scholarly journals Altered expression of a unique set of genes reveals complex etiology of Schizophrenia

2017 ◽  
Author(s):  
Ashutosh Kumar ◽  
Himanshu Narayan Singh ◽  
Vikas Pareek ◽  
Khursheed Raza ◽  
Pavan Kumar ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Mrna Expression ◽  
Brain Regions ◽  
Contributing Factors ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Affy Package ◽  
Post Mortem Brain ◽  
A Genome ◽  
Neuronal Functions

AbstractPurposeThe etiology of schizophrenia is extensively debated, and multiple factors have been contended to be involved. A panoramic view of the contributing factors in a genome-wide study can be an effective strategy to provide a comprehensive understanding of its causality.Materials and MethodsGSE53987 dataset downloaded from GEO-database, which comprised mRNA expression data of post-mortem brain tissue across three regions from control and age-matched subjects of schizophrenia (N= Hippocampus (HIP): C-15, T-18, Prefrontal cortex (PFC): C-15, T-19, Associative striatum (STR): C-18, T-18). Bio-conductor-affy-package used to compute mRNA expression, and further t-test applied to investigate differential gene expression. The analysis of the derived genes performed using PANTHER Classification System and NCBI database.ResultsA set of 40 genes showed significantly altered (p<0.01) expression across all three brain regions. The analyses unraveled genes implicated in biological processes and events, and molecular pathways relating basic neuronal functions.ConclusionsThe deviant expression of genes maintaining basic cell machinery explains compromised neuronal processing in SCZ.AbbreviationsSchizophrenia (SCZ), Hippocampus (HIP), Associative striatum (STR), Prefrontal cortex (PFC)

scholarly journals Mitochondrial gene signature in the prefrontal cortex for differential susceptibility to chronic stress

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Meltem Weger ◽  
Daniel Alpern ◽  
Antoine Cherix ◽  
Sriparna Ghosal ◽  
Jocelyn Grosse ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mitochondrial Dna ◽  
Prefrontal Cortex ◽  
Mitochondrial Dysfunction ◽  
Chronic Stress ◽  
Mitochondrial Gene ◽  
Brain Regions ◽  
Mitochondrial Gene Expression ◽  
Data Set ◽  
A Genome

Abstract Mitochondrial dysfunction was highlighted as a crucial vulnerability factor for the development of depression. However, systemic studies assessing stress-induced changes in mitochondria-associated genes in brain regions relevant to depression symptomatology remain scarce. Here, we performed a genome-wide transcriptomic study to examine mitochondrial gene expression in the prefrontal cortex (PFC) and nucleus accumbens (NAc) of mice exposed to multimodal chronic restraint stress. We identified mitochondria-associated gene pathways as most prominently affected in the PFC and with lesser significance in the NAc. A more detailed mitochondrial gene expression analysis revealed that in particular mitochondrial DNA-encoded subunits of the oxidative phosphorylation complexes were altered in the PFC. The comparison of our data with a reanalyzed transcriptome data set of chronic variable stress mice and major depression disorder subjects showed that the changes in mitochondrial DNA-encoded genes are a feature generalizing to other chronic stress-protocols as well and might have translational relevance. Finally, we provide evidence for changes in mitochondrial outputs in the PFC following chronic stress that are indicative of mitochondrial dysfunction. Collectively, our work reinforces the idea that changes in mitochondrial gene expression are key players in the prefrontal adaptations observed in individuals with high behavioral susceptibility and resilience to chronic stress.

scholarly journals Dynamic expression of risk genes for schizophrenia and bipolar disorder across development

2018 ◽  
Author(s):  
Nicholas E Clifton ◽  
Eilís Hannon ◽  
Arianna Di Florio ◽  
Kerrie L Thomas ◽  
Peter A Holmans ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Prefrontal Cortex ◽  
Developmental Stages ◽  
Brain Regions ◽  
Risk Genes ◽  
Prefrontal Cortical ◽  
Expression Of Genes ◽  
Dynamic Expression ◽  
Genome Wide ◽  
And Control

