Neonatal Ogg1/Mutyh knockout mice have altered inflammatory gene response compared to wildtype mice in the brain and lung after hypoxia-reoxygenation

2018 ◽  
Vol 47 (1) ◽  
pp. 114-124 ◽  
Author(s):  
Anne Gro W. Rognlien ◽  
Embjørg J. Wollen ◽  
Monica Atneosen-Åsegg ◽  
Rajikala Suganthan ◽  
Magnar Bjørås ◽  
...  
Keyword(s):  
Gene Expression ◽  
Knockout Mice ◽  
A Priori ◽  
Gene Activation ◽  
Dna Glycosylase ◽  
Double Knockout ◽  
Inflammatory Gene ◽  
Gene Response ◽  
The Brain ◽  
Hypoxia Reoxygenation

Abstract Background 8-Oxoguanine DNA-glycosylase 1 (OGG1) and mutY DNA glycosylase (MUTYH) are crucial in the repair of the oxidative DNA lesion 7,8-dihydro-8-oxoguanine caused by hypoxia-reoxygenation injury. Our objective was to compare the gene expression changes after hypoxia-reoxygenation in neonatal Ogg1-Mutyh double knockout mice (OM) and wildtype mice (WT), and study the gene response in OM after hyperoxic reoxygenation compared to normoxic. Methods Postnatal day 7 mice were subjected to 2 h of hypoxia (8% O2) followed by reoxygenation in either 60% O2 or air, and sacrificed right after completed reoxygenation (T0h) or after 72 h (T72h). The gene expression of 44 a priori selected genes was examined in the hippocampus/striatum and lung. Results We found that OM had an altered gene response compared to WT in 21 genes in the brain and 24 genes in the lung. OM had a lower expression than WT of inflammatory genes in the brain at T0h, and higher expression at T72h in both the brain and lung. In the lung of OM, five genes were differentially expressed after hyperoxic reoxygenation compared to normoxic. Conclusion For the first time, we report that Ogg1 and Mutyh in combination protect against late inflammatory gene activation in the hippocampus/striatum and lung after neonatal hypoxia-reoxygenation.

scholarly journals The effects of n-6 polyunsaturated fatty acid deprivation on the inflammatory gene response to lipopolysaccharide in the mouse hippocampus

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Shoug M. Alashmali ◽  
Lin Lin ◽  
Marc-Olivier Trépanier ◽  
Giulia Cisbani ◽  
Richard P. Bazinet
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Diet Group ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Left Lateral Ventricle ◽  
Gene Response ◽  
Mouse Hippocampus ◽  
Total Fatty Acids ◽  
The Brain

Abstract Background Neuroinflammation is thought to contribute to psychiatric and neurological disorders such as major depression and Alzheimer’s disease (AD). N-6 polyunsaturated fatty acids (PUFA) and molecules derived from them, including linoleic acid- and arachidonic acid-derived lipid mediators, are known to have pro-inflammatory properties in the periphery; however, this has yet to be tested in the brain. Lowering the consumption of n-6 PUFA is associated with a decreased risk of depression and AD in human observational studies. The purpose of this study was to investigate the inflammation-modulating effects of lowering dietary n-6 PUFA in the mouse hippocampus. Methods C57BL/6 male mice were fed either an n-6 PUFA deprived (2% of total fatty acids) or an n-6 PUFA adequate (23% of total fatty acids) diet from weaning to 12 weeks of age. Animals then underwent intracerebroventricular surgery, in which lipopolysaccharide (LPS) was injected into the left lateral ventricle of the brain. Hippocampi were collected at baseline and following LPS administration (1, 3, 7, and 14 days). A microarray (n = 3 per group) was used to identify candidate genes and results were validated by real-time PCR in a separate cohort of animals (n = 5–8 per group). Results Mice administered with LPS had significantly increased Gene Ontology categories associated with inflammation and immune responses. These effects were independent of changes in gene expression in any diet group. Results were validated for the effect of LPS treatment on astrocyte, cytokine, and chemokine markers, as well as some results of the diets on Ifrd2 and Mfsd2a expression. Conclusions LPS administration increases pro-inflammatory and lipid-metabolizing gene expression in the mouse hippocampus. An n-6 PUFA deprived diet modulated inflammatory gene expression by both increasing and decreasing inflammatory gene expression, without impairing the resolution of neuroinflammation following LPS administration.

