ArticleNature communications2012
Uncoupling of the endocannabinoid signalling complex in a mouse model of fragile X syndrome.
Article in Nature communications, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers, 2 of them syntheses that pooled it.
What it found
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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
152 citing papers in PubMed, 2 syntheses or guidelines pooled it, 265 citations in OpenAlex.
- Alterations of the endocannabinoid system in autism spectrum disorder: a systematic review and meta-analysis.European archives of psychiatry and clinical neuroscience · 2025Pooled it
- Efficacy of cannabinoids in neurodevelopmental and neuropsychiatric disorders among children and adolescents: a systematic review.European child & adolescent psychiatry · 2024Pooled it
- Long-term safety and tolerability of transdermal cannabidiol gel in children and adolescents with Fragile X syndrome (ZYN2-CL-017): an interim analysis of an ongoing open-label extension study.Journal of neurodevelopmental disorders · 2025Trial
- A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT-FX).Journal of neurodevelopmental disorders · 2022Trial
- A phase 1/2, open-label assessment of the safety, tolerability, and efficacy of transdermal cannabidiol (ZYN002) for the treatment of pediatric fragile X syndrome.Journal of neurodevelopmental disorders · 2019Trial
- Altered striatal long-term potentiation in the eIF4E-TG mouse model of autism spectrum disorder.iScience · 2026Article
- N-Arachidonoyl-phosphatidylethanolamide phospholipase D activation by muscarinic receptors.The Journal of physiology · 2026Article
- Enhanced CB1 receptor function in GABAergic neurons mediates hyperexcitability and impaired sensory-driven synchrony of cortical circuits in Fragile X Syndrome model mice.Molecular psychiatry · 2026Article
- The how and why for multiple forms of hippocampal LTP.Frontiers in synaptic neuroscience · 2026Review
- Circuit mechanisms governing endocannabinoid modulation of affective behaviour and stress adaptation.Nature reviews. Neuroscience · 2025Review
- Nanoscale synaptic remodeling at corticostriatal circuits predicts flexible action control.bioRxiv : the preprint server for biology · 2025Article
- The endocannabinoidome-gut microbiome-brain axis as a novel therapeutic target for autism spectrum disorder.Journal of biomedical science · 2025Review
- Microglia Support Both the Singular Form of LTP Expressed by the Lateral Perforant Path and Episodic Memory.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- From Discovery to Innovative Translational Approaches in 80 Years of Fragile X Syndrome Research.Biomedicines · 2025Review
- Neuroligin 1 Regulates Autistic-Like Repetitive Behavior through Modulating the Activity of Striatal D2 Receptor-Expressing Medium Spiny Neurons.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Delayed onset of striatal projection neuron hyperexcitability inFrontiers in cellular neuroscience · 2025Article
- Cell- and Pathway-Specific Disruptions in the Accumbens of Fragile X Mouse.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Unraveling the Endocannabinoid System: Exploring Its Therapeutic Potential in Autism Spectrum Disorder.Neuromolecular medicine · 2024Review
- Topography and Ensemble Activity in the Auditory Cortex of a Mouse Model of Fragile X Syndrome.eNeuro · 2024Article
- Developmental Disruptions of the Dorsal Striatum in Autism Spectrum Disorder.Biological psychiatry · 2024Review
92 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
Abstract
Fragile X syndrome, the most commonly known genetic cause of autism, is due to loss of the fragile X mental retardation protein, which regulates signal transduction at metabotropic glutamate receptor-5 in the brain. Fragile X mental retardation protein deletion in mice enhances metabotropic glutamate receptor-5-dependent long-term depression in the hippocampus and cerebellum. Here we show that a distinct type of metabotropic glutamate receptor-5-dependent long-term depression at excitatory synapses of the ventral striatum and prefrontal cortex, which is mediated by the endocannabinoid 2-arachidonoyl-sn-glycerol, is absent in fragile X mental retardation protein-null mice. In these mutants, the macromolecular complex that links metabotropic glutamate receptor-5 to the 2-arachidonoyl-sn-glycerol-producing enzyme, diacylglycerol lipase-α (endocannabinoid signalosome), is disrupted and metabotropic glutamate receptor-5-dependent 2-arachidonoyl-sn-glycerol formation is compromised. These changes are accompanied by impaired endocannabinoid-dependent long-term depression. Pharmacological enhancement of 2-arachidonoyl-sn-glycerol signalling normalizes this synaptic defect and corrects behavioural abnormalities in fragile X mental retardation protein-deficient mice. The results identify the endocannabinoid signalosome as a molecular substrate for fragile X syndrome, which might be targeted by therapy.
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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.