Effect of developmental NMDAR antagonism on aspartame-induced hypothalamic and adrenal gene expression
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PROVIDER: PRJNA391333 | ENA |
REPOSITORIES: ENA
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Project description:Chronic dietary aspartame may impair rodent insulin tolerance and may affect behavior. Previous studies have shown the aspartame effects may be modulated by developmental NMDA receptor antagonism. Present study was designed to assess effects of aspartame and NMDAR antagonism on components of the HPA axis. We used microarray analysis to examine changes in adult rodent adrenal gene expression following chronic aspartame exposure and/or developmental NMDA receptor antagonism.
2018-03-11 | GSE100324 | GEO
Project description:Chronic dietary aspartame may impair rodent insulin tolerance and may affect behavior. Previous studies have shown the aspartame effects may be modulated by developmental NMDA receptor antagonism. Present study was designed to assess effects of aspartame and NMDAR antagonism on components of the HPA axis. We used microarray analysis to examine changes in adult rodent hypothalamic gene expression following chronic aspartame exposure and/or developmental NMDA receptor antagonism.
2018-03-11 | GSE100325 | GEO
Project description:AIM: to examine changes in hypothalamic gene expression following developmental N-Methyl D-aspartate (NMDA) receptor antagonism in adult female C57Bl/6J mice. AIM: to examine changes in hypothalamic gene expression following developmental N-Methyl D-aspartate (NMDA) receptor antagonism in adult female C57Bl/6J mice. This data will compliment on-going studies into the effect of developmental NMDA receptor antagonism on aspects of the Hypothalamic-Pituitary-Adrenal (HPA) axis.
2019-12-13 | GSE108042 | GEO
Project description:AIM: to examine changes in adrenal gene expression following developmental N-Methyl D-aspartate (NMDA) receptor antagonism in adult female C57Bl/6J mice. This data will compliment on-going studies into the effect of developmental NMDA receptor antagonism on aspects of the Hypothalamic-Pituitary-Adrenal (HPA) axis.
2019-12-13 | GSE108032 | GEO
Project description:RationaleAspartame (L-aspartyl phenylalanine methyl ester) is a non-nutritive sweetener (NNS) approved for use in more than 6000 dietary products and pharmaceuticals consumed by the general public including adults and children, pregnant and nursing mothers. However a recent prospective study reported a doubling of the risk of being overweight amongst 1-year old children whose mothers consumed NNS-sweetened beverages daily during pregnancy. We have previously shown that chronic aspartame (ASP) exposure commencing in utero may detrimentally affect adulthood adiposity status, glucose metabolism and aspects of behavior and spatial cognition, and that this can be modulated by developmental N-methyl-D-aspartate receptor (NMDAR) blockade with the competitive antagonist CGP 39551 (CGP). Since glucose homeostasis and certain aspects of behavior and locomotion are regulated in part by the NMDAR-rich hypothalamus, which is part of the hypothalamic-pituitary-adrenal- (HPA) axis, we have elected to examine changes in hypothalamic and adrenal gene expression in response to ASP exposure in the presence or absence of developmental NMDAR antagonism with CGP, using Affymetrix microarray analysis.ResultsUsing 2-factor ANOVA we identified 189 ASP-responsive differentially expressed genes (DEGs) in the adult male hypothalamus and 2188 in the adrenals, and a further 23 hypothalamic and 232 adrenal genes significantly regulated by developmental treatment with CGP alone. ASP exposure robustly elevated the expression of a network of genes involved in hypothalamic neurosteroidogenesis, together with cell stress and inflammatory genes, consistent with previous reports of aspartame-induced CNS stress and oxidative damage. These genes were not differentially expressed in ASP mice with CGP antagonism. In the adrenal glands of ASP-exposed mice, GABA and Glutamate receptor subunit genes were amongst those most highly upregulated. Developmental NMDAR antagonism alone had less effect on adulthood gene expression and affected mainly hypothalamic neurogenesis and adrenal steroid metabolism. Combined ASP + CGP treatment mainly upregulated genes involved in adrenal drug and cholesterol metabolism.ConclusionASP exposure increased the expression of functional networks of genes involved in hypothalamic neurosteroidogenesis and adrenal catecholamine synthesis, patterns of expression which were not present in ASP-exposed mice with developmental NMDAR antagonism.
| S-EPMC5862471 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-03-11 | GSE100326 | GEO
Project description:Maternal stress during late pregnancy can lead to intrauterine hyperthermia affecting fetal hypothalamic-pituitary-adrenal axis development and function. This study aimed to characterize the impact of in utero heat stress on the postnatal offspring's adrenal gland transcriptome.
2023-06-21 | GSE235160 | GEO
Project description:Recent genome-wide association studies (GWAS) identified Dusp8, a dual-specificity phosphatase targeting MAP kinases, as type 2 diabetes risk gene. Here, we unravel Dusp8 as gatekeeper in the hypothalamic control of glucose homeostasis in mice and humans. Male but not female Dusp8 loss-of-function mice, either with global or CRH neuron-specific deletion, had impaired systemic glucose tolerance and insulin sensitivity when exposed to high-fat diet (HFD). Mechanistically, we found impaired hypothalamic–pituitary–adrenal (HPA) axis feedback, blunted sympathetic responsiveness, and chronically elevated corticosterone levels driven by hypothalamic hyperactivation of Jnk signaling. Accordingly, global Jnk1 ablation, AAV-mediated Dusp8 overexpression in the mediobasal hypothalamus, or metyrapone-induced chemical adrenalectomy rescued the impaired glucose homeostasis of male Dusp8 KO mice, respectively. This sex-specific and rheostatic role of murine Dusp8 in governing hypothalamic Jnk signaling, insulin sensitivity and systemic glucose tolerance was consistent with fMRI data in human volunteers that revealed an association of the DUSP8 rs2334499 risk variant with hypothalamic insulin resistance in men. In summary, our findings suggest GWAS-identified gene Dusp8 as novel hypothalamic factor that plays a functional role in the etiology of type 2 diabetes.
2020-08-17 | PXD019451 | Pride
Project description:Genetic linkage analysis suggested that GKAP, a scaffold protein of the NMDA receptor (NMDAR), was a potential modifier of invasion in a mouse model of pancreatic neuroendocrine cancer (PanNET). Here we establish that GKAP governs invasive growth and treatment response of PanNET via its pivotal role in regulating the NMDAR pathway activity. Combining genetic knockdown of GKAP and pharmacological inhibition of NMDAR, we distilled gene expression signatures orchestrated by the NMDAR-GKAP axis, in addition to identifying two downstream effectors FMRP and HSF-1. Additionally, GKAP, FMRP, and HSF1 are functionally implicated in invasiveness of pancreatic ductal adenocarcinoma. Finally, gene expression signatures in tumors with low NMDAR activity are significantly associated with favorable patient prognosis in several cancer types.
2018-04-18 | GSE102598 | GEO
Project description:Fructose consumption has increased by over 25% since 1970, and excess consumption has deleterious metabolic effects. Additionally, fructose can alter hypothalamic pituitary adrenal axis function, potentially resulting in increased vulnerability to mood disorders. Adolescents are the greatest consumers of fructose and also at a critical period of development. Here, we examine the effects of consumption of a 55% fructose diet from weaning until adulthood on the hypothalamic transcriptome.
2015-03-25 | GSE56238 | GEO