Role of the Kynurenine Metabolism Pathway in Inflammation-Induced Depression: Preclinical Approaches.
Role of the Kynurenine Metabolism Pathway in Inflammation-Induced Depression: Preclinical Approaches.
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DOI：
10.1007/7854_2016_6
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发表时间：
2017
影响因子：
--
通讯作者：
Dantzer R
中科院分区：
文献类型：
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作者：
Dantzer R
患有慢性炎症的身体疾病患者通常会出现抑郁症状。我们对炎症相关抑郁症的病理生理学的理解受益于对疾病机制的临床前研究以及对免疫治疗患者中出现的疾病和抑郁症状的临床研究。当免疫系统被病原体或损伤相关的分子模式激活时，疾病行为就会发生。这是对感染和细胞损伤的正常生物反应。它帮助有机体动员其免疫和代谢防御来对抗危险。当炎症反应过于强烈且持续时间过长或消退过程不足时，抑郁症会在疾病的背景下出现。从疾病到抑郁症的转变是通过激活犬尿氨酸代谢途径介导的，该途径导致形成神经毒性犬尿氨酸代谢物，包括喹啉酸，N-甲基-D-天冬氨酸受体的激动剂。在炎症相关抑郁症的研究中已经确定的神经免疫过程和分子因子代表了开发用于治疗重度抑郁症的创新疗法的潜在新靶点。
Physically ill patients with chronic inflammation often present with symptoms of depression. Our understanding of the pathophysiology of inflammation-associated depression has benefited from preclinical studies on the mechanisms of sickness and clinical studies on the symptoms of sickness and depression that develop in patients treated with immunotherapy. Sickness behavior develops when the immune system is activated by pathogen- or damage-associated molecular patterns. It is a normal biological response to infection and cell injury. It helps the organism to mobilize its immune and metabolic defenses to fight the danger. Depression emerges on the background of sickness when the inflammatory response is too intense and long lasting or the resolution process is deficient. The transition from sickness to depression is mediated by activation of the kynurenine metabolism pathway that leads to the formation of neurotoxic kynurenine metabolites including quinolinic acid, an agonist of N-methyl-D-aspartate receptors. The neuroimmune processes and molecular factors that have been identified in the studies of inflammation-associated depression represent potential new targets for the development of innovative therapies for the treatment of major depressive disorders.