Abstract
Background: Many investigations indicate that prenatal stress caused depressive-like disturbances in offspring rats. The underlying pathogenic mechanisms have not yet been fully unravelled. The PFC has been shown to play a role in susceptibility to stress during fetal, thus we focus our attention on differential protein phosphorylation in this region of PS-S(Susceptibility to PS) offspring rats.Method: SPT was used to screen for susceptibility to PS. The validity of prenatally stressed model was verified by other common depression-like behaviors. We used MS-based TMT quantitative proteomics in combination with phosphopeptide enrichment method to compare phosphoproteomic profiling in prefrontal cortex of of PS-S and CON offspring rats. Results: Totally, 3418 phosphoproteins, 8404 phosphopeptides and 12175 phosphosites were identified in this analysis. According to the screening criteria, 902 phosphopeptides increased and 609 decreased in the PFC of PS-S group compared to the control rats. GO enrichment analysis indicated that the main enriched terms in CC category were ‘synapse part’, ‘myelin sheath’, ‘synapse’, ‘neuron part’ and ‘axon’. The phosphorproteins enriched in MF and BP category were mainly related to cytoskeleton and projection morphogenesis associated proteins. KEGG pathway enrichment analyses identified 30 significant KEGG pathways, the top five pathways included salivary secretion, Endocrine and other factor-regulated calcium reabsorption, Pancreatic secretion and Insulin secretion. Motifs such as......_S_P...RR, ......_S_PE...., ......_S_PV...., ......_S_P.H...and ..S..._S_PT....were the top five motifs enriched in phosphorylated sites.Conclusion: PS may induce depressive-like behaviors in offspring rats through regulating the phosphorylation of protein mainly related to synapse, myelin sheath, neuron and cytoskeleton. And the phosphorylation of related proteins may act as key pathogenic hits. Data are available via ProteomeXchange with identifier PXD026563.