GNPS - Protein restriction slows the progression of Alzheimer's disease in a mouse model
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Mus Musculus (ncbitaxon:10090)
SUBMITTER: 
John Denu
PROVIDER: MSV000094992 | GNPS | Tue Jun 11 12:18:00 BST 2024
REPOSITORIES: GNPS
Similar Datasets
Project description:plasma metabolomics done after restriction of dietary protein in AD mice.
2024-06-11 | MSV000094992 | MassIVE
Project description:To identify molecular pathological alterations in AD brains, we performed interspecies comparative microarray analyses using RNAs prepared from postmortem human brain tissues donated for the Hisayama study and hippocampal RNAs from the triple-transgenic mouse model of AD (3xTg-AD) Three-way ANOVA of microarray data from frontal cortex, temporal cortex and hippocampus with presence/absence of AD and vascular dementia, and sex, as factors revealed that the gene expression profile is most significantly altered in the hippocampi of AD brains. Comparative analyses of the brains of AD patients and a mouse model of AD showed that genes involved in non-insulin dependent DM and obesity were significantly altered in both, as were genes related to psychiatric disorders and AlzheimerM-bM-^@M-^Ys disease. 3xTg-AD-H mice harboring a homozygous Psen1M146V mutation and homozygous mutant transgenes for APPSwe and tauP301L, 3xTg-AD-h mice harboring hemizygous APPSwe and tauP301L transgenes with a homozygous Psen1M146V mutation, and non-transgenic control mice (non-Tg) were used in this study, (male, n=3 for each group). RNA samples prepared from hippocampi were subjected to microarray analysis using the Affymetrix Mouse Gene 1.0 ST platform (GPL6246).
2013-04-17 | E-GEOD-36981 | biostudies-arrayexpress
Project description:To identify molecular pathological alterations in AD brains, we performed interspecies comparative microarray analyses using RNAs prepared from postmortem human brain tissues donated for the Hisayama study and hippocampal RNAs from the triple-transgenic mouse model of AD (3xTg-AD) Three-way ANOVA of microarray data from frontal cortex, temporal cortex and hippocampus with presence/absence of AD and vascular dementia, and sex, as factors revealed that the gene expression profile is most significantly altered in the hippocampi of AD brains. Comparative analyses of the brains of AD patients and a mouse model of AD showed that genes involved in non-insulin dependent DM and obesity were significantly altered in both, as were genes related to psychiatric disorders and Alzheimer’s disease.
2013-04-17 | GSE36981 | GEO
Project description:Alzheimer’s disease (AD) is a common neurodegenerative condition involving a complex blend of disturbances in synaptic development and maintenance, neurovascular cross-talk, ionic and nutrient transport, and mitochondrial metabolism. The precise molecular profile of AD onset with insight for major pathological contributors remains unclear with corresponding impedances in therapeutic development. The current study sought two objectives, as (i) to resolve the molecular pathogenesis from cognitive impairment to the onset of AD-like neuropathology and (ii) whether the novel agent cannabidiol (CBD), noted for its neuroprotective effects, influences the molecular transition associated with AD onset. Dietary CBD was administered daily (80-100 mg/kg/day) in male 3xTg-AD mice and wild-type B6129SF2/J animals from 4.5 to 6.5 mo of age with inclusion of vehicle controls. RNA sequencing encompassed longitudinal and cross-sectional blood and brain samples respectively. Metabolomics and behavioral analyses examined brain regions (cortex, hippocampus) and associated integrated neurocircuitry. There were >1,000 differentially expressed markers of AD onset, whereby >75% were either eliminated or reversed in the direction of expression in response to CBD. Signaling pathways encompassed synaptic development and plasticity (e.g., Foxp2), neurovascular interactions (Smad9, Angptl6), receptors and ion channels (Gria4, Chrna2, Rgs7/Rgs7bp), mitochondrial genes (Ndufa7, Cox7a2), immunity (Ncr1), oxidation-reduction (Esr1), lipid synthesis (Fasn, ApoE), and carbohydrate metabolism (Mafa, Mlxipl). As potentially addressable with CBD treatment, AD onset represents molecular integration of neurovascular interactions, channelopathies, metabolic disturbances, and aberrations in developmental genes with involvement of major pathological contributors such as inflammation, oxidative signaling, dyslipidemia, and insulin resistance.
