Gene expression analysis in the absence of Creb in Pomc-expressing neurons of the hypothalamus
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE26037 | GEO | 2010/12/14
SECONDARY ACCESSION(S): PRJNA135509
REPOSITORIES: GEO
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Project description:Brain-derived serotonin favors appetite in mice following its binding to the Htr1a and Htr2b receptors in arcuate neurons of the hypothalamus. In this study, we identified that CREB is the transcriptional effector of brain-derived serotonin control of appetite in arcuate nuclei. In this dataset, we identified the downstream genes of CREB in arcuate neurons of the hypothalamus controling appetite. We isolated hypothalami of wild type and Creb-pomcCre-/- (deleted for Creb selectively in arcuate neurons of the hypothalamus) mice and performed microarray experiments.
2010-12-14 | E-GEOD-26037 | biostudies-arrayexpress
Project description:From the arcuate nucleus of mice, we have dissociated neurons that express Proopiomelanocortin(POMC) and captured them on the Fluidigm C1 platform. These neuronsplay important roles in the regulation of appetite and sexual behavior. Here we propose tosequence RNA from 96 single POMC-expressing neurons to understand the variance in theirtranscriptomes.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
2015-04-28 | E-ERAD-357 | biostudies-arrayexpress
Project description:It is known that reducing circulating serotonin by inhibiting Tph1 increases the sensitivity of BAT cells and this drives thermogenesis by fat and glucose oxidation. In our results inhibiting Tph1 in muscle showed activation of SIRT1/LKB1/AMPK pathway in skeletal muscle cells and increased p-ACC. Also, it's known that inhibiting adipose Htr2b signaling ameliorates HFD-induced systemic insulin resistance. Here we report insulin sensitivity changes by regulating serotonin in skeletal muscle by Htr2b. Inhibiting Htr2b increases AMPK activity, glucose uptake, and myofiber size and decreases lipid droplet accumulation in HFD mice skeletal muscle. These results indicate improved insulin resistance and myosteatosis in skeletal muscle by lack of Serotonin by Tph1/Htr2b on skeletal muscle.
2024-08-29 | GSE275857 | GEO
Project description:The hypothalamus coordinates neuroendocrine functions in vertebrates, including circadian rhythm, metabolism, and appetite. To explore its evolutionary origin, we attempt to create integrated transcription/connectome brain maps for swimming tadpoles of the ascidian, Ciona intestinalis, which serves as an approximation of the ancestral proto-vertebrate. This map features several cell types related to different regions of the vertebrate hypothalamus, including coronet cells, magnocellular neurons and the arcuate nucleus. Coronet cells express melanopsin and share additional properties with the saccus vasculosus, a specialized region of the hypothalamus that mediates photoperiodism in non-tropical fishes such as salmon. Comparative transcriptome analyses identified orthologous cell types for mechanosensory switch neurons, and VP+ and VPR+ relay neurons in different regions of the mouse hypothalamus. These observations provide evidence that the hypothalamus predates the evolution of the vertebrate brain. We discuss the possibility that switch neurons, coronet cells, and FoxP+/VPR relay neurons comprise a behavioral circuit that helps trigger metamorphosis of Ciona larvae in response to twilight.
2021-04-28 | GSE166235 | GEO
Project description:Appetite is frequently affected in cancer patients, leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer cachectic mouse model with increased food intake. In this model, mice bearing C26 colon adenocarcinoma have an increased food intake subsequently to the loss of body weight. We hypothesize that in this model, appetite regulating systems in the hypothalamus, which apparently fail in anorexia, are still able to adapt adequately to changes in energy balance. Therefore studying the changes that occur on appetite regulators in the hypothalamus might reveal targets for treatment of cancer-induced eating disorders. By applying transcriptomics, many appetite regulating systems in the hypothalamus could be taken into account, providing an overview of changes that occur in the hypothalamus during tumour growth. We show that hypothalamic expression of orexigenic neuropeptides NPY and AgRP was higher, whereas expression of anorexigenic genes CCK and POMC were lower in TB compared to controls. In addition, serotonin and dopamine signalling pathways were found to be significantly altered in TB mice. Serotonin levels in brain showed to be lower in TB mice compared to control mice, while dopamine levels did not change. Moreover, serotonin levels inversely correlated with food intake. Transcriptomic analysis of the hypothalamus of cachectic TB mice with an increased food intake showed changes in NPY, AgRP and serotonin signalling. Serotonin levels in the brain showed to correlate with changes in food intake. Targeting these systems seems a promising strategy to avoid the development of cancer-induced eating disorders. C26-colon adenocarcinoma cells were subcutaneously inoculated in CDF1 mice. After 20 days, hypothalami were dissected and subjected to gene expression profiling. The total dataset consists of 2 parts; dataset 1, a pilot stuy in which mice were injected with increasing number of tumour cells and pooled samples were arrayed; and dataset 2, the main study in which mice were injected with 1 million tumour cells and samples were individually arrayed.
