scholarly journals Functional predication of differentially expressed circRNAs/lncRNAs in the prefrontal cortex of Nrf2-knockout mice

Aging ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 8797-8816
Author(s):  
Yan-Jing Gao ◽  
Run-Jiao Zhang ◽  
Qing Liu ◽  
Shao-Guang Sun ◽  
Mao-Yang Qi ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Knockout Mice ◽  
Differentially Expressed ◽  
Nrf2 Knockout

scholarly journals Behavioral sensitization induced by methamphetamine causes differential alterations in gene expression and histone acetylation of the prefrontal cortex in rats

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hui Li ◽  
Jing-An Chen ◽  
Qian-Zhi Ding ◽  
Guan-Yi Lu ◽  
Ning Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Histone Acetylation ◽  
Differentially Expressed Genes ◽  
Behavioral Sensitization ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Adult Rats ◽  
Mrna Microarray ◽  
H3 Acetylation

Abstract Background Methamphetamine (METH) is one of the most widely abused illicit substances worldwide; unfortunately, its addiction mechanism remains unclear. Based on accumulating evidence, changes in gene expression and chromatin modifications might be related to the persistent effects of METH on the brain. In the present study, we took advantage of METH-induced behavioral sensitization as an animal model that reflects some aspects of drug addiction and examined the changes in gene expression and histone acetylation in the prefrontal cortex (PFC) of adult rats. Methods We conducted mRNA microarray and chromatin immunoprecipitation (ChIP) coupled to DNA microarray (ChIP-chip) analyses to screen and identify changes in transcript levels and histone acetylation patterns. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were performed to analyze the differentially expressed genes. We then further identified alterations in ANP32A (acidic leucine-rich nuclear phosphoprotein-32A) and POU3F2 (POU domain, class 3, transcription factor 2) using qPCR and ChIP-PCR assays. Results In the rat model of METH-induced behavioral sensitization, METH challenge caused 275 differentially expressed genes and a number of hyperacetylated genes (821 genes with H3 acetylation and 10 genes with H4 acetylation). Based on mRNA microarray and GO and KEGG enrichment analyses, 24 genes may be involved in METH-induced behavioral sensitization, and 7 genes were confirmed using qPCR. We further examined the alterations in the levels of the ANP32A and POU3F2 transcripts and histone acetylation at different periods of METH-induced behavioral sensitization. H4 hyperacetylation contributed to the increased levels of ANP32A mRNA and H3/H4 hyperacetylation contributed to the increased levels of POU3F2 mRNA induced by METH challenge-induced behavioral sensitization, but not by acute METH exposure. Conclusions The present results revealed alterations in transcription and histone acetylation in the rat PFC by METH exposure and provided evidence that modifications of histone acetylation contributed to the alterations in gene expression caused by METH-induced behavioral sensitization.

P.3.a.007 GABAergic expression is differentially expressed in subregions of the prefrontal cortex in rats sensitized to methamphetamine

2013 ◽  
Vol 23 ◽  
pp. S425-S426
Author(s):  
T.A. Wearne ◽  
L.M. Parker ◽  
J.L. Franklin ◽  
A.K. Goodchild ◽  
J.L. Cornish
Keyword(s):  
Prefrontal Cortex ◽  
Differentially Expressed

scholarly journals Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yu-bao Qiu ◽  
Bin-bin Wan ◽  
Gang Liu ◽  
Ya-xian Wu ◽  
Dan Chen ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Knockout Mice ◽  
Lipid Peroxide ◽  
Dimethyl Fumarate ◽  
Redox Balance ◽  
Glutathione Depletion ◽  
Stress Injury ◽  
Nrf2 Knockout

Abstract Background Ferroptosis is a new type of nonapoptotic cell death model that was closely related to reactive oxygen species (ROS) accumulation. Seawater drowning-induced acute lung injury (ALI) which is caused by severe oxidative stress injury, has been a major cause of accidental death worldwide. The latest evidences indicate nuclear factor (erythroid-derived 2)-like 2 (Nrf2) suppress ferroptosis and maintain cellular redox balance. Here, we test the hypothesis that activation of Nrf2 pathway attenuates seawater drowning-induced ALI via inhibiting ferroptosis. Methods we performed studies using Nrf2-specific agonist (dimethyl fumarate), Nrf2 inhibitor (ML385), Nrf2-knockout mice and ferroptosis inhibitor (Ferrostatin-1) to investigate the potential roles of Nrf2 on seawater drowning-induced ALI and the underlying mechanisms. Results Our data shows that Nrf2 activator dimethyl fumarate could increase cell viability, reduced the levels of intracellular ROS and lipid ROS, prevented glutathione depletion and lipid peroxide accumulation, increased FTH1 and GPX4 mRNA expression, and maintained mitochondrial membrane potential in MLE-12 cells. However, ML385 promoted cell death and lipid ROS production in MLE-12 cells. Furthermore, the lung injury became more aggravated in the Nrf2-knockout mice than that in WT mice after seawater drowning. Conclusions These results suggested that Nrf2 can inhibit ferroptosis and therefore alleviate ALI induced by seawater drowning. The effectiveness of ferroptosis inhibition by Nrf2 provides a novel therapeutic target for seawater drowning-induced ALI.

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 Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Lisa E. Gralinski ◽  
Armand Bankhead ◽  
Sophia Jeng ◽  
Vineet D. Menachery ◽  
Sean Proll ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Severe Acute Respiratory Syndrome ◽  
Lung Injury ◽  
Disease Severity ◽  
Knockout Mice ◽  
Differentially Expressed ◽  
Lung Pathology ◽  
Priority List ◽  
Disease Outcomes ◽  
Pathological Disease

ABSTRACT Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV. IMPORTANCE Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and 2003, and infected patients developed an atypical pneumonia, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS) leading to pulmonary fibrosis and death. We identified sets of differentially expressed genes that contribute to ALI and ARDS using lethal and sublethal SARS-CoV infection models. Mathematical prioritization of our gene sets identified the urokinase and extracellular matrix remodeling pathways as the most enriched pathways. By infecting Serpine1-knockout mice, we showed that the urokinase pathway had a significant effect on both lung pathology and overall SARS-CoV pathogenesis. These results demonstrate the effective use of unbiased modeling techniques for identification of high-priority host targets that regulate disease outcomes. Similar transcriptional signatures were noted in 1918 and 2009 H1N1 influenza virus-infected mice, suggesting a common, potentially treatable mechanism in development of virus-induced ALI.

scholarly journals Aggressive mammary carcinoma progression in Nrf2 knockout mice treated with 7,12-dimethylbenz[a]anthracene

BMC Cancer ◽  
2010 ◽  
Vol 10 (1) ◽  
Author(s):  
Lisa Becks ◽  
Misty Prince ◽  
Hannah Burson ◽  
Christopher Christophe ◽  
Mason Broadway ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Mammary Carcinoma ◽  
Nrf2 Knockout
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