Olanzapine suppresses mPFC-norepinephrine releasing to alleviate CLOCK-induced cancer stemness under chronic stress
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE268860 | GEO | 2024/08/02
REPOSITORIES: GEO
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Project description:Central norepinephrine (NE) neurons, mainly located in the Locus coeruleus (LC), play roles in a wide range of behavioral and physiological processes. How the human LC-NE neurons develop and what roles they play in the pathophysiology of human diseases is poorly understood, partly due to the unavailability of functional human LC-NE neurons. Here we established a technology for efficient generation of LC-NE neurons from human pluripotent stem cells by identifying a novel role of ACTIVIN A in regulating the LC-NE transcription factors in the dorsal rhombomere 1 (r1) progenitors. The in vitro generated human LC-NE neurons not only display extensive axonal arborization and release/uptake NE, but also exhibit the pacemaker activity, calcium oscillation, and in particular chemoreceptor activity in response to CO2. Multiple timepoint single nucleus RNA-Seq (snRNA-Seq) analysis captured the dynamic NE differentiation process, confirmed the NE cell population and revealed the differentiation trajectory from hindbrain progenitors to NE neurons via ASCL1 expressing precursor stage. The LC-NE neurons engineered with a NE sensor reliably reported the extracellular NE level. The availability of functional human LC-NE neurons enables investigation of their roles in the pathogenesis of and development of therapeutics for neural psychiatric and degenerative diseases.
2023-08-24 | GSE221988 | GEO
Project description:The cellular mechanism(s) linking macrophages to norepinephrine (NE)-mediated regulation of thermogenesis has been a topic of debate. Here, we identify sympathetic neuron-associated macrophages (SAMs) as a population of macrophages that mediate clearance of NE via expression of Slc6a2, an NE transporter, and monoamine oxidase A (MAOa), a degradation enzyme. Optogenetic activation of the SNS upregulates NE uptake by SAMs and shifts the SAM profile to a more pro-inflammatory state. NE uptake by SAMs is prevented by genetic depletion of Slc6a2 or inhibition of the transporter. We also found that obesity increases SAM content in the SNS. In two mouse models of obesity, genetic ablation of Slc6a2 in SAMs increases brown adipose tissue (BAT) content, causes browning of white fat, increases thermogenesis and leads to significant and sustained weight loss. We further show that this pathway is conserved as human sympathetic ganglia also contain SAMs and the analogous molecular machinery for NE clearance, thus constituting a potential target for obesity treatment.
2017-10-09 | GSE103847 | GEO
Project description:During colonization in the host gastrointestinal tract, the enteric bacteria Campylobacter jejuni is exposed to a variety of signaling molecules including the catecholamine hormones epinephrine (Epi) and norepinephrine (NE). NE has been determined to stimulate the growth of C. jejuni as well as increase its pathogenicity. To investigate the mechanisms of NE or Epi on the biology of C. jejuni, the global gene expression profiles of C. jejuni NCTC 11168 cultured in iron-restricted medium were analyzed in response to NE or Epi. Totally, 183 and 156 genes were differentially expressed by NE and Epi respectively, with 102 differentially expressed genes common between the two treatments. These genes are involved in diverse cellular functions including iron uptake systems, motility, virulence, oxidative stress response, nitrosative stress tolerance, enzyme metabolism, DNA repair and metabolism and ribosomal protein biosynthesis. Adherence to and invasion of Caco-2 cells by C. jejuni were enhanced upon exposure to NE or Epi. These results indicated that NE and Epi have similar effects on the gene expression of C. jejuni and that the effects on gene expression may contribute to elucidate the mechanisms on interaction between host and C. jejuni.
