ArticleJournal of neurophysiology2016
Endogenous 24S-hydroxycholesterol modulates NMDAR-mediated function in hippocampal slices.
Article in Journal of neurophysiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 61 citations in OpenAlex.
- Pharmacokinetics, pharmacodynamics and safety assessment of multiple doses of soticlestat in healthy volunteers.British journal of clinical pharmacology · 2022Trial
- CYP46A1 activation by low-dose efavirenz uncovers the link between brain cholesterol metabolism, energetics, and vasculature.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- A novel sex-specific role for 27-hydroxycholesterol in early-onset schizophrenia.Annals of general psychiatry · 2026Article
- Oxysterol signaling in the central nervous system: cellular mechanisms and implications for neurodegeneration.Frontiers in molecular neuroscience · 2026Review
- New directions in neurosteroid therapeutics in neuropsychiatry.Neuroscience and biobehavioral reviews · 2025Review
- 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
- The cholesterol 24-hydroxylase CYP46A1 promotes α-synuclein pathology in Parkinson's disease.PLoS biology · 2025Article
- Role of cholesterol in modulating brain hyperexcitability.Epilepsia · 2025Review
- Effects of Complete and Partial Loss of the 24S-Hydroxycholesterol-Generating EnzymeBiomolecules · 2024Article
- Enzymatically Formed Oxysterols and Cell Death.Advances in experimental medicine and biology · 2024Review
- 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 normalizing effects of the CYP46A1 activator efavirenz on retinal sterol levels and risk factors for glaucoma in ApojCellular and molecular life sciences : CMLS · 2023Article
- Novel neuroactive steroids as positive allosteric modulators of NMDA receptors: mechanism, site of action, and rescue pharmacology on GRIN variants associated with neurological conditions.Cellular and molecular life sciences : CMLS · 2023Article
- Cholesterol and oxysterols in retinal neuron-glia interactions: relevance for glaucoma.Frontiers in ophthalmology · 2023Review
- Maternal stress induced anxiety-like behavior exacerbated by electromagnetic fields radiation in female rats offspring.PloS one · 2022Article
- Targeting cytochrome P450 46A1 and brain cholesterol 24-hydroxylation to treat neurodegenerative diseases.Exploration of neuroprotective therapy · 2021Article
- A Proinflammatory Stimulus Disrupts Hippocampal Plasticity and Learning via Microglial Activation and 25-Hydroxycholesterol.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Soticlestat, a novel cholesterol 24-hydroxylase inhibitor, reduces seizures and premature death in Dravet syndrome mice.Epilepsia · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
N-methyl-D-aspartate receptors (NMDARs), a major subtype of glutamate receptors mediating excitatory transmission throughout the central nervous system (CNS), play critical roles in governing brain function and cognition. Because NMDAR dysfunction contributes to the etiology of neurological and psychiatric disorders including stroke and schizophrenia, NMDAR modulators are potential drug candidates. Our group recently demonstrated that the major brain cholesterol metabolite, 24S-hydroxycholesterol (24S-HC), positively modulates NMDARs when exogenously administered. Here, we studied whether endogenous 24S-HC regulates NMDAR activity in hippocampal slices. In CYP46A1(-/-) (knockout; KO) slices where endogenous 24S-HC is greatly reduced, NMDAR tone, measured as NMDAR-to-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) excitatory postsynaptic current (EPSC) ratio, was reduced. This difference translated into more NMDAR-driven spiking in wild-type (WT) slices compared with KO slices. Application of SGE-301, a 24S-HC analog, had comparable potentiating effects on NMDAR EPSCs in both WT and KO slices, suggesting that endogenous 24S-HC does not saturate its NMDAR modulatory site in ex vivo slices. KO slices did not differ from WT slices in either spontaneous neurotransmission or in neuronal intrinsic excitability, and exhibited LTP indistinguishable from WT slices. However, KO slices exhibited higher resistance to persistent NMDAR-dependent depression of synaptic transmission induced by oxygen-glucose deprivation (OGD), an effect restored by SGE-301. Together, our results suggest that loss of positive NMDAR tone does not elicit compensatory changes in excitability or transmission, but it protects transmission against NMDAR-mediated dysfunction. We expect that manipulating this endogenous NMDAR modulator may offer new treatment strategies for neuropsychiatric dysfunction.
Indexed as
Identifiers
What OpenQuestion holds
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.