scholarly journals Network modules linking expression and methylation in prefrontal cortex of schizophrenia

2018 ◽  
Author(s):  
Dongdong Lin ◽  
Jiayu Chen ◽  
Nora Perrone-Bizzozero ◽  
Jing Sui ◽  
Vince Calhoun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Aging Process ◽  
Great Success ◽  
Genetic Components ◽  
Dorsolateral Prefrontal ◽  
Network Modules ◽  
Significant Enrichment ◽  
Oligodendrocyte Development ◽  
Network Approaches

Tremendous work has demonstrated the critical roles of genetics, epigenetics as well as their interplay in brain transcriptional regulations in the pathology of schizophrenia (SCZ). There is great success currently in the dissection of the genetic components underlying risk-conferring transcriptomic networks. However, the study of regulating effect of epigenetics, as a modulator of environmental factors, in the etiopathogenesis of SCZ still faces many challenges. In this work we investigated DNA methylation and gene expression from the dorsolateral prefrontal cortex (DLPFC) region of schizophrenia patients and healthy controls using weighted correlation network approaches. We identified and replicated two expression and two methylation modules significantly associated with SCZ. Among them, one pair of expression and methylation modules were significantly overlapped in the module genes which were enriched in astrocyte-associated functional pathways, and specifically expressed in astrocytes. Another two linked expression-methylation module pairs were involved aging process with module genes mostly related to oligodendrocyte development and myelination, and specially expressed in oligodendrocytes. Further examination of underlying quantitative trait loci (QTLs) showed significant enrichment in genetic risk of most psychiatric disorders for expression QTLs but not for methylation QTLs. These results support the coherence between methylation and gene expression in a network level, and suggest a combinatorial effect of genetics and epigenetics in regulating gene expression networks specific to glia cells in relation with SCZ and aging process.

scholarly journals Molecular pathology associated with altered synaptic transcriptome in the dorsolateral prefrontal cortex of depressed subjects

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuta Yoshino ◽  
Bhaskar Roy ◽  
Nilesh Kumar ◽  
M. Shahid Mukhtar ◽  
Yogesh Dwivedi
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Prefrontal Cortex ◽  
Dorsolateral Prefrontal Cortex ◽  
Gene Network ◽  
Nervous System Development ◽  
Network Analyses ◽  
Dorsolateral Prefrontal ◽  
Total Fraction ◽  
Transcriptomic Changes

AbstractDisrupted synaptic plasticity is the hallmark of major depressive disorder (MDD), with accompanying changes at the molecular and cellular levels. Often, the maladaptive molecular changes at the synapse are the result of global transcriptional reprogramming dictated by activity-dependent synaptic modulation. Thus far, no study has directly studied the transcriptome-wide expression changes locally at the synapse in MDD brain. Here, we have examined altered synaptic transcriptomics and their functional relevance in MDD with a focus on the dorsolateral prefrontal cortex (dlPFC). RNA was isolated from total fraction and purified synaptosomes of dlPFC from well-matched 15 non-psychiatric controls and 15 MDD subjects. Transcriptomic changes in synaptic and total fractions were detected by next-generation RNA-sequencing (NGS) and analyzed independently. The ratio of synaptic/total fraction was estimated to evaluate a shift in gene expression ratio in MDD subjects. Bioinformatics and network analyses were used to determine the biological relevance of transcriptomic changes in both total and synaptic fractions based on gene–gene network, gene ontology (GO), and pathway prediction algorithms. A total of 14,005 genes were detected in total fraction. A total of 104 genes were differentially regulated (73 upregulated and 31 downregulated) in MDD group based on 1.3-fold change threshold and p < 0.05 criteria. In synaptosomes, out of 13,236 detectable genes, 234 were upregulated and 60 were downregulated (>1.3-fold, p < 0.05). Several of these altered genes were validated independently by a quantitative polymerase chain reaction (qPCR). GO revealed an association with immune system processes and cell death. Moreover, a cluster of genes belonged to the nervous system development, and psychological disorders were discovered using gene–gene network analysis. The ratio of synaptic/total fraction showed a shift in expression of 119 genes in MDD subjects, which were primarily associated with neuroinflammation, interleukin signaling, and cell death. Our results suggest not only large-scale gene expression changes in synaptosomes, but also a shift in the expression of genes from total to synaptic fractions of dlPFC of MDD subjects with their potential role in immunomodulation and cell death. Our findings provide new insights into the understanding of transcriptomic regulation at the synapse and their possible role in MDD pathogenesis.

