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Integrated transcriptome and metabolome analysis of mechanism on intranasal spray insulin against vascular dementia

ABSTRACT: Integrated transcriptome and metabolome analysis of mechanism on intranasal spray insulin against vascular dementia

PROVIDER: PRJNA948436 | ENA |

REPOSITORIES: ENA

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Integrated transcriptome and metabolome analysis of mechanism on intranasal spray insulin against vascular dementia

Project description:to investigate the effects and mechanism of insulin on 2-VO induced vascular dementia (VD) rat models. We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different groups.

2023-06-07 | GSE228174 | GEO

Long-term intranasal insulin aspart: a profile of gene expression, memory, and insulin receptors in aged F344 rats

Project description:Intranasal insulin is a safe and effective method for ameliorating memory deficits associated with pathological brain aging. However, the impact of different formulations and the duration of treatment on insulin’s efficacy and the cellular processes targeted by the treatment remain unclear. Here, we tested whether intranasal insulin aspart, a short-acting insulin formulation, could alleviate memory decline associated with aging and whether long-term treatment affected regulation of insulin receptors and other potential targets. Outcome variables included measures of spatial learning and memory, autoradiography and immunohistochemistry of the insulin receptor, and hippocampal microarray analyses. Aged Fischer 344 rats receiving long-term (3 months) intranasal insulin did not show significant memory enhancement on the Morris water maze task. Autoradiography results showed that long-term treatment reduced insulin binding in the thalamus but not the hippocampus. Results from hippocampal immunofluorescence revealed age-related decreases in insulin immunoreactivity that were partially offset by intranasal administration. Microarray analyses highlighted numerous insulin-sensitive genes, suggesting insulin aspart was able to enter the brain and alter hippocampal RNA expression patterns including those associated with tumor suppression. Our work provides insights into potential mechanisms of intranasal insulin and insulin resistance, and highlights the importance of treatment duration and the brain regions targeted.

2019-04-20 | GSE130098 | GEO

Intranasal Insulin Treatment Alters Gene Expression Profile in the Hippocampus of Rats with Perinatal Iron Deficiency

Project description:Background: Perinatal iron deficiency (ID) targets the hippocampus and leads to long-term cognitive deficits. These deficits remain even after iron repletion, suggesting that further insight into the mechanisms of cognitive deficits and adjunct treatments are needed. Intranasal insulin improves cognitive deficits in adult humans with Alzheimer’s disease and type 2 diabetes and could provide benefits in ID-induced neurological dysfunction. Objective: Assess the effects of intranasal insulin administration on the hippocampal transcriptome in rat model of perinatal ID. Methods: Perinatal ID was induced using a low iron diet from gestational day 3 until postnatal day (P) 7, followed by an iron sufficient (IS) diet through P21. Intranasal insulin was administered at a dose of 0.3 IU, twice daily from P8 to P21. Hippocampi were removed on P21 from IS control, ID control, IS insulin, and ID insulin groups. Total RNA was isolated and profiled using TruSeq next-generation sequencing (Illumina). Gene expression profiles were characterized using custom Galaxy workflows and expression patterns were examined using Ingenuity Pathways Analysis (Qiagen) (n = 7-9 per group). Results: Transcriptomic profiling revealed that mitochondrial biogenesis and flux, oxidative phosphorylation, quantity of neurons, CREB signaling in neurons, and RICTOR-based mTOR signaling were disrupted with ID and positively affected by insulin treatment with the most benefit observed in the ID insulin group. Conclusions: Both perinatal ID and insulin administration altered gene expression in the developing hippocampus. Intranasal insulin treatment reversed the adverse effects of ID on many molecular pathways and should be further explored as an adjunct therapy in perinatal ID.

2023-04-20 | GSE220770 | GEO

Long-term intranasal insulin aspart: a profile of gene expression, memory, and insulin receptors in aged F344 rats

Project description:Long-term intranasal insulin aspart: a profile of gene expression, memory, and insulin receptors in aged F344 rats

| PRJNA533832 | ENA

Integrated transcriptome and metabolome analysis to investigate the mechanism of intranasal insulin treatment in a rat model of vascular dementia.

