title: Is there a role for glutamate-mediated excitotoxicity in inflammation-induced depression?
abstract: 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.
authors.affiliation: Division of Internal Medicine, Department of Symptom Research, MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA, rdantzer@mdanderson.org.
authors.forename: Robert
authors.initials: R
authors.lastname: Dantzer
authors.forename: Adam K
authors.initials: AK
authors.lastname: Walker
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007249:Inflammation / Q000150:complications* / Q000378:metabolism*; D007737:Kynurenine / Q000378:metabolism; D015213:Neuroimmunomodulation; D017378:Quinolinic Acid / Q000378:metabolism
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D018698:Glutamic Acid; D017378:Quinolinic Acid