scholarly journals Publisher Correction: Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex

2021 ◽  
Author(s):  
Kristen R. Maynard ◽  
Leonardo Collado-Torres ◽  
Lukas M. Weber ◽  
Cedric Uytingco ◽  
Brianna K. Barry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Dorsolateral Prefrontal Cortex ◽  
Dorsolateral Prefrontal

scholarly journals Gene expression profiling of the dorsolateral and medial orbitofrontal cortex in schizophrenia

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Mihovil Mladinov ◽  
Goran Sedmak ◽  
Heidi R. Fuller ◽  
Mirjana Babić Leko ◽  
Davor Mayer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Cognitive Processing ◽  
Orbitofrontal Cortex ◽  
Right Hemisphere ◽  
Transcriptome Profiling ◽  
Differentially Expressed ◽  
Unknown Etiology ◽  
Dorsolateral Prefrontal ◽  
The Right

AbstractSchizophrenia is a complex polygenic disorder of unknown etiology. Over 3,000 candidate genes associated with schizophrenia have been reported, most of which being mentioned only once. Alterations in cognitive processing - working memory, metacognition and mentalization - represent a core feature of schizophrenia, which indicates the involvement of the prefrontal cortex in the pathophysiology of this disorder. Hence we compared the gene expression in postmortem tissue from the left and right dorsolateral prefrontal cortex (DLPFC, Brodmann's area 46), and the medial part of the orbitofrontal cortex (MOFC, Brodmann's area 11/12), in six patients with schizophrenia and six control brains. Although in the past decade several studies performed transcriptome profiling in schizophrenia, this is the first study to investigate both hemispheres, providing new knowledge about possible brain asymmetry at the level of gene expression and its relation to schizophrenia. We found that in the left hemisphere, twelve genes from the DLPFC and eight genes from the MOFC were differentially expressed in patients with schizophrenia compared to controls. In the right hemisphere there was only one gene differentially expressed in the MOFC. We reproduce the involvement of previously reported genes TARDBP and HNRNPC in the pathogenesis of schizophrenia, and report seven novel genes:

scholarly journals Synaptophysin gene expression in schizophrenia

2000 ◽  
Vol 176 (3) ◽  
pp. 236-242 ◽  
Author(s):  
Sharon L. Eastwood ◽  
Nigel J. Cairns ◽  
Paul J. Harrison
Keyword(s):  
Gene Expression ◽  
Cerebral Cortex ◽  
Prefrontal Cortex ◽  
Messenger Rna ◽  
Regional Distribution ◽  
Anterior Cingulate ◽  
Cortical Areas ◽  
Dorsolateral Prefrontal ◽  
Synaptic Pathology

BackgroundDecreased expression of proteins such as synaptophysin in the hippocampus and prefrontal cortex in schizophrenia is suggestive of synaptic pathology. However, the overall profile of changes is unclear.AimsTo investigate synaptophysin gene expression in the cerebral cortex in schizophrenia.MethodThe dorsolateral prefrontal (Brodmann area [BA] 9/46), anterior cingulate (BA 24), superior temporal (BA 22) and occipital (BA 17) cortex were studied in two series of brains, totalling 19 cases and 19 controls. Synaptophysin was measured by immunoautoradiography and immunoblotting. Synaptophysin messenger RNA (m RNA) was measured using in situ hybridisation.ResultsSynaptophysin was unchanged in schizophrenia, except for a reduction in BA 17 of one brain series. Synaptophysin mRNA was decreased in BA 17, and in BA 22 in the women with schizophrenia. No alterations were seen in BA 9/46.ConclusionsSynaptophysin expression is decreased in some cortical areas in schizophrenia. The alterations affect the mRNA more than the protein, and have an unexpected regional distribution. The characteristics of the implied synaptic pathology remain to be determined.

