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Extension of glycogene expression pattern analysis in the prefrontal cortical region of Schizophrenic human post-mortem brain samples

ABSTRACT: This laboratory focuses on the molecular mechanisms of neuropsychiatric and neurodegenerative disorders Extension of previous studies investigating Glyco-Gene Expression in Schizophrenia (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27356 ). From previous analyses, a group of 9 genes associated with the biosynthesis of glycosphingolipids were identified as altered in subjects with schizophrenia, with most differences detected in subjects with short DOI and not in chronic illness. The enzyme expression changes are of particular interest as they are important to the synthesis of cerebrosides and sulfatides, which are enriched in membranes making up myelin. There are known deficits in myelin and white matter in schizophrenia so changes in these enzymes may represent a mechanism accounting for these deficits. Furthermore, clusters of co-regulated genes were identified using new software for weighted gene co-networks. This may represent the first molecular definition of different subtypes of schizophrenia, a very heterogeneous psychiatric disorder.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE27601 | GEO | 2011/03/02

SECONDARY ACCESSION(S): PRJNA138275

REPOSITORIES: GEO

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Extension of glycogene expression pattern analysis in the prefrontal cortical region of Schizophrenic human post-mortem brain samples

Project description:This laboratory focuses on the molecular mechanisms of neuropsychiatric and neurodegenerative disorders Extension of previous studies investigating Glyco-Gene Expression in Schizophrenia (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27356 ). From previous analyses, a group of 9 genes associated with the biosynthesis of glycosphingolipids were identified as altered in subjects with schizophrenia, with most differences detected in subjects with short DOI and not in chronic illness. The enzyme expression changes are of particular interest as they are important to the synthesis of cerebrosides and sulfatides, which are enriched in membranes making up myelin. There are known deficits in myelin and white matter in schizophrenia so changes in these enzymes may represent a mechanism accounting for these deficits. Furthermore, clusters of co-regulated genes were identified using new software for weighted gene co-networks. This may represent the first molecular definition of different subtypes of schizophrenia, a very heterogeneous psychiatric disorder. For this follow up study, microarray analyses experiments were performed on an additional cohort of subjects with schizophrenia in order to, 1) Assess how this group of glycosphingolipid-related genes is altered in disease and control states, and 2) Further determine if co-regulated genes will cluster in the new cohort, which will consist of subjects with a range of durations of illness. For these studies, 32 human samples (16 control and 16 Schizophrenic) were labeled and hybridized to 26 GLYCOv2 arrays

2011-03-02 | E-GEOD-27601 | biostudies-arrayexpress

To analyze expression in the conjunctival epithelium of patients with severe dry eye disease

2011-04-29 | GSE28941 | GEO

Gene expression in human post-mortem brain samples from schizophrenic subjects and matched controls

Project description:This laboratory focuses on the molecular mechanisms of neuropsychiatric and neurodegenerative disorders Gene expression patterns from the pefrontal cortical region (Brodmann Area 46) of subjects with schizophrenia and age- and sex-match control subjects was analyzed. The prefrontal cortex was chosen since it is a primary brain region implicated in the pathophysiological of schizophrenia. Furthermore, this region was used in our previous proteomics studies, allowing for the direct comparison of changes in protein levels to gene expression results. 16 schizophrenic subjects were studied, consisting of 8 subjects with duration of illness (DOI) < 5 years and 8 subjects with DOI > 22 years. 16 age- and sex-matched controls were also studied. Gene expression profiles were analyzed from individual subjects; a total of 32 samples were hybridized to the custom designed CFG GLYCOv2 glycogene array.

2011-02-17 | E-GEOD-27356 | biostudies-arrayexpress

RNA-seq of oligodendroglia progenitor cells(OPCs) isolated from WT and DISC1-Δ3 mice

Project description:Disrupted-in-schizophrenia-1 (DISC1), as one of the schizophrenia susceptibility genes highly expressed in oligodendrocyte precursor cells (OPCs), impacts oligodendroglial differentiation and myelination. Several DISC1 splicing variants, including DISC1-Δ3 (a DISC1 transcript with deleted exon 3 in a single allele), are abnormally upregulated in human schizophrenia patients, however, how they trigger the onset of the disease has not been explored yet. Here, we generate a mouse line that mimics human DISC1-Δ3 in oligodendrocyte lineage cells, and demonstrate that hypertrophic OPCs rather than myelin, are responsible for the neuronal deficits and schizophrenia-like symptoms. RNAseq was performed to analyze the transcriptome change in DISC1-Δ3 OPC, revealing that DISC1-Δ3 elevates the Wnt pathway activity in OPCs, which promotes Wif1 expression, thereby leading to disrupted synapse formation in neighboring neurons. Interfering or knockout of Wif1 in DISC1-Δ3 OPCs could rescue neuronal synaptic and functional deficits in our mouse model. Our findings shed light on the myelination-independent role of OPCs on the onset of schizophrenia, and may pave the way for new rational lines of inquiry in developing therapeutic strategies for schizophrenia.