2015-02-10 | GSE65187 | GEO
Project description:Bacteria can use host hormones as environment cue to modulate their pathogenic processes, which was discovered to play essential role in disease development. Actinobacillus pleuropneumoniae is one of the most important porcine respiratory pathogens causing great economic losses in the pig industry worldwide. Stress factors were found to contribute to the outcome of A. pleuropneumoniae infection. To test whether A. pleuropneumoniae could respond to host stress hormone catecholamines, the gene expression profiles after epinephrine (Epi) and norepinephrine (NE) treatment were compared with the untreated bacteria using microarray. Although the bacterial growth was not affected in the conditions tested, 157 and 104 genes associated with various function categories including many virulence factors were differentially expressed by Epi and NE treatment. 18 common genes were regulated by the two hormones, these genes included genes encoding virulence factors and potential responsors of Epi and NE. Further investigations on virulence traits demonstrated that cytotoxic activity was enhanced by Epi but repressed by NE in accordance with the regulations on apxIA. Biofilm formation was not affected by the two hormones despite that the biofilm formation gene pgaB was affected. Adhesion to host cells was induced by NE but not by Epi, possibly involving other putative adhesins affected by the hormones in addition to the autotransporter adhesin (APL_0443). Our study demonstrated that A. pleuropneumoniae could actively respond to catecholamines to control its virulence traits. The different regulated genes and effects caused by Epi and NE suggested A. pleuropneumoniae may have multiple responsive systems to sense different type of catecholamine hormones. Transcriptional profiles were analyzed using microarray to compared the epinephrine (Epi) or norepinephrine(NE) treated and untreated A. pleuropneumoniae. All samples were harvested from middle exponential phase (4 hours after sub-culture) at the OD600=1.435M-BM-10.065 for control, OD600=1.461M-BM-10.019 for Epi treated strain and OD600=1.545M-BM-10.115 for NE treated strain. Three biological replicates were conducted for each treatment. The total RNA were extracted and hybridized with the whole genome microarray of A. pleuropneumoniae. The signal intensities were normalized and transformed into log2 values. The genes with fold change M-bM-^IM-% 1.5 and P < 0.05 were selected as differentially expressed.
2012-03-19 | E-GEOD-25516 | biostudies-arrayexpress
Project description:The goal of this study was to identify transcriptional changes that occur in response to long-term norepinephrine (NE) treatment on normal immortalized fallopian tube cells (iFTSEC283). We treated isogenic cell lines (iFTSEC283 and iFTSEC283p53R175H) with 10μM NE or vehicle control (water) for 137 days with media change every two days followed by whole-transcriptome RNA seq. We identified 123 differentially expressed genes in 10μM NE vs mock-treated iFTSEC283. In iFTSEC283p53R175H cells, we identified 23 differentially expressed genes in response to chronic NE treatment.
2021-03-08 | GSE168097 | GEO
Project description:We investigated the early transcriptional responses of human white adipocytes to NE. Already after 3 h of NE stimulation we revealed a wide transcriptional response and a wide range of pathways.
2018-10-20 | E-MTAB-6345 | biostudies-arrayexpress
Project description:During colonization in the host gastrointestinal tract, the enteric bacteria Campylobacter jejuni is exposed to a variety of signaling molecules including the catecholamine hormones epinephrine (Epi) and norepinephrine (NE). NE has been determined to stimulate the growth of C. jejuni as well as increase its pathogenicity. To investigate the mechanisms of NE or Epi on the biology of C. jejuni, the global gene expression profiles of C. jejuni NCTC 11168 cultured in iron-restricted medium were analyzed in response to NE or Epi. Totally, 183 and 156 genes were differentially expressed by NE and Epi respectively, with 102 differentially expressed genes common between the two treatments. These genes are involved in diverse cellular functions including iron uptake systems, motility, virulence, oxidative stress response, nitrosative stress tolerance, enzyme metabolism, DNA repair and metabolism and ribosomal protein biosynthesis. Adherence to and invasion of Caco-2 cells by C. jejuni were enhanced upon exposure to NE or Epi. These results indicated that NE and Epi have similar effects on the gene expression of C. jejuni and that the effects on gene expression may contribute to elucidate the mechanisms on interaction between host and C. jejuni. Transcriptional profiles were analyzed using microarray to compared the epinephrine (Epi) or norepinephrine (NE) treated and untreated Campylobacter jejuni NCTC 11168. NE or Epi treated and untreated cultures of C. jejuni NCTC 11168 were collected at the mid-log phase (?36 h cultures). Three (for NE or Epi treated culture) or four (for untreated control culture) independent biological replicates were performed. Total RNA was extracted using RiboPure™-Bacteria Kit (Ambion, Life Technologies) according to the manufacturer’s instructions. The quality and quantity of total RNA were determined by an Agilent Bioanalyzer 2100. Total RNA was amplified and labeled by Low Input Quick Amp Labeling Kit, One-Color, following the manufacturer’s instructions. Labeled cRNA were purified by RNeasy mini kit (QIAGEN, GmBH, Germany). Each Slide was hybridized with 600ng Cy3-labeled cRNA using Gene Expression Hybridization Kit (Agilent technologies, Santa Clara, CA, US) in Hybridization Oven, according to the manufacturer’s instructions. After 17 hours hybridization, slides were washed in staining dishes with Gene Expression Wash Buffer Kit (Agilent technologies, Santa Clara, CA, US), followed the manufacturer’s instructions. Slides were scanned by Agilent Microarray Scanner with default settings, Dye channel: Green, Scan resolution=5?m, PMT 100%, 10%, 16bit. Data were extracted with Feature Extraction software 10.7. Raw data were normalized by Quantile algorithm, Gene Spring Software 11.0. The genes with fold change ? 1.5 and P < 0.05 were selected as differentially expressed.
