Transcriptional changes occurring in end-stage human SCA1 cerebellum.
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 4000
ORGANISM(S): Homo sapiens
SUBMITTER: Stamatia Laidou
PROVIDER: E-MTAB-7714 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Transcriptional changes occurring in end-stage human SCA1 cerebellum.
| PRJEB31342 | ENA
Project description:The cerebellum contains a circadian clock, generating internal temporal signals. The daily oscillations of cerebellar proteins were investigated here in mice using large-scale two-dimensional differences in gel electrophoresis (2D-DIGE). Analysis of 2D-DIGE gels highlighted the rhythmic variation in the intensity of 27/588 protein spots (5%) over 24-h based on cosinor regression. Notably, rhythmic expression of most abundant cerebellar proteins was clustered in two main phases (i.e., midday and midnight), leading to bimodal distribution. Only 6 proteins identified here to be rhythmic in the cerebellum are also known to oscillate in the suprachiasmatic nuclei, including 2 proteins involved in synapse activity (Synapsin 2 (Syn2) and vesicle-fusing ATPase (Nsf)), 2 others participating in carbohydrate metabolism (triosephosphate isomerase (Tpi1) and alpha-enolase (Eno1)), and Glutamine synthetase (Glul), as well as Tubulin alpha (Tuba4a). Most oscillating cerebellar proteins were not previously identified in circadian proteomic analyses of any tissue. Strikingly, daily accumulation of mitochondrial proteins was clustered to the mid-resting phase, as previously observed for distinct mitochondrial proteins in the liver. This study highlights extensive rhythmic aspects of the cerebellar proteome.
2019-04-23 | PXD013039 | Pride
Project description:Hepatic Encephalopathy is the brain disorder caused by liver damage, characterized by cognitive and motor impairments. Glutamate a predominant excitatory neurotransmitter over activate post-synaptic neuron via NMDAR receptors leads to neuronal derangement. NMDAR as a therapeutic target is not viable option due to its crucial role in brain physiology. In order to discover new non-NMDAR therapeutic targets high resolution mass spectrometry (HRMS) technique was used for proteomic profiling of MoHE rat’s model.
2026-04-29 | PXD036573 | Pride
Project description:The cerebellum harbors a circadian clock that can be shifted by scheduled mealtime and participates in behavioral anticipation of food access. To determine which cerebellar proteins are modified by time-of-day and/or feeding time, we determined day-night variations of proteome in the cerebellum of mice fed either ad libitum or only during daytime (from noon to lights off). Two-dimensional differences in gel electrophoresis (2D-DIGE) combined with two-way analyses of variance reveals that a majority of cerebellar proteins are significantly regulated by feeding conditions (food availability). Levels of few other cerebellar proteins were modulated exclusively by daily (or circadian) cues, independent of meal time, and others due to combined influence of meal time and time-of-day. Changes reflect behavioral anticipation of mealtime and/or feeding-induced shift in the circadian clock of the cerebellum.
2021-04-06 | PXD021056 | Pride
Project description:Transcriptome analysis of Ts1Cje (mouse model of Down syndrome) and euploids murine cerebellum during postnatal development Keywords = Down syndrome Keywords = Chromosome 21 Keywords = Transcriptome Keywords = Microarray Keywords = Cerebellum Keywords = Development Keywords: other
2004-12-05 | E-GEOD-1611 | biostudies-arrayexpress
Project description:Purkinje cells (PC) of the cerebellum degenerate in adult mice with mutations in the Niemann-Pick type C (NPC) disease 1 (Npc1) gene. We subjected BALB/c Npc1+/+ and Npc1-/- mouse cerebella from an early and a later time point of PC degeneration to a genome-wide microarray gene expression analysis. We found general underrepresentation of PC-specific transcripts, consistent with PC loss, and elevated markers of microglia activation at the later time point. Experiment Overall Design: 12 BALB/c Npc1 mice of the two ages P21 and P49 and the two genotypes Npc1+/+ and Npc1-/- were used, 3 replicates for each age and genotype. The animals were of the same breed and lived under identical housing conditions. All except one animal were female. The animals were not further treated, but only sacrificed at P21 or P49.
