What is the excitotoxicity hypothesis?

The concept of excitotoxicity, neuronal death produced by overstimulation of excitatory amino acid receptors, has become a popular way of explaining the pathogenesis of neuronal death in a variety of acute and chronic neurologic diseases.

What happens excitotoxicity?

Excitotoxicity is the pathological process by which neurons are damaged and killed by the overactivations of receptors for the excitatory neurotransmitter glutamate, such as the NMDA receptor and AMPA receptor.

What causes excitotoxicity in the brain?

Excitotoxicity occurs when neurons are exposed to high levels of glutamate that causes a persistent activation of the N-methyl-d-aspartate acid (NMDA) and α-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) receptors and voltage-gated calcium channels resulting in a lethal influx of extracellular calcium.

What is glutamate induced excitotoxicity?

Glutamate excitotoxicity is a cell death mechanism triggered by excessive glutamate release from neurons as well as glial cells. It was described almost 50 years ago as “a certain kind of regionally specific neuropathology” in the hypothalamus of infant mice (Olney, 1971).

How does hypoxia lead to excitotoxic neuron death?

During hypoxia-ischemia, as cellular energy reserves and Na+ gradients fall, increased release and impaired uptake of glutamate mediate a toxic buildup of extracellular glutamate, leading to overstimulation of glutamate receptors and consequent neuronal cell death.

What is excitotoxicity and how is it related to calcium levels What role might this play in neurodegeneration?

Various mechanisms involving excitotoxicity have been proposed to explain the neuronal cell death characteristic of neurodegenerative diseases, including elevation of intracellular calcium, accumulation of oxidizing free radicals, impairment of mitochondrial function and activation of apoptotic and autophagic programs.

How do I reduce excitotoxicity?

Vitamin C, vitamin E, vitamin D, and riboflavin are key dietary antioxidants which simultaneously protect against excitotoxicity, oxidative stress, and neuroinflammation.

What does glutamate do to the brain?

Glutamate is the principal excitatory neurotransmitter in the CNS. It plays a central role in fundamental brain functions, including synaptic plasticity (important for learning and memory), formation of neural networks during development and repair of the CNS.

What causes too much glutamate in the brain?

When a stroke or head injury releases a flood of the chemical messenger glutamate, the excess glutamate leaves damaged neurons in its wake.

Does glutamate cause anxiety?

Specifically, central system glutamate dysregulation has been associated with symptoms of anxiety, posttraumatic stress, obsessive-compulsive disorder (OCD), mania, depression, and psychosis [5, 31], with the strongest evidence for glutamate’s role in schizophrenia [3, 4].

What is excitotoxicity?

Excitotoxicity is the pathological process for neuronal killing.103 Glutamate-induced excitotoxicity is produced by excessive glutamate. It leads to neuronal injury by inducing an influx of calcium, which causes neuronal injury through the stimulation of Ca 2+ -dependent enzymes.

What causes excitotoxicity in amyotrophic lateral sclerosis?

Glutamate Excitotoxicity. A recently identified ALS-linked genetic mutation in D-amino acid oxidase (DAO) can contribute to excitotoxic motor neuron injury. DAO is an enzyme responsible for oxidation deamination of d-amino acids, one of which is D-serine, an activator of NMDA receptors.

What is the pathophysiology of ischemia and excitotoxicity?

Ischemia is followed by accumulation of glutamate and aspartate in the extracellular fluid, causing cell death, which is aggravated by lack of oxygen and glucose. The biochemical cascade resulting from ischemia and involving excitotoxicity is called the ischemic cascade.

What is excitotoxicity in Parkinson’s disease (PD)?

Excitotoxicity from excessive glutamatergic activity results in an increase in intracellular calcium and can damage mitochondria; this has been implicated in PD (Beal, 1998 ). Parthanatos is the death pathway.