Rattus norvegicus
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ABSTRACT:
PROVIDER: PRJNA189231 | ENA |
REPOSITORIES: ENA
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Project description:Intestinal paracellular permeability (IPP) is high at birth and is involved in gut barrier maturation and liver development. Chronic maternal separation (MS) in early life alters intestinal barrier function in adulthood. However, only transient MS commonly occurs in human newborns, but whether a single episode of MS in early postnatal days (PND) affects the maturation of the gut-liver axis has not been explored. The aim of the current study was to evaluate the effect of a single MS of short duration in neonate rats on epithelial barrier integrity in the gut and on gene expression in the liver. Male and female pups were separated from their dams for 4h or not (controls) at PND10 or PND20. Total intestinal paracellular permeability (IPP) was measured through mucosal-to-plasma passage of oral FITC-Dextran 4 KD with or without ML7, a blocker of myosin light chain kinase (MLCK), or Mifepristone (RU486), an antagonist of the glucocorticoid receptor. Dose response to dexamethasone (DEX) on IPP was studied at PND10 and PND20. Bacterial translocation (BT) was assessed in mesenteric lymph nodes (MLN), liver and spleen in the presence or absence of ML7. The hepatic transcriptome was studied using Agilent microarrays and qPCR on PND10 rats pretreated or not with ML7. At PND10, control pups showed basal BT to MLN while liver and spleen were sterile. A short-term MS procedure increased IPP and plasma corticosterone levels, resulted in BT to the liver and spleen and had a clear impact on the hepatic transcriptome. Most notably, several genes involved in cell division were downregulated by MS. In PND10 rats, MS-induced increase of IPP and BT were blocked by ML7 or RU486, thus demonstrating a role of the MLCK pathway and of increased plasma levels of corticosterone in these effects of MS. All these effects of MS were absent in PND20 rats. Consistently, PND20 rats were found less sensitive to DEX exposure than PND10 rats. These results show that the early life period is a critical window for a short-term mother-infant separation, which can alter the development of the gut-liver axis and facilitate bacterial passage to systemic organs.
2016-02-01 | GSE44241 | GEO
Project description:Inflammatory bowel disease induced by treatment with DSS induce destruction of gut barrier inducing massive bacterial translocation to distal tissue. Our findings suggest that gut microbiota translocation induces trained immunity in Granulocyte-monocyte progenitors that can underlie pathologies related to low-grade systemic inflammation. The identification of E.faecalis translocation to the bone marrow as a main driver of this effect and its sensing by Mincle receptor in bone marrow progenitors offers potential targets for intervention in pathophysiological settings where gut permeability is altered. Moreover, intravenously and intranasal administration of HK-EF provided protection against systemic candidiasis in wild-type and Rag1-deficient mice lacking functional lymphocytes, indicative of innate immune-mediated protection.
2025-01-22 | GSE281376 | GEO
Project description:Inflammatory bowel disease induced by treatment with DSS induce destruction of gut barrier inducing massive bacterial translocation to distal tissue. Our findings suggest that gut microbiota translocation induces trained immunity in Granulocyte-monocyte progenitors that can underlie pathologies related to low-grade systemic inflammation. The identification of E.faecalis translocation to the bone marrow as a main driver of this effect and its sensing by Mincle receptor in bone marrow progenitors offers potential targets for intervention in pathophysiological settings where gut permeability is altered. Moreover, intravenously and intranasal administration of HK-EF provided protection against systemic candidiasis in wild-type and Rag1-deficient mice lacking functional lymphocytes, indicative of innate immune-mediated protection.
2025-01-22 | GSE281375 | GEO
Project description:Inflammatory bowel disease induced by treatment with DSS induce destruction of gut barrier inducing massive bacterial translocation to distal tissue. Our findings suggest that gut microbiota translocation induces trained immunity in Granulocyte-monocyte progenitors that can underlie pathologies related to low-grade systemic inflammation. The identification of E.faecalis translocation to the bone marrow as a main driver of this effect and its sensing by Mincle receptor in bone marrow progenitors offers potential targets for intervention in pathophysiological settings where gut permeability is altered. Moreover, intravenously and intranasal administration of HK-EF provided protection against systemic candidiasis in wild-type and Rag1-deficient mice lacking functional lymphocytes, indicative of innate immune-mediated protection.
2025-01-22 | GSE230337 | GEO
Project description:Ten-Eleven-translocation (Tet2) encodes an epigenetic modifier enzyme and is mutated somatically during age-associated clonal hematopoiesis of indeterminate potential (CHIP) as well as in myeloid malignancies 1-7. Tet2 deficiency leads to increased hematopoietic stem cell (HSC) renewal in human 7 and mouse 8. However, the development of myeloproliferation and myeloid malignancies occurs at late age, and only occasionally in humans 2,6,7,9 and in 50-75% of Tet2 deficient animals 8,10,11, suggesting that undefined triggers are required for pre-leukemic myeloid expansion. Our studies reveal that Tet2 deficient mice can exhibit high levels of plasma IL-6, systemic dissemination of indigenous gut bacteria and increased intestinal permeability that correlate with the development of a pre-leukemic myeloproliferative phenotype. Increased intestinal permeability was linked to a large number of transcriptional changes in the jejunum, especially among genes involved in defense response to bacterium and intestinal barrier function. Strikingly, antibiotic treatment reduced plasma IL-6 levels and both, prevented early myeloid expansion and reversed the pre-leukemic myeloproliferative phenotype in Tet2-/- mice. In summary, we show that Tet2 deficiency promotes intestinal bacterial translocation and subsequent systemic inflammation, and that gut-derived microbial signals are required for the development of pre-leukemic myeloproliferation in a Tet2-deficient host. Our studies suggest that controlling bacterial translocation and bacteria-associated systemic inflammation could decrease the risk of myeloid malignancies significantly in individuals with somatic Tet2 mutations.