ABSTRACTCommon genetic variation contributes a substantial proportion of risk for both schizophrenia and bipolar disorder. Furthermore, there is evidence of significant, but not complete, overlap in genetic risk between schizophrenia and bipolar disorder. It has been hypothesised that genetic variants conferring risk for these disorders do so by influencing brain development, leading to the later emergence of symptoms. The comparative profile of risk gene expression for schizophrenia and bipolar disorder across development over different brain regions however remains unclear. Using genotypes derived from genome wide associations studies of the largest available cohorts of patients and control subjects, we investigated whether genes enriched for schizophrenia and bipolar disorder association show a bias for expression across any of 13 developmental stages in prefrontal cortical and subcortical brain regions. We show that genes associated with schizophrenia have a strong bias towards increased expression in the prefrontal cortex during early midfetal development and early infancy, and decreased expression during late childhood which normalises in adolescence. Risk-associated genes for bipolar disorder shared this postnatal expression profile but did not exhibit a bias towards expression at any prenatal stage. These results emphasise the dynamic expression of genes harbouring risk for schizophrenia and bipolar disorder across prefrontal cortex development and support the view that prenatal neurodevelopmental events are more strongly associated with schizophrenia than bipolar disorder.

scholarly journals Widespread Decrease of Cerebral Vimentin-Immunoreactive Astrocytes in Depressed Suicides

2021 ◽  
Vol 12 ◽  
Author(s):  
Liam Anuj O'Leary ◽  
Claudia Belliveau ◽  
Maria Antonietta Davoli ◽  
Jie Christopher Ma ◽  
Arnaud Tanti ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Blood Vessels ◽  
Close Association ◽  
Brain Regions ◽  
Quantitative Comparison ◽  
Post Mortem ◽  
Dorsomedial Prefrontal Cortex ◽  
Post Mortem Brain ◽  
Morphometric Features ◽  
Fine Morphology

Post-mortem investigations have implicated cerebral astrocytes immunoreactive (-IR) for glial fibrillary acidic protein (GFAP) in the etiopathology of depression and suicide. However, it remains unclear whether astrocytic subpopulations IR for other astrocytic markers are similarly affected. Astrocytes IR to vimentin (VIM) display different regional densities than GFAP-IR astrocytes in the healthy brain, and so may be differently altered in depression and suicide. To investigate this, we compared the densities of GFAP-IR astrocytes and VIM-IR astrocytes in post-mortem brain samples from depressed suicides and matched non-psychiatric controls in three brain regions (dorsomedial prefrontal cortex, dorsal caudate nucleus and mediodorsal thalamus). A quantitative comparison of the fine morphology of VIM-IR astrocytes was also performed in the same regions and subjects. Finally, given the close association between astrocytes and blood vessels, we also assessed densities of CD31-IR blood vessels. Like for GFAP-IR astrocytes, VIM-IR astrocyte densities were found to be globally reduced in depressed suicides relative to controls. By contrast, CD31-IR blood vessel density and VIM-IR astrocyte morphometric features in these regions were similar between groups, except in prefrontal white matter, in which vascularization was increased and astrocytes displayed fewer primary processes. By revealing a widespread reduction of cerebral VIM-IR astrocytes in cases vs. controls, these findings further implicate astrocytic dysfunctions in depression and suicide.

scholarly journals Widespread transcriptional disruption of the microRNA biogenesis machinery in brain and peripheral tissues of individuals with schizophrenia

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Romain Rey ◽  
Marie-Françoise Suaud-Chagny ◽  
Jean-Michel Dorey ◽  
Jean-Raymond Teyssier ◽  
Thierry d’Amato
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Candidate Genes ◽  
Dorsolateral Prefrontal Cortex ◽  
Brain Regions ◽  
Altered Expression ◽  
Peripheral Tissues ◽  
Microrna Biogenesis ◽  
Control Subjects ◽  
Dorsolateral Prefrontal

