Altered gene expression in prefrontal cortex of a Fabry disease mouse model
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ABSTRACT:
PROVIDER: PRJNA434186 | ENA |
REPOSITORIES: ENA
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Project description:Fabry disease is an X-chromosome linked hereditary disease that is caused by loss of function mutations in the α-galactosidase A (α-Gal A) gene, resulting in defective glycolipid degradation and subsequent accumulation of globotriaosylceramide (Gb3) in different tissues, including vascular endothelial cells and neurons in the peripheral and central nervous system. We recently reported a differential gene expression profile of α-Gal A(-/0) mouse dorsal root ganglia, an established animal model of Fabry disease, thereby providing new gene targets that might underlie the neuropathic pain related symptoms. To investigate the cognitive symptoms experienced by Fabry patients, we performed one-color based hybridization microarray expression profiling of prefrontal cortex samples from adult α-Gal A(-/0) mice and age-matched wildtype controls, followed by protein-protein interaction and pathway analyses for the differentially regulated mRNAs. We found that from a total of 381 differentially expressed genes, 135 genes were significantly upregulated, whereas 246 genes were significantly downregulated between α-Gal A(-/0) mice and wildtype controls. Enrichment analysis for downregulated genes revealed mainly immune related pathways, including immune/defense responses, regulation of cytokine production, as well as signaling and transport regulation pathways. Further analysis of the regulated genes revealed a large number of genes involved in neurodegeneration. The current analysis for the first time presents a differential gene expression profile of central nervous system tissue from α-Gal A(-/0) mice, thereby providing novel knowledge on the deregulation and a possible contribution of gene expression to Fabry disease related brain pathologies.
| S-EPMC6036252 | biostudies-literature
Project description:In the current study we performed mRNA microarray expression profiling of PFC samples from α-Gal A(-/0) mice aged >20 weeks when the disease is fully developed to investigate the mRNA signatures associated with FD cognitive symptoms. We found that in total 381 genes from the overall 21’393 detected mRNAs were significantly different between PFC samples from wildtype and α-Gal A(-/0) mice (criteria p ≤ 0.01, absolute fold change ≥ 1.2). Of those, 135 genes were significantly upregulated and 246 genes were significantly downregulated as compared to wildtype controls. More stringent filtering (criteria p ≤ 0.01, absolute fold change ≥ 2) of those significantly regulated genes revealed an assessable number of 50 genes in total . Using these criteria 19 genes were significantly upregulated, of which 11 showed FDR corrected p ≤ 0.1. Furthermore, 31 genes were significantly downregulated, of which 17 showed FDR corrected p ≤ 0.1.
2018-07-01 | GSE110645 | GEO
Project description:Objective. The goal of this study was to examine the microRNA (miRNA) profile of Parkinsonâ??s disease (PD) frontal cortex as compared to normal control brain, allowing for the identification of PD specific signatures as well as the study of disease-related phenotypes, such as onset age or dementia Methods. Small RNA sequence analysis was performed from prefrontal cortex for 29 PD samples and 33 control samples. After sample QC, normalization and batch correction, linear regression was used to identify miRNAs altered in PD, and a PD classifier was developed using weighted voting class prediction. The relationship of miRNA levels to onset age and PD with dementia (PDD) was also characterized in case-only analyses. Results. 125 miRNAs were differentially expressed in PD at a genome-wide level of significance (FDR q<0.05). A set of 29 miRNAs classified PD from non-diseased brain (93.9% specificity, 96.6% sensitivity). The majority of differentially expressed miRNAs (105/125) showed an ordinal relationship from control, to PD without dementia (PDN), to PDD. Among PD brains, 36 miRNAs classified PDD from PDN (sensitivity =81.2%, specificity =88.9%). Among differentially expressed miRNAs, miR-10b-5p had a positive association with onset age (q=4.7e-2). Conclusions. Based on cortical miRNA levels, PD brains were accurately classified from non-diseased brains. Additionally, the PDD miRNA profile exhibited a more severe pattern of alteration among those differentially expressed in PD. To evaluate the clinical utility of miRNAs as potential clinical biomarkers, further characterization and testing of brain-related miRNA alterations in peripheral biofluids is justified. 29 Parkinson's disease prefrontal cortex samples analyzed with 33 control samples from Series GSE64977.
2016-03-16 | E-GEOD-72962 | biostudies-arrayexpress
Project description:The dorsolateral prefrontal cortex (DLPFC) is the association area in the anterior part of the frontal lobe and has a crucial role in cognitive functioning and negative symptoms in SZschizophrenia. However, limited information of altered protein networks is available in this region in schizophrenia. We performed a proteomic analysis using single-shot liquid chromatography-tandem mass spectrometry of grey matter of postmortem DLPFC in chronic schizophrenia subjects (n=20) and healthy individuals (n=20) followed by bioinformatic analysis to identify altered protein networks in SZ.
