ArticleJournal of neuroinflammation2023
Inhibition of 2-arachidonoylglycerol degradation enhances glial immunity by single-cell transcriptomic analysis.
Article in Journal of neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Computational discovery and dynamic profiling of dual acetylcholinesterase and monoacylglycerol lipase inhibitors for Alzheimer's disease.Molecular diversity · 2026Article
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- Inhibition of endocannabinoid degradation in astrocytes reprograms glial reactivity and prevents seizure sequelae.Journal of neuroinflammation · 2026Article
- Impact of Cannabis and Cannabis Legalization on US Atrial Septal Defect Rates.Journal of xenobiotics · 2026Article
- Bridging reward and resilience: the endocannabinoid system as a unifying mechanism in exercise-induced protection against major depressive disorder.Frontiers in psychiatry · 2026Review
- Selective Inactivation of Astrocytic Monoacylglycerol Lipase for Alzheimer's Disease Therapy.bioRxiv : the preprint server for biology · 2025Article
- Unlocking the Secrets: Causal Associations Between Blood Metabolites and Aspergillosis.Current microbiology · 2025Article
- Lipid droplet accumulation in microglia and their potential roles.Lipids in health and disease · 2025Review
- Adhesion-Related Pathways and Functional Polarization of Astrocytes in Traumatic Brain Injury: Insights from Single-cell RNA Sequencing.Neuromolecular medicine · 2025Article
- Overabundant endocannabinoids in neurons are detrimental to cognitive function.bioRxiv : the preprint server for biology · 2024Article
- Distribution and Level of Bioactive Monoacylglycerols in 12 Marine Microalgal Species.Marine drugs · 2024Article
- The role of the sensory input intervention in recovery of the motor function in hypoxic ischemic encephalopathy rat model.Journal of neurophysiology · 2024Article
- Endocannabinoid Hydrolase Inhibitors: Potential Novel Anxiolytic Drugs.Drug design, development and therapy · 2024Review
- Monoacylglycerol Lipase Inhibition Prevents Short-Term Mitochondrial Dysfunction and Oxidative Damage in Rat Brain Synaptosomal/Mitochondrial Fractions and Cortical Slices: Role of Cannabinoid Receptors.Neurotoxicity research · 2023Article
- Imaging and Genetic Tools for the Investigation of the Endocannabinoid System in the CNS.International journal of molecular sciences · 2023Review
- Cannabis and Paternal Epigenetic Inheritance.International journal of environmental research and public health · 2023Review
- Inhibiting degradation of 2-arachidonoylglycerol as a therapeutic strategy for neurodegenerative diseases.Pharmacology & therapeutics · 2023Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
background2-Arachidonoylglycerol (2-AG) is the most abundant endogenous cannabinoid. Inhibition of 2-AG metabolism by inactivation of monoacylglycerol lipase (MAGL), the primary enzyme that degrades 2-AG in the brain, produces anti-inflammatory and neuroprotective effects in neurodegenerative diseases. However, the molecular mechanisms underlying these beneficial effects are largely unclear.
methodsHippocampal and cortical cells were isolated from cell type-specific MAGL knockout (KO) mice. Single-cell RNA sequencing was performed by 10 × Genomics platform. Cell Ranger, Seurat (v3.2) and CellChat (1.1.3) packages were used to carry out data analysis.
resultsUsing single-cell RNA sequencing analysis, we show here that cell type-specific MAGL KO mice display distinct gene expression profiles in the brain. Inactivation of MAGL results in robust changes in expression of immune- and inflammation-related genes in microglia and astrocytes. Remarkably, upregulated expression of chemokines in microglia is more pronounced in mice lacking MAGL in astrocytes. In addition, expression of genes that regulate other cellular functions and Wnt signaling in astrocytes is altered in MAGL KO mice.
conclusionsOur results provide transcriptomic evidence that cell type-specific inactivation of MAGL induces differential expression of immune-related genes and other fundamental cellular pathways in microglia and astrocytes. Upregulation of the immune/inflammatory genes suggests that tonic levels of immune/inflammatory vigilance are enhanced in microglia and astrocytes, particularly in microglia, by inhibition of 2-AG metabolism, which likely contribute to anti-inflammatory and neuroprotective effects produced by inactivation of MAGL in neurodegenerative diseases.
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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.