Monomeric pilose antler peptide improves depression-like behavior in mice by inhibiting FGFR3 protein expression

It has been found that pilose antler peptide has an antidepressant effect on depression. However, the exact molecular mechanism of its antidepressant effect is still unclear. The study sought to determine the impact of monomeric pilose antler peptide (PAP; sequence LVLVEAELRE) on depression as well as investigate potential molecular mechanisms. Chronic unexpected mild stress (CUMS) was used to establish the model, and the effect of PAP on CUMS mice was detected by the behavioral test. The influence of PAP on neuronal cells and dendritic spine density was observed by immunofluorescence and Golgi staining. FGFR3 and the CaMKII-associated pathway were identified using quantitative real-time polymerase chain reaction, and Western blot analysis was utilized to measure their proteins and gene expression levels. Molecular docking and microscale thermophoresis were applied to detect the binding of PAP and FGFR3. Finally, the effect of FGFR3's overexpression on PAP treatment of depression was detected. PAP alleviated the changes in depressive behavior induced by CUMS, promoted the growth of nerve cells, and the density of dendritic spines was increased to its original state. PAP therapy successfully downregulated the expression of FGFR3 and ERK1/2 while upregulating the expression of CREB, BDNF, and CaMKII. Based on the current research, PAP has a therapeutic effect on depression brought on by CUMS by inhibiting FGFR3 expression and enhancing synaptic plasticity.