ArticleProceedings of the National Academy of Sciences of the United States of America2016
Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 91 papers, 1 of them a synthesis 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
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 citations in OpenAlex.
- Cross-ancestry genome-wide association study and systems-level integrative analyses implicate new risk genes and therapeutic targets for depression.Nature human behaviour · 2025Pooled it
- Bioorthogonal Chemistry in Neurobiology: From Imaging to Proteomics.Chembiochem : a European journal of chemical biology · 2026Review
- CB1 receptor signaling at the cingulate-striatal circuit is anxiogenic.Nature communications · 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
- Chemical Probes for Investigating the Endocannabinoid System.Current topics in behavioral neurosciences · 2026Review
- Dosage effect of copy number variation in epilepsy and ten regions of the human brain.Scientific reports · 2025Article
- Differential increase in endocannabinoid levels at the plasma and intracellular membranes.iScience · 2025Article
- Behavioral Decoding Reveals Cortical Endocannabinoid Potentiation during ΔbioRxiv : the preprint server for biology · 2025Article
- Ppp2r1a haploinsufficiency increases excitatory synaptic transmission and decreases spatial learning by impairing endocannabinoid signaling.The Journal of clinical investigation · 2025Article
- Corticosterone stimulates synthesis of 2-arachidonoylglycerol via putative membrane-bound glucocorticoid receptors and inhibits GABA release via CB1 cannabinoid receptors in the ventrolateral periaqueductal gray.Molecular pharmacology · 2025Article
- Prefrontal correlates of fear generalization during endocannabinoid depletion.The Journal of clinical investigation · 2025Article
- The endocannabinoid 2-arachidonoylglycerol is released and transported on demand via extracellular microvesicles.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Stress disrupts engram ensembles in lateral amygdala to generalize threat memory in mice.Cell · 2025Article
- ABHD6 loss-of-function in mesoaccumbens postsynaptic but not presynaptic neurons prevents diet-induced obesity in male mice.Nature communications · 2024Article
- Endocannabinoid Receptor 2 Function is Associated with Tumor-Associated Macrophage Accumulation and Increases in T Cell Number to Initiate a Potent Antitumor Response in a Syngeneic Murine Model of Glioblastoma.Cannabis and cannabinoid research · 2024Article
- A multi-regional human brain atlas of chromatin accessibility and gene expression facilitates promoter-isoform resolution genetic fine-mapping.Nature communications · 2024Article
- Lipid Alterations in Chronic Nonspecific Low Back Pain in the Chinese Population: A Metabolomic and Lipidomic Study.Bioengineering (Basel, Switzerland) · 2024Article
- From Classical to Alternative Pathways of 2-Arachidonoylglycerol Synthesis: AlterAGs at the Crossroad of Endocannabinoid and Lysophospholipid Signaling.Molecules (Basel, Switzerland) · 2024Review
- P2XBritish journal of pharmacology · 2024Article
- Inhibition of 2-AG hydrolysis alleviates posttraumatic headache attributed to mild traumatic brain injury.The journal of headache and pain · 2024Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedCorrection for Ogasawara et al., Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition.2016 · van den Nieuwendijk, Adriann M C H [corrected to van den Nieuwendijk, Adrianus M C H]; Mo, Simone [corrected to Mori, Simone]
Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
Abstract
Diacylglycerol lipases (DAGLα and DAGLβ) convert diacylglycerol to the endocannabinoid 2-arachidonoylglycerol. Our understanding of DAGL function has been hindered by a lack of chemical probes that can perturb these enzymes in vivo. Here, we report a set of centrally active DAGL inhibitors and a structurally related control probe and their use, in combination with chemical proteomics and lipidomics, to determine the impact of acute DAGL blockade on brain lipid networks in mice. Within 2 h, DAGL inhibition produced a striking reorganization of bioactive lipids, including elevations in DAGs and reductions in endocannabinoids and eicosanoids. We also found that DAGLα is a short half-life protein, and the inactivation of DAGLs disrupts cannabinoid receptor-dependent synaptic plasticity and impairs neuroinflammatory responses, including lipopolysaccharide-induced anapyrexia. These findings illuminate the highly interconnected and dynamic nature of lipid signaling pathways in the brain and the central role that DAGL enzymes play in regulating this network.
Indexed as
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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.