these co-factors include D-Serine and glycine as well as various ions (2).

In order for calcium to be allowed into the cell, magnesium must be removed from the NMDA receptors (2). We must attempt to keep magnesium concentrations high in order to prevent this ion from being removed from the receptor because when magnesium is removed, calcium is allowed entry. This may lead you to ask, what happens when too much calcium continually enters the neuron?

The answer to this question will show you the overall mechanism of toxin-induced brain toxicity (neurotoxicity). It has been proposed that when glutamate elevates, it induces calcium to enter the neuron; when calcium enters, it causes the neuron’s electricity to increase (3). To prove this, conditions were set, allowing glutamate to be elevated. Calcium was then removed to prove whether the increase in electricity was caused solely by the elevated glutamate or by a glutamate-induced calcium influx. When calcium was removed, no electricity was elicited thus proving the overall mechanism and relationship between calcium, glutamate, and toxins (1, 3).

Glutamate and Disease

As an abundance of calcium enters the neuron, excess electricity causes brain cells to die because the inhibitory chemicals cannot handle the load capacity and adequately balance this increase in voltage. If this elevated rate persists, this increased electricity will destroy the neurons. Therefore, it comes as no surprise that elevated glutamate and the NMDA receptors have been linked to a variety of abnormalities, which include acute CNS diseases, including ischemia, trauma, epilepsy,  stroke, hypoxia,  head trauma, Huntington’s, Parkinson’s, and Alzheimer’s diseases, neuropathic pain, alcoholism, schizophrenia, and mood disorders (3, 4).

If you have read the Mold Toxicity page, you will see many overlapping abnormalities, and we hope you now understand the mechanism that proves this overlap to be true. Moreover, as these conditions affect brain receptors, they are considered brain disorders; however, Mold Toxicity can affect nearly all organs, including the kidneys, liver, heart, lungs, and the brain. If you combine the brain mechanism of neurotoxicity caused by glutamate, in addition to the other complications from Mold Toxicity, we would wager that many of the ailments that you or your loved ones are experiencing can be encompassed in these proven disorders.

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