2023-05-10 | PXD024939 | Pride
Project description:Fabry nephropathy (FN) is a rare disorder caused by mutations in the alpha-galactosidase A gene. In this study we aim at providing a framework allowing selection of biomarkers and drug-targets. Two independent Fabry Nephropathy cohorts (FA.NO and CH.RO) were subjected to RNAseq from archival kidney biopsies taken prior and up to 10 years of Enzyme Replacement Therapy. Four compartments were laser capture microdissected (glomeruli, proximal tubuli, distal tubuli and arteries). We found several pathways that were consistently altered and that these kidney compartments’ transcriptional landscapes can be leveraged in the search for drug-targets and biomarkers.
2023-07-17 | GSE178947 | GEO
Project description:There has been an incresing body of epidemiologic and biochemical evidence implying the role of cerebral insulin resistance in Alzheimer-type dementia. For a better understanding of the insulin effect on the central nervous system we performed microarray-based gene expression profiling in the hippocampus, striatum and prefrontal cortex of streptozotocin-induced and spontaneously diabetic Goto-Kakizaki rats as model animals for type 1 and type 2 diabetes, respectively. Following pathway analysis and validation of gene lists by RT-PCR, 30 genes from hippocampus, such as the inhibitory neuropeptide galanin, synuclein gamma and uncoupling protein 2, and 22 genes from the prefrontal cortex, e.g. galanin receptor 2, protein kinase gamma and epsilon, ABCA1, CD47 and the RET protooncogene, were found to exhibit altered expression levels in type 2 diabetic model animals in comparison to non-diabetic control animals. These gene lists proved to be partly overlapping and encompassed genes related to neurotransmission, lipidmetabolism, neuronal development, insulin secretion, oxidative damage and DNA repair. On the other hand, no significant alterations were found in the transcriptomes of the corpus sriatum in the same animals. Changes in the cerebral gene expression profiles seemed to be specific for the type 2 diabetic model, as no such alterations were found in streptozotocin-treated animals. According to our knowledge this is the first characterization of the whole-genome expression changes of specific brain regions in a diabetic model. Our findings shed light on the complex role of insulin signaling in fine-tuning brain functions, and provide further experimental evidence in support of the recently elaborated theory of type 3diabetes. Experiments were performed with 9 animals from each group. Wistar rats (control), streptoztocin-treated Wistar rats (type 1 diabetes) and Goto-Kakizaki rats (type 2 diabetes). The brain was removed and the striatum, hippocampus and prefrontal cortex were dissected. Samples from 3-3 identically treated animals were pooled. That means, 3 biological parallels were prepared from each brain region of type 1 or type 2 diabetic and control animals, amounting to a total of 27 different pooled samples.
2011-12-15 | E-GEOD-34451 | biostudies-arrayexpress
Project description:The prefrontal cortex is greatly associated with a wide range of mental health illnesses including schizophrenia, depression, bipolar disorder, anxiety and autism spectrum disorders. It richly expresses neuroreceptors which are the target for typical and atypical antipsychotics. However as the precise mechanism of action of antipsychotic medications are not known, proteomic studies of the effects of antipsychotic drugs on the brain are warranted. In the current study we aimed to characterise protein expression in the adult rodent prefrontal cortex (n=5 per group) following low dose treatment with the atypical antipsychotic Risperidone or saline (control) in adolescence (postnatal days 34-47). The prefrontal cortex was examined by triplicate one hour runs of label-free LC-MS/MS. The raw mass spectral data were analyzed with the MaxQuantTM software. Statistical analysis was carried out using SAS Version 9.1. Functional and pathway analysis was performed with DAVID.nih and Ingenuity Pathway Analysis respectively and the top five most implicated pathways were found to be clathrin mediated endocytosis, the tri cyclic acid cycle, remodelling of epithelial junctions, rho family GTPase signalling and mitochondrial dysfunction.This brief report summarises the proteomic data obtained from the study described, adds to the current repertoire of data available concerning the effects of atypical antipsychotic drugs on the brain and sheds light on their biological mechanisms.
2014-05-13 | PXD000480 | Pride
Project description:Whole genome expression in Parkinson disease and neurologically healthy control prefrontal cortex Brodmann area 9 samples
2012-09-19 | E-MTAB-812 | biostudies-arrayexpress
Project description:We report the application of high-throughput RNA sequencing to the human prefrontal cortex. The brain dataset was obtained by sequencing total RNAs extracted from the dorsolateral prefrontal cortex of five deceased human patients with no apparent pathology, followed by depletion of ribosomal RNA to obtain all non-rRNA coding and non-coding RNAs in the human brain transcriptome. Five samples were sequenced, four coming from frozen brain tissue (frontal cortex) of deceased female human patients with no remarkable pathology, and one from a male patient with no remarkable pathology.
2013-07-01 | E-GEOD-46523 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE17757: Gene expression data from primate postnatal brain in prefrontal cortex: time course GSE18012: miRNA expression data from human postnatal brain in prefrontal cortex: time course GSE18013: miRNA expression data from rhesus macaque postnatal brain in prefrontal cortex: time course Refer to individual Series
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