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PubMed Journals Articles About "Increased Expression Schizophrenia Associated Gene Leads Hypoconnectivity Prefrontal" RSS

12:59 EST 20th February 2020 | BioPortfolio

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Showing "Increased expression schizophrenia associated gene leads hypoconnectivity prefrontal" PubMed Articles 1–25 of 25,000+

Increased expression of schizophrenia-associated gene C4 leads to hypoconnectivity of prefrontal cortex and reduced social interaction.

Schizophrenia is a severe mental disorder with an unclear pathophysiology. Increased expression of the immune gene C4 has been linked to a greater risk of developing schizophrenia; however, it is not known whether C4 plays a causative role in this brain disorder. Using confocal imaging and whole-cell electrophysiology, we demonstrate that overexpression of C4 in mouse prefrontal cortex neurons leads to perturbations in dendritic spine development and hypoconnectivity, which mirror neuropathologies found in ...


Schizophrenia-associated MicroRNA-gene Interactions in the Dorsolateral Prefrontal Cortex.

Schizophrenia-associated anomalies in gene expression in postmortem brain can be attributed to a combination of genetic and environmental influences. Given the small effect size of common variants, it is likely that we may only see the combined impact of some of these at the pathway level in small postmortem studies. At the gene level, however, there may be more impact from common environmental exposures mediated by influential epigenomic modifiers, such as microRNA (miRNA). We hypothesise that dysregulatio...

Prefrontal cortex alterations in glia gene expression in schizophrenia with and without suicide.

Patients with schizophrenia (SCZ) run a lifelong risk of suicide. Alterations in glia activities in the prefrontal cortex (PFC) have been reported in relation to suicide in patients with SCZ. While immune processes in the CNS have been related to the susceptibility and course of SCZ, there are hardly any direct comparisons between individuals with SCZ, both those who died of natural causes and those that committed suicide, and healthy controls.


ALDH4A1 expression levels are elevated in postmortem brains of patients with schizophrenia and are associated with genetic variants in enzymes related to proline metabolism.

The molecular mechanisms underlying schizophrenia remain largely unclear, and we recently identified multiple proteins significantly altered in the postmortem prefrontal cortex (PFC) of schizophrenia patients amongst which aldehyde dehydrogenase 4 family member A1 (ALDH4A1) was especially elevated. In this study, we aimed to investigate the expression of ALDH4A1 in the PFC and superior temporal gyrus (STG) and to elucidate functional correlations between schizophrenia risk alleles and molecular expression p...

Evidence for enhanced androgen action in the prefrontal cortex of people with bipolar disorder but not schizophrenia or major depressive disorder.

Anxiety and depressive disorders are more prevalent in hypogonadal men. Low testosterone levels are associated with greater negative symptoms and impaired cognition in men with schizophrenia. Thus, androgens may contribute to brain pathophysiology in psychiatric disorders. We investigated androgen-related mRNAs in post-mortem dorsolateral prefrontal cortex of psychiatric disorders. We also assessed androgen receptor (AR) CAG trinucleotide repeat length, a functional AR gene variant associated with AR gene e...

Electroretinographic Abnormalities and Sex Differences Detected with Mesopic Adaptation in a Mouse Model of Schizophrenia: A and B Wave Analysis.

Mesopic flash electroretinography (fERG) as a tool to identify N-methyl-d-aspartate receptor (NMDAR) hypofunction in subjects with schizophrenia shows great potential. We report the first fERG study in a genetic mouse model of schizophrenia characterized by NMDAR hypofunction from gene silencing of serine racemase (SR) expression (SR-/-), an established risk gene for schizophrenia. We analyzed fERG parameters under various background light adaptations to determine the most significant variables to allow for...

A Network Analysis of Epigenetic and Transcriptional Regulation in a Neurodevelopmental Rat Model of Schizophrenia With Implications for Translational Research.

Prenatal administration of mitotoxin methylazoxymethanol acetate (MAM) in rats produces behavioral, pharmacological, and anatomical abnormalities once offspring reach adulthood, thus establishing a widely used neurodevelopmental model of schizophrenia. However, the molecular aspects underlying this disease model are not well understood. Therefore, this study examines epigenetic and transcriptional dysregulation in the prefrontal cortex and hippocampus of MAM rats as these are brain regions closely associate...

Evidence of association of the DISC1 interactome gene set with schizophrenia from GWAS.

DISC1 was discovered as a gene disrupted by a balanced translocation in a large pedigree that segregated with major mental disorders, including schizophrenia. Further attempts to find genetic association with schizophrenia were inconclusive. Most of the biology of DISC1 was inferred from the functionality of its protein partners. Recently, a gene set constituted by DISC1 and several of its partners has been associated with cognitive performance during development, a well-known schizophrenia endophenotype, b...

