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.
Chronic social defeat reduces myelination in the mouse medial prefrontal cortex.
Specimen part
View SamplesMaternal immune activation is a risk factor for the development of schizophrenia and autism. Infections during pregnancy activate the mother's immune system and alter the fetal environment with sub-sequence effects of CNS function and behavior in the offspring, but the cellular and molecular links between infection-induced altered fetal development and risk for neuropsychiatric disorders are unknown. We investigated the immunological, molecular, and behavioral effects of MIA in the offspring of pregnant Sprague-Dawley rats given an intraperitoneal (0.25 mg/kg) injection of lipopolysaccharide (LPS) on embryonic day 15. LPS significantly elevated pro-inflammatory cytokines in maternal serum, amniotic fluid, and fetal brain at 4 h, and levels decreased but remained elevated at 24 h. Offspring born to LPS-dams exhibited reduced social and exploration behaviors as juveniles and young adults. Whole genome microarray analysis of the fetal brain at 4 h post maternal LPS was performed to elucidate possible molecular mechanisms by which MIA effects the fetal brain. We observed dysregulation of 3,285 genes in restricted functional categories, with increased mRNA expression of cellular stress and cell death genes and reduced expression of developmentally-regulated and brain-specific genes, specifically those that regulate neuronal migration of GABAergic interneurons.
Maternal immune activation by LPS selectively alters specific gene expression profiles of interneuron migration and oxidative stress in the fetus without triggering a fetal immune response.
Specimen part
View SamplesAn animals ability to cope with or succumb to deleterious effects of chronic psychological stress may be rooted in the brains immune responses manifested in microglial activity. Mice subjected to chronic social defeat (CSD) were categorized as susceptible (CSD-S) or resilient (CSD-R) based on behavioral phenotyping, and their microglial RNAs were isolated and analyzed by global gene expression microarrays. Microglia transcriptome from CSD-S mice was enriched for pathways that describe phases of CNS healing to sterile injury including, inflammation, oxidative stress, debris clearance, and wound resolution. Histochemical experiments confirmed the array predictions: CSD-S microglia showed elevated phagocytosis and oxidative stress, and the brains of CSD-S but not CSD-R or HC mice showed vascular leakage of intravenously injected fluorescent tracers. The results suggest that the inflammatory profile of CSD-S microglia may be precipitated by leakage of blood-born substances into brain parenchyma. We hypothesize that these CNS-centric responses contribute to the stress-susceptible behavioral phenotype.
Decoding microglia responses to psychosocial stress reveals blood-brain barrier breakdown that may drive stress susceptibility.
Specimen part
View SamplesAdministration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extends the lifespan of various model organisms including yeast, flies and worms. In ageing yeast, spermidine treatment triggeres epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), leading to induction of autophagy and thereby suppressing oxidative stress and necrosis. In order to further characterize the effects by spermidine supplementation of aging yeast cultures and to understand how global histone deacetylation affects gene transcription during aging, Affymetrix-based microarray analyses of three day old as well as ten day old cultures with and without administration of spermidine was performed.
Induction of autophagy by spermidine promotes longevity.
Age, Compound, Time
View SamplesPreeclampsia complicates more than 3% of all pregnancies in the United States and Europe. High-risk populations include women with diabetes, dyslipidemia, thrombotic disorders, hyperhomocysteinemia, hypertension, renal diseases, previous preeclampsia, twin pregnancies, and low socioeconomic status. In the latter case, the incidence may increase to 20% to 25%. Preeclampsia is a major cause of maternal and fetal morbidity and mortality. Preeclampsia is defined by systolic blood pressure of more than 140 mm Hg and diastolic blood pressure of more than 90 mm Hg after 20 weeks gestation in a previously normotensive patient, and new-onset proteinuria. Abnormal placentation associated with shallow trophoblast invasion (fetal cells from outer cell layer of the blastocyst) into endometrium (decidua) and improper spiral artery remodeling in the decidua are initial pathological steps.
Dysregulation of the circulating and tissue-based renin-angiotensin system in preeclampsia.