Abstract In schizophrenia, altered transcription in brain and peripheral tissues may be due to altered expression of the microRNA biogenesis machinery genes. In this study, we explore the expression of these genes both at the cerebral and peripheral levels. We used shinyGEO application to analyze gene expression from ten Gene Expression Omnibus datasets, in order to perform differential expression analyses for eight genes encoding the microRNA biogenesis machinery. First, we compared expression of the candidate genes between control subjects and individuals with schizophrenia in postmortem cerebral samples from seven different brain regions. Then, we compared the expression of the candidate genes between control subjects and individuals with schizophrenia in three peripheral tissues. In brain and peripheral tissues of individuals with schizophrenia, we report distinct altered expression patterns of the microRNA biogenesis machinery genes. In the dorsolateral prefrontal cortex, associative striatum and cerebellum of individuals with schizophrenia, we observed an overexpression pattern of some candidate genes suggesting a heightened miRNA production in these brain regions. Additionally, mixed transcriptional abnormalities were identified in the hippocampus. Moreover, in the blood and olfactory epithelium of individuals with schizophrenia, we observed distinct aberrant transcription patterns of the candidate genes. Remarkably, in individuals with schizophrenia, we report DICER1 overexpression in the dorsolateral prefrontal cortex, hippocampus and cerebellum as well as a congruent DICER1 upregulation in the blood compartment suggesting that it may represent a peripheral marker. Transcriptional disruption of the miRNA biogenesis machinery may contribute to schizophrenia pathogenesis both in brain and peripheral tissues.

scholarly journals Transcriptional Response of Candida parapsilosis following Exposure to Farnesol

2007 ◽  
Vol 51 (7) ◽  
pp. 2304-2312 ◽  
Author(s):  
Tristan Rossignol ◽  
Mary E. Logue ◽  
Kieran Reynolds ◽  
Muriel Grenon ◽  
Noel F. Lowndes ◽  
...  
Keyword(s):  
Candida Parapsilosis ◽  
Transcriptional Response ◽  
Hyphal Growth ◽  
Cellular Growth ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Genome Sequence Survey ◽  
A Genome ◽  
Specific Stage ◽  
Design And Manufacture

ABSTRACT In Candida albicans, the quorum-sensing molecule farnesol inhibits the transition from yeast to hyphae but has no effect on cellular growth. We show that the addition of exogenous farnesol to cultures of Candida parapsilosis causes the cells to arrest, but not at a specific stage in the cell cycle. The cells are not susceptible to additional farnesol. However, the cells do eventually recover from arrest. Unlike in C. albicans, in C. parapsilosis sterols are localized to the tips of budding cells, and this polarization is disrupted by the addition of farnesol. We used the results of a genome sequence survey to design and manufacture partial genomic microarrays that were applied to determining the transcriptional response of C. parapsilosis to the presence of exogenous farnesol. In both C. albicans and C. parapsilosis, exposure to farnesol results in increased expression of the oxidoreductases GRP2 and ADH7 and altered expression of genes involved in sterol metabolism. There is no effect on expression of C. parapsilosis orthologs of genes involved in hyphal growth in C. albicans. Farnesol therefore differs significantly in its effects on C. parapsilosis and C. albicans.

scholarly journals Impact of maternal malnutrition on gut barrier defence: implications for pregnancy health and fetal development.