2025-08-18 | GSE304212 | GEO
Project description:Lifestyle-based interventions, including dietary modifications, can reduce dementia risk. In this regard, dietary supplementation with medium-chain triglycerides (MCT) has shown potential therapeutic benefits in individuals with Alzheimer's disease (AD). These effects are widely presumed to be mediated by hepatic conversion of MCT into circulating ketones. However, the physiological and cellular mechanisms underlying the benefits of MCT remain understudied, particularly in the context of AD. Here, we investigated the cellular and molecular changes occurring in the brain and systemically in response to dietary supplementation with MCT versus a ketogenic diet (KD). The experimental design consisted of comparing a 70% carbohydrate control diet to either a control diet supplemented with 10% MCT or a carbohydrate-free high fat KD. Diets were tested in two AD mouse models, slow-progressing 3xTg-AD mice that model pre-symptomatic/early stages and rapidly-progressing 5xFAD mice that model late stages of the disease. We found that MCT supplementation and KD both improved hippocampal-dependent spatial learning and memory, increased dendritic spine density of hippocampal neurons, and modulated hippocampal expression of genes associated with mitochondrial functions, synaptic structure, and insulin signaling in AD mouse models. However, unlike KD, MCT supplementation did not elevate circulating ketones, suggesting different mechanisms. Indeed, MCT enhanced the peripheral insulin response of AD mice, while KD conversely unveiled their latent metabolic vulnerability, increasing their hyperglycaemia, body weight gain, and adiposity. The systemic metabolic disturbances of AD mice correlated with transcriptomic alterations in hepatic lipid metabolism and ketogenesis genes and increased lipid droplet accumulation. These liver metabolic abnormalities were partially reversed by both MCT supplementation and KD, but in distinct ways. Notably, KD selectively triggered hepatic neutral lipid depletion and prominent proinflammatory gene expression while MCT down-regulated expression of cholesterol-related genes. Collectively, these findings reveal that MCT supplementation in the context of AD improves cognition and systemic metabolism without elevating circulating ketone levels.
2025-08-11 | GSE273337 | GEO
Project description:Lifestyle-based interventions, including dietary modifications, can reduce dementia risk. In this regard, dietary supplementation with medium-chain triglycerides (MCT) has shown potential therapeutic benefits in individuals with Alzheimer's disease (AD). These effects are widely presumed to be mediated by hepatic conversion of MCT into circulating ketones. However, the physiological and cellular mechanisms underlying the benefits of MCT remain understudied, particularly in the context of AD. Here, we investigated the cellular and molecular changes occurring in the brain and systemically in response to dietary supplementation with MCT versus a ketogenic diet (KD). The experimental design consisted of comparing a 70% carbohydrate control diet to either a control diet supplemented with 10% MCT or a carbohydrate-free high fat KD. Diets were tested in two AD mouse models, slow-progressing 3xTg-AD mice that model pre-symptomatic/early stages and rapidly-progressing 5xFAD mice that model late stages of the disease. We found that MCT supplementation and KD both improved hippocampal-dependent spatial learning and memory, increased dendritic spine density of hippocampal neurons, and modulated hippocampal expression of genes associated with mitochondrial functions, synaptic structure, and insulin signaling in AD mouse models. However, unlike KD, MCT supplementation did not elevate circulating ketones, suggesting different mechanisms. Indeed, MCT enhanced the peripheral insulin response of AD mice, while KD conversely unveiled their latent metabolic vulnerability, increasing their hyperglycaemia, body weight gain, and adiposity. The systemic metabolic disturbances of AD mice correlated with transcriptomic alterations in hepatic lipid metabolism and ketogenesis genes and increased lipid droplet accumulation. These liver metabolic abnormalities were partially reversed by both MCT supplementation and KD, but in distinct ways. Notably, KD selectively triggered hepatic neutral lipid depletion and prominent proinflammatory gene expression while MCT down-regulated expression of cholesterol-related genes. Collectively, these findings reveal that MCT supplementation in the context of AD improves cognition and systemic metabolism without elevating circulating ketone levels.