scholarly journals Onecut-2 knockout mice fail to thrive during early postnatal period and have altered patterns of gene expression in small intestine

2010 ◽  
Vol 42 (1) ◽  
pp. 115-125 ◽  
Author(s):  
Mary R. Dusing ◽  
Elizabeth A. Maier ◽  
Bruce J. Aronow ◽  
Dan A. Wiginton
Keyword(s):  
Gene Expression ◽  
Knockout Mice ◽  
Critical Period ◽  
Postnatal Period ◽  
Double Knockout ◽  
Temporal Regulation ◽  
Liver And Pancreas ◽  
In Utero Development ◽  
Knockout Allele

Ablation of the mouse genes for Onecut-2 and Onecut-3 was reported previously, but characterization of the resulting knockout mice was focused on in utero development, principally embryonic development of liver and pancreas. Here we examined postnatal development of these Onecut knockout mice, especially the critical period before weaning. Onecut-3 knockout mice develop normally during this period. However, Onecut-2 knockout mice fail to thrive, lagging behind their littermates in size and weight. By postnatal day (d)19, they are consistently 25–30% smaller. Onecut-2 knockout mice also have a much higher level of mortality before weaning, with only ∼70% survival. Interestingly, Onecut-2 knockout mice that are heterozygous for the Onecut-3 knockout allele are diminished even further in their ability to thrive. They are ∼50–60% as large as their normal-sized littermates at d19, and less than half of these mice survive to weaning. As reported previously, the Onecut-2/Onecut-3 double knockout is a perinatal lethal. Microarray technology was used to determine the effect of Onecut-2 ablation on gene expression in duodenum, whose epithelium has among the highest levels of Onecut-2. A subset of intestinally expressed genes showed dramatically altered patterns of expression. Many of these genes encode proteins associated with the epithelial membrane, including many involved in transport and metabolism. Previously, we reported that Onecut-2 was critical to temporal regulation of the adenosine deaminase gene in duodenum. Many of the genes with altered patterns of expression in Onecut-2 knockout mouse duodenum displayed changes in the timing of gene expression.

Gene Expression Analysis of Photoreceptor Cell Loss inBbs4-Knockout Mice Reveals an Early Stress Gene Response and Photoreceptor Cell Damage

2007 ◽  
Vol 48 (7) ◽  
pp. 3329 ◽  
Author(s):  
Ruth E. Swiderski ◽  
Darryl Y. Nishimura ◽  
Robert F. Mullins ◽  
Marissa A. Olvera ◽  
Jean L. Ross ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
Knockout Mice ◽  
Gene Expression Analysis ◽  
Photoreceptor Cell ◽  
Cell Damage ◽  
Cell Loss ◽  
Early Stress ◽  
Gene Response ◽  
Stress Gene

Turn-over of meningeal and perivascular macrophages in the brain of MCP-1-, CCR-2- or double knockout mice

2009 ◽  
Vol 219 (2) ◽  
pp. 583-585 ◽  
Author(s):  
Matthias Schilling ◽  
Jan-Kolja Strecker ◽  
E. Bernd Ringelstein ◽  
Reinhard Kiefer ◽  
Wolf-Rüdiger Schäbitz
Keyword(s):  
Knockout Mice ◽  
Double Knockout ◽  
Perivascular Macrophages ◽  
Turn Over ◽  
The Brain

scholarly journals RNA editing at a limited number of sites is sufficient to prevent MDA5 activation in the mouse brain

