ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Absence of 2-hydroxylated sphingolipids is compatible with normal neural development but causes late-onset axon and myelin sheath degeneration.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 1 of them a synthesis that pooled it.
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Who cites it
97 citing papers in PubMed, 1 synthesis or guideline pooled it, 171 citations in OpenAlex.
- Pooled it
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- Clinical, Radiological, and Genetic Profile of Patients withTremor and other hyperkinetic movements (New York, N.Y.) · 2026Review
- Causality of blood metabolites and narcolepsy type 1: A Mendelian randomization study.Medicine · 2025Article
- Spatial lipidomics reveals demyelination and remyelination dynamics in the mouse brain.Journal of lipid research · 2025Article
- Resistant Potato Starch Supplementation Increases the Serum Levels of Choline and Sphingomyelins Without Affecting Trimethylamine Oxide Levels.Metabolites · 2025Article
- Disrupted Myelination in FAHN: Insights from a Patient-Specific hiPSC Neuron-Oligodendrocyte Model.Cells · 2025Article
- Quantum magnetization exchange through transient hydrogen bond matrix defines magnetic resonance signal relaxation and anisotropy in central nervous system.Scientific reports · 2025Article
- Disorders of fatty acid homeostasis.Journal of inherited metabolic disease · 2025Review
- Apolipoprotein M expression modifies the sphingolipid landscape in murine blood and lymph.Frontiers in immunology · 2025Article
- Human genetic defects of sphingolipid synthesis.Journal of inherited metabolic disease · 2025Review
- Investigating the genetic basis of hereditary spastic paraplegia and cerebellar Ataxia in Pakistani families.BMC neurology · 2024Article
- Quantum dipole interactions and transient hydrogen bond orientation order in cells, cellular membranes and myelin sheath: Implications for MRI signal relaxation, anisotropy, and TMagnetic resonance in medicine · 2024Article
- Seipin deficiency-induced lipid dysregulation leads to hypomyelination-associated cognitive deficits via compromising oligodendrocyte precursor cell differentiation.Cell death & disease · 2024Article
- Iron chelators: as therapeutic agents in diseases.Annals of medicine and surgery (2012) · 2024Review
- Early whole-body mutant huntingtin lowering averts changes in proteins and lipids important for synapse function and white matter maintenance in the LacQ140 mouse model.Neurobiology of disease · 2023Article
- Role of 2-hydroxy acyl-CoA lyase HACL2 in odd-chain fatty acid production via α-oxidation in vivo.Molecular biology of the cell · 2023Article
- Early whole-body mutant huntingtin lowering averts changes in proteins and lipids important for synapse function and white matter maintenance in the LacQ140 mouse model.bioRxiv : the preprint server for biology · 2023Article
- Compromised Myelin and Axonal Molecular Organization Following Adult-Onset Sulfatide Depletion.Biomedicines · 2023Article
37 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sphingolipids containing 2-hydroxylated fatty acids are among the most abundant lipid components of the myelin sheath and therefore are thought to play an important role in formation and function of myelin. To prove this hypothesis, we generated mice lacking a functional fatty acid 2-hydroxylase (FA2H) gene. FA2H-deficient (FA2H(-/-)) mice lacked 2-hydroxylated sphingolipids in the brain and in peripheral nerves. In contrast, nonhydroxylated galactosylceramide was increased in FA2H(-/-) mice. However, oligodendrocyte differentiation examined by in situ hybridization with cRNA probes for proteolipid protein and PDGFalpha receptor and the time course of myelin formation were not altered in FA2H(-/-) mice compared with wild-type littermates. Nerve conduction velocity measurements of sciatic nerves revealed no significant differences between FA2H(-/-) and wild-type mice. Moreover, myelin of FA2H(-/-) mice up to 5 months of age appeared normal at the ultrastructural level, in the CNS and peripheral nervous system. Myelin thickness and g-ratios were normal in FA2H(-/-) mice. Aged (18-month-old) FA2H(-/-) mice, however, exhibited scattered axonal and myelin sheath degeneration in the spinal cord and an even more pronounced loss of stainability of myelin sheaths in sciatic nerves. These results show that structurally and functionally normal myelin can be formed in the absence of 2-hydroxylated sphingolipids but that its long-term maintenance is strikingly impaired. Because axon degeneration appear to start rather early with respect to myelin degenerations, these lipids might be required for glial support of axon function.
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