Dantzer Robert, Walker Adam K
Division of Internal Medicine, Department of Symptom Research, MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA,
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.
身体患病患者的慢性炎症通常与抑郁症状的出现有关。在过去几年中，已经阐明了与炎症相关的抑郁症的发病机制。色氨酸在吲哚胺2,3-双加氧酶催化的反应中产生犬尿氨酸，犬尿氨酸被转运到大脑中，在那里它被小胶质细胞酶代谢成多种神经营养化合物，包括喹啉酸，一种N-甲基-D-天冬氨酸受体激动剂。喹啉酸可以与活化的小胶质细胞释放的谷氨酸协同作用。这一系列事件为使用针对犬尿氨酸通过血脑屏障的转运、活化的小胶质细胞产生喹啉酸和谷氨酸，或谷氨酸从大脑向血液外流的疗法来治疗炎症性抑郁症开辟了可能性。
