Synergistic and common effects of insulin and IGF-1 receptors on healthy murine ageing
Ontology highlight
ABSTRACT:
INSTRUMENT(S): NextSeq 2000
ORGANISM(S): Mus musculus
SUBMITTER: Chew Cheng
PROVIDER: E-MTAB-13481 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Ancestral environmental exposures that promote epigenetic transgenerational inheritance influence all aspects of an individual’s life history. Stress experienced during adolescence can affect adult physiological and behavioural phenotypes. The current study utilized a systems biology approach to investigate the interactions of these two forms of epigenetic modification, one carried in the germline transgenerationally and the other contained in the context of life history. A transgenerational epigenetic imprint left by the fungicide vinclozolin promoted regional specific brain gene networks that influenced chronic restraint stress responses to alter adult physiological, brain and behavioural phenotypes. The environmentally-induced epigenetic transgenerational inheritance was found to interact with early life stress response to impact the adult brain genome activity to bring “the phenotype into being”. We used microarrays to determine genes expressed differentially in rats' 4 brain areas - basolateral amygdala (BLA), primary and secondary motor cortex (Crtx), CA1 of the hippocampus (CA1), and CA3 of the hippocampus (CA3) - due to Vinclozolin treatments of their grand-grandmothers and/or to stress in adolescence age. For each of 4 brain areas (BLA, CRTX, CA1, and CA3), RNA samples from 4 treatment groups - stressed control (St-Con), non-stressed control (NSt-Con), stressed vinclozolin (St-Vin), and non-stressed vinclozolin (NSt-Vin) - were compared to each other. Each treatment groups contained 3 biological replica. RNA for each replica was pooled from 4 individual animals forming a certain dyad group.
2012-02-01 | E-GEOD-26737 | biostudies-arrayexpress
Project description:Mice heterozygous for the bifunctional enzyme glucosamine-2-epimerase/N-acetylmannosamine kinase (GNE+/-), which is essential for sialic acid biosynthesis, showed reduced gne transcription and sialylation in different brain regions. We found synapse loss in the hippocampus of GNE+/- mice at 6 months followed by a gradual loss of neurons in the hippocampus and substantia nigra at 12 months. Moreover, GNE+/- mice showed reduced arborization of microglia already at 6 months. A transcriptomic analysis revealed only minor inflammatory changes with slightly increased Interleukin 1β levels, indicating a homeostatic removal of synapses and neurons. Crossbreeding with complement component 3-deficient mice rescued the early onset loss of neurons and synapses in the GNE+/- mice. Thus, an intact sialic acid covered glycocalyx plays an essential role in maintaining brain homeostasis. Even a minor reduction in the sialic acid level leads to reduced microglial arborization and complement-mediated loss of neurons and synapses.
2019-10-07 | E-MTAB-7790 | biostudies-arrayexpress
Project description:Sexual selection involves mate preference behavior and is a critical determinant for natural selection and evolutionary biology. Previously an environmental compound (fungicide vinclozolin) was found to promote epigenetic transgenerational inheritance of modified mate selection characteristics in all progeny for three generations after exposure of a gestating female. The current study investigated gene networks involved in various regions of the brain that correlated with the mate preference behavior altered in F3-Vinclozolin lineage animals. Statistically significant correlations of differentially expressed gene clusters and modules were identified to associate with specific mate preference behaviors. This novel systems biology approach identified critical gene networks involved in mate preference behavior and demonstrated the ability of environmental factors to promote epigenetic transgenerational inheritance of this altered evolutionary biology determinant. Combined observations elucidate the potential molecular control of mate preference behavior and suggests environmental epigenetics can have a role in evolutionary biology. We used Affymetrix Rat Gene 1.0 ST microarrays to determine genes expressed differentially in F3 Vinclozolin lineage male or female rats' 6 brain areas - amygdala (Amy), hippocampus (Hipp), olfactory bulb (OlfB), cingulate cortex (CngCtx), entorhinal cortex (EnCtx), and preoptic area-anterior hypothalamus (POAH) - due to Vinclozolin treatments of their grand-grandmothers (F0). For each of 6 brain areas of male or female rats (female: amygdala (F-Amy), cingulate cortex (F-CngCTX), enterorhinal cortex (F-EnCTX), hippocampus (F-Hipp), olfactory bulbs (F-OlfB), and preoptic area-anterior hypothalamus (F-POAH); male: amygdala (M-Amy), cingulate cortex (M-CngCTX), enterorhinal cortex (M-EnCTX), hippocampus (M-Hipp), olfactory bulbs (M-OlfB), and preoptic area-anterior hypothalamus (M-POAH)), RNA samples from 2 treatment groups - F3 Control lineage (Con) or F3 Vinclozolin lineage (Vin) - were compared to each other. Each of treatment groups contained 4-6 biological replicas for each brain region. RNA for each replica was isolated from an individual animal in order to compare to individual animal mate preference behavior studied with the same rats before sacrifice. Totally, 132 RNA samples from 24 animals (6 male F3 Control, 6 male F3 Vinclozolin,6 female F3 Control, and 6 female F3 Vinclozolin) were isolated and studied.
