Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Molecular correlation between mouse retina and striatum in HD

ABSTRACT: Huntington’s disease (HD) is a devastating disorder caused by an aberrant expansion of CAG repeats in the HTT gene. Striatal dysfunction has been widely studied in HD mouse models as part of the basal ganglia, the main brain areas affected in patients that explain the most evident symptomatology. However, cumulative evidence indicates that the retina can also be functionally altered with consequences for visual function and circadian rhythms. Moreover, the retina is the most exposed part of the CNS that can be used for monitoring the health status of patients using non-invasive techniques and for treatment screenings in preclinical models. To establish the retina as an appropriate tissue for HD studies, it is first required to link retinal alterations at the cellular and molecular levels with those of the inner brain. In this work, we confirmed that the retinas of R6/1 mice were functionally and morphologically affected, and suffered a rearrangement of its transcriptome as extensive as in the striatum. Tissue-enriched genes were downregulated in both areas, but a neuroinflammation signature was specific to the R6/1 retina through the glial activation that was apparently absent in the striatum of the same animals. These phenomena were confirmed in the zQ175 strain, and were accompanied by a differential impairment of the autophagy system between both tissues that may have implications for autophagic-based therapies in HD. Overall, these results demonstrated the suitability of the retina as a research model for HD and general neurodegeneration.

ORGANISM(S): Mus musculus

PROVIDER: GSE216520 | GEO | 2024/01/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Huntington disease mice exhibit a TCF7L2-responsive suppression of both homeostatic and compensatory remyelination

Project description:PDGFRA-EGFP+ striaal cells were isolated for bulk RNA-sequencing from R6/2 (6wk and 12wk) and zQ175 (12wk and 1yr) HD mice and littermate controls.

2022-08-01 | GSE181370 | GEO

DREAM silencing is part of a neuroprotective mechanism in Huntington's disease

Project description:Deregulated intracellular Ca2+ homeostasis underlies synaptic dysfunction and is a common feature in neurodegenerative processes, including Huntington's disease (HD). DREAM/calsenilin/KChIP-3 is a multifunctional Ca2+ binding protein that controls the expression level and/or the activity of several proteins related to Ca2+ homeostasis, neuronal excitability and neuronal survival. We found that expression of endogenous DREAM (DRE antagonist modulator) is reduced in the striatum of R6 mice, in STHdh-Q111/111 knock in striatal neurons and in HD patients. DREAM down regulation in R6 striatum occurs early after birth, well before the onset of motor coordination impairment, and could be part of an endogenous mechanism of neuroprotection, since i) R6/2 mice hemizygous for the DREAM gene (R6/2xDREAM+/-) showed delayed onset of locomotor impairment and prolonged lifespan, ii) motor impairment after chronic administration of 3-NPA was reduced in DREAM knockout mice and enhanced in daDREAM transgenic mice and, iii) lentiviral-mediated DREAM expression in STHdh-Q111/111 knock in cells sensitizes them to oxidative stress. Transcriptomic analysis showed that changes in gene expression in R6/2 striatum were notably reduced in R6/2xDREAM+/- striatum. Chronic administration of repaglinide, a molecule able to bind to DREAM in vitro and to accelerate its clearance in vivo, delayed the onset of motor dysfunction, reduced striatal loss and prolonged the lifespan in R6/2 mice. Furthermore, exposure to repaglinide protected STHdh-Q111/111 knock in striatal neurons sensitized to oxidative stress by lentiviral-mediated DREAM overexpression. Thus, genetic and pharmacological evidences disclose a role for DREAM silencing in early neuroprotective mechanisms in HD.

2016-02-01 | GSE48104 | GEO

Study of the effect of Protein Kinase CK2 alpha prime in the transcriptional deficits associated with Huntington's disease

Project description:Protein kinase CK2 alpha prime (CK2a') is preferentially upregulated in the striatum of patients with HD and in different cellular and mouse models of HD. CK2a' happloinsufficiency in the zQ175 HD mouse model restored several HD-like phenotypes. We hypothesized that CK2a' neuronal up-regulation is linked to key transcriptional alterations in the zQ175 mouse model. We found that CK2a' haploinsufficiency rescued the expression of genes associated with synaptogenesis and glutamatergic signaling whose upstream regulator seems to be alpha-synuclein. These transcriptomic studies revealed a conection between CK2a', alpha-synuclein dysfunction and transcriptional changes in key signaling pathways.

2022-06-23 | GSE160586 | GEO

Gene expression profiling of striatum in Huntington's disease model mouse

Project description:Gene expression profiling of striatum in R6/2 Huntington’s disease (HD) model mouse. Striatum gene set contained gene expression alterations in other neuronal populations, such as oligodendrocyte, astrocyte, microglia and interneuron.

