SnRNA seq revealed astrocytic MAGL-KO rescued cognitive impairments in 5xFAD 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 astrocytic MAGL inhibition in 5xFAD mice were still unclear. To address this question, behavioral tests were performed and hippocampal nuclei were isolated from WT, TG, TG-aKO, TG-nKO, and TG-tKO mice. Our behavioral and electrophysiological results showed that cognitive and synaptic functions were rescued in TG-aKO 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 transgenic mice were analyzed by snRNA-seq.