No sample metadata fields
View SamplesTumor growth and metastasis is controlled by paracrine signaling between cells of the tumor microenvironment and malignant cells. Cancer-associated fibroblasts (CAFs), are functionally important components of the tumor microenvironment. Although some steps involved in the cross-talk between these cells are known, there is still a lot that is not clear. Thus, the addition of, the consideration of microenvironment in the development of the disease, to the clinical and pathological procedures (currently admitted as the consistent value cancer treatments) could lay the foundations for the development of new treatment strategies to control the disease.
Functional heterogeneity of cancer-associated fibroblasts from human colon tumors shows specific prognostic gene expression signature.
Specimen part
View SamplesPurpose: Evaluate gene expression profiles after inducing differentiation in cultured interstitial cystitis (IC) and control urothelial cells. Materials and Methods: Bladder biopsies were taken from IC patients and controls (women having surgery for stress incontinence). Primary cultures were grown in Keratinocyte Growth Medium with supplements. To induce differentiation, in some plates the medium was changed to DMEM-F12 with supplements. RNA was analyzed with Affymetrix chips. Three nonulcer IC patients were compared with three controls. Results: After inducing differentiation, 302 genes with a described function were altered at least 3-fold with p <0.01 in both IC and control cells. Functions of the162 upregulated genes included cell adhesion (e.g. claudins, occludin, cingulin); urothelial differentiation, retinoic acid pathway and keratinocyte differentiation (e.g. skin cornified envelope components). The 140 downregulated genes included genes associated with basal urothelium (e.g. p63, integrins ?4, ?5 and ?6, basonuclin 1 and extracellular matrix components), vimentin, metallothioneins and members of the Wnt and Notch pathways. Comparing IC vs. control cells after differentiation, only seven genes with a described function were altered at least 3-fold with p <0.01. PI3, SERPINB4, CYP2C8, EFEMP2 and SEPP1 were decreased in IC; AKR1C2 and MKNK1 were increased in IC. Conclusions: Differentiation-associated changes occurred in both IC and control cells. Comparing IC vs. control revealed very few differences. This study may have included IC patients with minimal urothelial deficiency and/or selected the cells that were most robust in culture. Also, the abnormal urothelium in IC may be due to post-translational changes and/or the bladder environment.
Differentiation associated changes in gene expression profiles of interstitial cystitis and control urothelial cells.
Disease
View SamplesTo analyze expression differences between Trp53 pro-and deficient as well as Atm pro- and deficient murine CLL tumors developing in the E-TCL1 mouse model, we analyzed splenocytes isolated from heavily infiltrated spleens of sick mice.
Two mouse models reveal an actionable PARP1 dependence in aggressive chronic lymphocytic leukemia.
Specimen part
View SamplesThe cell differentiation potential of 13-cis retinoic acid (RA) has not succeeded in the clinical treatment of glioblastoma (GBM) so far. However, RA may also induce the expression of disistance genes such as HOXB7 which can be suppressed by Thalidomide (THAL). Therefore, we tested if combined treatment with RA+THAL may inhibit growth of glioblastoma in vivo. Treatment with RA+THAL but not RA or THAL alone significantly inhibited tumour growth. The synergistic effect of RA and THAL was corroborated by the effect on proliferation of glioblastoma cell lines in vitro. HOXB7 was not upregulated but microarray analysis validated by real-time PCR identified four potential resistance genes (IL-8, HILDPA, IGFBPA, and ANGPTL4) whose upregulation by RA was suppressed by THAL. Furthermore, genes coding for small nucleolar RNAs (snoRNA) were identified as a target for RA for the first time, and their upregulation was maintained after combined treatment. Pathway analysis showed upregulation of the Ribosome pathway and downregulation of pathways associated with proliferation and inflammation. Combined treatment with RA + THAL delayed growth of GBM xenografts and suppressed putative resistance genes associated with hypoxia and angiogenesis. This encourages further pre-clinical and clinical studies of this drug combination in GBM.
Inhibition of 13-cis retinoic acid-induced gene expression of reactive-resistance genes by thalidomide in glioblastoma tumours in vivo.
Cell line, Treatment
View SamplesMicroarray analysis of gene expression in the olfactory epithelium of Harlequin mouse as a model of oxidative-stress induced neurodegeneration of olfactory sensory neurons
Cellular and molecular characterization of oxidative stress in olfactory epithelium of Harlequin mutant mouse.
No sample metadata fields
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