Journal
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
Volume 408, Issue 11, Pages 2963-2973Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00216-015-9256-3
Keywords
Serotonin deficiency; Tryptophan hydroxylase 2 knockout (Tph2-/-) mice; Lipidomics; Lipid biomarkers; Two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry (2D LC-QToF-MS)
Funding
- National Natural Science Foundation of China [21322505, 21175008]
- Ministry of Science and Technology of China [2012YQ09019409, 2013YQ510391]
- National Science Foundation [DGE-1011744]
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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.
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