Fig. 7

Anti-GDF15 monoclonal antibody treatment reduces microglial phagocytosis-mediated synaptic elimination in the hippocampi of septic mice. (A) Representative images of immunofluorescence staining of Iba1 and C1q in the hippocampi of mice after intracerebroventricular injection of the anti-GDF15 monoclonal antibody ponsegromab or IgG control and intraperitoneal injection of LPS (10 mg/kg) for 7 days. Green, Iba1; Red, C1q; blue, DAPI; scale bar, 50 μm and 5 μm. (B) Quantification of the ratio of C1q⁺Iba1⁺/Iba1⁺ cells in (A). (C) Western blots showing PSD95 and Synapsin1 expression levels in primary microglia sorted from the hippocampi of mice after intracerebroventricular injection of the anti-GDF15 monoclonal antibody ponsegromab or IgG control and intraperitoneal injection of LPS (10 mg/kg) for 7 days. (D) Representative images of Golgi-Cox staining of hippocampi in mice after intracerebroventricular injection of the anti-GDF15 monoclonal antibody ponsegromab or IgG control and intraperitoneal injection of LPS (10 mg/kg) for 7 days. (E) Representative images of hippocampal pyramidal neuronal dendritic spines in mice after intracerebroventricular injection of ponsegromab or IgG control and intraperitoneal injection of LPS (10 mg/kg) for 7 days. Scale bar, 10 μm. (F) Quantification of dendritic spine densities in the CA1 region of mice after intracerebroventricular injection of ponsegromab or IgG control and intraperitoneal injection of LPS (10 mg/kg) for 7 days. n = 3 mice per group, and in each mouse, 3 fields from the hippocampal CA1 region were analyzed. **P < 0.01. ***P < 0.001