Objective: To discuss the effects and mechanisms of resveratrol on perimenopausal depression model in mice. Method: Clean-grade Kunming mice were randomly divided into the sham group

the model group

the fluovetine group (3 mg·kg-1) and resveratrol groups (10

20

40 mg·kg-1)

with 10 mice in each group. The mice were gavaged one hour before the daily stress

while the others were gavaged with physiological saline for consecutively 21 days. The perimenopausal depression model in mice was established by Ovariectomy and chronic unpredictable mild stress (CUMS). The general physical signs of the mice were observed

and experience of vaginal epithelial cells was conducted to detect changes in estrus cycle. The depressed behavior of mice was observed by body weight measurement (BWM)

open field test (OFT) and foece swimming test (FST). Changes in 5-HT

NE and DA contents in mice brain were detected by ELISA methods. ERα and ERβ protein expressions in hippocampus were detected by IHC method. Result: Compared with the sham group

the mice in OVX group did not show any change in estrous cycle for seven continuous days

indicating the successful modeling. The mice in model group appeared the behavior of depression

their body weight mice were decreased

the scores of horizontal and vertical motion in OFT were decreased

and the behavioral despair time were extended (P<0.01). Nissl's staining showed hippocampus neuron damage

atrophy and loss

and decrease in the number of Nissl bodies. The results of ELISA test showed that the content of 5-HT

NE and DA in brain tissues were decreased (P<0.01); IHC showed that the protein expressions of ERα and ERβ in hippocampus CA3 area were decreased

and IA of ERβ in DG area were decreased. Compared with the model group

after administration with different doses of resveratrol

all of mice in the perimenopausal depression model showed relieve in the abnormalities of behavior

which were characterized by rapid body mass increase

increase in spontaneous activities and exploratory behavior of OFT

reduction in the behavioral despair time of FST (P<0.01)

increase in the content of the brain tissue 5-HT

NE and DA (P<0.01)

and rise in ERα and ERβ in hippocampus CA3 area and IA of ERβ in DG area (P<0.01). Among each dose group

the medium-dose group was more obvious (P<0.05). Conclusion: Phytoestrogens resveratrol can alleviate perimenopausal depression in mice depressive behavior. Its mechanism is correlated with inhibition in neurons injury

up-regulation in the content of monoamine neurotransmitters 5-HT

NE and DA in brain tissues

and increase in the expression in ERα and ERβin hippocampus CA3 area and IA of ERβin DG area.