Antenucci Nico, D'Errico Giovanna, Fazio Francesco, Nicoletti Ferdinando, Bruno Valeria, Battaglia Giuseppe
Department of Physiology and Pharmacology, Sapienza University, Rome, Italy.
Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Schizophrenia (Heidelb). 2024 Feb 27;10(1):27. doi: 10.1038/s41537-024-00447-3.
Alterations in the kynurenine pathway of tryptophan metabolism have been implicated in the pathophysiology of schizophrenia. Here, we performed an in-depth analysis of all metabolites of the kynurenine pathway, i.e., tryptophan (TRY), kynurenic acid (KYNA), L-kynurenine (KYN), 3-hydroxykynurenine (3-HK), anthranylic acid (ANA), 3-hydroxyanthranylic acid (3-HANA), xanthurenic acid (XA) and quinolinic acid (QUINA), in postmortem samples of the dorsolateral prefrontal cortex (DLPFC, Brodmann area 46, 9) of individuals affected by schizophrenia and non-schizophrenic controls. The analysis was carried out in the gray and white matter. Levels of KYN, 3-HK, ANA, and 3-HANA were significantly increased in both the gray and white matter of the DLPFC of individuals affected by schizophrenia, whereas levels of TRY, KYNA, and QUINA were increased exclusively in the white matter and remained unchanged in the gray matter. These increases in kynurenine metabolites did not correlate with age, sex, duration of the disease, and duration and type of antipsychotic medication. These findings suggest that the two major branches of the kynurenine pathway, i.e., the transamination of KYN into KYNA, and hydroxylation of KYN into 3-HK are activated in the white matter of individuals affected by schizophrenia, perhaps as a result of neuroinflammation, and support the evidence that abnormalities of the white matter are consistenly associated with schizophrenia.
色氨酸代谢的犬尿氨酸途径改变与精神分裂症的病理生理学有关。在此，我们对精神分裂症患者和非精神分裂症对照者的背外侧前额叶皮质（DLPFC，布罗德曼区46、9区）尸检样本中犬尿氨酸途径的所有代谢物，即色氨酸（TRY）、犬尿喹啉酸（KYNA）、L-犬尿氨酸（KYN）、3-羟基犬尿氨酸（3-HK）、邻氨基苯甲酸（ANA）、3-羟基邻氨基苯甲酸（3-HANA）、黄尿酸（XA）和喹啉酸（QUINA）进行了深入分析。分析在灰质和白质中进行。在精神分裂症患者的DLPFC灰质和白质中，KYN、3-HK、ANA和3-HANA的水平均显著升高，而TRY、KYNA和QUINA的水平仅在白质中升高，在灰质中保持不变。这些犬尿氨酸代谢物的升高与年龄、性别、疾病持续时间以及抗精神病药物的使用时间和类型无关。这些发现表明，犬尿氨酸途径的两个主要分支，即KYN转氨生成KYNA以及KYN羟基化生成3-HK，在精神分裂症患者的白质中被激活，这可能是神经炎症的结果，并支持了白质异常与精神分裂症始终相关的证据。
