Introduction: To explore the changes in C‐reactive protein (CRP) level in different regions of one old offspring rats exposed to prenatal stress (PS).Methods: The rat model was constructed with prenatal restraint stress on pregnant dams on days 14–20 of gestation. Offspring rats were randomly divided into PS susceptibility (PS‐S) group and control (CON) group. Behavioral experiments including sucrose preference test (SPT), open‐field test (OFT), and forced swimming test (FST) were used to measure depressive‐like behaviors. Immunohistochemistry, qRT‐PCR, and Western blotting were applied to detect the changes in CRP level.Results: The results showed that PS could cause depressive‐like behaviors in all SPT, OFT, and FST. Concomitantly, CRP mRNA and protein expression significantly increased in hippocampus, prefrontal cortex, and hypothalamus in the PS‐S group when compared that in the CON group, while no significantly changes in liver, heart, olfactory bulb, striatum, and cerebellum in the PS‐S group when compared that in the CON group.Conclusion: Increasing of CRP expression in hippocampus, prefrontal cortex, and hypothalamus may play a critical role in the mechanism under depressive‐like behavior in offspring rats exposed to PS.

Introduction: Prenatal stress (PS) can cause depression in offspring. However, the underlying biological mechanism of these influences is still unclear. This work was implemented to investigate the molecular mechanisms of depressive‐like behavior of offspring rats insulted with PS.Methods: Relative quantitative phosphoproteomics of the hippocampus of PS susceptibility (PS‐S) and control (CON) rat offspring was performed using liquid chromatography‐tandem mass spectrometry to confirm known pathways and to identify new mechanisms involved in depression.Results: A total of 6790 phosphopeptides, 9817 phosphorylation sites, and 2978 phosphoproteins were detected. Among the 2978 phosphoproteins, 1760 (59.09%) had more than two phosphorylated sites, the ENSRNOP00000023460 protein had more than 117 phosphorylated sites, and the average distribution of modification sites per 100 amino acids was 2.97. There were 197 different phosphopeptides, including 140 increased phosphopeptides and 57 decreased phosphopeptides in the PS‐S offspring rats, compared to the CON offspring rats. These differential phosphopeptides corresponded to 100 upregulated and 44 downregulated phosphoproteins, respectively. Gene ontology enrichment analysis revealed that these different phosphoproteins in the top five enriched terms in the cellular component, molecular function, and biological proces categories were involved in a total of 35 different phosphoproteins, and these phosphoproteins were mainly related to myelin‐, microtubule‐ and synapse‐associated proteins. The enrichment of Kyoto Encyclopedia of Genes and Genome pathways was found to be involved in many essential biological pathways, and the top five pathways included amphetamine addiction, insulin secretion, Cushing syndrome, and the circadian entrainment signaling pathway. These first five pathways were related to nine phosphoproteins, including Adcy9, Apc, Cacna1c, Camk2a, Camk2b, Camk2g, Ctnnd2, Grin2a, and Stx1a. The full data are available via ProteomeXchange with identifier PXD019117.Conclusion: We preliminarily identified 144 different phosphoproteins involved in myelin, microtubule, and synapse formation and plasticity in the hippocampus of susceptible offspring rats exposed to PS.

Background: Prenatal stress (PS) can induce depression in offspring, but the underlying mechanisms are still unknown. Objective: The aim of this work was to investigate the mechanism that underlies PS-induced depressive-like behavior in offspring. Methods: A prenatal restraint stress procedure was developed in which pregnant rats at GD14 to GD20 were placed head-first into a well-ventilated bottle three times each day and for 45 min each time. Depressive-like behavior in the male offspring was examined using the sucrose preference test (SPT) and the forced swim test (FST). The level of glutamate and the expression levels of GluN2A, p-CaMKII and myelin basic protein (MBP) in the hippocampus of PS-susceptible (PS-S) offspring were also evaluated. To clarify the mechanism by which PS leads to depression in offspring, the effects of excessive corticosterone were also investigated using an in vitro “injured neuronal” model. Results: The glutamate level in the hippocampus of PS-S male offspring was significantly elevated compared to controls. The expression levels of GluN2A and p-CaMKII were also altered. In addition, the optical density of MBP staining and the expression levels of MBP mRNA and MBP protein were decreased, demonstrating impaired myelinization in the hippocampus. Treatment of PS-S offspring with the GluN2A receptor antagonist NVP-AAM077 resulted in antidepressant-like effects in the FST, as well as rescue of the MBP and p-CaMKII abnormalities. Conclusions: These findings indicate that GluN2A is a promising target in the development of pharmacotherapies for PS-induced depression.