An activatable fluorescence probe for visualization of DAGL activity in hippocampal tissue of brain-injured mice

Diacylglycerol lipase (DAGL) is an important biosynthetic enzyme of endocannabinoid 2-arachidonoyl-glycerol (2-AG) that activates the endocannabinoid receptors to mediate basic biological processes, such as inflammation, pain sensation, epileptogenesis, synaptic plasticity, neuroprotection and adult neurogenesis. However, the changes of DAGL activity are still unclear in neurophysiological and pathological processes due to a lack of effective method for in situ detection of DAGL activity. Herein, based on the specific cleavage of the sn-1 acyl group of diacylglycerol (DAG) hydrolyzed by DAGL, we rational design an activatable fluorescence probe by simulating the substrate of DAGL for detecting the DAGL activity. Coumarin and rhodamine fluorophores are introduced into 1- and 2-site of glycerol through ester bonds to construct a fluorescence resonance energy transfer probe CGR. The probe CGR shows high selectivity and can be used to detect the activity of endogenous DAGL in tissue and brain. Notably, we used the probe CGR to reveal the changes of DAGL activity after brain injury. • An activatable fluorescence probe (CGR) was designed and synthesized for detecting the DAGL activity in vivo. • The probe CGR shows high selectivity and rapid response to DAGL. • CGR was used to reveal the changes of DAGL activity after brain injury.