2019 ◽  
Author(s):  
Sebastian A. Srugo ◽  
Enrrico Bloise ◽  
Tina Tu-Thu Ngoc Nguyen ◽  
Kristin L. Connor
Keyword(s):  
Mrna Expression ◽  
Control Diet ◽  
Paneth Cell ◽  
Goblet Cells ◽  
Maternal Malnutrition ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Enteric Glial Cells ◽  
Host Microbe Interactions ◽  
And Function

Small intestinal Paneth cells, enteric glial cells (EGC), and goblet cells maintain gut mucosal integrity, homeostasis, and influence host physiology locally and through the gut-brain axis. Little is known about their roles during pregnancy, or how maternal malnutrition impacts these cells and their development. Pregnant mice were fed a control diet (CON), undernourished by 30% vs. control (UN), or fed a high-fat diet (HF). At day 18.5 (term=19), gut integrity and function were assessed by immunohistochemistry and qPCR. UN mothers displayed reduced mRNA expression of Paneth cell antimicrobial peptides (AMP; Lyz2, Reg3g) and an accumulation of villi goblet cells, while HF had reduced Reg3g and mucin (Muc2) mRNA and increased lysozyme protein. UN fetuses had increased mRNA expression of gut transcription factor Sox9, associated with reduced expression of maturation markers (Cdx2, Muc2), and increased expression of tight junctions (TJ; Cldn-7). HF fetuses had increased mRNA expression of EGC markers (S100b, Bfabp, Plp1), AMP (Lyz1, Defa1, Reg3g), and TJ (Cldn-3, Cldn-7), and reduced expression of an AMP-activator (Tlr4). Maternal malnutrition altered expression of genes that maintain maternal gut homeostasis, and altered fetal gut permeability, function, and development. This may have long-term implications for host-microbe interactions, immunity, and offspring gut-brain axis function.

scholarly journals Exposure to Prenatal Stress Is Associated With an Excitatory/Inhibitory Imbalance in Rat Prefrontal Cortex and Amygdala and an Increased Risk for Emotional Dysregulation

2021 ◽  
Vol 9 ◽  
Author(s):  
Francesca Marchisella ◽  
Kerstin Camile Creutzberg ◽  
Veronica Begni ◽  
Alice Sanson ◽  
Luis Eduardo Wearick-Silva ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Prenatal Stress ◽  
Synapse Formation ◽  
Maternal Stress ◽  
Brain Regions ◽  
Emotional Dysregulation ◽  
Brain Maturation ◽  
Adult Males ◽  
Expression Of Genes ◽  
Increased Risk

Epidemiological studies have shown that environmental insults and maternal stress during pregnancy increase the risk of several psychiatric disorders in the offspring. Converging lines of evidence from humans, as well as from rodent models, suggest that prenatal stress (PNS) interferes with fetal development, ultimately determining changes in brain maturation and function that may lead to the onset of neuropsychiatric disorders. From a molecular standpoint, transcriptional alterations are thought to play a major role in this context and may contribute to the behavioral phenotype by shifting the expression of genes related to excitatory and inhibitory (E/I) transmission balance. Nevertheless, the exact neurophysiological mechanisms underlying the enhanced vulnerability to psychopathology following PNS exposure are not well understood. In the present study, we used a model of maternal stress in rats to investigate the distal effects of PNS on the expression of genes related to glutamatergic and GABAergic neurotransmissions. We inspected two critical brain regions involved in emotion regulation, namely, the prefrontal cortex (PFC) and the amygdala (AMY), which we show to relate with the mild behavioral effects detected in adult rat offspring. We observed that PNS exposure promotes E/I imbalance in the PFC of adult males only, by dysregulating the expression of glutamatergic-related genes. Moreover, such an effect is accompanied by increased expression of the activity-dependent synaptic modulator gene Npas4 specifically in the PFC parvalbumin (PV)-positive interneurons, suggesting an altered regulation of synapse formation promoting higher PV-dependent inhibitory transmission and increased overall circuit inhibition in the PFC of males. In the AMY, PNS more evidently affects the transcription of GABAergic-related genes, shifting the balance toward inhibition. Collectively, our findings suggest that the E/I dysregulation of the PFC-to-AMY transmission may be a long-term signature of PNS and may contribute to increase the risk for mood disorder upon further stress.

scholarly journals Impact of Maternal Malnutrition on Gut Barrier Defense: Implications for Pregnancy Health and Fetal Development