PLoS Genetics ◽  
2021 ◽  
Vol 17 (5) ◽  
pp. e1009516 ◽  
Author(s):  
Jung In Kim ◽  
Taisuke Nakahama ◽  
Ryuichiro Yamasaki ◽  
Pedro Henrique Costa Cruz ◽  
Tuangtong Vongpipatana ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Rna Editing ◽  
Mouse Brain ◽  
Knockout Mice ◽  
Embryonic Lethality ◽  
Wild Type ◽  
Double Knockout ◽  
Elevated Expression ◽  
The Brain

Adenosine deaminase acting on RNA 1 (ADAR1), an enzyme responsible for adenosine-to-inosine RNA editing, is composed of two isoforms: nuclear p110 and cytoplasmic p150. Deletion of Adar1 or Adar1 p150 genes in mice results in embryonic lethality with overexpression of interferon-stimulating genes (ISGs), caused by the aberrant recognition of unedited endogenous transcripts by melanoma differentiation-associated protein 5 (MDA5). However, among numerous RNA editing sites, how many RNA sites require editing, especially by ADAR1 p150, to avoid MDA5 activation and whether ADAR1 p110 contributes to this function remains elusive. In particular, ADAR1 p110 is abundant in the mouse brain where a subtle amount of ADAR1 p150 is expressed, whereas ADAR1 mutations cause Aicardi–Goutières syndrome, in which the brain is one of the most affected organs accompanied by the elevated expression of ISGs. Therefore, understanding RNA editing–mediated prevention of MDA5 activation in the brain is especially important. Here, we established Adar1 p110–specific knockout mice, in which the upregulated expression of ISGs was not observed. This result suggests that ADAR1 p150–mediated RNA editing is enough to suppress MDA5 activation. Therefore, we further created Adar1 p110/Adar2 double knockout mice to identify ADAR1 p150–mediated editing sites. This analysis demonstrated that although the elevated expression of ISGs was not observed, only less than 2% of editing sites were preserved in the brains of Adar1 p110/Adar2 double knockout mice. Of note, we found that some sites were highly edited, which was comparable to those found in wild-type mice, indicating the presence of ADAR1 p150–specific sites. These data suggest that RNA editing at a very limited sites, which is mediated by a subtle amount of ADAR1 p150, is sufficient to prevents MDA5 activation, at least in the mouse brain.

Increased cytokine and chemokine gene expression in the CNS of mice during heat stroke recovery

2013 ◽  
Vol 305 (9) ◽  
pp. R978-R986 ◽  
Author(s):  
Joseph C. Biedenkapp ◽  
Lisa R. Leon
Keyword(s):  
Gene Expression ◽  
Heat Stroke ◽  
Stroke Recovery ◽  
Activation Markers ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Cox Inhibitor ◽  
Cox 2 ◽  
The Brain ◽  
Cox 1

Heat stroke (HS) is characterized by a systemic inflammatory response syndrome (SIRS) consisting of profound core temperature (Tc) changes in mice. Encephalopathy is common at HS collapse, but inflammatory changes occurring in the brain during the SIRS remain unidentified. We determined the association between inflammatory gene expression changes in the brain with Tc disturbances during HS recovery in mice. Gene expression changes of heat shock protein (HSP)72, heme oxygenase (hmox1), cytokines (IL-1β, IL-6, TNF-α), cyclooxygenase enzymes (COX-1, COX-2), chemokines (MCP-1, MIP-1α, MIP-1β, CX3CR1), and glia activation markers (CD14, aif1, vimentin) were examined in the hypothalamus (HY) and hippocampus (HC) of control (Tc ∼ 36.0°C) and HS mice at Tc,Max (42.7°C), hypothermia depth (HD; 29.3 ± 0.4°C), and fever (37.8 ± 0.3°C). HSP72 (HY<HC) and IL-1β (HY only) were the only genes that showed increased expression at Tc,Max. HSP72 (HY < HC), hmox1 (HY < HC), cytokine (HY = HC), and chemokine (HY = HC) expression was highest at HD and similar to controls during fever. COX-1 expression was unaffected by HS, whereas HD was associated with approximately threefold increase in COX-2 expression (HY only). COX-2 expression was not increased during fever and indomethacin (COX inhibitor) had no effect on this Tc response indicating fever is regulated by other inflammatory pathways. CD14, aif1, and vimentin activation at HD coincided with maximal cytokine and chemokine expression suggesting glia cells are a possible source of brain cytokines and chemokines during HS recovery. The inflammatory gene expression changes during HS recovery suggest cytokines and/or chemokines may be initiating development or rewarming from hypothermia, whereas fever pathway(s) remain to be elucidated.

