Related Experiment Video
Updated: Sep 4, 2025
Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD
Published on: October 10, 2012
Comparative Phosphoproteomic Profiling in the Prefrontal Cortex of Prenatally Stressed Male Offspring Rats
Wei He1, Huimei Huang2, Huiping Zhang1
1Shaanxi Institute for Pediatric Diseases, Xi'an Key Laboratory of Children's Health and Diseases, Xi'an Children's Hospital (The Affiliated Children's Hospital of Xi'an Jiaotong University), Xi'an, China.
Insights
Prenatal stress in rats leads to depression-like behaviors by altering protein phosphorylation in the prefrontal cortex, particularly affecting synapses and neuronal structures. These changes in protein phosphorylation are key to understanding the development of these stress-induced behaviors.
Area of Science:
- Neuroscience
- Molecular Biology
- Proteomics
Background:
- Prenatal stress (PS) is linked to depressive-like disturbances in offspring.
- The prefrontal cortex (PFC) is implicated in stress susceptibility during development.
- Mechanisms underlying PS-induced depressive-like behaviors remain unclear.
Purpose of the Study:
- To investigate differential protein phosphorylation in the PFC of rats exposed to prenatal stress.
- To elucidate the pathogenic mechanisms of prenatal stress-induced depressive-like behaviors.
Main Methods:
- Screening for susceptibility to prenatal stress using the sucrose preference test.
- Utilizing MS-based TMT quantitative proteomics and phosphopeptide enrichment.
- Comparing phosphoproteomic profiles in the PFC of PS-susceptible and control rats.
Main Results:
- Identified 3,418 phosphoproteins, 8,404 phosphopeptides, and 12,175 phosphosites.
- Observed significant changes in 902 increased and 609 decreased phosphopeptides in PS-susceptible rats.
- Enrichment analysis highlighted proteins related to synapses, myelin sheath, neurons, cytoskeleton, and morphogenesis.
Conclusions:
- Prenatal stress induces depressive-like behaviors in male offspring by altering protein phosphorylation in the PFC.
- Key affected areas include proteins regulating synapses, myelin sheaths, neurons, and the cytoskeleton.
- Altered protein phosphorylation is proposed as a critical pathogenic mechanism.
Abstract:
Many investigations have indicated that prenatal stress (PS) causes depressive-like disturbances in offspring rats. However, the underlying pathogenic mechanisms have not yet been fully elucidated. The prefrontal cortex (PFC) has been shown to play a role in susceptibility to stress during fetal development; thus, we focused our attention on differential protein phosphorylation in this region of PS-S (susceptibility to PS) offspring rats. The sucrose preference test was used to screen for susceptibility to PS. The validity of the prenatally stressed model was verified by other common depression-like behaviors. We used MS-based TMT quantitative proteomics in combination with the phosphopeptide enrichment method to compare phosphoproteomic profiling in the PFC of PS-S and control male offspring rats. In total, 3,418 phosphoproteins, 8,404 phosphopeptides, and 12,175 phosphosites were identified in this analysis. According to the screening criteria, 902 phosphopeptides increased and 609 decreased in the PFC of the PS-S group compared to the control rats. Gene ontology enrichment analysis indicated that the main enriched terms in the cellular component category were "synapse part," "myelin sheath," "synapse," "neuron part," and "axon." The phosphoproteins enriched in the molecular function and biological process categories 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. PS may induce depressive-like behaviors in male offspring rats by regulating the phosphorylation of proteins mainly related to synapses, myelin sheaths, neurons, and the cytoskeleton. The phosphorylation of related proteins may act as key pathogenic hits. Data are available via ProteomeXchange with identifier PXD026563.
More Related Videos
09:06A Rat Methyl-Seq Platform to Identify Epigenetic Changes Associated with Stress Exposure
Published on: October 24, 2018
09:12Assessing Cellular Stress and Inflammation in Discrete Oxytocin-secreting Brain Nuclei in the Neonatal Rat Before and After First Colostrum Feeding
Published on: November 14, 2018