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: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: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:Aspartame is a non carbohydrate artificial sweetener widely used in medicine and food. Some scholars believe that aspartame has neurotoxicity, mainly due to the presence of phenylalanine in its metabolites, which can pass through the blood-brain barrier, change the brain amino acid ratio, and interfere with neurotransmitter transmission. However, whether aspartame has an impact on human innate immunity is still unknown. This experiment will use Caenorhabditis elegans as a model to study its effect on innate immunity and provide reliable data support for the safety of aspartame as a sweetener.
2025-12-31 | GSE273859 | GEO
Project description:Aspartame has been widely used as a sweetener in foods and beverages since the 1980s. In this study, we aimed to assess the effect of aspartame on gut epithelial cell biology, inflammation, and the epithelial barrier. Aspartame shows cytotoxic effects and epithelial barrier damage as well as proinflammatory cytokine release in gastrointestinal epithelial cells, organoids and organ-on-a-chips at concentrations corresponding to daily used doses in food products. Cellular cytotoxicity was observed in as low as 1.25 mg/ml doses. RNA sequencing analysis revealed that aspartame significantly altered the transcriptome in gut-on-a-chip models, showing upregulation of pathways such as unfolded protein response, activated pro-apoptotic and inflammatory, and downregulation of DNA repair and replication mechanisms pathways. Aspartame exposure upregulated proinflammatory genes, particularly in the TNF signalling pathway, and induced multiple chemokine responses. It activated the NF-κB pathway via oxidative stress, promoting inflammation on NF-κB reporter monocyte cells and causing gut epithelial cell death. Aspartame affected genes involved in tight and adherens junctions, disrupting gut epithelial barrier integrity in a dose-dependent manner in gut-on-a-chip models. Additionally, aspartame suppressed key DNA repair and replication genes involved in double-strand break repair, mismatch repair, and DNA replication. Overall, our findings indicate that at commonly consumed levels, aspartame induces cellular stress, inflammation, and epithelial barrier damage in gastrointestinal epithelial cells. These findings underscore the biological relevance of our results and raise concerns that daily dietary intake of aspartame may pose previously underappreciated risks to gut health.
2026-01-01 | GSE285905 | 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:We show that daily exposure of mice to aspartame, an artificial sweetener found in over 5,000 diet foods and drinks at doses equivalent to only 15% of the FDA recommended maximum daily intake for humans produces anxiety. The anxiety is alleviated by diazepam, a drug used in the treatment of generalized anxiety disorder. We completed RNA sequencing of the amygdala of male mice that were exposed to aspartame or plain drinking water (control), as this brain region regulates anxiety and fear. The aspartame exposure produces changes in the expression of genes regulating excitation-inhibition balance in the amygdala. The anxiety, its response to diazepam and the changes in amygdala gene expression are not limited to the aspartame-exposed individuals but also appear in up to two generations descending from the aspartame-exposed males. Thus, aspartame’s neurobehavioral effects are not limited to those who consume it but also impact generations of descendants, a finding that highlights the need for a re-evaluation of current policies on artificial sweetener use.
2022-10-12 | GSE210561 | GEO