scholarly journals The Toll‐Like Receptor 3 Agonist Poly(I:C) Induces Rapid and Lasting Changes in Gene Expression Related to Glutamatergic Function and Increases Ethanol Self‐Administration in Rats

2018 ◽  
Author(s):  
Patrick A. Randall ◽  
Ryan P. Vetreno ◽  
Viren H. Makhijani ◽  
Fulton T. Crews ◽  
Joyce Besheer
Keyword(s):  
Gene Expression ◽  
Poly I:C ◽  
Toll Like Receptor ◽  
Self Administration

SS3-6 IRF-8 negatively controls constitutive and Poly(I:C)-Regulated Toll-like receptor-3 gene expression

Cytokine ◽  
2010 ◽  
Vol 52 (1-2) ◽  
pp. 16
Author(s):  
Fragale Alessandra ◽  
Stellacci Emilia ◽  
Ilari Ramona ◽  
Shytaj Iart ◽  
Remoli Anna Lisa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Poly I:C ◽  
Toll Like Receptor

scholarly journals Increased alcohol self-administration following repeated Toll-like receptor 3 agonist treatment in male and female rats

2021 ◽  
Author(s):  
Dennis Lovelock ◽  
Patrick A Randall ◽  
Kalynn Van Voorhies ◽  
Ryan P Vetreno ◽  
Fulton T Crews ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
The Body ◽  
Female Rats ◽  
Poly I:C ◽  
Toll Like Receptor ◽  
Self Administration ◽  
Male And Female ◽  
Neuroimmune System ◽  
Male And Female Rats ◽  
History Of

Toll-like receptor (TLR) signaling may play an important role in the involvement of the neuroimmune system in the development and maintenance of alcohol use disorder. In the present study we administered TLR3 agonist poly(I:C) in male and female Long-Evans rats to determine whether TLR3 agonism can increase alcohol consumption in a daily 15% alcohol operant self-administration paradigm. We found few effects when poly(I:C) was given every-other-day at 0.3 or 1.0 mg/kg, however when instead 1.0 mg/kg was given on consecutive days alcohol intake increased in the days following injections specifically in females. Furthermore, in a second experiment we found that this effect only emerged when rats had a history of multiple poly(I:C) injections. In the final experiment the dose was increased to 3.0 mg/kg on consecutive days which resulted in significant reductions on injection days in females that were not accompanied by subsequent increases. The dose was increased to 9 mg/kg for one final pair of injections which led to reductions in intake in both males and females but only increased subsequent alcohol consumption in males. Overall, poly(I:C) was able to increase subsequent alcohol consumption in both sexes, with females being sensitive to lower doses than males both in terms of changes in alcohol consumption and general locomotor reduction. These findings show that TLR3 agonism may be involved in driving increased alcohol consumption and add to the body of work identifying the neuroimmune system as a potential therapeutic target for AUD.

scholarly journals Toll-like receptor 4-mediated cytokine synthesis and post-stroke depressive symptoms

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michal Korostynski ◽  
Dzesika Hoinkis ◽  
Marcin Piechota ◽  
Slawomir Golda ◽  
Joanna Pera ◽  
...  
Keyword(s):  
Gene Expression ◽  
Depressive Symptoms ◽  
Ex Vivo ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Post Stroke ◽  
Cytokines And Chemokines ◽  
Patient Health ◽  
Post Stroke Depression ◽  
Cytokine Synthesis

AbstractAltered cytokine synthesis thought to contribute to the pathophysiology of post-stroke depression (PSD). Toll-like receptor 4 (TLR4) is a master regulator of innate immunity. The aim of this study was to explore the putative association between TLR4-mediated cytokine synthesis and subsequent symptoms of PSD. In total, 262 patients with ischemic stroke and without a history of PSD were included. Depressive symptoms were assessed using the Patient Health Questionnaire-9 in 170 patients on Day 8 and in 146 at 3 months after stroke. Blood samples taken on Day 3 after stroke were stimulated ex vivo with lipopolysaccharide (LPS). Ex vivo synthesized cytokines (TNFα, IP-10, IL-1β, IL-6, IL-8, IL-10, and IL-12p70) and circulating cytokines (TNFα, IL-6, sIL-6R, and IL-1ra) were measured using the enzyme-linked immunoassay or cytometric method. RNA sequencing was used to determine the gene expression profile of LPS-induced cytokines and chemokines. LPS-induced cytokine synthesis and the gene expression of TLR4-dependent cytokines and chemokines did not differ between patients with and without greater depressive symptoms. The plasma level of IL-6, but not TNFα, sIL-6R, and IL-1ra, was higher in patients who developed depressive symptoms at 3 months after stroke (median: 4.7 vs 3.4 pg/mL, P = 0.06). Plasma IL-6 predicted the severity of depressive symptoms at 3 months after stroke (β = 0.42, P = 0.03). In conclusion, TLR4-dependent cytokine synthesis was not associated with greater post-stroke depressive symptoms in this study. Circulating IL-6 might be associated with depressive symptoms occurring at 3 months after stroke.

