Gene expression profile at single nucleus level of hippocampal cells from monoacylglycerol lipase conditional knockout mice

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 Overall design: Single nucleus transcriptomics of hippocampus from WT and transgenic mice were analyzed by snRNA-seq.