2013-11-14 | E-GEOD-44080 | biostudies-arrayexpress
Project description:Appetite is frequently affected in cancer patients, leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer cachectic mouse model with increased food intake. In this model, mice bearing C26 colon adenocarcinoma have an increased food intake subsequently to the loss of body weight. We hypothesize that in this model, appetite regulating systems in the hypothalamus, which apparently fail in anorexia, are still able to adapt adequately to changes in energy balance. Therefore studying the changes that occur on appetite regulators in the hypothalamus might reveal targets for treatment of cancer-induced eating disorders. By applying transcriptomics, many appetite regulating systems in the hypothalamus could be taken into account, providing an overview of changes that occur in the hypothalamus during tumour growth. We show that hypothalamic expression of orexigenic neuropeptides NPY and AgRP was higher, whereas expression of anorexigenic genes CCK and POMC were lower in TB compared to controls. In addition, serotonin and dopamine signalling pathways were found to be significantly altered in TB mice. Serotonin levels in brain showed to be lower in TB mice compared to control mice, while dopamine levels did not change. Moreover, serotonin levels inversely correlated with food intake. Transcriptomic analysis of the hypothalamus of cachectic TB mice with an increased food intake showed changes in NPY, AgRP and serotonin signalling. Serotonin levels in the brain showed to correlate with changes in food intake. Targeting these systems seems a promising strategy to avoid the development of cancer-induced eating disorders. C26-colon adenocarcinoma cells were subcutaneously inoculated in CDF1 mice. After 20 days, hypothalami were dissected and subjected to gene expression profiling. The total dataset consists of 2 parts; dataset 1, a pilot stuy in which mice were injected with increasing number of tumour cells and pooled samples were arrayed; and dataset 2, the main study in which mice were injected with 1 million tumour cells and samples were individually arrayed.
2013-11-14 | E-GEOD-44081 | biostudies-arrayexpress
Project description:Appetite is frequently affected in cancer patients, leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer cachectic mouse model with increased food intake. In this model, mice bearing C26 colon adenocarcinoma have an increased food intake subsequently to the loss of body weight. We hypothesize that in this model, appetite regulating systems in the hypothalamus, which apparently fail in anorexia, are still able to adapt adequately to changes in energy balance. Therefore studying the changes that occur on appetite regulators in the hypothalamus might reveal targets for treatment of cancer-induced eating disorders. By applying transcriptomics, many appetite regulating systems in the hypothalamus could be taken into account, providing an overview of changes that occur in the hypothalamus during tumour growth. We show that hypothalamic expression of orexigenic neuropeptides NPY and AgRP was higher, whereas expression of anorexigenic genes CCK and POMC were lower in TB compared to controls. In addition, serotonin and dopamine signalling pathways were found to be significantly altered in TB mice. Serotonin levels in brain showed to be lower in TB mice compared to control mice, while dopamine levels did not change. Moreover, serotonin levels inversely correlated with food intake. Transcriptomic analysis of the hypothalamus of cachectic TB mice with an increased food intake showed changes in NPY, AgRP and serotonin signalling. Serotonin levels in the brain showed to correlate with changes in food intake. Targeting these systems seems a promising strategy to avoid the development of cancer-induced eating disorders.
2013-11-14 | GSE44081 | GEO
Project description:Appetite is frequently affected in cancer patients, leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer cachectic mouse model with increased food intake. In this model, mice bearing C26 colon adenocarcinoma have an increased food intake subsequently to the loss of body weight. We hypothesize that in this model, appetite regulating systems in the hypothalamus, which apparently fail in anorexia, are still able to adapt adequately to changes in energy balance. Therefore studying the changes that occur on appetite regulators in the hypothalamus might reveal targets for treatment of cancer-induced eating disorders. By applying transcriptomics, many appetite regulating systems in the hypothalamus could be taken into account, providing an overview of changes that occur in the hypothalamus during tumour growth. We show that hypothalamic expression of orexigenic neuropeptides NPY and AgRP was higher, whereas expression of anorexigenic genes CCK and POMC were lower in TB compared to controls. In addition, serotonin and dopamine signalling pathways were found to be significantly altered in TB mice. Serotonin levels in brain showed to be lower in TB mice compared to control mice, while dopamine levels did not change. Moreover, serotonin levels inversely correlated with food intake. Transcriptomic analysis of the hypothalamus of cachectic TB mice with an increased food intake showed changes in NPY, AgRP and serotonin signalling. Serotonin levels in the brain showed to correlate with changes in food intake. Targeting these systems seems a promising strategy to avoid the development of cancer-induced eating disorders.
