A NIR fluorescent probe tracing norepinephrine exocytosis and depression occurrence at the cellular level

Abstract

NIR fluorescent probe tracing norepinephrine exocytosis and depression occurrence at the cellular level, and revealed that norepinephrine exocytosis rather than inherent intracellular concentration was related with depression.

Fast-Specific Fluorescent Probes to Visualize Norepinephrine Signaling Pathways and Its Flux in the Epileptic Mice Brain

“…The intracellular fluorescence intensity was 66.9% at 95 s compared to the control group (without venlafaxine, only stimulated by 1.5 mM K + ), indicating that venlafaxine successfully reduced NE reuptake by inhibiting NE transporter (NET) activity, thereby increasing the concentration of NE in the intercellular space. As a result, increasing the concentration of NE in the synaptic space is beneficial in the treatment of depression …”

“…Conventional probes could only detect the NE release process. 6,7,13 This intriguing phenomenon perceived by our probe could be that the NE-probe adduct (similar to a pseudo neurotransmitter) is retaken by the cell. Visualization of NE reuptake by cells following exocytosis induced by K + was realized.…”

“…The locus coeruleus (LC) is employed to synthesize norepinephrine (NE), a catecholamine neurotransmitter widely projected throughout the brain and spinal cord. It is primarily responsible for the precise regulation of attention, arousal, learning, memory, stress, heart rate, and blood pressure, − among other things, and is closely linked to several mental and neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, depression, and attention deficit. − …”

“…Glass’s team pioneered NE-specific detection using reactive small organic molecular fluorescent probes. − They developed a series of probes to distinguish NE from other amines and catecholamine neurotransmitters using binding constants, primarily through aldehyde-amine condensation or weak hydrogen bond interactions. − These studies serve as inspiration for the further design of specific response NE fluorescent probes . Based on the NE-specific β-hydroxyethylamine, the Yin group created a series of NE-specific probes with different emission wavelengths using a cascade nucleophilic reaction using a ″protection-de-protection″ strategy. ,, In fact, the rate-determined intermolecular nucleophile reaction between amino and ester groups is inefficient, resulting in a very slow detection process. In vitro studies were also affected by Cys with a ″similar moiety″ and high reactivity.…”

“…11 Based on the NE-specific β-hydroxyethylamine, the Yin group created a series of NE-specific probes with different emission wavelengths using a cascade nucleophilic reaction using a ″protection-de-protection″ strategy. 6,12,13 In fact, the ratedetermined intermolecular nucleophile reaction between amino and ester groups is inefficient, resulting in a very slow detection process. In vitro studies were also affected by Cys with a ″similar moiety″ and high reactivity.…”