Lipidomic profiling of tryptophan hydroxylase 2 knockout mice reveals novel lipid biomarkers associated with serotonin deficiency
Abstract
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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5-hydroxytryptamine (5HT) synthesis by misfolding and aggregation due to the cysteine-rich structure could also be highly susceptible to oxidative damage.
“In addition, it seems that 5-hydroxytryptamine (5HT) synthesis by miss folding and aggregation due to the cysteine-rich structure could also be highly susceptible to oxidative damage [235].”
From Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches (2016) · cites this paper as [235]
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“In addition, it seems that 5-hydroxytryptamine (5HT) synthesis by miss folding and aggregation due to the cysteine-rich structure could also be highly susceptible to oxidative damage [235].”
BackgroundLipidomics in Major Depressive Disorder
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- Authors
- Weng, R., Shen, S., Burton, C., Yang, L., Nie, H., Tian, Y., Bai, Y., & Liu, H.
- Affiliations
- Peking University (CN)
- Missouri University of Science and Technology (US)
- Corresponding author
- Bai, Yu
- Venue
- Analytical and Bioanalytical Chemistry
- Published
- 2016-01-15
- Volume
- 408
- Issue
- 11
- Pages
- 2963-2973
- ISSN
- 1618-2642 (ISSN-L)
- 1618-2650
- OpenAlex
- W2286139037
- Cited by
- 31
- References
- 47
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 6 · 2017: 4 · 2016: 1
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Analytical and Bioanalytical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- tryptophan hydroxylase 2, serotonin deficiency, lipid biomarkers, lipidomics, glycerophospholipids, sphingolipids, free fatty acids, oxidative stress, lipid metabolism, neurodegenerative diseases
- MeSH terms
- Animals, Lipids, Serotonin, Tryptophan Hydroxylase, Biomarkers, Mice, Knockout, Oxidative Stress, Mice
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