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Targeted transcriptomic analysis of C57BL/6 and BALB/c mice during progressive chronic Toxoplasma gondii infection reveals changes in host and parasitic gene expression relating to neuropathology and resolution

ABSTRACT: Targeted transcriptomic analysis of C57BL/6 and BALB/c mice during progressive chronic Toxoplasma gondii infection reveals changes in host and parasitic gene expression relating to neuropathology and resolution

PROVIDER: PRJNA702084 | ENA |

REPOSITORIES: ENA

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Targeted transcriptomic analysis of C57BL/6 and BALB/c mice during progressive chronic Toxoplasma gondii infection reveals changes in host and parasitic gene expression relating to neuropathology and resolution [Neuropathology]

Project description:Toxoplasma gondii is a resilient parasite that infects a multitude of warm-blooded hosts and results in a lifelong chronic infection requiring continuous responses by the host. Chronic infection is characterized by a balanced immune response and neuropathology that are driven by changes in gene expression. Previous research pertaining to these processes has been conducted in various mouse models, and much knowledge of infection-induced gene expression changes has been acquired through the use of high throughput sequencing techniques in different mouse strains and post-mortem human studies. However, lack of infection time course data poses a prominent missing link in the understanding of chronic infection, and there is still much that is unknown regarding changes in genes specifically relating to neuropathology and resulting repair mechanisms as infection progresses throughout the different stages of chronicity. In this paper, we present a targeted approach to gene expression analysis during T. gondii infection through the use of NanoString nCounter gene expression assays. Wild type C57BL/6 and BALB/c background mice were infected, and transcriptional changes in the brain were evaluated at 14, 28, and 56 days post infection. Results demonstrate a dramatic shift in both previously demonstrated and novel gene expression relating to neuropathology and resolution in C57BL/6 mice. In addition, comparison between BALB/c and C57BL/6 mice demonstrate initial differences in gene expression that evolve over the course of infection and indicate decreased neuropathology and enhanced repair in BALB/c mice. In conclusion, these studies provide a targeted approach to gene expression analysis in the brain during infection and provide elaboration on previously identified transcriptional changes and also offer insights into further understanding the complexities of chronic T. gondii infection.

2021-03-12 | GSE166825 | GEO

2021-03-12 | GSE166827 | GEO

2021-03-12 | GSE166826 | GEO

Project description:Targeted transcriptomic analysis of C57BL/6 and BALB/c mice during progressive chronic Toxoplasma gondii infection reveals changes in host and parasitic gene expression relating to neuropathology and resolution [Neuropathology]

| PRJNA702088 | ENA

| PRJNA702089 | ENA

| PRJNA702090 | ENA

Transcriptional signatures of progressive neuropathology in tau and amyloid mouse models

Project description:Transcriptional signatures of progressive neuropathology in tau and amyloid mouse models

| PRJNA518104 | ENA

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-03-12 | GSE166828 | GEO

Cortical hypermethylation across an extended region spanning the HOXA gene cluster on chromosome 7 is robustly associated with Alzheimer's disease neuropathology

Project description:Alzheimer's disease is a progressive neurodegenerative disorder that is hypothesized to involve epigenetic dysfunction. We undertook an epigenome-wide association study across three independent brain tissue cohorts (total n = 999) to identify differential DNA methylation associated with neuropathology in the superior temporal gyrus and prefrontal cortex. We present robust evidence for elevated DNA methylation associated with AD neuropathology across an extended region spanning the HOXA gene cluster on chromosome 7. Prefrontal cortex and superior temporal gyrus tissue from 147 individuals with varying levels of AD pathology. DNA modifications for these samples were quantified using the Illumina Infinium Human 450K Methylation Array.

2016-08-01 | E-GEOD-80970 | biostudies-arrayexpress

Cross-tissue methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer’s disease neuropathology

Project description:Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that is characterized by progressive neuropathology and cognitive decline. We performed a cross-tissue analysis of methylomic variation in AD using samples from three independent human post-mortem brain cohorts. We identified a differentially methylated region in the ankyrin 1 (ANK1) gene that was associated with neuropathology in the entorhinal cortex, a primary site of AD manifestation. This region was confirmed as being substantially hypermethylated in two other cortical regions (superior temporal gyrus and prefrontal cortex), but not in the cerebellum, a region largely protected from neurodegeneration in AD, or whole blood obtained pre-mortem from the same individuals. Neuropathology-associated ANK1 hypermethylation was subsequently confirmed in cortical samples from three independent brain cohorts. This study represents, to the best of our knowledge, the first epigenome-wide association study of AD employing a sequential replication design across multiple tissues and highlights the power of this approach for identifying methylomic variation associated with complex disease. For the first (discovery) stage of our analysis, we used multiple tissues from donors (N = 122) archived in the MRC London Brainbank for Neurodegenerative Disease. From each donor, we isolated genomic DNA from four brain regions (EC, superior temporal gyrus (STG), prefrontal cortex (PFC) and CER) and, where available, from whole blood obtained pre-mortem. Our analyses focused on identifying differentially methylated positions (DMPs) associated with Braak staging, a standardized measure of neurofibrillary tangle burden determined at autopsy.

2014-08-17 | E-GEOD-59685 | biostudies-arrayexpress

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