Is there a role for glutamate-mediated excitotoxicity in inflammation-induced depression?

J Neural Transm (Vienna). 2014 Aug;121(8):925-32. doi: 10.1007/s00702-014-1187-1. Epub 2014 Mar 15.


Chronic inflammation in physically ill patients is often associated with the development of symptoms of depression. The mechanisms that are responsible for inflammation-associated depression have been elucidated over the last few years. Kynurenine produced from tryptophan in a reaction catabolized by indoleamine 2,3 dioxygenase is transported into the brain where it is metabolized by microglial enzymes into a number of neurotropic compounds including quinolinic acid, an agonist of N-methyl-D-aspartate receptors. Quinolinic acid can synergize with glutamate released by activated microglia. This chain of events opens the possibility to treat inflammation-induced depression using therapies that target the transport of kynurenine through the blood-brain barrier, the production of quinolinic acid and glutamate by activated microglia, or the efflux of glutamate from the brain to the blood.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism
  • Depressive Disorder / drug therapy
  • Depressive Disorder / epidemiology
  • Depressive Disorder / etiology*
  • Depressive Disorder / metabolism*
  • Glutamic Acid / metabolism*
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Inflammation / complications*
  • Inflammation / metabolism*
  • Kynurenine / metabolism
  • Neuroimmunomodulation
  • Quinolinic Acid / metabolism


  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Kynurenine
  • Glutamic Acid
  • Quinolinic Acid