C1q-neutralizing antibodies improves postpartum depressive-like behaviors in mice by regulating the C1q/C3 pathway

doi:10.12122/j.issn.1673-4254.2025.10.07

Abstract

Abstract:

Objective To explore the role of C1q, the promoter of the classical pathway of the complement system, in regulating postpartum depressive-like behaviors in mice and the therapeutic mechanism of C1q-neutralizing antibodies. Methods Female C57BL/6 mouse models of postpartum depression established by hormone-simulated pregnancy (HSP) were evaluated for depression-like behaviors, and peripheral blood levels and hippocampal expressions of C1q were detected using ELISA and Western blotting. Immunofluorescence staining was used for detecting co-labeling of C1q and microglia, and the differentially expressed mRNAs in the hippocampus of HSP mice were analyzed using RNA sequencing. The Edinburgh Postnatal Depression Scale was used to screen patients with postpartum depression, from whom peripheral blood mononuclear cells were extracted for detecting C1q expression levels with Western blotting. The HSP mice were subjected to stereotactic injection of C1q-neutralizing antibody or a control IgG in the hippocampus, and the changes in depressive-like behaviors and hippocampal expression of C3 were examined. Results The HSP mice exhibited obvious depressive behaviors, demonstrated by significantly decreased preference for sugar water and increased forced swimming and tail suspension time. The mouse models showed significantly increased peripheral blood C1q level and hippocampal expression level of C1q, accompanied by an increase in Iba1 and C1q co-labeling in the hippocampus. The expression level of C1q in peripheral monocytes was also significantly increased in patients with postpartum depression. In HSP mice, stereotactic injection of C1q-neutralizing antibody, but not the control IgG, obviously alleviated depressive-like behaviors, shown by significantly increased preference for sugar water and decreased forced swimming and tail suspension time, resulting also in decreased expression of C3 in the hippocampus and lowered serum levels of IL-6 and TNF-α. Conclusion C1q-neutralizing antibodies improve postpartum depressive-like behaviors in mice possibly by regulating the C1q/C3 signaling pathway.

Key words: complement C1q, complement C3, neutralizing antibody, microglia, postpartum depression

Yiming SUN, Xinran XU, Xuerui ZHUO, Hui CAI, Yan WANG. C1q-neutralizing antibodies improves postpartum depressive-like behaviors in mice by regulating the C1q/C3 pathway[J]. Journal of Southern Medical University, 2025, 45(10): 2111-2117.

Figures/Tables 7

Fig.1 Preparation of the post pattern depression mouse model. A: The preparation process of the postpartum depression model. B: The preparation process of the postpartum depression model and stereotactic injection of C1q neutralizing antibody in the hippocampal brain region.

Fig.2 Evaluation of postpartum depression model in mice with hormone-simulated pregnancy (HSP). A-C: Sucrose preference test, tail suspension test and forced swimming test for evaluation of depressive-like behaviors of the mice. *P<0.05, **P<0.01 vs CON.

Fig.3 Expression of C1q in the hippocampus of HSP mice. A: RNA sequencing for analyzing differentially expressed mRNAs. B: Serum C1q level of the mice. C, D: Expression of C1q in different brain regions. *P<0.05, **P<0.01 vs CON.

Fig.4 Co-labeling of C1q and Iba1 in the hippocampus of HSP mice. A: Immunofluorescence staining for detecting co-labeling of C1q and Iba1 in the hippocampus (Scale bar=100 μm). B: Quantitative analysis of C1q and Iba1 co-labeling in control and HSP mice. *P<0.05 vs CON.

Fig.5 Peripheral blood C1q level (A) and expression of C1q in peripheral blood mononuclear cells (B, C) in patients with postpartum depression. *P<0.05 vs CON.

Fig.6 Effect of stereotactic injection of C1q-neutralizing antibody in the hippocampus on depressive-like behaviors of HSP mice. A-C: Sucrose preference test, tail suspension test and forced swimming test for evaluation of depressive-like behaviors of the mice. *P<0.05 vs CON+IgG, **P<0.01 vs CON+IgG, #P<0.05 vs CON+C1q Ab.

Fig.7 Hippocampal expression level of C3 and serum levels of pro-inflammatory factors in HSP mice following stereotactic injection of C1q-neutralizing antibody in the hippocampus. A, B: Expression of C3 in different brain regions of the mice detected by Western blotting. C: Serum IL-6 level. D: Serum TNF-α level. **P<0.01 vs CON+IgG, #P<0.05 vs CON+C1q Ab, ##P<0.01 vs CON+C1q Ab.

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