2022-12-28 | GSE183341 | GEO

Comparison of post-mortem tissue from Brodman Brain BA22 region between schizophrenic and control patients

Project description:Transcriptional analysis of the superior temporal cortex (BA22) in schizophrenia: Pathway insight into disease pathology and drug development Schizophrenia is a highly debilitating psychiatric disorder which is known to have heritable genetic and environmental components. To gain some insight into the mechanisms underpinning both positive and negative symptoms of the disease, we determined the genome wide expression of mRNA transcripts in post-mortem tissue from the superior temporal cortex (Brodmann Area 22, BA22) in schizophrenic and control patients. The BA22 region is known to mediate the positive pathophysiology of schizophrenia; we compared this to the anterior prefrontal cortex (BA10) from the same subjects, which is known to mediate negative symptoms. Following adjustments for confounding clinical, sample and experimental sources of variation, we carried out gene set enrichment analysis in each region using pathway data. We identified an over-representation of genes involved in cytoskeletal remodelling, neurodevelopment, cell adhesion, cellular signalling, neurotransmission and autophagy. Collectively our analysis indicates a disruption of processes underpinning synaptic plasticity in both regions. Region-specific changes support the dysregulation of distinct pathways in the BA10 and BA22 regions. This may highlight new therapeutic opportunities to treat both negative and positive symptoms of the disease.

2011-12-31 | GSE21935 | GEO

To analyze expression in the conjunctival epithelium of patients with severe dry eye disease

Project description:In 2005, we determined the glyco-gene expression profile of three normal subjects ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27593). This led to information on the biosynthesis of mucin O-glycans and glycoproteins that may be involved in the protection of the ocular surface. The interaction of the most highly expressed glycoprotein identified by the glyco-gene chip, galectin-3, with other ligands at the ocular surface (i.e., mucin O-glycans), is now under intense study in our laboratory, and has lead to a collaboration with another group in the glycobiology field. Patients with dry eye disease have an alteration of mucin O-glycans at the ocular surface, but the molecular mechanism(s) leading to this alteration remain unknown. In this experiment we (i) pooled three pathological samples per chip to reduce variability, and (ii) used three additional chips to include pooled control samples (normal subjects). Currently, we have RNA from 9 patients with dry eye disease, which have been divided it in 3 groups (D1, D2, and D3)—each group containing RNA pooled from 3 patients. We request three additional chips to include control samples (normal subjects). At this moment, we have RNA from 9 normal subjects, which have been divided it in 3 groups (N1, N2, and N3)—each group containing RNA pooled from 3 normal subjects. RNA was extracted in Trizol, purified using RNeasy column, and dissolved in water were sent to Microarray Core (E). The RNA was amplified, labeled, and hybridized to the GLYCOv3 microarrays. Data Analysis was done by Microarray Core (E).

2011-04-29 | E-GEOD-28941 | biostudies-arrayexpress

Comparing Control and Schizophrenic hiPSC-derived Neurons

Project description:Schizophrenia is a debilitating neurological disorder for which no cure exists. Few defining characteristics of schizophrenic neurons have been identified and the molecular mechanisms responsible for schizophrenia are not well understood, in part due to the lack of patient material for study. Human induced pluripotent stem cells (hiPSCs) offer a new strategy for studying schizophrenia. We have created the first cell-based human model of a complex genetic psychiatric disease by generating hiPSCs from schizophrenic patients and subsequently differentiating these cells to hiPSC-derived neurons in vitro. Schizophrenic hiPSC-derived neurons showed diminished neuronal connectivity in conjunction with decreased neurite number, PSD95-protein levels and glutamate receptor expression. Gene expression profiles of schizophrenic hiPSC-derived neurons identified altered expression of many components of the cAMP and WNT signaling pathways. Key cellular and molecular elements of the schizophrenic phenotype were ameliorated following treatment of schizophrenic hiPSC-derived neurons with the antipsychotic loxapine.

2011-05-01 | GSE25673 | GEO

Comparison of post-mortem tissue from Brodman Brain BA22 region between schizophrenic and control patients

2011-12-31 | E-GEOD-21935 | biostudies-arrayexpress

Comparing Control and Schizophrenic hiPSC-derived Neurons

2011-05-01 | E-GEOD-25673 | biostudies-arrayexpress

Epigenome analysis of normal and schizophrenic samples

Project description:We analyzed fresh frozen post-mortem brain tissue from a cohort of 73 schizophrenic and 52 control samples, using the Illumina Infinium HumanMethylation450 Bead Chip, to investigate genome-wide DNA methylation patterns in patients diagnosed with schizophrenia.

2019-03-21 | GSE128601 | GEO

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