2012-03-01 | E-GEOD-33830 | biostudies-arrayexpress
Project description:Glioblastoma (GBM) is a highly heterogeneous malignant brain tumour. We took multi-region spatially separated samples from tumours and isolated invasive GBM cells using FACS based on 5ALA of near normal brain parenchyma. RNAseq was then performed to compare expression profiles for tumour cells from different microenvironment.
2020-12-15 | E-MTAB-8743 | biostudies-arrayexpress
Project description:Background: Examining transcriptional regulation by existing antidepressants in key neural circuits implicated in depression, and understanding the relationship to transcriptional mechanisms of susceptibility and natural resilience, may help in the search for new therapeutics. Further, given the heterogeneity of treatment response in human populations, examining both treatment response and non-response is critical. Methods: We compared the effects of a conventional monoamine-based tricyclic antidepressant, imipramine (14 daily injections), and a rapidly acting, experimental, non-monoamine-based antidepressant, ketamine (single injection), in mice subjected to chronic social defeat stress, a validated model of depression, and used RNA-sequencing to analyze transcriptional profiles associated with susceptibility, resilience and antidepressant response and non-response in prefrontal cortex (PFC), nucleus accumbens, hippocampus, and amygdala. Results: We identified approximately equal numbers of responder and non-responder mice following ketamine or imipramine treatment. Ketamine induced more expression changes in hippocampus than other brain regions; imipramine induced more expression changes in nucleus accumbens and amygdala. Transcriptional profiles in ketamine and imipramine responders were most similar in PFC, where the least transcriptional regulation occurred for each drug. Non-response reflected both the lack of response-associated gene expression changes and unique gene regulation. In responders, both drugs reversed susceptible associated transcriptional changes as well as induced resilient associated transcription in PFC, with effects varying by drug and brain region studied. Conclusions: We generated a uniquely large resource of gene expression data in four inter-connected limbic brain regions implicated in depression and its treatment with imipramine or ketamine. Our analyses highlight the PFC as a key site of common transcriptional regulation by both antidepressant drugs and in both reversing susceptibility and inducing resilience associated molecular adaptations. In addition, we found region-specific effects of each drug suggesting both common and unique effects of imipramine versus ketamine. mRNA profiles of susceptibility to chronic social defeat stress as well as treatment response were generated across 4 separate brain regions, with a sample size of 3-5 per group.