2008-06-14 | E-GEOD-5944 | biostudies-arrayexpress
Project description: Not available
2007-03-01 | E-TOXM-40 | biostudies-arrayexpress
Project description:The integrated stress response (ISR) is a conserved signaling pathway triggered by a variety of insults that include ER stress, mitochondrial stress, amino acid deprivation, and viral infection. The essential stress sensor and key effector of this pathway is eIF2B, and loss-of-function mutations in any of its 5 subunits can lead to Vanishing White Matter disease (VWM) in humans. We generated and characterized mouse models harboring different pathogenic mutations to model VWM and to understand the impact of chronic ISR activation on organismal and cellular physiology. Here, we performed bulk RNA-seq on the cerebellum, kidney, liver, lung, muscle, spinal cord, and spleen from 4-month-old homozygous Eif2b1[N208Y] and WT mice, either maintained on a 30 mg/kg 2BAct diet or withdrawn from the diet for 3 days. 2BAct is a small molecule eIF2B activator that can stabilize eIF2B and improve its function. This study also includes WT control mice naive to 2BAct diet.
2025-07-10 | E-MTAB-15273 | biostudies-arrayexpress
Project description:Background: Autism spectrum disorder (ASD) is a severe early onset neurodevelopmental disorder with high heritability but significant heterogeneity. Traditional genome-wide approaches to test for association of common variants with autism susceptibility risk has met with limited success. However, novel methods to identify moderate risk alleles in attainable sample sizes are now gaining momentum. Methods:M-BM- In this study, we utilized publically available GWAS data from the Autism Genome Project (AGP) and annotated the results (p < 0.001) for eQTLs present in the parietal lobe, cerebellum, and lymphoblastoid cell lines. We then performed a test of enrichment by comparing these results to simulated data conditioned on minor allele frequency in order to generate an empirical p-value indicating statistically significant enrichment of eQTLs in top results from the autism GWAS. Results:M-BM- Our findings show a global enrichment of brain eQTLs, but not LCL eQTLs, among top SNPs from an autism GWAS. Additionally, the data implicates individual genesM-BM- SLC25A12,M-BM- PANX1M-BM- andM-BM- PANX2, as well as pathways previously implicated in autism. Conclusions:M-BM- These findings provide supportive rationale for the use of annotation-based approaches to GWAS. We use microarray technology to understand the etiology and pathology of psychiatric diseases at the transcriptomic level. Postmortem human brain samples came from the Stanley Medical Research InstituteM-bM-^@M-^Ys Neuropathology Consortium and Array collections, including schizophrenia, bipolar disorder and control samples.
2012-12-31 | E-GEOD-35974 | biostudies-arrayexpress
Project description:Neuropsychiatric disorders are highly complex conditions and the risk of developing a disorder has been tied to hundreds of genomic variants that alter the expression and/or products (isoforms) made by risk genes. However, how these genes contribute to disease risk and onset through altered expression and RNA splicing is not well understood. Here we show our current understanding of gene isoforms is far from complete and reveal the precise splicing profiles of neuropsychiatric disorder risk genes. Combining our new bioinformatic pipeline IsoLamp with nanopore long-read amplicon sequencing, we deeply profiled the RNA isoform repertoire of 31 high-confidence neuropsychiatric disorder risk genes in human brain. We show most risk genes are more complex than previously reported, identifying 443 novel isoforms and 28 novel exons, including isoforms which alter protein domains, and genes such as ATG13 and GATAD2A where most expression was from previously undiscovered isoforms. The greatest isoform diversity was present in the schizophrenia risk gene ITIH4. Mass spectrometry of brain protein isolates confirmed translation of a novel exon skipping event in ITIH4, suggesting a new regulatory mechanism for this gene in brain
2025-07-25 | PXD063836 | Pride