Serotonin plays a crucial role in understanding depression, affecting diagnosis, treatment, and drug innovation. A team from China has created a sensitive and selective fluorescent probe specifically for studying serotonin-related processes, as detailed in the journal Angewandte Chemie. They also share initial findings from experiments conducted on cell and animal models.
Depression remains a major health concern globally. Existing treatments often fall short, largely due to the challenges in pinpointing the exact mechanisms behind depression. Recent studies suggest that low serotonin levels might not be the sole cause of depressive disorders.
To investigate how serotonin impacts depression, Weiying Lin and his team from Guangxi University aimed to design a highly selective fluorescent probe. One challenge they faced is that serotonin shares structural and chemical traits with other molecules like melatonin and tryptophan. However, through detailed analysis, they identified slight differences in how these substances react. The team developed a specialized reactive group, 3-mercaptopropionate, that can interact with serotonin very selectively through a series of reactions. This group was connected to a fluorescent dye derived from dicyanomethylene-benzopyran.
This modification initially keeps the probe “off.” When the probe meets serotonin, one part reacts first; specifically, the SH group of the reactive component binds to a double bond in serotonin through a thiol-ene reaction. This initial reaction paves the way for a second bond to form due to proximity (a nucleophilic reaction occurs between an amino group in serotonin and a carbonyl group in the reactive component). Consequently, the reactive unit is detached from the fluorescent dye, turning the fluorescence “on.” This new probe can now detect serotonin selectively and sensitively, even within cells.
The researchers utilized the probe to visualize a neuronal cell line that can model depression through the application of corticosterone. Their findings showed that serotonin levels in both normal and “depressed” cells were relatively high, yet the depressed cells released significantly less serotonin when stimulated. Even current antidepressants, specifically serotonin reuptake inhibitors, only slightly boosted the release of serotonin.
It has been hypothesized that mTOR, a biomolecule involved in various cellular signaling pathways, may play a role in the reduced serotonin release. The study indicated that activating mTOR increased serotonin release in depressive cells, while inhibiting mTOR decreased serotonin release in normal cells. These outcomes were confirmed in both neuron and mouse models.
These imaging investigations suggest that the quantity of serotonin present in the depression model is not the key factor; rather, the ability of neurons to release serotonin appears to be far more critical. This release capability shows a strong correlation with mTOR activity, potentially guiding future advancements in depression treatment.
