探討在性別差異下dysbindin-1對大腦前額葉多巴胺系統及社交行為之機轉

Genetic variants of dystribrevin-binding protein 1 gene (Dtnbp1), also known asdysbindin-1, has been implicated in schizophrenia. Dysregulation of thedopamine system in the prefrontal cortex (PFC) and PFC-dependent cognitivefunction have been observed in schizophrenia human patients with Dtnbp1variants. Our preliminary results also showed that social interaction was impairedin female mice with mutation of Dtnbp1(Dys-/-), but not in male mice.Furthermore, a decreased of dopamine D2 receptors (D2R) in the PFC wasfound in female Dys-/- mice, while an increase of the dopamine D3 receptors(D3R) in the PFC was observed in male Dys-/. Mice. How dysbindin-1 interactingwith social behavior and the dopamine system in a sex-specific manner remainsunclear. Therefore, in this study, we propose to unravel above question bystudying the following aims: (1) sex-specific social behaviors in Dys-/- mice, (2)sex-specific dopamine system in the PFC of Dys-/- mice. (3) balancing ofdopamine system improves social behavior in Dys-/- mice, (4) restoration ofdysbindin-1 in the PFC of Dys-/- rescues dopamine system and social behavior,and (5) deletion of Dtnbp1 specifically in the PFC of wild-type mice diminishesdopamine system and social behavior. The results from this proposed researchwill shed light on the roles of dysbindin-1 on dopamine system and socialbehavior in a sex-specific manner, and possibly open a new avenue fortreatment of schizophrenia.