ArticleThe EMBO journal2012
Cholesterol loss during glutamate-mediated excitotoxicity.
Article in The EMBO journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 88 citations in OpenAlex.
- STIM-Orai signaling in neurons: integrating calcium dynamics and synaptic plasticity.Cell communication and signaling : CCS · 2026Review
- Frequency-Dependent Mechanism of 24-Hydroxycholesterol-Mediated Modulation of Neurotransmitter Release at the Mouse Neuromuscular Junction: The Role of Reactive Oxygen Species.Neurochemical research · 2025Article
- A review of the putative antiseizure and antiepileptogenic mechanisms of action for soticlestat.Epilepsia · 2025Review
- The Cross-Talk Between the Peripheral and Brain Cholesterol Metabolisms.Current issues in molecular biology · 2025Review
- Role of cholesterol in modulating brain hyperexcitability.Epilepsia · 2025Review
- Sex differences in physiological response to increased neuronal excitability in a knockin mouse model of pediatric epilepsy.Clinical science (London, England : 1979) · 2024Article
- 24S-Hydroxycholesterol in Neuropsychiatric Diseases: Schizophrenia, Autism Spectrum Disorder, and Bipolar Disorder.Advances in experimental medicine and biology · 2024Article
- Oxysterols in Central and Peripheral Synaptic Communication.Advances in experimental medicine and biology · 2024Article
- The translational potential of cholesterol-based therapies for neurological disease.Nature reviews. Neurology · 2023Review
- Benefits and Meaning of Lipids Profile in Relation to Oxidative Balance and Brain Morphology in Schizophrenia.International journal of molecular sciences · 2023Article
- Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy.Science advances · 2022Article
- Labelfree mapping and profiling of altered lipid homeostasis in the rat hippocampus after traumatic stress: Role of oxidative homeostasis.Neurobiology of stress · 2022Article
- Cholesterol in Brain Development and Perinatal Brain Injury: More than a Building Block.Current neuropharmacology · 2022Review
- Plasma membrane and brain dysfunction of the old: Do we age from our membranes?Frontiers in cell and developmental biology · 2022Review
- Altered Cholesterol Homeostasis in Huntington's Disease.Frontiers in aging neuroscience · 2022Review
- Network Preservation Analysis Reveals Dysregulated Synaptic Modules and Regulatory Hubs Shared Between Alzheimer's Disease and Temporal Lobe Epilepsy.Frontiers in genetics · 2022Article
- Cholesterol metabolism and brain injury in neonatal encephalopathy.Pediatric research · 2021Review
- Shared Biological Pathways between Antipsychotics and Omega-3 Fatty Acids: A Key Feature for Schizophrenia Preventive Treatment?International journal of molecular sciences · 2021Review
- Chronic Neuroinflammation Induced by Lipopolysaccharide Injection into the Third Ventricle Induces Behavioral Changes.Journal of molecular neuroscience : MN · 2021Article
- Oxysterols Modulate the Acute Effects of Ethanol on HippocampalThe Journal of pharmacology and experimental therapeutics · 2021Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The deregulation of brain cholesterol metabolism is typical in acute neuronal injury (such as stroke, brain trauma and epileptic seizures) and chronic neurodegenerative diseases (Alzheimer's disease). Since both conditions are characterized by excessive stimulation of glutamate receptors, we have here investigated to which extent excitatory neurotransmission plays a role in brain cholesterol homeostasis. We show that a short (30 min) stimulation of glutamatergic neurotransmission induces a small but significant loss of membrane cholesterol, which is paralleled by release to the extracellular milieu of the metabolite 24S-hydroxycholesterol. Consistent with a cause-effect relationship, knockdown of the enzyme cholesterol 24-hydroxylase (CYP46A1) prevented glutamate-mediated cholesterol loss. Functionally, the loss of cholesterol modulates the magnitude of the depolarization-evoked calcium response. Mechanistically, glutamate-induced cholesterol loss requires high levels of intracellular Ca(2+), a functional stromal interaction molecule 2 (STIM2) and mobilization of CYP46A1 towards the plasma membrane. This study underscores the key role of excitatory neurotransmission in the control of membrane lipid composition, and consequently in neuronal membrane organization and function.
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Registered trials
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.