Bertollo Amanda Gollo, Mingoti Maiqueli Eduarda Dama, Ignácio Zuleide Maria
Laboratory of Physiology, Pharmacology and Psychopathology, Graduate Program in Biomedical Sciences, Federal University of Fronteira Sul, Chapecó, SC, Brazil.
Rev Neurosci. 2024 Sep 9;36(2):169-187. doi: 10.1515/revneuro-2024-0065. Print 2025 Feb 25.
Major depressive disorder (MDD) is a prevalent psychiatric disorder that has damage to people's quality of life. Tryptophan is the precursor to serotonin, a critical neurotransmitter in mood modulation. In mammals, most free tryptophan is degraded by the kynurenine pathway (KP), resulting in a range of metabolites involved in inflammation, immune response, and neurotransmission. The imbalance between quinolinic acid (QA), a toxic metabolite, and kynurenic acid (KynA), a protective metabolite, is a relevant phenomenon involved in the pathophysiology of MDD. Proinflammatory cytokines increase the activity of the enzyme indoleamine 2,3-dioxygenase (IDO), leading to the degradation of tryptophan in the KP and an increase in the release of QA. IDO activates proinflammatory genes, potentiating neuroinflammation and deregulating other physiological mechanisms related to chronic stress and MDD. This review highlights the physiological mechanisms involved with stress and MDD, which are underlying an imbalance of the KP and discuss potential therapeutic targets.
重度抑郁症（MDD）是一种常见的精神疾病，会损害人们的生活质量。色氨酸是血清素的前体，血清素是情绪调节中的一种关键神经递质。在哺乳动物中，大多数游离色氨酸通过犬尿氨酸途径（KP）被降解，产生一系列参与炎症、免疫反应和神经传递的代谢产物。有毒代谢产物喹啉酸（QA）和保护性代谢产物犬尿烯酸（KynA）之间的失衡是MDD病理生理学中涉及的一个相关现象。促炎细胞因子会增加吲哚胺2,3-双加氧酶（IDO）的活性，导致KP中色氨酸的降解以及QA释放的增加。IDO激活促炎基因，增强神经炎症并使与慢性应激和MDD相关的其他生理机制失调。本综述强调了与应激和MDD相关的生理机制，这些机制是KP失衡的基础，并讨论了潜在的治疗靶点。
