The Role and Mechanism of Citrate Carrier SLC25A1 in Anxiety-like Behavior in Mice

• 1、Medical School (Cambridge-Soochow Genomic Resource Center), Soochow University ,Suzhou,Jiangsu,215123,China

Abstract：Anxiety disorder is a common mental illness with a complex pathogenesis that has not been fully elucidated. Histone acetylation, as an important epigenetic modification, has been proven to play a significant role in animal models of anxiety and stress. SLC25A1, as a citrate transporter on the mitochondrial membrane, affects the synthesis of acetyl-CoA and is closely related to the histone acetylation modification process. SLC25A1 plays an important role in glycolipid metabolism, but there are few studies on its role in neurological diseases, especially mental and emotional disorders such as anxiety disorder. Therefore, this study explores the role and mechanism of SLC25A1 in anxiety disorder. By using adeno-associated virus to construct a mouse model with specific knockout of Slc25a1 in the brain (Slc25a1bKO), it was found that SLC25A1 was successfully knocked out in brain regions such as the cortex and hypothalamus. Behavioral experiments showed that Slc25a1bKO mice exhibited significant anxiety-like behaviors in anxiety behavioral paradigms such as the open field and elevated plus maze, accompanied by reduced sleep. Finally, ELISA and WB experiments were used to explore the preliminary molecular mechanism. The results showed that the content of acetyl-CoA in the cortical brain region of Slc25a1bKO mice was significantly reduced, and the level of H3K27ac was significantly decreased. These results suggest that SLC25A1 may regulate anxiety behavior in mice by controlling the level of acetyl-CoA and affecting histone H3K27ac modification.

Keywords： Cell Biology Citrate transporter Anxiety disorder Histone acetylation modification