Cytokine-serotonin interaction through IDO: a neurodegeneration hypothesis of depression.
There are different theories and hypotheses related to the aetiology of depression. The interaction between brain 5-HT level and the activity of its autoreceptors plays a role in mood changes and depression. In major depression, activation of the inflammatory response system (IRS) and, increased concentrations of proinflammatory cytokines, prostaglandin E2 and negative immuno-regulatory cytokines in peripheral blood have been reported. Recently, pro-inflammatory cytokines have been found to have profound effects on the metabolism of brain serotonin through the enzyme indoleamine-2,3-dioxygenase (IDO) that metabolizes the tryptophan, the precursor of 5-HT to neurodegenerative quinolinate and neuroprotective kynurenate. The cytokine-serotonin interaction that leads to the challenge between quinolinate and kynurenate in the brain explains the neurodegeneration hypothesis of depression.
Myint
A M
AM
University of Maastricht, The Netherlands.
Kim
Y K
YK
D016207:Cytokines / Q000378:metabolism*; D003863:Depression / Q000175:diagnosis* / Q000209:etiology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007736:Kynurenic Acid / Q000378:metabolism; D008954:Models, Biological; D008962:Models, Theoretical; D019636:Neurodegenerative Diseases / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D011485:Protein Binding; D012701:Serotonin / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism; D014366:Tryptophan Oxygenase / Q000378:metabolism
D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012701:Serotonin; D014364:Tryptophan; D014366:Tryptophan Oxygenase; D007736:Kynurenic Acid