A Near-Infrared Fluorescent Probe for Visualization of Acetylcholinesterase Flux in the Acute Epileptic Mice Brain

Neurotransmitter imbalance is an important pathological basis for epilepsy seizures. Acetylcholinesterase (AChE) as a key hydrolase in the cholinergic system directly affects the metabolism of neurotransmitter. Unfortunately, owing to the lack of reliable in situ imaging tools in the brain, the association between AChE and epilepsy has not been fully elucidated yet. Here, we rationally designed a near-infrared (NIR) fluorescent probe (<b>QXMC</b>) by employing <i>N</i>,<i>N</i>-dimethyl carbamyl as an AChE sensing group in the quinolinium-xanthene NIR skeleton. <b>QXMC</b> exhibited high sensitivity, excellent selectivity, and ultrafast response time (within 0.5 s) toward AChE. Moreover, <b>QXMC</b> can sensitively monitor the fluctuations of AChE activity in the neuronal cells and zebrafish during the apoptosis or oxidative stress process. Significantly, using <b>QXMC</b> with superb blood-brain barrier (BBB) permeability, for the first time, we discovered a down-regulated AChE level in the acute epileptic mice brain through noninvasive NIR in vivo imaging. Moreover, the visualization of therapeutic evaluation of epilepsy has also been achieved by monitoring AChE with <b>QXMC</b>. This work demonstrated the great potential of <b>QXMC</b> as an effective imaging tool for epilepsy diagnosis, therapeutic evaluation, and pathogenesis study.