3′ sequencing from human Huntington's disease and control motor cortex and cerebellum.
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ABSTRACT:
PROVIDER: PRJNA378801 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: We applied polyA site sequencing (Passeq) to human Huntington's disease and control motor cortex and cerebellum to test if any genes change 3′UTR isoforms abundance. Methods: 3′ sequencing was performed on 6 motor cortices from grade 1 Huntington's patient brains, 4 motor cortices from grade 2 Huntington's patient brains, and 5 motor cortices from control brains. Cerebellum samples included 9 cerebella from grade 2-3 Huntington's patient brains, and 7 cerebella from control brains. To verify HTT isoforms in mice, sequencing was performed on 5 Q140 mouse striata and 3 wild-type mouse striata. Results: We report 11% of genes from Huntington's disease patient motor cortex exhibit a change in at least one of their 3′UTR isoforms, commensurate with the 11% of genes which show different total expression in HD motor cortex versus control. In contrast, gene isoform and expression changes are minimal (<5%) in Huntington's disease cerebellum versus controls. In the motor cortex, we show isoform and gene expression differs between between grade 1 and grade 2 brains. We identify a novel isoform of huntingtin mRNA which is conserved in wild-type and Huntington's model mice. Conclusions: This is the first study characterizing widespread alterations in 3′UTR isoform abundance in Huntington's disease. Alterations in isoform abundance may affect mRNA metabolism in Huntington's disease brains.
2017-09-21 | GSE96099 | GEO
Project description:Ion channel splice array data from cerebellum brain tissue samples collected from control (non Alzheimer's disease) subjects. Temporal cortex (Alzheimer's disease affected brain tissue structure) and cerebellum (Alzheimer's disease unaffected brain tissue structure) samples from control subjects were compared to temporal cortex and cerebellum of patients with Alzheimer's disease.
2010-06-11 | E-GEOD-6778 | biostudies-arrayexpress
Project description:The properties of the cell types that are most vulnerable in the Huntington's disease (HD) cortex have not been delineated. Here we have employed serial fluorescence activated nuclear sorting (sFANS) and deep molecular profiling to demonstrate that layer 5a pyramidal neurons are selectively vulnerable in primary motor cortex and other cortical areas.
2024-01-17 | GSE233408 | GEO
Project description:Ion channel splice array data from temporal cortex brain tissue samples collected from control subjects (no Alzheimer's disease). Temporal cortex (Alzheimer's disease affected brain tissue structure) and cerebellum (Alzheimer's disease unaffected brain tissue structure) samples from control subjects were compared to temporal cortex and cerebellum of patients with Alzheimer's disease.
2010-06-11 | E-GEOD-6774 | biostudies-arrayexpress
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
Project description:To identify genome-wide differentially expressed microRNAs (miRNAs) between Huntington's disease (HD) and control Human pre-frontal cortex samples
2014-01-30 | E-MTAB-2206 | biostudies-arrayexpress
Project description:The neurodegenerative disease spinocerebellar ataxia type 1 (SCA1) is known to lead to progressive degeneration of specific neuronal populations, including cerebellar Purkinje cells (PCs), brainstem cranial nerve nuclei and inferior olive nuclei, and spinocerebellar tracts. The disease-causing protein ataxin-1 is fairly ubiquitously expressed throughout the brain and spinal cord, but most studies have primarily focused on the role of ataxin-1 in the cerebellum and brainstem. Therefore, the functions of ataxin-1 and the effects of SCA1 mutations in other brain regions including the cortex are not well known. Here, we characterized pathology in the motor cortex of a SCA1 mouse model and performed RNA sequencing in this brain region to investigate the impact of mutant ataxin-1 towards transcriptomic alterations. We identified progressive cortical pathology and significant transcriptomic changes in the motor cortex of a SCA1 mouse model. We also identified progressive, region-specific, colocalization of p62 with mutant ataxin-1 aggregates in broad brain regions, but not the cerebellum or brainstem. A cross-regional comparison of the SCA1 cortical and cerebellar transcriptomic changes identified both common and unique gene expression changes between the two regions, including shared synaptic dysfunction and region-specific kinase regulation. These findings suggest that the cortex is progressively impacted via both shared and region-specific mechanisms in SCA1.
2022-08-22 | GSE211678 | GEO
Project description:Ion channel splice array data from cerebellum brain tissue samples collected from Alzheimer's disease patients. Temporal cortex (Alzheimer's disease affected brain tissue structure) and cerebellum (Alzheimer's disease unaffected brain tissue structure) samples from control subjects were compared to temporal cortex and cerebellum of patients with Alzheimer's disease.
2010-06-11 | E-GEOD-6777 | biostudies-arrayexpress
Project description:Human brain tissue was obtained from the New Zealand Brain Bank from donors with Alzheimer's disease (AD) or age-matched controls (n=9/group). Mean post mortem delays were ~12h. Six distinct brain regions were dissected, Hippocampus, Cingulate Gyrus, Entorhinal Cortex (severely affected), Motor and Sensory Cortex (less affected) and Cerebellum (spared). Protein was extracted from each sample and, each region was analysed independently. For each region, samples were divided into 3 sets of 3 cases and 3 controls and assigned to an iTRAQ 8 plex, alongside two aliquots of a pooled QC sample. Samples were digested, iTRAQ labelled and analysed. For each region, between 3000 and 4200 proteins were compared between AD and control, identifying a series of known and novel protein expression changes associated with the progression of AD.
2019-02-15 | PXD008807 | Pride
Project description:Progressive motor alterations and selective death of striatal medium spiny neurons (MSNs) are key pathological hallmarks of Huntington's disease (HD), a neurodegenerative condition caused by a CAG trinucleotide repeat expansion in the coding region of the huntingtin (HTT) gene. Most research has focused on the pathogenic effects of the resultant protein product(s); however, growing evidence indicates that expanded CAG repeats within mutant HTT mRNA and derived small CAG repeat RNAs (sCAG) participate in HD pathophysiology. The individual contribution of protein versus RNA toxicity to HD pathophysiology remains largely uncharacterized and the role of other classes of small RNAs (sRNA) that are strongly perturbed in HD is uncertain. Here, have injected vehicle, CTL-sRNA (obtained from non-affected individuals) or HD-sRNA (obtained from patients with HD) from different brain areas (putamen, PT; cortex, CTX and cerebellum, CB) into the striatum of wild type (WT) mice and demonstrate that sRNA produced in the putamen and cortex of HD patients are sufficient to induce HD pathology in vivo. We have performed small RNA (sRNA) sequencing of the human samples used for injection. Here we describe the procedure to obtain and sequence human sRNA isolated from the different brain areas.
2021-02-16 | GSE165663 | GEO