2020-06-03 | GSE113929 | GEO

Astrocyte-neuron contributions to Huntington’s disease dissected with ZFPs

Project description:We performed cell-type specific RNAseq in astrocytes and neurons in the presence or absence of ZFP transcriptional repressors in the striatum of R6/2 mouse model of HD.

2022-12-15 | GSE189647 | GEO

The HDAC inhibitor 4b ameliorates the disease phenotype and transcriptional abnormalities in Huntington's disease transgenic mice

Project description:Transcriptional dysregulation has emerged as a core pathologic feature of Huntington's disease (HD), one of several triplet-repeat disorders characterized by movement deficits and cognitive dysfunction. Although the mechanisms contributing to the gene expression deficits remain unknown, therapeutic strategies have aimed to improve transcriptional output via modulation of chromatin structure. Recent studies have demonstrated therapeutic effects of commercially available histone deacetylase (HDAC) inhibitors in several HD models; however, the therapeutic value of these compounds is limited by their toxic effects. Here, beneficial effects of a novel pimelic diphenylamide HDAC inhibitor, HDACi 4b, in an HD mouse model are reported. Chronic oral administration of HDACi 4b, beginning after the onset of motor deficits, significantly improved motor performance, overall appearance, and body weight of symptomatic R6/2(300Q) transgenic mice. These effects were associated with significant attenuation of gross brain-size decline and striatal atrophy. Microarray studies revealed that HDACi 4b treatment ameliorated, in part, alterations in gene expression caused by the presence of mutant huntingtin protein in the striatum, cortex, and cerebellum of R6/2(300Q) transgenic mice. For selected genes, HDACi 4b treatment reversed histone H3 hypoacetylation observed in the presence of mutant huntingtin, in association with correction of mRNA expression levels. These findings suggest that HDACi 4b, and possibly related HDAC inhibitors, may offer clinical benefit for HD patients and provide a novel set of potential biomarkers for clinical assessment. Analysis of striatum, cortex, and cerebellum from R6/2(300Q) transgenic mice before and after treatment with the HDAC inhibitor 4b

2010-12-27 | E-GEOD-26317 | biostudies-arrayexpress

Mus musculus

Project description:Six-week-old R6/2 HD mouse striatum

| PRJNA90411 | ENA

Targeting H3K4 methylation as a therapeutic strategy for Huntington's disease (RNA-seq)

Project description:Transcriptional dysregulation is an early feature of Huntington's disease (HD). We observed gene-specific changes in H3K4me3 at transcriptionally repressed promoters in R6/2 mouse and human HD brain. Genome-wide analysis showed a novel chromatin signature for this mark. Reducing the levels of the H3K4 demethylase SMCX/Jarid1c in primary neurons reversed down-regulation of key neuronal genes caused by mutant Huntingtin (Htt) expression. Finally, reduction of SMCX/Jarid1c in primary neurons from BACHD mice or the single Jarid1 in a Drosophila HD model was protective. Therefore, targeting this epigenetic signature may be an effective strategy to ameliorate the consequences of HD. mRNA-seq in wild type and R6/2 cortex and striatum at 8 and 12 weeks.

2013-07-18 | E-GEOD-48962 | biostudies-arrayexpress

Targeting H3K4 methylation as a therapeutic strategy for Huntington's disease (ChIP-seq)

Project description:Transcriptional dysregulation is an early feature of Huntington's disease (HD). We observed gene-specific changes in H3K4me3 at transcriptionally repressed promoters in R6/2 mouse and human HD brain. Genome-wide analysis showed a novel chromatin signature for this mark. Reducing the levels of the H3K4 demethylase SMCX/Jarid1c in primary neurons reversed down-regulation of key neuronal genes caused by mutant Huntingtin (Htt) expression. Finally, reduction of SMCX/Jarid1c in primary neurons from BACHD mice or the single Jarid1 in a Drosophila HD model was protective. Therefore, targeting this epigenetic signature may be an effective strategy to ameliorate the consequences of HD. ChIP-seq for H3K4me3 in wild type and R6/2 cortex and striatum at 8 and 12 weeks.

2013-07-18 | E-GEOD-48960 | biostudies-arrayexpress

Transcriptional profiling of striatum from a zQ175 KI mouse model of Huntington's disease with or without homozygous knockout of the Msh3 gene

Project description:Previous studies have suggested a strong association between lower MSH3 expression, reduced somatic repeat expansion, and slower disease onset and progression. The effects of a homozygous knock-out in the Msh3 gene on transcriptome phenotypes in striatum in six-month-old WT and zQ175 mice were studied. Striatum was isolated from 6-month-old mice. Transcriptomic analysis (RNASeq) was performed on four genotypes with 8 replicates per genotype: WT (WT for Htt and Msh3), zQ175 (zQ175 for Htt, WT for Msh3), WT.Msh3.HOM (WT for Htt, Homozygous for Msh3 KO), and zQ175.Msh3.HOM (zQ175 for Htt, Homozygous for Msh3 KO).

2024-05-24 | GSE245510 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data