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1375 ◽  
Author(s):  
Sebastian A. Srugo ◽  
Enrrico Bloise ◽  
Tina Tu-Thu Ngoc Nguyen ◽  
Kristin L. Connor
Keyword(s):  
Mrna Expression ◽  
Control Diet ◽  
Paneth Cell ◽  
Goblet Cells ◽  
Maternal Malnutrition ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Enteric Glial Cells ◽  
Host Microbe Interactions ◽  
And Function

Small intestinal Paneth cells, enteric glial cells (EGC), and goblet cells maintain gut mucosal integrity, homeostasis, and influence host physiology locally and through the gut-brain axis. Little is known about their roles during pregnancy, or how maternal malnutrition impacts these cells and their development. Pregnant mice were fed a control diet (CON), undernourished by 30% vs. control (UN), or fed a high fat diet (HF). At day 18.5 (term = 19), gut integrity and function were assessed by immunohistochemistry and qPCR. UN mothers displayed reduced mRNA expression of Paneth cell antimicrobial peptides (AMP; Lyz2, Reg3g) and an accumulation of villi goblet cells, while HF had reduced Reg3g and mucin (Muc2) mRNA and increased lysozyme protein. UN fetuses had increased mRNA expression of gut transcription factor Sox9, associated with reduced expression of maturation markers (Cdx2, Muc2), and increased expression of tight junctions (TJ; Cldn-7). HF fetuses had increased mRNA expression of EGC markers (S100b, Bfabp, Plp1), AMP (Lyz1, Defa1, Reg3g), and TJ (Cldn-3, Cldn-7), and reduced expression of an AMP-activator (Tlr4). Maternal malnutrition altered expression of genes that maintain maternal gut homeostasis, and altered fetal gut permeability, function, and development. This may have long-term implications for host-microbe interactions, immunity, and offspring gut-brain axis function.

scholarly journals The Caudate Nucleus Undergoes Dramatic and Unique Transcriptional Changes in Human Prodromal Huntington’s Disease Brain

2019 ◽  
Author(s):  
Filisia Agus ◽  
Diego Crespo ◽  
Richard H. Myers ◽  
Adam Labadorf
Keyword(s):  
Caudate Nucleus ◽  
Transcriptional Response ◽  
Brain Regions ◽  
Complete Agreement ◽  
Biological Processes ◽  
Altered Expression ◽  
Brain Gene Expression ◽  
Gene Carriers ◽  
Post Mortem Brain ◽  
Transcriptional Changes

ABSTRACTThe mechanisms underlying degeneration of the specific neurons in the striatum of Huntingon’s Disease (HD) brain are currently unknown. The striatum is massively degenerated in late stage HD, making examination of post-mortem brain tissue from symptomatic individuals problematic. Striatal tissue is largely intact in the brains of asymptomatic HD positive (HD+) gene carriers, but these samples are exceedingly rare. In this study, caudate nucleus (CAU) tissue from two asymptomatic HD+ individuals was subjected to high throughput mRNA sequencing (mRNA-Seq) for comparison with similar datasets from symptomatic HD individuals and healthy controls. The overall transcriptional response in HD+ CAU shares much of the same response observed in HD Brodmann Area 9 (BA9) samples, an area that is relatively spared from significant degeneration. A set of differentially expressed (DE) genes predominantly related to the heat shock response are found in common between brain regions, and show much higher induction in HD+ CAU than HD BA9. The most highly perturbed pathways show near complete agreement when comparing diseased tissue with control, and a random forest classifier predicted that the two HD+ CAU samples strongly resemble HD BA9 and not control BA9. Nonetheless, when genes were prioritized by their specificity to HD+ CAU, a large number of pathways spanning many biological processes emerged. Further comparison of HD+ BA9 with HD BA9 identified genes that may be early responders to disease, and have altered expression in symptomatic individuals. This study presents the first and largest examination of asymptomatic brain gene expression to date, and suggests many new avenues of investigation into the mechanisms underlying neurodegeneration in HD.

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