Neuroinflammation in Depression

Tumor necrosis factor as neuroinflammatory mediator in Alzheimer's disease and stroke. Molecular mechanisms and neuroinflammatory imaging The role of indoleamine 2,3-dioxygenase in a mouse model of neuroinflammation induced depression Interferon Ƣ induces the upregulation of indoleamine 2,3-dioxygenase and leads to depressive-like behavior and memory impairment in mice via the interferon ơ/Ƣ receptor Dorinának PREFACE ''In these several sessions we heard exciting new data which indicate the critical role of induced IDO activity in several important areas. The activation of dendritic cells (macrophages, astrocytes, etc.) results in IDO induction with the depletion of tryptophan levels locally or systemically. This seems to be the mechanism by which interferon inhibits the growth of certain bacteria, intracellular parasites, and viruses. Most exciting were the reports that tryptophan depletion also inhibits T lymphocyte replication which results in immunosuppression and tolerogenicity. This has far reaching implications in many fields of medicine, including fetal rejection, and organ transplant survival. However, in some cases the effects of the IDO activity may be the result of elevated kynurenine pathway metabolites rather than the depletion of tryptophan. For example, many studies have described the excitatory and toxic effects of quinolinic acid on neuronal activity. Furthermore, the depletion of tryptophan leads to decreased levels of serotonin which may produce a wide range of effects. In closing, I would like to ask us all to recognize Professor Osamu Hayaishi for his brilliant, pioneering work in elucidating the tryptophan metabolism, particularly for his important finding of indoleamine dioxygenase (IDO) and for induction by interferon-c. These findings now allow us to reinterpret many older empirical observations of the tryptophan metabolism in animals and man, which has now opened up a whole new era of better understanding the role of tryptophan in the fields of immunology, AIDS, organ transplant, autoimmune diseases, cancer, and mental functions. The next few years will, I am sure, see unbelievable advances in these areas of biology and medicine.'' Prof. Raymond Brown's closing remarks in the 10th meeting of the The history of indoleamine 2,3-dioxygenase (IDO), the key enzyme of the kynurenine pathway and tryptophan catabolism began in 1967 when Professor Hayaishi and his colleagues described an enzyme, which converted D-tryptophan to D-kynurenine (Higuchi and Hayaishi 1967; Yamamoto and Hayaishi 1967). Since then, especially in the last decade, extensive research focuses on the role of IDO in many approaches. Tryptophan is an abundant essential amino acid, a key molecule for proteins …