Integrated transcriptome and metabolome analysis of mechanism on intranasal spray insulin against vascular dementia
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE228174 | GEO | 2023/06/07
REPOSITORIES: GEO
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Project description:Integrated transcriptome and metabolome analysis of mechanism on intranasal spray insulin against vascular dementia
| PRJNA948436 | ENA
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
Project description:Objective: The aim of this study was to identify novel diagnostic biomarkers of diabetic vascular dementia (DVD) and unraveling the underlying mechanisms using mass spectrometry (MS). Methods: Label-Free LC-MS/MS proteomics analysis was applied to urine samples from four groups including 14 vascular dementia CC(VD), 22 type 2 diabetes mellitus (T2DM), 12 DVD, 21 Normal Control (NC). Searching the MS data by Proteome Discoverer software, protein abundances were analyzed qualitatively and quantitatively and compared between these groups. Combining bioinformatics analysis using GO, pathway crosstalk analysis using KEGG, PPI network analysis using STRING and literature searching, the differentially expressed proteins (DEPs) of DVD can be comprehensively judged and were further quantified by receiver operating characteristic (ROC) curve methods. Results: The proteomic findings showed quantitative changes in DVD was compared to NC, T2DM, and VD groups; among 7,527 identified urine proteins, 1222, 1152, and 1180 of the proteins displayed quantitative changes unique to DVD vs NC, T2DM, and VD, respectively, including 481 overlapped common DEPs. Then 9 unique proteins and 2 composite markers (CM) were confirmed by a ROC curve method. Conclusion: This study provided a novel insight into the potential pathogenesis of DVD and elucidated a method for the earlier detection.
2021-01-14 | PXD022189 | Pride
Project description:Transcriptional profiling of cells in white matter of the brain from cases with vascular dementia vs control cases
2022-09-28 | GSE213897 | GEO
Project description:Single-nucleus RNA sequencing of human periventricular white matter comparing healthy age-matched controls with vascular dementia patients.
2024-12-06 | GSE282111 | GEO
Project description:snRNAseq of human vascular dementia white matter vs control
| PRJNA882878 | ENA
Project description:There are many subtypes of dementia without any minimally invasive, low-cost and efficient diagnostic biomarkers. MicroRNA (miRNA) are easily gained and accessible from patients, which may be a promising biomarker for dementia diagnosis and differential diagnosis. We make a completely expression analysis of serum miRNA from 24 participants including post-stroke cognitive impairment (PSCI) group (n=6), post-stroke non-cognitive impairment (PSCI) group, Alzheimer's Disease (AD) group (n=6) and normal control group (NC) group (n=6). Different expression miRNA (DE -miRNA) were screened by LIMMA ebayes method, Benjamini-Hochberg check and fold change (P < 0.05, |log2FC|≥1), we construct a DE-miRNA-key gene-signaling pathway network, the roles of DE-miRNA and related genes and signaling pathways in AD and PSCI were deduced through comprehensive network construction and literature search.
2024-04-17 | GSE218605 | GEO
Project description:Alzheimer’s disease (AD) and vascular dementia (VaD) are the two most common forms of dementia, neither of which can be effectively treated. There is growing evidence on vascular contributions to cognitive impairment and dementia such as AD, but their pathogenic molecular links are not defined yet. Notably, neurofibrillary tangles made of hyperphosphorylated tau (P-tau) are a hallmark lesion of AD, but are not found in VaD. Although brain ischemia induces some tau changes and tau knockout reduces stroke-induced acute brain damage, little is known about the role of tau in mediating progression from vascular insufficiency to later development of VaD. Cis P-tau is a pre-tangle pathology in AD and an early driver of neurodegeneration resulting from brain injury, but its role in AD treatment or in VaD is unknown. Here we identify cis P-tau as an antibody-neutralizable major common early driver of AD and VaD. We show that cis P-tau elimination using cis antibody not only prevents, but also treats AD-like neurodegeneration and memory loss in a hTau mouse model of AD. Purified cis P-tau causes and spreads neurodegeneration with behavioral changes when injected into wild-type mouse brains, but is prevented by cis antibody. Surprisingly, we also find robust cis P-tau with no evidence of tau tangles in human VaD brains and a mouse model of chronic cerebral hypoperfusion that mimics key aspects of clinical VaD. Cis mAb treatment of hypoperfusive mice for 1 or 6 months blocks VaD-like neuropathological and functional outcomes. Single-cell transcriptomic profiling reveals that cerebral hypoperfusion induces numerous global changes in diverse brain cells including those of human AD brains. Remarkably, ~90% of these global changes are fully recovered with cis antibody, correlating with tau expression in cells. Thus, cis P-tau is a major common early driver of AD and VaD, and cis antibody has a potential role in the early detection, prevention and treatment of these devastating diseases.
2021-02-10 | GSE126815 | GEO
Project description:Aging, Dementia, and TBI Study
| PRJNA413517 | ENA
Project description:Despite the strong association between diabetes and dementia, it remains to be fully elucidated how insulin deficiency adversely affects brain functions. We show that insulin deficiency in streptozotocin-induced diabetic mice decreased mitochondrial ATP production and/or citrate synthase and cytochrome oxidase activities in the cerebrum, hypothalamus, and hippocampus. Concomitant decrease in mitochondrial fusion proteins and increased fission proteins in these brain regions likely contributed to altered mitochondrial function. Although insulin deficiency did not cause any detectable increase in reactive oxygen species (ROS) emission, inhibition of monocarboxylate transporters increased ROS emission and further reduced ATP production, indicating the causative roles of elevated ketones and lactate in counteracting oxidative stress and as a fuel source for ATP production during insulin deficiency. Moreover, in healthy mice, intranasal insulin administration increased mitochondrial ATP production, demonstrating a direct regulatory role of insulin on brain mitochondrial function. Proteomics analysis of the cerebrum showed that although insulin deficiency led to oxidative post-translational modification of several proteins that cause tau phosphorylation and neurofibrillary degeneration, insulin administration enhanced neuronal development and neurotransmission pathways. Together these results render support for the critical role of insulin to maintain brain mitochondrial homeostasis and provide mechanistic insight into the potential therapeutic benefits of intranasal insulin.-Ruegsegger, G. N., Manjunatha, S., Summer, P., Gopala, S., Zabeilski, P., Dasari, S., Vanderboom, P. M., Lanza, I. R., Klaus, K. A., Nair, K. S. Insulin deficiency and intranasal insulin alter brain mitochondrial function: a potential factor for dementia in diabetes.
| S-EPMC6404590 | biostudies-literature