Cecelia Li
Summer Research Description: One side effect of Citalopram, a selective serotonin reuptake inhibitor (SSRI), is the increased risk of bleeding due to depressed clot formation of platelets. Citalopram plays an important role in regulating serotonin (5-HT) homeostasis by inhibiting the 5-HT transporter (SERT) from uptaking 5-HT into platelets. Recent studies have demonstrated that loss of 5-HT in 6-day Citalopram-treated mice result in reduced platelet spreading and attachment, which contribute to clot formation. Here we will determine how alterations in serotonin homeostasis influence platelet adhesion and clotting. We will examine whether the effects of Citalopram depend on SERT, or indirectly via an off-target modulator, by utilizing mice expressing a Citalopram-insensitive SERT (I172M). We will investigate the relationship between changes in blood 5-HT concentrations, which will be assed using enzyme-linked immunosorbent assay (ELISA), and clot formation using a time-course consisting of a 4-day, 2-day, 30 minute, and sham treatments using 15mg/kg intraperitoneal injections of Citalopram in mice. Parallel experiments to determine clot formation in response to changing 5-HT levels include examining clotting time, clot retraction, platelet spreading, and attachment. By understanding the factors that affect platelet function and regulate clotting, we can develop preventative measures to combat the risk of increased bleeding for those who take SSRIs.