2016-07-27 | E-GEOD-81672 | biostudies-arrayexpress
Project description:Changes in gravitational force such as that experienced by astronauts during space flight induce a redistribution of fluids from the caudad to the cephalad portion of the body together with an elimination of normal head-to-foot hydrostatic pressure gradients. To assess brain gene profile changes associated with microgravity and fluid shift, a large-scale analysis of mRNA expression levels was performed in the brains of 2 weeks control and hindlimb-unloaded (HU) mice using cDNA microarrays. Although to different extent, all functional categories displayed significantly regulated genes indicating that considerable transcriptomic alterations are induced by HU. Interestingly, the TIC class (transport of small molecules and ions into the cells) had the highest percentage of up-regulated genes, while the most down-regulated genes were those of the JAE class (Cell junction, Adhesion, Extracellular Matrix). TIC genes comprised 16% of those whose expression was altered, including sodium channel, nonvoltage-gated 1 beta (Scnn1b), glutamate receptor (Grin1), voltage-dependent anion channel 1 (Vdac1), calcium channel beta 3 subunit (Cacnb3) and others. The analysis performed by GeneMAPP revealed several altered protein classes and functional pathways such as blood coagulation and immune response, learning and memory, ion channels and cell junction. In particular, data indicate that HU causes an alteration in hemostasis which resolves in a shift toward a more hyper-coagulative state with an increased risk of venous thrombosis. Furthermore, HU treatment seems to impact on key steps of synaptic plasticity and learning processes. We used brains of four control (C1, C2, C3, C4) and four tail-suspended hindlimb-unloaded (E1, E2, E3, E4) mice to ensure statistical relevance of the study. 60 ug of total RNA extracted in TRIzol from each brain was reversed transcribed into labeled cDNAs using fluorescent Cy5 or Cy3-dUTP (Amersham Biosciences, NJ). Differently labeled cDNAs obtained from a pair of biological replicas were co-hybridized overnight at 50C with a microscope slide spotted with ~ 27,000 mouse cDNA sequences produced by the Microarray Core Facility of the Albert Einstein College of Medicine in the “multiple yellow” design (i.e.: C1C2, C3C4, E1E2, E3E4), described in Iacobas DA, Fan C, Iacobas S et al., Transcriptomic changes in developing kidney exposed to chronic hypoxia. Biochem Biophys Res Commun. 2006 349(1):329-38).
2008-08-07 | E-GEOD-12312 | biostudies-arrayexpress
Project description:Chronic lymphocytic leukaemia (CLL) is the most common haematological malignancy in developed countries. Ibrutinib (PCI-32765), a specific and irreversible inhibitor of Bruton's Tyrosine Kinase (BTK) represents a major step forward in the treatment of CLL. We have undertaken a detailed analysis of the changes happening to the chromatin structure in CLL cells from patients continuously receiving oral doses of ibrutinib. ChIP-seq has been performed for H3K4me3, H3K27ac, H3K27me3 and EZH2 up to 56 days following the beginning of the treatment. We observed that Ibrutinib-dependent lymphocytosis correlates with a global and transient recruitment of EZH2 to active cis-regulatory elements and increased H3K27me3.
2019-06-01 | E-MTAB-6410 | biostudies-arrayexpress
Project description:We report a new method for genome-wide methylation profiling that is able to probe methylation status in both single-copy DNA and interspersed repeats. This method, MethylMAPS, uses methylation-sensitive and -dependent enzymes to fractionate the genome according to methylation state. Methylated and unmethylated fragments are then sequenced with Next-Gen sequencing to map methylated and unmethylated CpG sites in the genome. We have used this method to determine the methylation status of >275 million CpG sites in human and mouse DNA from breast and brain tissues. We conclude that methylation is the default state of most CpG dinucleotides and that a combination of local dinucleotide frequencies, the interaction of repeated sequences, and the presence or absence of histone variants or modifications shields a population of CpG sites (most of which are in and around promoters) from DNA methyltransferases that lack intrinsic sequence specificity. Genome-wide methylation mapping in two normal human breast tissues, human brain tissue and mouse brain tissue.
2010-04-16 | E-GEOD-21242 | biostudies-arrayexpress
Project description:This study addresses this gap by conducting a direct comparison of eight platforms, representing both affinity-based and diverse mass spectrometry approaches, and covering over 13,000 proteins. By applying these platforms to the same cohort, we systematically assess their performance, identifying key differences and complementary strengths. Our findings offer valuable insights for researchers, highlighting trade-offs in coverage and their implications for biomarker discovery and clinical applications. This study serves as an essential resource, offering both technical evaluation and biological insights to support the development of novel diagnostics and therapeutics through plasma proteomics.
2025-10-10 | PAD000019 | Pride
Project description:This study addresses this gap by conducting a direct comparison of eight platforms, representing both affinity-based and diverse mass spectrometry approaches, and covering over 13,000 proteins. By applying these platforms to the same cohort, we systematically assess their performance, identifying key differences and complementary strengths. Our findings offer valuable insights for researchers, highlighting trade-offs in coverage and their implications for biomarker discovery and clinical applications. This study serves as an essential resource, offering both technical evaluation and biological insights to support the development of novel diagnostics and therapeutics through plasma proteomics.
2025-11-06 | PAD000022 | Pride