2015-02-10 | E-GEOD-65187 | biostudies-arrayexpress
Project description:Bacteria can use host hormones as environment cue to modulate their pathogenic processes, which was discovered to play essential role in disease development. Actinobacillus pleuropneumoniae is one of the most important porcine respiratory pathogens causing great economic losses in the pig industry worldwide. Stress factors were found to contribute to the outcome of A. pleuropneumoniae infection. To test whether A. pleuropneumoniae could respond to host stress hormone catecholamines, the gene expression profiles after epinephrine (Epi) and norepinephrine (NE) treatment were compared with the untreated bacteria using microarray. Although the bacterial growth was not affected in the conditions tested, 157 and 104 genes associated with various function categories including many virulence factors were differentially expressed by Epi and NE treatment. 18 common genes were regulated by the two hormones, these genes included genes encoding virulence factors and potential responsors of Epi and NE. Further investigations on virulence traits demonstrated that cytotoxic activity was enhanced by Epi but repressed by NE in accordance with the regulations on apxIA. Biofilm formation was not affected by the two hormones despite that the biofilm formation gene pgaB was affected. Adhesion to host cells was induced by NE but not by Epi, possibly involving other putative adhesins affected by the hormones in addition to the autotransporter adhesin (APL_0443). Our study demonstrated that A. pleuropneumoniae could actively respond to catecholamines to control its virulence traits. The different regulated genes and effects caused by Epi and NE suggested A. pleuropneumoniae may have multiple responsive systems to sense different type of catecholamine hormones.
2012-03-19 | GSE25516 | GEO
Project description:Interventions: Phenylephrine (PE):When hypotension occurred,Patients received PE infusion at a starting rate of 5 ml/h of 100µg/ml solution (prepared by diluting 10 mg of PE in 100 ml saline);Norepinephrine (NE):When hypotension occurred,Patients received NE infusion at a starting rate of 5 ml/h of 8 ug/ml solution (prepared by diluting 2 mg NE in 250 ml saline)
Primary outcome(s): First flatus time after surgery;All complications, all-cause mortality, and readmission rates within 28 days after surgery
Study Design: Parallel
| 80763 | ecrin-mdr-crc
Project description:Background: The goal of this study was to determine the transcriptional consequences of norepinephrine transporter (NET) gene deletion in noradrenergic neuron differentiation. The norepinephrine transporter (NET) is the target of powerful mind-altering substances, such as tricyclic antidepressants and the drug of abuse, cocaine. NET function in adult noradrenergic neurons of the peripheral and central nervous systems is that of a scavenger that internalizes norepinephrine from the synaptic cleft. By contrast, norepinephrine (NE) transport has a different role in embryogenesis. It promotes differentiation of neural crest cells and locus ceruleus progenitors into noradrenergic neurons, whereas NET inhibitors, such as the tricyclic antidepressant desipramine and the drug of abuse, cocaine, inhibit noradrenergic differentiation. While NET structure und regulation of NET function is well described, little is known about downstream targets of NE transport. Results: We have determined by long serial analysis of gene expression (LongSAGE) the gene expression profiles of in vitro differentiating wild type and norepinephrine transporter-deficient (NETKO) neural crest derivatives. Comparison analyses with the wild type library (GSM 105765) have identified a number of important differentially expressed genes, including genes relevant to noradrenergic neuron differentiation and to the phenotype of NETKO mice. Furthermore we have identified novel differentially expressed genes. Conclusions: Loss of NET function during embryonic development deregulates signaling pathways that are critically involved in neural crest formation and noradrenergic neuron differentiation. The library was constructed from total RNA of 60 neural crest culture at culture day 7. The neural tubes were dissected from E9.5 embryos that lack the norepinephrine transporter gene.
2008-06-23 | E-GEOD-11788 | biostudies-arrayexpress