ArticleHuman molecular genetics2019
Disturbed neurotransmitter homeostasis in ether lipid deficiency.
Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 106 citations in OpenAlex.
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- The role of astrocytes in autism spectrum disorder and associated syndromes: Evidence, animal models, mechanisms, and therapeutic potential.Zoological research · 2026Review
- Spatial lipidomic and neuron-specific transcriptomic signatures in the nucleus accumbens reveal phospholipid dyshomeostasis in depression-related maladaptations.Translational psychiatry · 2026Article
- Lipidomic and neurobehavioral alterations from developmental lead exposure in zebrafish.Journal of hazardous materials · 2026Article
- Serum Metabolomic Profiles Predict Sensitivity and Toxicity to Platinum- Fluorouracil Chemotherapy in a Gastric Cancer Xenograft Model.Combinatorial chemistry & high throughput screening · 2026Article
- Bifunctional Probes Reveal the Rules of Intracellular Ether Lipid Transport.Angewandte Chemie (International ed. in English) · 2025Article
- Peroxisomal ether-glycerophospholipid synthesis is dysregulated after TBI.Journal of lipid research · 2025Article
- Benchmarking of Trapped Ion Mobility Spectrometry in Differentiating Plasmalogens from Other Ether Lipids in Lipidomics Experiments.Analytical chemistry · 2025Article
- Plasmalogens Improve Lymphatic Clearance of Amyloid Beta from Mouse Brain and Cognitive Functions.International journal of molecular sciences · 2024Article
- Peroxisome and pexophagy in neurological diseases.Fundamental research · 2024Review
- Association between seizure reduction during ketogenic diet treatment of epilepsy and changes in circulatory metabolites and gut microbiota composition.EBioMedicine · 2024Observational
- Reduction of eEF2 kinase alleviates the learning and memory impairment caused by acrylamide.Cell & bioscience · 2024Article
- A Plasma Metabolite Score Related to Psychological Distress and Diabetes Risk: A Nested Case-control Study in US Women.The Journal of clinical endocrinology and metabolism · 2024Article
- Per- and Polyfluoroalkyl Substances: Impacts on Morphology, Behavior and Lipid Levels in Zebrafish Embryos.Toxics · 2024Article
- Metabolic dynamics in astrocytes and microglia during post-natal development and their implications for autism spectrum disorders.Frontiers in cellular neuroscience · 2024Review
- Article
- UPLC-QTOF-MS-based lipidomic study of wedelolactone in acute colitis mice induced by dextran sulfate sodium.Heliyon · 2023Article
- Overlapping and Distinct Features of Cardiac Pathology in Inherited Human and Murine Ether Lipid Deficiency.International journal of molecular sciences · 2023Article
- Synthesis of ether lipids: natural compounds and analogues.Beilstein journal of organic chemistry · 2023Review
- Structural Characterization and Quantitation of Ether-Linked Glycerophospholipids in Peroxisome Biogenesis Disorder Tissue by Ultraviolet Photodissociation Mass Spectrometry.Analytical chemistry · 2022Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Plasmalogens, the most prominent ether (phospho)lipids in mammals, are structural components of most cellular membranes. Due to their physicochemical properties and abundance in the central nervous system, a role of plasmalogens in neurotransmission has been proposed, but conclusive data are lacking. Here, we targeted this issue in the glyceronephosphate O-acyltransferase (Gnpat) KO mouse, a model of complete deficiency in ether lipid biosynthesis. Throughout the study, focusing on adult male animals, we found reduced brain levels of various neurotransmitters. In the dopaminergic nigrostriatal tract, synaptic endings but not neuronal cell bodies were affected. Neurotransmitter turnover was altered in ether lipid-deficient murine as well as human post-mortem brain tissue. A generalized loss of synapses did not account for the neurotransmitter deficits, since the levels of several presynaptic proteins appeared unchanged. However, reduced amounts of vesicular monoamine transporter indicate a compromised vesicular uptake of neurotransmitters. As exemplified by norepinephrine, the release of neurotransmitters from Gnpat KO brain slices was diminished in response to strong electrical and chemical stimuli. Finally, addressing potential phenotypic correlates of the disturbed neurotransmitter homeostasis, we show that ether lipid deficiency manifests as hyperactivity and impaired social interaction. We propose that the lack of ether lipids alters the properties of synaptic vesicles leading to reduced amounts and release of neurotransmitters. These features likely contribute to the behavioral phenotype of Gnpat KO mice, potentially modeling some human neurodevelopmental disorders like autism or attention deficit hyperactivity disorder.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.