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Spatial transcriptomics analysis of wild type, 5XFAD mice, 5XFAD mice treated with either vehicle or human neural stem cells (hNSC)

ABSTRACT: Spatial transcriptomics analysis was performed to detect differential gene expression in brain sections of of wild type, 5XFAD mice (model of Alzheimer's Disease), 5XFAD mice treated with either vehicle or human neural stem cells (hNSC)

ORGANISM(S): Mus musculus

PROVIDER: GSE209583 | GEO | 2023/12/31

REPOSITORIES: GEO

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Spatial transcriptomics analysis of wild type, 5XFAD mice, 5XFAD mice treated with either vehicle or human neural stem cells (hNSC)

Project description:Spatial transcriptomics analysis of wild type, 5XFAD mice, 5XFAD mice treated with either vehicle or human neural stem cells (hNSC)

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Project description:Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. There are two types of AMD: dry AMD and wet AMD. While laser-induced choroidal neovascularization has been used extensively in the studies of wet AMD by presenting the main features of human wet AMD, there was no established mouse model which fully recapitulates the cardinal features of human dry AMD. In this regard, lack of appropriate mouse model for dry AMD hampered the translational research on the pathogenesis and development of therapeutic agents. We recently suggested that 5XFAD mice could be a mouse model of dry AMD with regard to the amyloid beta (AÎ²) related pathology. In this study, using transmission electron microscope, we analyzed ultrastructure of retinal pigment epithelium (RPE) of 5XFAD mice. Of importance, aged 5XFAD mice had ultrastructural changes of RPE and Bruchâs membrane compatible with cardinal features of dry AMD, including loss of apical microvilli and basal infolding of RPE, increased thickness of Bruchâs membrane, basal laminar and linear deposits, and accumulation of lipofuscin granules and undigested photoreceptor outer segment-laiden phagosomes. Using a threshold of 1.2 fold difference, we found â564â differentially expressed genes of which â190â were up-regulated and â374â were down-regulated in the RPE complex of aged 5XFAD mice. These altered genes were implicated in the pathogenesis of AMD including inflammation and immune response-related genes and retinol metabolism-related genes. Taken together, we suggest that aged 5XFAD mice can be used for dry AMD mouse model. All 5XFAD mice used were heterozygotes with respect to the transgene, and non-transgenic wild-type littermate (WT) mice served as controls.

2016-08-10 | E-GEOD-85408 | biostudies-arrayexpress

scRNAseq and scATACseq of Cd45+ cells from brains of 5XFAD mice bearing distinct APOE alleles and across age

Project description:Here we analyze the gene expression and chromatin accessibility landscape of immune cells in the brains of 5XFAD mice, a common model of Alzheimer's disease, bearing knock-in of human APOE variants in the mouse APOE locus, and aged to 10, 20, 60, or 96 weeks of age.

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Deep proteome profiling of hippocampus in 5xFAD mouse model

Project description:Alzheimer's disease (AD) is the most common neurodegenerative disease and characterized by the deposition of extracellular amyloid plaques and intracellular neurofibrillary tangles. Although extensive research was performed for Alzheimer's disease (AD) is the most common neurodegenerative disease and characterized by the deposition of extracellular amyloid plaques and intracellular neurofibrillary tangles. Although extensive research was performed for decades, the exact mechanisms and pathological causes of the disease still remain unknown. In order to perform comprehensive and integrative characterization of AD brain, assessment of global proteomic dynamics is required. We performed hippocampal proteome analysis to compare differentially expressed proteins in wild-type and 5XFAD model mice by label-free LC-MS. decades, the exact mechanisms and pathological causes of the disease still remain unknown. In order to perform comprehensive and integrative characterization of AD brain, assessment of global proteomic dynamics is required. We performed hippocampal proteome analysis to compare differentially expressed proteins in wild-type and 5XFAD model mice by label-free LC-MS.

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Limited effects of an eIF2αS51A allele on neurological impairments in the 5xFAD mouse model of Alzheimer’s disease

Project description:Transcriptome analysis of hippocampal RNA samples from wild-type, 5xFAD, 5xFAD;eIF2α+/S51A and eIF2α+/S51A mice Our transcriptome analyses showed clear transcriptional alterations in hippocampi of 5xFAD compared to wild type mice that were not corrected by the eIF2αS51A allele. Hemizygous 5xFAD mice, which were on a genetic background of B6/SJL, were crossed with eIF2α+/S51A mice (C57BL/6J background), to generate the offspring that was analyzed in the microarray. Hippocampal samples of 12 mice (4 groups: wild-type, 5xFAD, 5xFAD;eIF2α+/S51A and eIF2α+/S51A) were processed using Affymetrix Mouse Exon 1.0 ST platform. Array data was processed by Affymetrix Exon Array Computational Tool. No technical replicates were performed.

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Expression data from WT and TREM2 deficient microglia in a mouse model of Alzheimer's disease

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mRNA array in brain tissue samples of 5XFAD mice

Project description:In Alzheimer's disease pathology, several neuronal processes are dysregulated by excitotoxicity including neuroinflammation and oxidative stress (OS). New therapeutic agents capable of modulating such processes are needed to foster neuroprotection. Here, the effect of an optimised NMDA receptor antagonist, UB-ALT-EV and memantine, as a gold standard, have been evaluated in 5XFAD mice. Following treatment with UB-ALT-EV, nor memantine, changes in the calcineurin (CaN)/NFAT pathway were detected. UB-ALT-EV increased neurotropic factors (Bdnf, Vgf and Ngf) gene expression. Treatments reduced astrocytic and microglial activation as revealed by GFAP and Iba-1 quantification. Interestingly, only UB-ALT-EV was able to reduce gene expression of Trem2, a marker of microglial activation and NF-κB. Pro-inflammatory M1-microglial phenotype (Il-1β, Ifn-γ, Ccl2 and Ccl3) markers were down-regulated in UB-ALT-EV-treated mice but not in memantine-treated mice. Interestingly, the anti-inflammatory markers of the M2-migroglial phenotype, chitinase-like 3 (Ym1) and Arginase-1 (Arg1), were up-regulated after treatment with UB-ALT-EV. Since iNOS gene expression decreased after UB-ALT-EV treatment, a qPCR array containing 84 OS-related genes was performed. We found changes in Il-19, Il-22, Gpx6, Ncf1, Aox1 and Vim gene expression after UB-ALT-EV. In sum, our results reveal a robust effect on neuroinflammation and OS processes after UB-ALT-EV treatment, surpassing the memantine effect in 5XFAD.

2023-05-02 | GSE202061 | GEO

Sex-biased hippocampal pathology in the 5XFAD mouse model of Alzheimer's disease: A multi-omic analysis

Project description:Numerous neurological disorders, including Alzheimer's disease, display a sex-biased prevalence. To identify molecular correlates of this sex bias, we investigated sex-differences in molecular pathology in the hippocampus using the 5XFAD mouse model of Alzheimer's disease during early stages of disease progression (1, 2, and 4 months of age).

2019-02-13 | GSE97113 | GEO

Ligilactobacillus murinus strain:41-week-old Tg 5XFAD mice feces | isolate:41-week-old Tg 5XFAD mice feces

Project description:Ligilactobacillus murinus strain:41-week-old Tg 5XFAD mice feces | isolate:41-week-old Tg 5XFAD mice feces Genome sequencing

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Effect of PD-1 immune checkpoint in Alzheimer's disease transgenic mice

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