[Energy metabolism disorder and functional magnetic resonance imaging of the medial prefrontal cortex in mice with chronic unpredictable mild stress].

Abstract

OBJECTIVE\nTo analyze spontaneous activities and energy metabolism in the medial prefrontal cortex (mPFC) of mice with chronic unpredictable mild stress (CUMS) and explore the correlation of these changes with the mTORC1 signaling pathway.\n\n\nOBJECTIVE\nNormal C57Bl/6 mice were randomly divided into control group (n=16) and depression model group (n= 16), and the mice in the latter group were subjected to 8 weeks of modeling with CUMS. Behavioral tests including open field test, sucrose consumption test, tail suspension test and forced swimming test were performed, and the changes in prefrontal gray matter volume and the amplitude of low frequency fluctuation (ALFF) in the mice were detected with functional magnetic resonance imaging. The CUMS mice were then randomized into two groups for treatment with ketamine (n=8) or saline (n=8). The mPFC tissues of the mice were collected for detecting the phosphorylation levels of mTORC1-related proteins with Western blotting and ATP level and NADP +/NADPH ratio with ELISA in the 3 groups.\n\n\nOBJECTIVE\nCompared with the control mice, CUMS mice exhibited a distinct depressive phenotype with significantly decreased sucrose preference (P < 0.05) and shortened total distances (P < 0.01) and central exercise distances (P < 0.05) in the open field test without obvious changes of immobile time in tail suspension test and forced swimming test (P>0.05). Prefrontal gray matter volume and mALFF increased (P < 0.01), and the phosphorylation level of mTORC1- related proteins, ATP level and NADP +/NADPH ratio all decreased significantly (P < 0.05) in CUMS mice. After ketamine treatment, the phosphorylation level of mTORC1-related proteins and ATP level increased significantly in CUMS mice (P < 0.05), but the increase of NADP +/NADPH ratio was not statistically significant.\n\n\nOBJECTIVE\nThe mPFC of CUMS mice shows increased spontaneous activities but lowered productivity efficiency, indicating the presence of energy metabolism disorder in the mPFC, which is related with reduced mTORC1 phosphorylation and can be alleviated by activating the mTORC1 pathway with ketamine.