Weng Rui, Shen Sensen, Burton Casey, Yang Li, Nie Honggang, Tian Yonglu, Bai Yu, Liu Huwei
Beijing National Laboratory for Molecular Sciences, the Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agriculture Sciences, Beijing, 100081, China.
Anal Bioanal Chem. 2016 Apr;408(11):2963-73. doi: 10.1007/s00216-015-9256-3. Epub 2016 Jan 15.
Serotonin is an important neurotransmitter that regulates a wide range of physiological, neuropsychological, and behavioral processes. Consequently, serotonin deficiency is involved in a wide variety of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, schizophrenia, and depression. The pathophysiological mechanisms underlying serotonin deficiency, particularly from a lipidomics perspective, remain poorly understood. This study therefore aimed to identify novel lipid biomarkers associated with serotonin deficiency by lipidomic profiling of tryptophan hydroxylase 2 knockout (Tph2-/-) mice. Using a high-throughput normal-/reversed-phase two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry (NP/RP 2D LC-QToF-MS) method, 59 lipid biomarkers encompassing glycerophospholipids (glycerophosphocholines, lysoglycerophosphocholines, glycerophosphoethanolamines, lysoglycerophosphoethanolamines glycerophosphoinositols, and lysoglycerophosphoinositols), sphingolipids (sphingomyelins, ceramides, galactosylceramides, glucosylceramides, and lactosylceramides) and free fatty acids were identified. Systemic oxidative stress in the Tph2-/- mice was significantly elevated, and a corresponding mechanism that relates the lipidomic findings has been proposed. In summary, this work provides preliminary findings that lipid metabolism is implicated in serotonin deficiency.
血清素是一种重要的神经递质，可调节广泛的生理、神经心理和行为过程。因此，血清素缺乏与多种神经退行性疾病有关，包括阿尔茨海默病、帕金森病、精神分裂症和抑郁症。血清素缺乏背后的病理生理机制，尤其是从脂质组学角度来看，仍知之甚少。因此，本研究旨在通过对色氨酸羟化酶2基因敲除（Tph2-/-）小鼠进行脂质组分析，来鉴定与血清素缺乏相关的新型脂质生物标志物。使用高通量正相/反相二维液相色谱-四极杆飞行时间质谱（NP/RP 2D LC-QToF-MS）方法，鉴定出了59种脂质生物标志物，包括甘油磷脂（甘油磷酸胆碱、溶血甘油磷酸胆碱、甘油磷酸乙醇胺、溶血甘油磷酸乙醇胺、甘油磷酸肌醇和溶血甘油磷酸肌醇）、鞘脂（鞘磷脂、神经酰胺、半乳糖基神经酰胺、葡萄糖基神经酰胺和乳糖基神经酰胺）和游离脂肪酸。Tph2-/-小鼠的全身氧化应激显著升高，并提出了一种将脂质组学研究结果与之相关联的相应机制。总之，这项工作提供了脂质代谢与血清素缺乏有关的初步发现。
