Investigating the role of norepinephrine in regulating depression by a novel organic near-infrared fluorescent probe.

Depression is closely associated with alterations in concentration levels and release dynamics of a specific neurotransmitter, such as norepinephrine (NE), in the brain. Visualizing these dynamic changes is essential for understanding depression-associated neurotransmitter dysregulation. Herein, we developed a novel near-infrared fluorescent probe DIPCl-NE by employing a near-infrared fluorophore DIPCl-OH (Em = 689 nm) as the signal reporter and introducing a carbonothioate group as the recognition unit for selective NE detection. DIPCl-NE exhibits high sensitivity, excellent selectivity, good photostability, and effective tissue penetration capability. Using this probe, we visualized NE release dynamics in normal and CORT-induced depressive-like models and revealed that impaired NE exocytosis is associated with reduced mTOR phosphorylation levels. Pharmacological regulation of mTOR signaling further demonstrated its role in modulating NE release dynamics. Moreover, DIPCl-NE enabled visualization of NE alterations in mouse brains and revealed decreased NE availability in depressive model mice. This work provides a valuable chemical tool for monitoring NE dynamics and offers new insights into the relationship between mTOR signaling and depression-associated neurotransmitter dysfunction.