Serotonin 5-HT receptor expression and functionality in postmortem frontal cortex of subjects with schizophrenia: Selective biased agonism via G-proteins.

Serotonin 5-HT receptors (5-HTRs) have been implicated in schizophrenia. However, postmortem studies on 5-HTRs expression and functionality in schizophrenia are scarce. The 5-HTR mRNA and immunoreactive protein expression were evaluated in postmortem tissue from dorsolateral prefrontal cortex (DLPFC) of antipsychotic-free (n = 18) and antipsychotic-treated (n = 9) subjects with schizophrenia, and matched controls (n = 27). Functional coupling of 5-HTR to G-proteins was tested by measuring the ac...

Transgenic mice overexpressing miR-137 in the brain show schizophrenia-associated behavioral deficits and transcriptome profiles.

Schizophrenia is a psychiatric disorder characterized by positive and negative symptoms and cognitive deficits. The exact cause of schizophrenia is still unknown, but substantial evidence indicates that it has a genetic component. Genome wide association studies demonstrate variants within miR-137 host gene are a risk factor for schizophrenia. However, the direct relationship between the pathophysiology of schizophrenia and the dosage of miR-137 remains unclear. Therefore, in this study, we generated transg...

Examining resting-state functional connectivity in first-episode schizophrenia with 7T fMRI and MEG.

Schizophrenia is often characterized by dysconnections in the brain, which can be estimated via functional connectivity analyses. Commonly measured using resting-state functional magnetic resonance imaging (fMRI) in order to characterize the intrinsic or baseline function of the brain, fMRI functional connectivity has significantly contributed to the understanding of schizophrenia. However, these measures may not capture the full extent of functional connectivity abnormalities in schizophrenia as fMRI is te...

Cognitive Brain Signatures of Youth With Early Onset and Relatives With Schizophrenia: Evidence From fMRI Meta-analyses.

Deficits in cognitive function are a major characteristic of schizophrenia. Many functional magnetic resonance imaging (fMRI) studies examine brain correlates of cognitive function in adults with schizophrenia, showing altered implication of associative areas such as the prefrontal cortex and temporal cortex. fMRI studies also examine brain representation of cognitive function in adolescents with early onset schizophrenia and those at risk of the disorder, yet results are often inconsistent. We compile and ...

Identification of relevant hub genes for early intervention at gene coexpression modules with altered predicted expression in schizophrenia.

Genetic risk for schizophrenia is due to the joint effect of multiple genes acting mainly at two different processes, prenatal/perinatal neurodevelopment and adolescence/early adulthood synapse maturation. Identification of important genes at the second process is of relevance for early intervention. The aim of this work was to identify gene co-expression modules with altered expression in schizophrenia during adolescence/early adulthood. To this goal, we predicted frontal cortex gene expression in one disc...

Preliminary findings of four-week, task-based anodal prefrontal cortex transcranial direct current stimulation transferring to other cognitive improvements in schizophrenia.

Most transcranial Direct Current Stimulation (tDCS) trials of schizophrenia administer few sessions and do not assess transfer effects to other cognitive domains. In a randomized, double-blind, sham-controlled, parallel groups trial, we determined the extent to which 4-weeks of 2 mA tDCS at 20 min/day totalling 20 tDCS sessions administered during a spatial working memory test, with anodal right dorsolateral prefrontal cortex (DLPFC) and cathodal left tempo-parietal junction (TPJ) placement, as an adjunc...

The Schizophrenia Susceptibility Gene OPCML Regulates Spine Maturation and Cognitive Behaviors through Eph-Cofilin Signaling.

Previous genetic and biological evidence converge on the involvement of synaptic dysfunction in schizophrenia, and OPCML, encoding a synaptic membrane protein, is reported to be genetically associated with schizophrenia. However, its role in the pathophysiology of schizophrenia remains largely unknown. Here, we found that Opcml is strongly expressed in the mouse hippocampus; ablation of Opcml leads to reduced phosphorylated cofilin and dysregulated F-actin dynamics, which disturbs the spine maturation. Furt...

Reduced cortical somatostatin gene expression in a rat model of maternal immune activation.

Alterations in GABAergic interneurons and glutamic acid decarboxylase (GAD) are observed in the brains of people with schizophrenia. Studies also show increased density of interstitial white matter neurons (IWMN), including those containing GAD and somatostatin (SST) in the brain in schizophrenia. Maternal immune activation can be modelled in rodents to investigate the relationship between prenatal exposure to infections and increased risk of developing schizophrenia. We reported that maternal immune activa...

