Maternal Inflammation with Elevated Kynurenine Metabolites Is Related to the Risk of Abnormal Brain Development and Behavioral Changes in Autism Spectrum Disorder.
Maternal Inflammation with Elevated Kynurenine Metabolites Is Related to the Risk of Abnormal Brain Development and Behavioral Changes in Autism Spectrum Disorder.
复制标题
伴随犬尿氨酸代谢产物升高的母体炎症与自闭症谱系障碍的异常脑发育和行为改变的风险有关。
作者：
几项研究表明，遗传和环境因素对神经发育障碍的发生和发展起到了作用。孕期母体免疫激活(MIA)被认为是推动这一过程的主要环境因素之一。犬尿氨酸途径(KP)是哺乳动物细胞中必需氨基酸L色氨酸(Trp)分解代谢的主要途径。神经炎症后KP的激活可产生多种内源性神经活性代谢物，可能影响大脑功能和行为。此外，神经毒性代谢物和兴奋性毒性会导致KP激活后营养支持、谷氨酸能系统和突触功能的长期变化。因此，研究KP代谢物在神经发育中的作用可能有助于进一步了解神经发育障碍的其他病理生理学，包括自闭症谱系障碍(ASD)。在这篇综述中，我们描述了怀孕期间脑部KP代谢的变化，并阐述了母体炎症和遗传因素在发育过程中如何影响KP。我们综述了ASD患者的临床数据和动物模型，旨在验证围产期KP升高在以后生活中长期的生化、神经病理和行为缺陷中的作用。我们的综述将有助于阐明针对神经发育障碍的新的针对KP的治疗策略和干预措施。
Several studies show that genetic and environmental factors contribute to the onset and progression of neurodevelopmental disorders. Maternal immune activation (MIA) during gestation is considered one of the major environmental factors driving this process. The kynurenine pathway (KP) is a major route of the essential amino acid L-tryptophan (Trp) catabolism in mammalian cells. Activation of the KP following neuro-inflammation can generate various endogenous neuroactive metabolites that may impact brain functions and behaviors. Additionally, neurotoxic metabolites and excitotoxicity cause long-term changes in the trophic support, glutamatergic system, and synaptic function following KP activation. Therefore, investigating the role of KP metabolites during neurodevelopment will likely promote further understanding of additional pathophysiology of neurodevelopmental disorders, including autism spectrum disorder (ASD). In this review, we describe the changes in KP metabolism in the brain during pregnancy and represent how maternal inflammation and genetic factors influence the KP during development. We overview the patients with ASD clinical data and animal models designed to verify the role of perinatal KP elevation in long-lasting biochemical, neuropathological, and behavioral deficits later in life. Our review will help shed light on new therapeutic strategies and interventions targeting the KP for neurodevelopmental disorders.
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