Project description:Introduction: Insulin has an effect on neurodegenerative diseases. However, the role and mechanism of insulin in vascular dementia (VD) and its underlying mechanism are unknown. In this study, we aimed to investigate the effects and mechanism of insulin on VD. Methods: Experimental rats were randomly assigned to control (CK), Sham, VD, and insulin (INS) + VD groups. Insulin was administered by intranasal spray. Cognitive function was evaluated using the Morris's water maze. Nissl's staining and immunohistochemical staining were used to assess morphological alterations. Apoptosis was evaluated using TUNEL-staining. Transcriptome and metabolome analyses were performed to identify differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs), respectively. Results: Insulin significantly improved cognitive and memory functions in VD model rats (p < 0.05). Compared with the VD group, the insulin + VD group exhibited significantly reduced the number of Nissl's bodies numbers, apoptosis level, GFAP-positive cell numbers, apoptosis rates, and p-tau and tau levels in the hippocampal CA1 region (p < 0.05). Transcriptomic analysis found 1,257 and 938 DEGs in the VD vs. CK and insulin + VD vs. VD comparisons, respectively. The DEGs were mainly enriched in calcium signaling, cAMP signaling, axon guidance, and glutamatergic synapse signaling pathways. In addition, metabolomic analysis identified 1 and 14 DEMs between groups in negative and positive modes, respectively. KEGG pathway analysis indicated that DEGs and DEMs were mostly enriched in metabolic pathway. Conclusion: Insulin could effectively improve cognitive function in VD model rats by downregulating tau and p-tau expression, inhibiting astrocyte inflammation and neuron apoptosis, and regulating genes involved in calcium signaling, cAMP signaling, axon guidance, and glutamatergic synapse pathways, as well as metabolites involved in metabolic pathway.

| S-EPMC10225696 | biostudies-literature

Transcriptomic (DNA microarray) and Metabolome (LC-TOF-MS) analyses of the liver in high-fat diet mice after intranasal administration of GALP (Galanin-Like Peptide)

Project description:The aim of this basic research is to test the efficacy of intranasal administration of Galanin-like Peptide (GALP) and its clinical application under the hypothesis that GALP prevents obesity in mice fed a high-fat diet (HFD). Focusing on the mechanism of regulation of lipid metabolism in peripheral tissues via the autonomic nervous system, we confirmed body weight changes after intranasal administration of GALP in diet-induced obesity (DIO) mice.

2023-09-21 | GSE243376 | GEO

Intranasal Insulin Treatment Alters Gene Expression Profile in the Hippocampus of Rats with Perinatal Iron Deficiency

Project description:Intranasal Insulin Treatment Alters Gene Expression Profile in the Hippocampus of Rats with Perinatal Iron Deficiency

| PRJNA911294 | ENA

Identify factors associated with preserved hepatic insulin sensitivity despite of hepatic steatosis.

Project description:Among all the evaluated factors, only adipose tissue insulin sensitivity (assessed by clamped % suppression of serum free fatty acid), serum concentration of high molecular weight adiponectin, and plasma concentration of TCA cycle metabolites such as citric acid and cis-aconitic acid (assessed by metabolome analysis), associated significantly and positively with hepatic insulin sensitivity in NAFLD.

2016-12-23 | GSE92746 | GEO

Effect of intranasal insulin on cognitive function in elderly patients after laparoscopic radical resection of colorectal cancer: a double-blind, pilot study

Project description:Interventions: insulin group (group I):Starting two days before surgery, insulin nasal drops should be administered twice a day until the day of surgery, 20U each time (0.5 ml) ;control group (group C):Starting two days before surgery, physiological saline nasal drops of 0.5 ml were administered twice a day until the day of surgery Primary outcome(s): The incidence of postoperative cognitive dysfunction Study Design: Parallel

| 105486 | ecrin-mdr-crc

Aging, Dementia, and TBI Study

Project description:Aging, Dementia, and TBI Study

| PRJNA413517 | ENA