How Inflammation Increases Glutamate Overexcitation And Neurotoxicity

January 20, 2014 · Posted in Neurochemistry, Risk Factors · Comment 


Research has shown a link between inflammation and mental illness. Inflammation leads to a series of chemical changes that can overexcite neurons and interfere with the protection of neurons.

Inflammation increases the production of indoleamine-pyrrole 2,3-dioxygenase (IDO), an enzyme that breaks down the amino acid tryptophan into kynurenic acid and quinolinic acid. They in turn increase glutamate, the main excitatory neurotransmitter, and decrease brain-derived neurotrophic factor (BDNF), which keeps neurons healthy.

Kynurenic acid stimulates microglia, which clean up the central nervous system as a form of immune defense, to produce inflammatory cytokine proteins.

Quinolinic acid directly stimulates glutamate receptors and encourages glutamate release from astrocytes. Quinolinic acid also blocks glutamate removal that would normally occur through reuptake into the astrocytes, leading to more stimulation of extrasynaptic glutamate receptors and decreases in BDNF.

Quinolinic acid’s effects are opposite to those of the antidepressant ketamine, which blocks glutamate NMDA receptors and increases BDNF. When people are given interferon protein for the treatment of cancers, quinolinic acid increases in cerebrospinal fluid, inducing depression. The severity of depression induced is correlated with the patient’s levels of quinolinic acid.

It appears that ketamine has indirect anti-inflammatory effects through its ability to block glutamate receptors and increase BDNF.