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Overabundant endocannabinoids in neurons are detrimental to cognitive function

GSE274338 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2025/12/31 Platform GPL24247
Summary
In the brain, 2-Arachidonoylglycerol (2-AG) is the most abundant endogenous cannabinoid. Enhancing 2-AG signaling by inhibiting monoacylglycerol lipase (MAGL) in astrocytes, the primary enzyme that degrades 2-AG in the brain, produces anti-inflammatory and neuroprotective effects in neurodegenerative diseases. However, the effects of neuronal MAGL inhibition and the responsible molecular mechanisms are largely unclear. To address this question, behavioral tests were performed and hippocampal nuclei were isolated from cell type-specific MAGL knockout (KO) mice. Our behavioral and electrophysiological results showed that cognitive and synaptic functions were impaired in neuronal MAGL-KO mice. Using single-nucleus RNA sequencing analysis, we show here that neuronal MAGL KO mice display distinct gene expression profiles of synaptic DEGs in neurons and glial cells
Published in
Overabundant endocannabinoids in neurons are detrimental to cognitive function
Zhu D, Zhang J, Ma X et al. · bioRxiv : the preprint server for biology 2024 · PMID 39345517 · doi:10.1101/2024.09.17.613513
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Also filed as BioProject PRJNA1145993 and SRA study SRP525095. Searching any of these in the dataset finder brings you back here.

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