Excitotoxicity is due to the following
Correct Answer: All The Above
Description: (D) All The Above # EXCITOTOXICITY:> Low Ca2+ buffering and excitotoxicity under physiological stress and pathophysiological conditions in motor neuron (MNs). Low Ca2+ buffering in amyotrophic lateral sclerosis (ALS) vulnerable hypoglossal MNs exposes mitochondria to higher Ca2+ loads compared to highly buffered cells. Linder normal physiological conditions, the neurotransmitter opens glutamate, NMDA and AMPA receptor channels, and voltage dependent Ca2+ channels (VDCC) with high glutamate release, which is taken up again by EAAT1 and EAAT2.> This results in a small rise in intracellular calcium that can be buffered in the cell. In ALS, a disorder in the glutamate recep- tor channels leads to high calcium conductivity, resulting in high Ca2+ loads and increased risk for mitochondrial damage. This triggers the mitochondrial production of reactive oxygen species (ROS), which then inhibit glial EAAT2 function.> Excitotoxicity is the pathological process by which nerve cells are damaged and killed by glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate (glutamate receptors) such as the NMDA receptor and AMPA receptor are overactivated. Excitotoxins like NMDA and kainic acid which bind to these receptors, as we I as pathologically high levels of glutamate, can cause excitotoxicity by allowing high levels of calcium ions (Ca2+) to enter the cell. Ca2+ influx into cells activates a number of enzymes, including phospholipases, endonucleases, and proteases such as calpain. These enzymes go on to damage cell structures such as components of the cytoskeleton, membrane, and DNA.> Excitotoxicity may be involved in spinal cord injury, stroke, traumatic brain injury and neurodegenerative diseases of the central nervous system (CNS) such as Multiple sclerosis, Alzheimer's disease, Amyotrophic lateral sclerosis (ALS), Parkinson's disease, Alcoholism or alcohol withdrawal and Huntington's disease. Other common conditions that cause excessive glutamate concentrations around neurons are hypoglycemia and status epilepticus.
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