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The excitatory‐inhibitory imbalance has been considered an important mechanism underlying stress‐related psychiatric disorders. In the present study, rats were exposed to 6 days of inescapable foot shock (IFS) to induce stress. The open field test and elevated plus maze test showed that IFS‐exposed rats exhibited increased anxiety‐like behavior. Immunofluorescence showed that IFS rats had a decreased density of GAD67‐immunoreactive interneurons in the dorsal hippocampal CA1 region, while no significant change in the density of CaMKIIα‐immunoreactive glutamatergic neurons was seen. We investigated the expression of different interneuron subtype markers, including parvalbumin (PV), somatostatin (SST), and calretinin (CR), and noted a marked decline in the density of PV‐immunoreactive interneurons in the dorsal CA1 region of IFS rats. The perineuronal net (PNN) is a specialized extracellular matrix structure primarily around PV interneurons. We used Wisteria floribunda agglutinin lectin to label the PNNs and observed that IFS rats had an increased proportion of PNN‐coated PV‐positive interneurons in CA1. The number of PSD95‐positive excitatory synaptic puncta on the soma of PNN‐free PV‐positive interneurons was significantly higher than that of PNN‐coated PV‐positive interneurons. Our findings suggest that the effect of IFS on the hippocampal GABAergic interneurons could be cell‐type‐specific. Loss of PV phenotype in the dorsal hippocampal CA1 region may contribute to anxiety in rats. The dysregulated PV‐PNN relationship in CA1 after traumatic stress exposure might represent one of the neurobiological correlates of the observed anxiety‐like behavior. [ABSTRACT FROM AUTHOR]

This study was designed to examine the mechanisms underlying decline of stress resilience in aged rats from the perspective of CP-CSF-hippocampus. Male Wistar rats (7–8 weeks old or 20 months old) were subjected to chronic unpredictable mild stress (CUMS) for 6 weeks. The behavioral tests were conducted to assess anxiety, depression and cognitive function. Hippocampal neurogenesis, apoptosis and synaptic plasticity were detected by western blot (WB) and/or immunofluorescence (IF) assay. Differential expression of growth factors (GFs) and axon guidance proteins (AGPs) in CSF was analyzed using the quantitative proteomics approach. IF and WB were performed to detect expression of occludin-1, Ki-67/Transthyretin, and folate transporters in choroid plexus (CP). Decreased proliferation, impaired structure and transport function of CP were correlated with CSF composition alterations in stressed aging rats, including reduced 5-Methyltetrahydrofolate, growth factors and axon growth factors. Nutritional support of CSF upon hippocampus was attenuated, therefore affecting hippocampal plasticity. It has led to depression-like behaviors and cognitive deficits in stressful aged rats. Keeping normal structure and function of CP-CSF system may be a practical strategy for neuropsychological disorders in the elderly. This work provides evidential basis for CP transplant and CSF replacement therapy in future studies. [ABSTRACT FROM AUTHOR]

Early life stress (ELS) can cause long-term changes by epigenetic factors, especially histone acetylation modification, playing a crucial role, affect normal cognition, mood, and behavior, and increase susceptibility to post-traumatic stress disorder (PTSD) in adulthood. It has been found that paeoniflorin (PF) can cross the blood-brain barrier to exert anti -PTSD effects on adult PTSD rats. However, whether PF can alleviate the harmful effects caused by ELS in adulthood has not yet been reported. Therefore, to explore the relationship between ELS and PTSD susceptibility in adulthood and its mechanism, in this study, SPS was used as a stressor of ELS, and the mathematical tool Z-normalization was employed as an evaluation criterion of behavioral resilience susceptibility. To investigate the regulatory mechanism of PF on histone acetylation in the hippocampus and amygdala of ELS rats in adulthood, using changes in HATs/HDACs as the entry point, meanwhile, the epigenetic marks (H3K9 and H4K12) in the key brain regions of ELS (hippocampus and amygdala) were evaluated, and the effects of PF on behavioral representation and PTSD susceptibility were observed. This study found that ELS lead to a series of PTSD-like behaviors in adulthood and caused imbalance of HATs/HDACs ratio in the hippocampus and amygdala, which confirms that ELS is an important risk factor for the development of PTSD in adulthood. In addition, paeoniflorin may improve ELS-induced PTSD-like behaviors and reduce the susceptibility of ELS rats to develop PTSD in adulthood by modulating the HATs/HDACs ratio in the hippocampus and amygdala. • Adolescent exposure to SPS leads to a series of PTSD-like behaviors in adulthood. • ELS is a significant risk factor for the development of PTSD in adulthood. • PF exhibits strong binding activity with HATs and HDACs. • PF regulate HATs/HDACs ratios and histone acetylation modification levels. • PF has the potential to reduce the risk of developing PTSD in adulthood. [ABSTRACT FROM AUTHOR]

• Adolescent stress induced PTSD-like behaviors in adulthood. • Adolescent stress enhanced HPA negative feedback inhibition in adulthood. • Adolescent stress increased GR expression in the hypothalamus and hippocampus. • Environmental enrichment ameliorated behavioral abnormalities and HPA dysregulation. Exposure to early stressful events increases susceptibility to post-traumatic stress disorder (PTSD) in adulthood, in which the hypothalamic-pituitary-adrenal (HPA) axis plays a crucial role. Studies have found that environmental enrichment (EE) mitigates the detrimental outcomes of early adversity. However, the HPA-related mechanism remains unclear. In this study, we used the single prolonged stress (SPS) paradigm to explore the long-term effects of early adolescent stress on behavior, HPA axis activity, as well as expression levels of the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), corticotropin-releasing hormone receptor 1 (CRF1R) and CRF2R in the hypothalamus and hippocampus. Meanwhile, the protective effects of EE intervention were examined. We found that adult male rats exposed to adolescent stress showed reduced locomotor activity, increased anxiety-like behaviors, enhanced contextual fear memory, elevated basal plasma ACTH levels, and enhanced HPA negative feedback inhibition, as indicated by decreased plasma ACTH levels in the dexamethasone suppression test (DST). Furthermore, EE normalized the behavioral abnormalities and enhanced HPA negative feedback in stressed rats, possibly through down-regulating GR expression in the hippocampus and hypothalamus. These findings suggested that EE could ameliorate adolescent stress-induced PTSD-like behaviors and aberrant reprogramming of the HPA axis, reducing the risk of developing PTSD in adulthood. [ABSTRACT FROM AUTHOR]