Rs1625579 polymorphism in the MIR137 gene is associated with the risk of schizophrenia: an updated meta-analysis.

The Schizophrenia Psychiatric GWAS Consortium (PGC) has identified the rs1625579 polymorphism in the MIR137 gene, which encodes miR-137, as the strongest new association with schizophrenia in the European population. However, whether the influence of rs1625579 on schizophrenia in the Asian population is consistent with these results remains unclear. A total of 21 studies (9878 schizophrenic patients and 9447 control subjects) that met the inclusion criteria were included in our meta-analysis. Pooled analysi...

The effect of high vs. low dose lurasidone on eye movement biomarkers of prefrontal abilities in treatment-resistant schizophrenia.

Eye movement (EM) measures can serve as biomarkers to evaluate pharmacological effects on brain systems involved in cognition. In recent onset schizophrenia, antipsychotic treatment can improve attentional control on the antisaccade task and exacerbate working memory impairment on the memory guided saccade task; effects in treatment-resistant schizophrenia (TRS) are less clear. This study evaluated the effects of high versus low dose lurasidone on EM performance in TRS.

All of gene expression (AOE): An integrated index for public gene expression databases.

Gene expression data have been archived as microarray and RNA-seq datasets in two public databases, Gene Expression Omnibus (GEO) and ArrayExpress (AE). In 2018, the DNA DataBank of Japan started a similar repository called the Genomic Expression Archive (GEA). These databases are useful resources for the functional interpretation of genes, but have been separately maintained and may lack RNA-seq data, while the original sequence data are available in the Sequence Read Archive (SRA). We constructed an index...

Unmedicated patients with schizophrenia in economically underdeveloped areas of China.

Untreated schizophrenia commonly leads to poor prognosis. The medication treatment rate of schizophrenia patients in economically underdeveloped areas of China has not been well-studied. This study aimed to examine the pattern of unmedicated schizophrenia patients in economically underdeveloped rural and urban areas of China.

Downregulated AKT-mTOR signaling pathway proteins in dorsolateral prefrontal cortex in Schizophrenia.

Abnormal neurotransmission is central to schizophrenia (SZ). Alterations across multiple neurotransmitter systems in SZ suggest that this illness may be associated with dysregulation of core intracellular processes such as signaling pathways that underlie the regulation and integration of these systems. The AKT-mTOR signaling cascade has been implicated in SZ by gene association, postmortem brain and animal studies. AKT and mTOR are serine/threonine kinases which play important roles in cell growth, prolife...

Prior stress followed by a novel stress challenge results in sex-specific deficits in behavioral flexibility and changes in gene expression in rat medial prefrontal cortex.

Chronic stress leads to sex-specific changes in the structure and function of rat medial prefrontal cortex (mPFC). Little is known about whether these effects persist following the cessation of chronic stress, or how these initial effects may impact responses to future stressors. Here we examined attentional set-shifting in male and female rats following chronic restraint stress, a post-chronic stress rest period, and an acute novel stress challenge. Chronic stress resulted in a reversible impairment in ext...

Behavioral abnormalities and phosphorylation deficits of extracellular signal-regulated kinases 1 and 2 in rat offspring of the maternal immune activation model.

Extracellular signal-regulated kinase (ERK) signal transduction is known to be associated with neurogenesis and neuronal differentiation and as such may be related to the synaptic plasticity associated with cognitive function. Although antipsychotic drug studies have suggested a potential role for the ERK cascade in schizophrenia, the mechanistic basis is unknown. The maternal immune activation (MIA) rat model is a well-known to simulate many of the clinical symptoms of schizophrenia, including cognitive de...

Brain Abnormalities in Different Phases of Working Memory in Schizophrenia: An Integrative Multi-Modal MRI Study.

The current study aimed to examine both gray matter and functional activity changes in schizophrenia by combing both structural and task-related functional magnetic resonance imaging (fMRI). Nineteen patients with schizophrenia and 17 controls were recruited. The fMRI scan was performed while performing a working memory (WM) task. In terms of task performance, accuracy did not differ between groups, but there were significant differences in reaction time. Compared with controls, patients exhibited decreased...

Dosage regulation, and variation in gene expression and copy number of human Y chromosome ampliconic genes.

The Y chromosome harbors nine multi-copy ampliconic gene families expressed exclusively in testis. The gene copies within each family are >99% identical to each other, which poses a major challenge in evaluating their copy number. Recent studies demonstrated high variation in Y ampliconic gene copy number among humans. However, how this variation affects expression levels in human testis remains understudied. Here we developed a novel computational tool Ampliconic Copy Number Estimator (AmpliCoNE) that util...


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