2025-08-11 | GSE286571 | GEO
Project description:Lifestyle-based interventions, including dietary modifications, can reduce dementia risk. In this regard, dietary supplementation with medium-chain triglycerides (MCT) has shown potential therapeutic benefits in individuals with Alzheimer's disease (AD). These effects are widely presumed to be mediated by hepatic conversion of MCT into circulating ketones. However, the physiological and cellular mechanisms underlying the benefits of MCT remain understudied, particularly in the context of AD. Here, we investigated the cellular and molecular changes occurring in the brain and systemically in response to dietary supplementation with MCT versus a ketogenic diet (KD). The experimental design consisted of comparing a 70% carbohydrate control diet to either a control diet supplemented with 10% MCT or a carbohydrate-free high fat KD. Diets were tested in two AD mouse models, slow-progressing 3xTg-AD mice that model pre-symptomatic/early stages and rapidly-progressing 5xFAD mice that model late stages of the disease. We found that MCT supplementation and KD both improved hippocampal-dependent spatial learning and memory, increased dendritic spine density of hippocampal neurons, and modulated hippocampal expression of genes associated with mitochondrial functions, synaptic structure, and insulin signaling in AD mouse models. However, unlike KD, MCT supplementation did not elevate circulating ketones, suggesting different mechanisms. Indeed, MCT enhanced the peripheral insulin response of AD mice, while KD conversely unveiled their latent metabolic vulnerability, increasing their hyperglycaemia, body weight gain, and adiposity. The systemic metabolic disturbances of AD mice correlated with transcriptomic alterations in hepatic lipid metabolism and ketogenesis genes and increased lipid droplet accumulation. These liver metabolic abnormalities were partially reversed by both MCT supplementation and KD, but in distinct ways. Notably, KD selectively triggered hepatic neutral lipid depletion and prominent proinflammatory gene expression while MCT down-regulated expression of cholesterol-related genes. Collectively, these findings reveal that MCT supplementation in the context of AD improves cognition and systemic metabolism without elevating circulating ketone levels.
2025-08-09 | GSE298797 | GEO
Project description:Alzheimer's disease (AD) is a chronic neurological disease which characterized as memory loss and progressive cognitive impairment. The characteristic of AD pathologies include extracellular senile plaques formed by β-amyloid protein deposition, neurofifibrillary tangles formed byhyper-phosphorylation of tau protein, and neuronal loss caused by glial cell proliferation. However, the pathogenesis of AD is still unclear. Resent research have shown that the dysregulation of RNA methylation is related to many biological processes, including neurodevelopment and neurodegenerative diseases. N6-methyladenosine (m6A) is the mainly modification in eukaryotic RNA, and it may be associated with the pathophysiology of AD. Circular RNA (circRNA) is a new type of evolutionarily conserved non-coding RNA without 5’cap and 3’polyadenylic acid tail. Recent studies suggested that circRNA may involved in the pathogenesis of AD. m6A RNA methylation is also found in circRNAs. In this study, we performed high-throughput sequencing on the degree of circRNA m6A methylation in APP/PS1 AD and C57BL/6 mice. The results suggest that circRNA m6A methylation degree in AD mice is different compared to the control group. In addition, using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to predict related pathways, the results showed that the genes with different circRNA m6A methylation in AD mice is associated with axon guidance, long-term potentiation, glutama tergic synapse, cholinergic synapse, gabaergic synapse and long-term depression. The MeRIP-qPCR results showed that among the 8 selected circRNA m6A genes, there are 5 genes with increased methylation and others with decreased methylation. In summary, the results of this study indicate that circRNA m6A methylation may related to the pathogenesis of AD.
2022-11-03 | GSE216901 | GEO
Project description:To demonstrate the utility of the newly developed dendron-coated phosphokinase antibody array(DPA) in which the antibodies are immobilized on a dendron-coated glass slide, the phosphorylation profiles of brain tissue samples obtained from Alzheimer's disease (AD) model mice were generated. The phosphorylation profiles were generated from four conditions of mice brain tissues; normal at the age of 2month, AD at the age of 2month, normal at the age of 6month and AD at the age of 6month. For each conditions, the profiling was done with three biological replicates (n=3).
2015-02-24 | E-GEOD-55452 | biostudies-arrayexpress
Project description:Dietary protein is a critical regulator of metabolic health and aging. Low protein diets are associated with healthy aging in humans, and dietary protein restriction extends the lifespan and healthspan of mice. In this study, we examined the effect of protein restriction (PR) on metabolic health and the development and progression of Alzheimer's disease (AD) in the 3xTg mouse model of AD. Here, we show that PR promotes leanness and glycemic control in 3xTg mice, specifically rescuing the glucose intolerance of 3xTg females. PR induces sex-specific alterations in circulating and brain metabolites, downregulating sphingolipid subclasses in 3xTg females. PR also reduces AD pathology and mTORC1 activity, increases autophagy, and improves the cognition of 3xTg mice. Finally, PR improves the survival of 3xTg mice. Our results suggest that PR or pharmaceutical interventions that mimic the effects of this diet may hold promise as a treatment for AD.
| S-EPMC11189507 | biostudies-literature