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Excitotoxicity

Excitotoxicity

Excitotoxicity

Glutamate is the main excitatory neurotransmitter in the body.  It is essential for learning, and for both short-term and long-term memory.  It is also the precursor to the inhibitory neurotransmitter, GABA.  GABA is a calming neurotransmitter, and is essential for speech.

Problems occur if the normal process of regulation of Glutamate malfunctions and if toxic levels of this excitatory neurotransmitter build up in the synaptic junctions.  The brain requires sufficient levels of oxygen and energy to remove excess Glutamate.  However, Glutamate release leads to the release of insulin, which results in decreased glucose levels.  The amount of glucose in the brain regulates the removal of excess Glutamate from the synapses.  Therefore, a drop in blood glucose disrupts this removal process and allows the build up of toxic Glutamate.  In fact, conditions of hypoglycemia, or low calorie/starvation conditions induce the release of Glutamate and reduce the ability to remove excess levels of Glutamate from the brain.  This excess Glutamate depletes Glutathione.  Glutathione is one of the most powerful antioxidants found in the body and helps to protect neurons from damage.  Glutathione depletion consequently leads to the death of additional neurons.

The release of excess Glutamate triggers an inflammatory cascade that results in the death of neurons by the major influx of calcium into the nerve until it results in neural cell death.  Normal levels of calcium result in normal neuron functioning.  However, excessive levels of calcium make it impossible for the neuron to rest; the neuron continues to fire without stopping, causing the release of inflammatory mediators, the release of more Glutamate, thus resulting in more calcium influx.

Glutamate and aspartate are common as food additives as well as naturally occurring components of a large number of foods.  In cells, Glutamate and aspartate can be synthesized from each other.  The two main food additives that are sources for excitotoxins are MSG (monosodium glutamate) and aspartame (nutrasweet).

Body systems that have been affected by Glutamate toxicity include effects on white blood cells (elevations in the levels of eosinophils,), effects on blood vessels (causing migraines and reduced regulation of blood pressure), and inhibition of the conversion of Glutamate to GABA.

High levels of excitatory amino acids, and low levels of Glutathione have been associated with a number of neurodegenerative disorders.  The sites in the brain that have been reported to be damaged by excitotoxins.

Excess levels of Glutamate have been definitely implicated in a range of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s chorea, stroke, Multiple sclerosis, and ALS. In the case of autism, irregularities related to Glutamate have been observed.  In addition, Glutamate induced neurotoxicity is indicated in stroke, brain injury, heart disease, schizophrenia, and bipolar disorder.  

Glutamate, glutamic acid and aspartate and aspartic acid were found to be elevated in individuals exhibiting autistic behavior relative to controls.

In all cases of neurological inflammation leading to autistic behavior there seems to be an initial insult to the system, which results in a reduction of normal flora in the intestinal tract, with a subsequent loss of Vitamin K.  Most often this seems to occur as a result of chronicstreptococcal ear infections, the antibiotic use that follows, and a lack of re-population of the intestines with normal flora.

The liver contains high levels of enzymes, and enzyme systems that are required for detoxification processes.  The liver contains one of the highest levels of Glutathione.  Glutathione is one of the most powerful antioxidants found in the body.  Glutathione is essential for both the phase I and phase II detoxification systems of the liver.

A central theme in the current treatment of autism seems to be the removal of heavy metals.  While this is useful, heavy metal toxicity appears to be a consequence of the underlying problem and not the problem itself.  High extracellular levels of the excitotoxin Glutamate cause the extrusion of intracellular cysteine- resulting in Glutathione depletion.  Low levels of magnesium also result in decreased levels of Glutathione.

Another issue with children with this type of neurological inflammation is the lack of /or slow development of speech.  The calming neurotransmitter, GABA is essential for speech.  GABA neurons damp the propagation of sounds so that a distinction can be made between the onset of a sound and background noise. (GABA is often used to help restore speech in individuals who have suffered strokes.)

Normally, excess levels of the excitotoxin Glutamate can convert to GABA. There seems to be a disconnect in this process for autistic children so that the excitatory neurotransmission is high (stims) and the calming neurotransmission is low (lack of speech),

The chronic measles infection proposed by Wakefield may be related to this disconnect between Glutamate and GABA.  Active measles infection (as opposed to chronic) can lead to Type I diabetes.  In Type I diabetes the body makes antibodies against the enzyme that converts Glutamate to GABA.

In reviewing the predisposing factors, as well as the sequence of events that lead to autistic type behavior, the involvement of Glutamate, or other excitotoxins is a thread that winds its way through all of these factors.  From the standpoint of predisposing factors, excess Glutamate is correlated with intelligence, as well as early gender differences in neurological development. Imbalances in the GI tract and the normal flora balance can be exacerbated by Glutamate.  Vitamin K, a key vitamin in the pancreas is itself involved in Glutamate enzymatically.  Two of the major food issues for children with autistic type behavior are casein and gluten.  Both of these food proteins are high in natural Glutamate.

Vaccines can contain free Glutamate, and metals that are components of vaccine preparations are able to trigger Glutamate release.  Imbalances in the conversion of Glutamate to GABA have been noted as the sequelae of measles/mumps/rubella viral infections and low levels of GABA are related to speech difficulties.

Quoted from Source:
http://gordonresearch.com – Role of Excitotoxins by Dr. Amy A. Yasko 
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