2013-11-14 | GSE44080 | GEO
Project description:Sodium appetite is an instinct that involves avid specific intention. It is elicited by sodium deficiency, stress-evoked ACTH and by reproduction. Genome-wide microarrays in sodium deficient mice, or following ACTH infusion, showed upregulation of hypothalamic genes, including DARPP-32, dopamine receptors-1 and -2, alpha-2C-adrenoceptor, and STEP. Both DARPP-32 and neural plasticity regulator, ARC were upregulated in lateral hypothalamic orexinergic neurons by sodium deficiency. Administration of dopamine D1- (SCH23390) and D2-receptor (raclopride) antagonists reduced gratification of sodium appetite triggered by sodium deficiency. SCH23390 was specific, having no effect on osmotic-induced water drinking, whereas raclopride also reduced water intake. D1-receptor knockout mice had normal sodium appetite, indicating compensatory regulation. It was insensitive to SCH23390, confirming the absence of off-target effects. Bilateral microinjection of SCH23390 (100nM in 200nL) into rats? lateral hypothalamus greatly reduced sodium appetite. Gene Set Enrichment Analysis in hypothalami of mice with sodium appetite showed significant enrichment of gene sets previously linked to addiction (opiates, cocaine). This finding of concerted gene regulation was attenuated upon gratification with perplexingly rapid kinetics of only 10 minutes, anteceding significant absorption of salt from the gut. Salt appetite and hedonic liking of salt taste have evolved over more than a hundred million years e.g. being present in Metatheria. Drugs causing pleasure and addiction are comparatively recent and likely reflect usurping of evolutionary ancient systems with high survival value by the gratification of contemporary hedonic indulgences. Our findings outline a novel molecular logic for instinctive behavior encoded by the brain with possible important translational-medical implications. Transcripts were profiled in the hypothalamus and whole brain of control and salt craving animals to determine the gene expression profile corresponding to that behavioral state. We show an over-representation of addiction-related genes in the set that is common to different methods of salt craving. Mouse hypothalamus and whole brain under three conditions: control, furosemide treated, and ACTH treated. 4 or 5 biological replicated per group. Two channels - experimental and reference are used.
2011-07-04 | E-GEOD-29451 | biostudies-arrayexpress
Project description:During pregnancy, the energy requirements of the fetus impose changes in maternal metabolism. Increasing insulin resistance in the mother maintains nutrient flow to the growing fetus, while prolactin and placental lactogen counterbalance this resistance and prevent maternal hyperglycemia by driving expansion of the maternal population of insulin-producing beta-cells. However, the exact mechanisms by which the lactogenic hormones drive beta-cell expansion remain uncertain. Here we show that serotonin acts downstream of lactogen signaling to drive beta-cell proliferation. Serotonin synthetic enzyme Tph1 and serotonin production increased sharply in beta-cells during pregnancy or after treatment with lactogens in vitro. Inhibition of serotonin synthesis by dietary tryptophan restriction or Tph inhibition blocked beta-cell expansion and induced glucose intolerance in pregnant mice without affecting insulin sensitivity. Expression of the Gq-linked serotonin receptor Htr2b in maternal islets increased during pregnancy and normalized just prior to parturition, while expression of the Gi-linked receptor Htr1d increased at the end of pregnancy and postpartum. Blocking Htr2b signaling in pregnant mice also blocked beta-cell expansion and caused glucose intolerance. These studies reveal an integrated signaling pathway linking beta-cell mass to anticipated insulin need during pregnancy. Modulators of this pathway, including medications and diet, may affect the risk of gestational diabetes. Analysis of poly(A)+ RNA from 3 biological replicates of pancreatic islets isolated from normal female and pregnant female mice
2010-07-01 | E-GEOD-21860 | biostudies-arrayexpress