Effects of gut microbiota transplantation on depressive-like behaviors and expression of endocannabinoid-related molecules in the hippocampus of mice
Journal Title: Journal of Air Force Medical University - Year 2023, Vol 44, Issue 11
Abstract
Objective To observe the effects of gut microbiota transplantation in patients with depression on the behaviors and endocannabinoid (eCB) in the hippocampus of mice. Methods The gut microbiota of healthy subjects and patients with depression were transplanted into “ pseudo-sterile” mice, whose depressive-like behaviors were evaluated by sucrose preference test, open field test and tail suspension test, and the expression of eCB-related molecules in the hippocampus was detected. ① Preparation of model mice: “ cocktail” antibiotics were used to remove the original gut microbiota of mice by gavage, and the “pseudo-sterile” mouse model was prepared by gavage for 14 d. At 48 h after the last antibiotic gavage, mice were randomly divided into control group (n = 6) and depression group (n = 10). Fecal microbiota transplantation was performed on each group of mice on every Monday, Wednesday and Friday for 3 weeks, and the “humanized” mouse model was prepared. ②Behavioral tests: sucrose preference test, open field test, and tail suspension test were performed 24 h after the fecal microbiota transplantation to evaluate depressive-like behaviors in mice. ③Then mice were sacrificed 24 h after the behavioral tests, and the expression of eCB-related molecules in the hippocampus of mice was evaluated by Western blotting. Results ① Compared with the control group, mice in depression group showed significant depressive-like behaviors in open field test, sucrose preference test and tail suspension test, including less times of entering the central area, decreased distance in central area, lower total distance, and reduced ratio of residence time in the central area in open field test (P < 0. 01), lower sucrose preference rate in sucrose preference test (P < 0. 05), and longer immobility time of tail suspension in tail suspension test (P < 0. 01). ②The results of Western blotting showed that compared with the control group, the expressions of CB1R, NAPE-PLD, and DAGLα in the depression group were significantly down-regulated, with statistical significance ( P < 0. 05) . ③The expressions of NAPE-PLD and DAGLα in hippocampus were positively correlated with the times of mice entering the central area, the distance in central area, the ratio of residence time in the central area, and sucrose preference rate (all P < 0. 05), while the expressions of DAGLα and NAPE-PLD were negatively correlated with the immobility time of tail suspension ( both P < 0. 05). Conclusion The gut microbiota of patients with depression may induce depressive-like behaviors in mice by regulating eCB-related molecules in the hippocampus.
Authors and Affiliations
MA Xinxu, XUE Shanshan, ZHANG Tian, CHEN Yihuan, CAI Min
Keywords
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