Back to the basics? Transcriptomics offers integrative insights into the role of space, time and the environment for gene expression and behaviour

2021 ◽  
Vol 17 (9) ◽  
pp. 20210293
Author(s):  
Eva K. Fischer ◽  
Mark E. Hauber ◽  
Alison M. Bell
Keyword(s):  
Gene Expression ◽  
Rna Sequencing ◽  
Molecular Basis ◽  
Gene Activation ◽  
Rna Expression ◽  
Brain Gene Expression ◽  
Explicit Consideration ◽  
The Brain ◽  
Genomic Revolution

Fuelled by the ongoing genomic revolution, broadscale RNA expression surveys are fast replacing studies targeting one or a few genes to understand the molecular basis of behaviour. Yet, the timescale of RNA-sequencing experiments and the dynamics of neural gene activation are insufficient to drive real-time switches between behavioural states. Moreover, the spatial, functional and transcriptional complexity of the brain (the most commonly targeted tissue in studies of behaviour) further complicates inference. We argue that a Central Dogma-like ‘back-to-basics’ assumption that gene expression changes cause behaviour leaves some of the most important aspects of gene–behaviour relationships unexplored, including the roles of environmental influences, timing and feedback from behaviour—and the environmental shifts it causes—to neural gene expression. No perfect experimental solutions exist but we advocate that explicit consideration, exploration and discussion of these factors will pave the way toward a richer understanding of the complicated relationships between genes, environments, brain gene expression and behaviour over developmental and evolutionary timescales.

scholarly journals Histone Glutamine Modification by Neurotransmitters: Paradigm Shift in the Epigenetics of Neuronal Gene Activation and Dopaminergic VTA Reward Pathway

2020 ◽  
Author(s):  
Samir PATRA
Keyword(s):  
Gene Expression ◽  
Neuronal Development ◽  
Tissue Transglutaminase ◽  
Gene Activation ◽  
Central Element ◽  
Dopamine Neurons ◽  
Normal Brain ◽  
Reward Pathway ◽  
Neuronal Functions ◽  
The Brain

Normal brain function means fine-tuned neuronal circuitry with optimum neurotransmitter signaling. The classical views and experimental demonstrations established neurotransmitters release-uptake through synaptic vesicles. Current research highlighted that neurotransmitters not merely influence electrical impulses; however, contribute to gene expression, now we know, by posttranslational modifications of chromatinised histones. Epigenetic modifications of chromatin, like DNA methylation, histone methylation, acetylation, ubiquitilation etc., influence gene expression during neuronal development, differentiation and functions. Protein glutamine (Q) modification by tissue transglutaminase (TGM2) controls a wide array of metabolic and signaling activities, including neuronal functions. Dopamine neurons are central element in the brain reward system that controls the learning of numerous behaviours. The ventral tegmental area (VTA) consists of dopamine, GABA, or glutamate neurons. The VTA and adjacent substantia nigra are the two major dopaminergic areas in the brain. In view of this, and to focus insight into the neuronal functions caused by TGM2 mediated histone modifications at the Q residues, either serotonylation (for example, H3K4me3Q5 to H3K4me3Q5ser) in the context of cellular differentiation and signaling, or dopaminylation (for example, H3Q5 to H3Q5dop) in the dopaminergic VTA reward pathway and the precise role of cocaine withdrawal in this scenario are summarized and discussed in this contribution.

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