scholarly journals Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex

2020 ◽  
Author(s):  
Kristen R. Maynard ◽  
Leonardo Collado-Torres ◽  
Lukas M. Weber ◽  
Cedric Uytingco ◽  
Brianna K. Barry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Web Application ◽  
Dorsolateral Prefrontal Cortex ◽  
Large Scale ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Sequencing Data ◽  
Dorsolateral Prefrontal ◽  
Transcriptomics Data

AbstractWe used the 10x Genomics Visium platform to define the spatial topography of gene expression in the six-layered human dorsolateral prefrontal cortex (DLPFC). We identified extensive layer-enriched expression signatures, and refined associations to previous laminar markers. We overlaid our laminar expression signatures onto large-scale single nuclei RNA sequencing data, enhancing spatial annotation of expression-driven clusters. By integrating neuropsychiatric disorder gene sets, we showed differential layer-enriched expression of genes associated with schizophrenia and autism spectrum disorder, highlighting the clinical relevance of spatially-defined expression. We then developed a data-driven framework to define unsupervised clusters in spatial transcriptomics data, which can be applied to other tissues or brain regions where morphological architecture is not as well-defined as cortical laminae. We lastly created a web application for the scientific community to explore these raw and summarized data to augment ongoing neuroscience and spatial transcriptomics research (http://research.libd.org/spatialLIBD).

scholarly journals Regional heterogeneity in gene expression, regulation and coherence in hippocampus and dorsolateral prefrontal cortex across development and in schizophrenia

2018 ◽  
Author(s):  
L Collado-Torres ◽  
EE Burke ◽  
A Peterson ◽  
JH Shin ◽  
RE Straub ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Brain Region ◽  
Dorsolateral Prefrontal Cortex ◽  
Large Scale ◽  
Brain Regions ◽  
Second Phase ◽  
Regional Heterogeneity ◽  
Surrogate Variable Analysis ◽  
Dorsolateral Prefrontal

AbstractRecent large-scale genomics efforts have better characterized the molecular correlates of schizophrenia in postmortem human neocortex, but not hippocampus which is a brain region prominently implicated in its pathogenesis. Here in the second phase of the BrainSeq Consortium (Phase II), we have generated RiboZero RNA-seq data for 900 samples across both the dorsolateral prefrontal cortex (DLPFC) and the hippocampus (HIPPO) for 551 individuals (286 affected by schizophrenia disorder: SCZD). We identify substantial regional differences in gene expression, in both pre- and post-natal life, and find widespread differences in how genes are regulated across development. By extending quality surrogate variable analysis (qSVA) to multiple brain regions, we identified 48 and 245 differentially expressed genes (DEG) by SCZD diagnosis (FDR<5%) in HIPPO and DLPFC, respectively, with surprisingly minimal overlap in DEG between the two brain regions. We further identified 205,618 brain region-dependent eQTLs (FDR<1%) and found that 124 GWAS risk loci contain eQTLs in at least one of the regions. We also identify potential molecular correlates of in vivo evidence of altered prefrontal-hippocampal functional coherence in schizophrenia. These results underscore the complexity and regional heterogeneity of the transcriptional correlates of schizophrenia, and suggest future schizophrenia therapeutics may need to target molecular pathologies localized to specific brain regions.

scholarly journals DDX19B is differentially expressed in the brains of patients with psychotic disorders.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Microarray Data ◽  
Schizoaffective Disorder ◽  
Dorsolateral Prefrontal Cortex ◽  
Psychotic Disorders ◽  
Differentially Expressed ◽  
Dorsolateral Prefrontal ◽  
Significant Gene

We used public and published microarray data (1, 2) to identify the most significant gene expression changes in the brains of patients with psychotic disorders. We DDX19B as differentially expressed in the dorsolateral prefrontal cortex of patients with schizophrenia and schizoaffective disorder. In neurons of the dorsolateral prefrontal cortex from patients with psychotic disorders, DDX19B expression was significantly decreased.

scholarly journals Reduced interleukin 1A gene expression in the dorsolateral prefrontal cortex of individuals with PTSD and depression

2019 ◽  
Vol 692 ◽  
pp. 204-209 ◽  
Author(s):  
Filomene G. Morrison ◽  
Mark W. Miller ◽  
Erika J. Wolf ◽  
Mark W. Logue ◽  
Hannah Maniates ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Dorsolateral Prefrontal Cortex ◽  
Dorsolateral Prefrontal
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