Project description:sychological stress and affective disorders are clinically associated with hypertension and vascular disease, but the biological links between the conditions have not been fully explored. To examine this relationship, we used chronic social defeat (CSD) stress, which produces anxiety-like and depressive-like behavioral declines in susceptible mice. In such mice, CSD also produces cerebrovascular microbleeds in scattered locations. Here, we showed further evidence of vascular pathology and blood–brain barrier breakdown by visualizing plasma immunoglobulins and erythrocytes within the parenchyma and perivascular spaces of CSD brains. To further characterize the impact of stress on the cerebrovasculature, brain endothelial cells (bECs) were isolated, and global gene expression profiles were generated. Bioinformatic analysis of CSD-induced transcriptional changes in bECs showed enrichment in pathways that delineate the vascular response to injury. These pathways followed a temporal sequence of inflammation, oxidative stress, growth factor signaling, and wound healing (i.e., platelet aggregation, hemostasis, fibrinogen deposition, and angiogenesis). Immunohistochemical staining for markers of fibrinogen deposition and angiogenesis confirmed the existence of the markers at the sites of vascular disruptions. Recovery after CSD cessation was marked by recruitment of leukocytes perhaps participating in vascular repair. The data suggest that co-morbidity of affective disorders and vascular diseases may be attributed in part to a common link in altered endothelial cell function
Project description:Brain vascular integrity is critical for brain health, and its disruption is implicated in many brain pathologies, including psychiatric disorders. Brain-vascular barriers are a complex cellular landscape composed of endothelial, glial, mural, and immune cells. Yet currently, little is known about these brain vascular-associated cells (BVACs) in health and disease. Previously, we have demonstrated that 14 days of chronic social defeat (CSD), a mouse paradigm that produces anxiety and depressive-like behaviors, causes cerebrovascular damage in the form of scattered microbleeds. Here, we developed a technique to isolate barrier-related cells from the mouse brain and subjected the cells to single-cell RNA sequencing. Using this isolation technique, we found an enrichment in BVAC populations, including distinct subsets of endothelial and microglial cells. In CSD compared to home-cage control, differential gene expression patterns disclosed biological pathways involving vascular dysfunction, vascular healing, and immune system activation. Overall, our work demonstrates a unique technique to study rare BVAC populations from fresh brain tissue and suggests that neurovascular dysfunction is a key driver of psychosocial stress-induced brain pathology.
Project description:This study aimed to investigate the effects of depression on transcriptome in ileum using a subchronic and mild social defeat stress (sCSDS) model. In addition to exhibiting social deficit and hyperphagia-like behavior, the sCSDS mice keep much more water in their body than control mice. In order to investigate the effect of social defeat stress on not only central nervous system but also function of gastrointestinal tract, the gene expression in ileum of stressed mice was compared with control mice. We used microarrays to detail the gene expression after 10 days of social defeat stress and identified distinct classes of down-regulated genes during this process. The duration of physical contacts was set at 5 min after the first attack bite at Day 1, and then was reduced 0.5 min per day from Day 2 to Day 10.
Project description:Behavioral analysis confirmed that the 14-day social defeat sessions resulted in induction of depressive-like states measured in social interaction and light/dark tests. The combined data show that stress-induced depressive states are associated with molecular and structural changes that demyelinate the prefrontal cortex.
Project description:We have analysed changes in the hypothalamus using iTRAQ proteomics 4 plex from mice exposed to social defeat protocol using Qexactive and Orbitrap Velos
Project description:This study aimed to investigate the effects of depression on transcriptome in ileum using a subchronic and mild social defeat stress (sCSDS) model. In addition to exhibiting social deficit and hyperphagia-like behavior, the sCSDS mice keep much more water in their body than control mice. In order to investigate the effect of social defeat stress on not only central nervous system but also function of gastrointestinal tract, the gene expression in ileum of stressed mice was compared with control mice. We used microarrays to detail the gene expression after 10 days of social defeat stress and identified distinct classes of down-regulated genes during this process.
Project description:Psychological stress and affective disorders are clinically associated with hypertension and vascular disease, but the biological links between the conditions have not been fully explored. To examine this relationship, we used chronic social defeat (CSD) stress, which produces anxiety-like and depressive-like behavioral declines in susceptible mice. In such mice, CSD also produces cerebrovascular microbleeds in scattered locations. Here, we showed further evidence of vascular pathology and blood-brain barrier breakdown by visualizing plasma immunoglobulins and erythrocytes within the parenchyma and perivascular spaces of CSD brains. To further characterize the impact of stress on the cerebrovasculature, brain endothelial cells (bECs) were isolated, and global gene expression profiles were generated. Bioinformatic analysis of CSD-induced transcriptional changes in bECs showed enrichment in pathways that delineate the vascular response to injury. These pathways followed a temporal sequence of inflammation, oxidative stress, growth factor signaling, and wound healing (i.e., platelet aggregation, hemostasis, fibrinogen deposition, and angiogenesis). Immunohistochemical staining for markers of fibrinogen deposition and angiogenesis confirmed the existence of the markers at the sites of vascular disruptions. Recovery after CSD cessation was marked by recruitment of leukocytes perhaps participating in vascular repair. The data suggest that co-morbidity of affective disorders and vascular diseases may be attributed in part to a common link in altered endothelial cell function.
Project description:This study tested the effects of repeated social defeat (RSD) on gene expression in peripheral blood mononuclear cells (PBMC), and examined the extent to which these effects were abrogated by depletion of CD11b+ cells (monocytes). Study Type: Risk prediction Gene expression profiling was carried out on peripheral blood mononuclear cell (PBMC) mRNA samples collected from 18 mice randomized to either 6 cycles of repeated social defeat (RSD, n=9) or to home cage control (HCC, n=9) conditions. PBMC samples were pooled into 3 groups of n=3 samples in each condition, and Illumina Mouse Ref-8 BeadArray assays were performed on approximately 1 million total PBMC and 1 million PBMC from which CD11b+ cells were immunomagnetically depleted by MACS. The primary research questions are 1) whether expression of pro-inflammatory genes is altered by RSD, and 2) whether depletion of CD11b+ cells (monocytes) abrogates these effects.
Project description:We used microarrays to identify the gene with altered expression in the hippocampus of depression mouse model with repeated social defeat stress campared to control mice.