Excitotoxicity

Excitotoxicity is defined as neuronal death due to over-activation of cells by excitatory amino-acids like glutamate, aspartate, cystine, and the sulphinic and sulphonic acids. The same effect can be seen in toxins like: α-kinate, a toxin derived from seaweed, Digenea simplex

Excitatory amino-acids / neurotransmitters work on the receptor N-methyl-D-aspartate (NMDA) receptor. When an excitatory amino-acid binds to the NMDA receptor, it causes neuronal death by: Na+, Cl-, and H2O2 influx into the cell (causes osmotic lysis); or by influx of Ca2+ causing activation of variety of enzymes that causes neuronal prolonged excitation to death. Overstimulation of the NMDA receptor with concomitant production of high levels of nitric oxide results in high production of reactive oxygen species (ROS)

After central nervous system injury, the release of large amounts of glutamate (an excitatory neurotransmitter) acting on NMDAreceptors leads to an increase in intracellular sodium and depolarization of the neurons. This leads to an influx of free calcium through voltage-dependent calcium channels, which in turn causes cell swelling and death, and may contribute to raised intracranial pressure

Glutamate toxicity, overload of calcium (Ca+2) ions, and oxidative stress contribute to a spiraling cascade that ends in neuronal death. Oxidative stress initiates a neutrophil-mediated inflammatory response that leads to secondary damage via free radicals formation. Free radicals are responsible for many “Degenerative diseases” like Alzheimer’s disease, Parkinson’s disease, arthritis, cataract, cancer, multiple sclerosis, diabetes mellitus, and liver disease

Food additives contain excitotoxic substances like “Monosodium glutamate – MSG”, the most widely-used salty substances in food (Chinese salt); other excitotoxic food additives include “Aspartam”, a flavor sweetener mainly used in soft drinks. Glutamate and aspratate unlike all other amino acids are metabolized in the “intestine”, rather than absorbed into the portal system to be metabolized in the liver. A large glutamate load (10 g = 150 mg/kg, in saline) produces an increase in plasma “Prolactin” and “Cortisol” levels in normal adults!

 

Selected references

1. Blaylock RL. Excitotoxins: The Taste That Kills. 1996; Health Press (NM); 1st edition

http://www.amazon.com/Excitotoxins-Taste-Russell-L-Blaylock/dp/0929173252/ref=sr_1_1?s=books&ie=UTF8&qid=1439310535&sr=1-1&keywords=Excitotoxins

2. Farooqui AA et al. Neurochemical Aspects of Excitotoxicity. 2008; Springer-Verlag; 1st edition

http://www.amazon.com/Neurochemical-Aspects-Excitotoxicity-Akhlaq-Farooqui/dp/0387730222/ref=sr_1_2?s=books&ie=UTF8&qid=1439310517&sr=1-2&keywords=Excitotoxicity

3. Mehta A et al. Excitotoxicity: bridge to various triggers in neurodegenrative disorders. European Journal of Pharmacology 2013; 698: 6-18

4. Olney JW. Excitatory amino acids and neuropsychiatric disorders. Biol Physchiatry 1989; 26: 505-525

5. Meldrum B. Amino acids as dietary excitotoxins: a contribution to understanding neurodegenrative disorders. Brain Research Reviews 1993; 18: 293-314