The Role of Glial Cell Activation Mediated by Complement System C1q/C3 in Depression-like Behavior in Mice
10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2021.0102
- VernacularTitle:补体系统C1q/C3介导的胶质细胞激活在小鼠抑郁样行为中的作用
- Author:
Rui WANG
1
;
Qing-bo WANG
1
;
Ting XIE
1
;
Kai-hua GUO
1
Author Information
1. Department of Anatomy and Neurobiology， Zhongshan School of Medicine， Sun Yat-Sen University， Guangzhou 510080，China
- Publication Type:Journal Article
- Keywords:
chronic restraint stress;
amygdala;
complement
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2021;42(3):328-337
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the pathway of C1q/C3 complement system in the amygdala of mice in the induction of depressive-like behavior. MethodsThree parts were included. Firstly， the depression model of mice was established by chronic restraint stress. Twelve 8-week-old male C57BL/6 mice were randomly divided into control （WT） group （n = 6） and depression model （CRS） group （n = 6）. The depression model group was established for 2 weeks. The depressive state of mice was tested by tail suspension test （the tail suspension test， TST） and forced swimming test （the forced swimming test， FST）. The fluorescence intensity of the changes of synaptic Synaptophysin （Syn） and post synaptic density protein 95 （PSD95）， microglia （Iba-1） and astrocytes （GFAP） and the contents of complement component （C1q） and C3 in amygdala were detected by immunofluorescence staining. Secondly， six 8-week-old CX3CR1-GFP male mice were randomly divided into GFP group （n = 3） and GFP model group （GFP+CRS） with 3 mice in each group. The interaction between microglia and astrocytes was observed by immunofluorescence staining. Thirdly， twelve 8-week-old male C57BL/6 and C1q-/- mice were randomly divided into control （WT） group， depression model （CRS） group， C1q knockout （C1q-/-） group and C1q knockout model （C1q-/-+CRS） group， with 6 mice in each group. depression model was established for 2 weeks. Behavioral test TST and FST were used to detect the state of depression in four groups. Immunofluorescence staining was used to detect the changes of synaptic Syn and PSD95 in the amygdala of the four groups. ResultThe results of behavioral measurement showed that the immobility time in TST and FST in CRS group was significantly higher than that in WT group （P < 0.000 1）；the result immunofluorescence assay shows that the content of Syn and PSD95 in amygdala in CRS group was significantly lower than that in WT group （P < 0.000 1； P=0.003 8）；the activation of Iba-1 and GFAP in amygdala in CRS group was significantly higher than that in WT group（P=0.000 4， P=0.003）； and the interaction between microglia and astrocytes in amygdala in CRS group was more obvious than that in WT group； compared with WT group， the production of C1q and C3 in amygdala was significantly increased in CRS group （P=0.000 2， P=0.011 9）； Comprehensive comparison of WT， CRS， C1q-/-， C1q-/-+CRS，the immobility time in TST in WT group was significantly lower than that in CRS group and in C1q-/-+CRS group was also significantly lower than that in CRS group （both P <0.001）， the immobility time in FST in WT group was significantly lower than that in CRS group and in C1q-/-+CRS group was significantly lower than that in CRS group （both P<0.001） . The Syn in amygdala in WT group and C1q-/-+CRS group were significantly higher than those in CRS group （P<0.001）.The PSD95 in amygdala in WT group and C1q-/-+CRS group were significantly higher than those in CRS group （P<0.05）. ConclusionIn the depressive model mice， neuroinflammation occurred in the amygdala， where glial cells were activated to express C1q and C3， which further activated microglia and astrocytes to prune synapses， resulting in the decrease of synaptic content and the depression-like behavior in mice. C1q-/- deficiency prevented CRS-induced synaptic loss and depressive-like behavior.
