A Mitochondria-Targeted AIE-ESIPT Fluorescent Probe for Imaging Monoamine Oxidase A Dynamics in Depression Models

Abstract Depression is closely associated with dysregulation of monoamine neurotransmitter metabolism, in which monoamine oxidase A (MAO-A), located on the outer mitochondrial membrane, plays a key role by catalyzing monoamine degradation coupled with hydrogen peroxide (H2O2) generation. This process links neurotransmitter imbalance with mitochondrial oxidative stress; however, the spatiotemporal dynamics of mitochondrial MAO-A activity in vivo remain poorly understood due to the lack of effective imaging tools. Herein, we report a mitochondria-targeted small-molecule fluorescent probe, BAT, for real-time imaging of MAO-A activity in living systems. BAT integrates a propylamine recognition unit with a 2′-hydroxychalcone fluorophore featuring aggregation-induced emission (AIE) and excited-state intramolecular proton transfer (ESIPT), enabling low-background fluorescence activation upon MAO-A-catalyzed oxidative deamination. BAT enables sensitive visualization of MAO-A activity in SH-SY5Y cells, primary neurons, and mouse brains. In vivo imaging further reveals elevated MAO-A activity accompanied by increased H2O2 levels in stress-susceptible mice, highlighting mitochondrial oxidative stress associated with MAO-A dysregulation. Collectively, this work provides a robust chemical imaging tool for investigating MAO-A-related pathological process.