Unveiling the Unique Mechanism of Allopregnanolone, a GABA-A Receptor Selective PAM, on Antidepressant Action (2024)

Undergraduates: Aditi Shah, William Taft Stevens (tafts@email.unc.edu), Lillian Seymour (lseymour@unc.edu), Nikita Elkin (elnick@unc.edu), George Hayden Bullard (hayden23@live.unc.edu)

Faculty Advisor: Rachel Penton
Department: Psychology and Neuroscience

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The aim of the scientific project is to create a comprehensive 3D printed model illustrating allosteric interactions of a GABA-A receptor with the novel antidepressant Allopregnanolone. Leveraging recent research papers providing the basis for the project, this 3D model presents the mechanism of action of the novel antidepressant on GABA-A, namely the dynamic conformational changes induced by Allopregnanolone binding. In the process of polishing the model, three prototype designs were considered and evaluated for clarity, simplicity, and accuracy of representation of the intended purpose – a flower-like model, a click-and-lock model, and a dynamic gear mechanism. Meticulous iterative prototyping led to the final design incorporating magnets and rotating gears to simulate receptor dynamics upon drug binding. The resulting model provides a great tactile and visual representation of the GABA-A receptor’s behavior, specifically showing how Allopregnanolone enhances GABA-ergic neurotransmission and alleviates depressive symptoms. Targeted at students, teachers, researchers, and pharmaceutical companies, this model serves to enhance understanding of drug-receptor interactions and aids in studying the therapeutic efficacy of the novel antidepressant Allopregnanolone.