The impact of neuroimmune dysregulation on neuroprotection and neurotoxicity in psychiatric disorders--relation to drug treatment.
The impact of neuroimmune dysregulation on neuroprotection and neurotoxicity in psychiatric disorders--relation to drug treatment.
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DOI：
10.31887/dcns.2009.11.3/nmueller
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发表时间：
2009
影响因子：
8.3
通讯作者：
Schwarz MJ
中科院分区：
文献类型：
--
作者：
Müller N;Myint AM;Schwarz MJ
炎症发病机制已被假定为精神分裂症和抑郁症（MD）。在精神分裂症和抑郁症中，1型与2型免疫反应的相反模式似乎与吲哚胺2，3-双加氧酶激活和Dahan-犬尿氨酸代谢的差异有关，导致精神分裂症中犬尿烯酸的产生增加，抑郁症中犬尿烯酸的产生减少。这些差异与多巴胺能神经传递的不平衡有关，这可能导致抑郁症中N-甲基-D-天冬氨酸（NMDA）的过度激动剂作用和精神分裂症中NMDA拮抗作用。关于犬尿烯酸的神经保护功能和喹啉酸（QUIN）的神经毒性作用，不同的免疫激活模式也可能导致犬尿氨酸代谢的神经保护作用和神经毒性作用之间的不平衡。小胶质细胞和星形胶质细胞的差异活化可能是导致这种不平衡的另一种机制。免疫失衡导致炎性状态，并伴有前列腺素E2产生增加和环氧合酶-2（考克斯-2）表达增加。然而，许多现有的抗精神病药和抗抑郁药的免疫学作用部分地纠正了免疫失衡和神经毒性QUIN的过量产生，考克斯-2抑制剂已经在抑郁症的动物模型和初步临床试验中进行了测试，指出了在精神分裂症和MD中的有利作用。
An inflammatory pathogenesis has been postulated for schizophrenia and major depression (MD). In schizophrenia and depression, opposing patterns oftype-1 vs type-2 immune response seem to be associated with differences in the activation of the enzyme indoleamine 2,3-dioxygenase and in the tryptophan-kynurenine metabolism, resulting in increased production of kynurenic acid in schizophrenia and decreased production of kynurenic acid in depression. These differences are associated with an imbalance in the glutamatergic neurotransmission, which may contribute to an excessive agonist action of N-methyl-D-aspartate (NMDA) in depression and of NMDA antagonism in schizophrenia. Regarding the neuroprotective function of kynurenic acid and the neurotoxic effects of quinolinic acid (QUIN), different patterns of immune activation may also lead to an imbalance between the neuroprotective and the neurotoxic effects of the tryptophanlkynurenine metabolism. The differential activation of microglia cells and astrocytes may be an additional mechanism contributing to this imbalance. The immunological imbalance results in an inflammatory state combined with increased prostaglandin E2 production and increased cyclo-oxygenase-2 (COX-2) expression. The immunological effects of many existing antipsychotics and antidepressants, however, partly correct the immune imbalance and the excess production of the neurotoxic QUIN, COX-2 inhibitors have been tested in animal models of depression and in preliminary clinical trials, pointing to favorable effects in schizophrenia and in MD.