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Age-dependent changes in nervonic acid-containing sphingolipids in mouse hippocampus
Valentina Vozella1, Abdul Basit1, Alessandra Misto1
1Drug Discovery and Development, Istituto Italiano di Tecnologia, Via Morego 30, I-16163 Genova, Italy.
Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids
|September 1, 2017
Summary
Aging significantly alters brain sphingolipid metabolism in both male and female mice, with notable increases in specific lipids like nervonic acid. These findings underscore the role of sphingolipids in brain aging and neurodegeneration.
Area of Science:
- Neuroscience
- Metabolomics
- Aging Research
Background:
- Sphingolipids are crucial for brain function and have been linked to neurodegeneration.
- Previous research indicated elevated ceramide levels in aged rodent brains, but a comprehensive analysis of aging's impact on brain sphingolipid metabolism was missing.
Purpose of the Study:
- To systematically investigate the age- and sex-dependent changes in hippocampal sphingolipid profiles.
- To explore the relationship between sphingolipid alterations and the expression of key biosynthetic enzymes during brain aging.
Main Methods:
- Quantification of 17 key sphingolipid species in the hippocampus of young, middle-aged, and old male and female mice using liquid chromatography/mass spectrometry.
- Evaluation of the transcription levels of enzymes involved in sphingolipid biosynthesis via quantitative polymerase chain reaction (qPCR).
Main Results:
- Significant age-dependent alterations in multiple sphingolipid species, including ceramides, sphingomyelins, and hexosylceramides, were observed in both sexes.
- Sex-dependent changes were noted for specific hexosylceramide and sphingomyelin species.
- A marked accumulation of sphingolipids containing nervonic acid (24:1) occurred in old mice, accompanied by upregulated transcription of stearoyl-CoA desaturase (Scd1 and Scd2) in females.
Conclusions:
- Aging induces substantial sex-dependent and independent changes in the hippocampal sphingolipid profile.
- Sphingolipids, particularly those containing nervonic acid, warrant further investigation for their role in normal and pathological brain aging.
