ArticlePloS one2014
Monoacylglycerol lipase inhibitor JZL184 improves behavior and neural properties in Ts65Dn mice, a model of down syndrome.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 57 citations in OpenAlex.
- Endocannabinoid Enhancement via MAGL Inhibition in CDKL5 Deficiency: Selective Cellular Benefits and Domain-Specific Functional Effects in AdultInternational journal of molecular sciences · 2026Article
- Chronic suppression of monoacylglycerol lipase restores adult neurogenesis in the septal but not the temporal DG in Ts65Dn mouse model of Down syndrome.Brain research bulletin · 2026Article
- Targeting dysregulated CB1 receptors in a Down syndrome mouse model improves neurological outcomes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Flavonoid carbamate hybrids: design, synthesis, and evaluation as multi-target enzyme inhibitors for Alzheimer's disease.RSC advances · 2025Article
- Multisensory gamma stimulation enhances adult neurogenesis and improves cognitive function in male mice with Down Syndrome.PloS one · 2025Article
- Dissection of a Down syndrome-associated trisomy to separate the gene dosage-dependent and -independent effects of an extra chromosome.Human molecular genetics · 2023Article
- Inhibiting degradation of 2-arachidonoylglycerol as a therapeutic strategy for neurodegenerative diseases.Pharmacology & therapeutics · 2023Review
- GIRK2 Channels in Down Syndrome and Alzheimer's Disease.Current Alzheimer research · 2022Article
- Enhanced GIRK2 channel signaling in Down syndrome: A feasible role in the development of abnormal nascent neural circuits.Frontiers in genetics · 2022Review
- On the Biomedical Properties of Endocannabinoid Degradation and Reuptake Inhibitors: Pre-clinical and Clinical Evidence.Neurotoxicity research · 2021Review
- Increased 2-arachidonoyl-sn-glycerol levels normalize cortical responses to sound and improve behaviors in Fmr1 KO mice.Journal of neurodevelopmental disorders · 2021Article
- Targeting increased levels of APP in Down syndrome: Posiphen-mediated reductions in APP and its products reverse endosomal phenotypes in the Ts65Dn mouse model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Article
- Intermittent ethanol exposure during adolescence impairs cannabinoid type 1 receptor-dependent long-term depression and recognition memory in adult mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Article
- Druggable targets of the endocannabinoid system: Implications for the treatment of HIV-associated neurocognitive disorder.Brain research · 2019Review
- Effects of Fatty Acid Amide Hydrolase Inhibitors Acute Administration on the Positive and Cognitive Symptoms of Schizophrenia in Mice.Molecular neurobiology · 2019Article
- OLIG2 Drives Abnormal Neurodevelopmental Phenotypes in Human iPSC-Based Organoid and Chimeric Mouse Models of Down Syndrome.Cell stem cell · 2019Article
- Neuroinflammation and adult hippocampal neurogenesis in neuropathic pain and alkyl glycerol ethers treatment in aged mice.International journal of molecular medicine · 2019Article
- Monoacylglycerol Lipase Inhibitor is Safe when Combined with Delayed r-tPA Administration in Treatment of Stroke.Inflammation · 2018Article
- Therapeutic endocannabinoid augmentation for mood and anxiety disorders: comparative profiling of FAAH, MAGL and dual inhibitors.Translational psychiatry · 2018Article
- Neuroprotective Effects of MAGL (Monoacylglycerol Lipase) Inhibitors in Experimental Ischemic Stroke.Stroke · 2018Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Genetic alterations or pharmacological treatments affecting endocannabinoid signaling have profound effects on synaptic and neuronal properties and, under certain conditions, may improve higher brain functions. Down syndrome (DS), a developmental disorder caused by triplication of chromosome 21, is characterized by deficient cognition and inevitable development of the Alzheimer disease (AD) type pathology during aging. Here we used JZL184, a selective inhibitor of monoacylglycerol lipase (MAGL), to examine the effects of chronic MAGL inhibition on the behavioral, biochemical, and synaptic properties of aged Ts65Dn mice, a genetic model of DS. In both Ts65Dn mice and their normosomic (2N) controls, JZL184-treatment increased brain levels of 2-arachidonoylglycerol (2-AG) and decreased levels of its metabolites such as arachidonic acid, prostaglandins PGD2, PGE2, PGFα, and PGJ2. Enhanced spontaneous locomotor activity of Ts65Dn mice was reduced by the JZL184-treatement to the levels observed in 2N animals. Deficient long-term memory was also improved, while short-term and working types of memory were unaffected. Furthermore, reduced hippocampal long-term potentiation (LTP) was increased in the JZL184-treated Ts65Dn mice to the levels observed in 2N mice. Interestingly, changes in synaptic plasticity and behavior were not observed in the JZL184-treated 2N mice suggesting that the treatment specifically attenuated the defects in the trisomic animals. The JZL184-treatment also reduced the levels of Aβ40 and Aβ42, but had no effect on the levels of full length APP and BACE1 in both Ts65Dn and 2N mice. These data show that chronic MAGL inhibition improves the behavior and brain functions in a DS model suggesting that pharmacological targeting of MAGL may be considered as a perspective new approach for improving cognition in DS.
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Registered trials
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