2018-03-15 | GSE99333 | GEO
Project description:The postnatal development of the mouse is characterized by a stress hyporesponsive period (SHRP), where basal corticosterone levels are low and responsiveness to mild stressors is reduced. Maternal separation is able to disrupt the SHRP and is widely used to model early trauma. In this study we aimed at identifying of brain systems involved in acute and possible long-term effects of maternal separation. We conducted a microarray-based gene expression analysis in the hypothalamic paraventricular nucleus after maternal separation, which revealed 52 differently regulated genes compared to undisturbed controls, among them are 37 up-regulated and 15 down-regulated genes. One of the prominently unregulated genes, angiotensinogen, was validated using a in-situ hybridization. Angiotensinogen is the precursor of angiotensin II the main effector of the brain renin-angiotensin system (RAS), which is known to be involved in stress system modulation in adult animals. Using the selective angiotensin type I receptor (AT(1)) antagonist candesartan we found strong effects on CRH and GR mRNA expression in the brain and ACTH release following maternal separation. AT(1) receptor blockade appears to enhance central effects of maternal separation in the neonate, suggesting a suppressing function of brain RAS during the SHRP. Taken together, our results illustrate the molecular adaptations that occur in the paraventricular nucleus following maternal separation and identify signaling cascades, that control stress system activity in the neonate. Keywords: phenotype Litters were randomly assigned to either a maternally non-separated or 24 hour maternally separated condition. At the time of testing, all pups from a litter were sacrificed immediately by decapitation.
2010-05-16 | E-GEOD-14687 | biostudies-arrayexpress
Project description:The postnatal development of the mouse is characterized by a stress hyporesponsive period (SHRP), where basal corticosterone levels are low and responsiveness to mild stressors is reduced. Maternal separation is able to disrupt the SHRP and is widely used to model early trauma. In this study we aimed at identifying of brain systems involved in acute and possible long-term effects of maternal separation. We conducted a microarray-based gene expression analysis in the hypothalamic paraventricular nucleus after maternal separation, which revealed 52 differently regulated genes compared to undisturbed controls, among them are 37 up-regulated and 15 down-regulated genes. One of the prominently unregulated genes, angiotensinogen, was validated using a in-situ hybridization. Angiotensinogen is the precursor of angiotensin II the main effector of the brain renin-angiotensin system (RAS), which is known to be involved in stress system modulation in adult animals. Using the selective angiotensin type I receptor (AT(1)) antagonist candesartan we found strong effects on CRH and GR mRNA expression in the brain and ACTH release following maternal separation. AT(1) receptor blockade appears to enhance central effects of maternal separation in the neonate, suggesting a suppressing function of brain RAS during the SHRP. Taken together, our results illustrate the molecular adaptations that occur in the paraventricular nucleus following maternal separation and identify signaling cascades, that control stress system activity in the neonate. Keywords: phenotype
2009-07-22 | GSE14687 | GEO
Project description:Short term transition to high-fat diet (HFD) feeding causes rapid changes in the molecular architecture of the blood-brain-barrier (BBB), BBB permeability and brain glucose uptake. However, the precise mechanisms responsible for these changes remain elusive. Here we detected a rapid downregulation of Notch signaling after short-term HFD feeding. Conversely, Notch activation restores HFD-fed mouse serum induced reduction of Glut1 expression and glycolysis in cultured brain microvascular endothelial cells (BMECs). Selective, inducible expression of Notch-intracellular domain (IC) in BMECs prevents HFD-induced reduction of Glut1 expression and hypothalamic glucose uptake. Caveolin (Cav)-1 expression in BMECs is increased upon short term HFD feeding. However, NotchICBMECs mice display reduced caveola formation and BBB permeability. This ultimately translates into reduced hypothalamic insulin transport, action and systemic insulin sensitivity. Collectively, we highlight a critical role of Notch-signaling in the pleiotropic effects of short-term dietary transitions on BBB functionality.
2025-04-01 | GSE210620 | GEO
Project description:Impairment of the intestinal barrier allows the systemic translocation of commensal bacteria, inducing a pro-inflammatory state in the host. To explore this link, we investigated innate immune responses following increased gut permeability upon administration of dextran sulfate sodium (DSS) in mice. We found that microbiota translocation induced trained immunity (TI) in mouse myeloid bone marrow progenitors (BMPs). Enterococcus faecalis was isolated from bone marrow following DSS treatment and induced trained immunity hallmarks in bone marrow-derived mouse macrophages and human monocytes. Notably, DSS treatment or heat-killed E. faecalis reprogrammed BMPs, resulting in enhanced inflammatory responses in vitro and in vivo, and protection against pathogen infections. The C-type lectin receptor Mincle (Clec4e) was essential for E. faecalis-induced TI in BMPs. Clec4e-/- mice showed impaired TI upon E. faecalis and reduced pathology following DSS treatment. Thus, Mincle sensing of E. faecalis induces TI that may contribute to pathologies associated with increased gut permeability. This SuperSeries is composed of the SubSeries listed below.
2025-01-22 | GSE281377 | GEO
Project description:The aim of this study is to test the hypothesis that adjuvant administration of probiotics in cancer patients undergoing chemotherapy can reduce a chemo-induced increased intestinal permeability. Furthermore, we hypothesize that the use of probiotics may reduce the occurrence of gastrointestinal side effects such as diarrhea, abdominal pains, bacterial translocation and infections following chemotherapy.
| 2286720 | ecrin-mdr-crc