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非靶向和靶向质谱分析揭示了茶氨酸对幼年大鼠慢性不可预测轻度应激诱导抑郁的中枢和外周代谢组学的影响。

Untargeted and targeted mass spectrometry reveal the effects of theanine on the central and peripheral metabolomics of chronic unpredictable mild stress-induced depression in juvenile rats.

作者信息

Zhu Yanru, Wang Feng, Han Jiatong, Zhao Yunli, Yu Miao, Ma Mingyan, Yu Zhiguo

机构信息

Laboratory of Pharmaceutical Analysis, School of Pharmacy, Zhejiang Pharmaceutical University, Ningbo, Zhejiang, 315100, China.

Laboratory of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.

出版信息

J Pharm Anal. 2023 Jan;13(1):73-87. doi: 10.1016/j.jpha.2022.10.001. Epub 2022 Oct 13.

DOI:10.1016/j.jpha.2022.10.001
PMID:36816539
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9937789/
Abstract

l-theanine has been shown to have a therapeutic effect on depression. However, whether l-theanine has an excellent preventive effect on depression in children and adolescents and what its mechanism is have not been well explained. Given the complexity of the pathogenesis of depression, this study investigated the preventive effect and mechanism of l-theanine on depression in juvenile rats by combining serum and hippocampal metabolomic strategies. Behavioral tests, hippocampal tissue sections, and serum and hippocampal biochemical indexes were studied, and the results confirmed the preventive effect of l-theanine. Untargeted reversed-phase liquid chromatography-quadrupole-time-of-flight mass spectrometry and targeted hydrophilic interaction liquid chromatography-triple quadrupole mass spectrometry were developed to analyze the metabolism changes in the serum and hippocampus to screen for potential biomarkers related to l-theanine treatment. The results suggested that 28 abnormal metabolites in the serum and hippocampus that were considered as potential biomarkers returned to near-normal levels after l-theanine administration. These biomarkers were involved in various metabolic pathways, mainly including amino acid metabolism and lipid metabolism. The levels of amino acids and neurotransmitters in the phenylalanine, tryptophan, and glutamic acid pathways were significantly reduced after l-theanine administration compared with chronic unpredictable mild stress-induced rats. In summary, l-theanine had a significant preventive effect on depression and achieved its preventive results on depression by regulating various aspects of the body, such as amino acids, lipids, and inflammation. This research systematically analyzed the mechanism of l-theanine in preventing depression and laid the foundation for applying l-theanine to prevent depression in children and adolescents.

摘要

L-茶氨酸已被证明对抑郁症具有治疗作用。然而,L-茶氨酸对儿童和青少年抑郁症是否具有良好的预防作用及其机制尚未得到充分阐释。鉴于抑郁症发病机制的复杂性,本研究通过结合血清和海马代谢组学策略,探讨了L-茶氨酸对幼年大鼠抑郁症的预防作用及其机制。研究了行为测试、海马组织切片以及血清和海马生化指标,结果证实了L-茶氨酸的预防作用。采用非靶向反相液相色谱-四极杆-飞行时间质谱和靶向亲水相互作用液相色谱-三重四极杆质谱分析血清和海马中的代谢变化,以筛选与L-茶氨酸治疗相关的潜在生物标志物。结果表明,血清和海马中28种被视为潜在生物标志物的异常代谢物在给予L-茶氨酸后恢复到接近正常水平。这些生物标志物参与了各种代谢途径,主要包括氨基酸代谢和脂质代谢。与慢性不可预测轻度应激诱导的大鼠相比,给予L-茶氨酸后,苯丙氨酸、色氨酸和谷氨酸途径中的氨基酸和神经递质水平显著降低。综上所述,L-茶氨酸对抑郁症具有显著的预防作用,并通过调节身体的各个方面,如氨基酸、脂质和炎症,实现其对抑郁症的预防效果。本研究系统分析了L-茶氨酸预防抑郁症的机制,为将L-茶氨酸应用于预防儿童和青少年抑郁症奠定了基础。

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