Research On Establishment Of A Mouse Model Of Depression And Intervention, Behavior And Hippocampal GFAP Change

[Objective] To establish depression model in mice; To detect the foraging behavior in rodents, and the changes of GFAP expression after treatment in the brain. The present study aimed to research whether food foraging activity is associated with CUMS-exposed model. It might also be interesting to examine GFAP after foraging behaviors to see if this behavior can impact GFAP expression. Our study suggests that the mechanism of the food foraging behavior is differentially involved. The study has implications in depression diagnosis and treatment.[Methods]1. Based on the CUMS protocol proposed by Molina, we successfully established a mouse model of depression. The food foraging activity of mice after CUMS was significantly reduced.2. We utilize the Western and RT-PCR technologies to identify the expression of GFAP both at the protein and transcription levels. Detect GFAP expression in the different regions of hippocampus by immunohistochemistry.3. After CUMS, mice were randomly divided into three different groups. CUMS-exposure mice treated with daily intraperitoneal (IP) injections of different drugs for14days. We observe changes in behavior and GFAP expression to further explore the mechanisms of the onset of depression.[Results]1.There are significant difference between controls and CUMS-exposure mice in behavioral tests (P<0.05). The food foraging activity of mice after CUMS was significantly reduced (P<0.05).2.The statistical results demonstrate that CUMS significantly decreased GFAP protein and mRNA levels in the hippocampus but not in the cortex of mice, as compared to the controls (P<0.05)3.The treatment of anti-depressant fluoxetine reversed most symptoms but was less effect on the reduction of foraging activities. However, nonspecific tricyclic antipsychotic, clozapine reversed all symptoms of CUMS-exposure mice including impaired foraging activity (P<0.05). GFAP protein and mRNA levels in the hippocampus are increased (P<0.05).[Conclusion]1.We successfully established a mouse model of depression using the chronic unpredictable mild stress (CUMS) paradigm. After CUMS, almost all C57BL mice developed depression symptoms such as reduced body weight and sucrose consumption, increased immobility by forced swimming test and tail suspension test and decreased activity by open field test. Most interestingly, the food foraging activity of mice after CUMS was significantly reduced.2.CUMS significantly decreased GFAP protein and mRNA levels in the hippocampus.3.In addition, the treatment of anti-depressant fluoxetine reversed most symptoms but was less effect on the reduction of foraging activities. However, nonspecific tricyclic antipsychotic, clozapine reversed all symptoms of CUMS-exposure mice including impaired foraging activity.4.Our findings demonstrated that the reduced food foraging is probably a new behavioural marker of depression.