scholarly journals Cocaine induces paradigm-specific changes to the transcriptome within the ventral tegmental area

2021 ◽  
Author(s):  
Rianne R. Campbell ◽  
Siwei Chen ◽  
Joy H. Beardwood ◽  
Alberto J. López ◽  
Lilyana V. Pham ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ventral Tegmental Area ◽  
Home Cage ◽  
Expression Patterns ◽  
Energy Regulation ◽  
Biological Processes ◽  
Cocaine Exposure ◽  
Self Administration ◽  
Drug Reinforcement ◽  
Ventral Tegmental

AbstractDuring the initial stages of drug use, cocaine-induced neuroadaptations within the ventral tegmental area (VTA) are critical for drug-associated cue learning and drug reinforcement processes. These neuroadaptations occur, in part, from alterations to the transcriptome. Although cocaine-induced transcriptional mechanisms within the VTA have been examined, various regimens and paradigms have been employed to examine candidate target genes. In order to identify key genes and biological processes regulating cocaine-induced processes, we employed genome-wide RNA-sequencing to analyze transcriptional profiles within the VTA from male mice that underwent one of four commonly used paradigms: acute home cage injections of cocaine, chronic home cage injections of cocaine, cocaine-conditioning, or intravenous-self administration of cocaine. We found that cocaine alters distinct sets of VTA genes within each exposure paradigm. Using behavioral measures from cocaine self-administering mice, we also found several genes whose expression patterns corelate with cocaine intake. In addition to overall gene expression levels, we identified several predicted upstream regulators of cocaine-induced transcription shared across all paradigms. Although distinct gene sets were altered across cocaine exposure paradigms, we found, from Gene Ontology (GO) term analysis, that biological processes important for energy regulation and synaptic plasticity were affected across all cocaine paradigms. Coexpression analysis also identified gene networks that are altered by cocaine. These data indicate that cocaine alters networks enriched with glial cell markers of the VTA that are involved in gene regulation and synaptic processes. Our analyses demonstrate that transcriptional changes within the VTA depend on the route, dose and context of cocaine exposure, and highlight several biological processes affected by cocaine. Overall, these findings provide a unique resource of gene expression data for future studies examining novel cocaine gene targets that regulate drug-associated behaviors.

scholarly journals LSD1 enzyme inhibitor TAK-418 unlocks aberrant epigenetic machinery and improves autism symptoms in neurodevelopmental disorder models

2021 ◽  
Vol 7 (11) ◽  
pp. eaba1187
Author(s):  
Rina Baba ◽  
Satoru Matsuda ◽  
Yuuichi Arakawa ◽  
Ryuji Yamada ◽  
Noriko Suzuki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Enzyme Activity ◽  
Neurodevelopmental Disorders ◽  
Neurodevelopmental Disorder ◽  
Specific Inhibitor ◽  
Autism Spectrum ◽  
Poly I:C ◽  
Control Of Gene Expression ◽  
Epigenetic Machinery ◽  
The Brain

Persistent epigenetic dysregulation may underlie the pathophysiology of neurodevelopmental disorders, such as autism spectrum disorder (ASD). Here, we show that the inhibition of lysine-specific demethylase 1 (LSD1) enzyme activity normalizes aberrant epigenetic control of gene expression in neurodevelopmental disorders. Maternal exposure to valproate or poly I:C caused sustained dysregulation of gene expression in the brain and ASD-like social and cognitive deficits after birth in rodents. Unexpectedly, a specific inhibitor of LSD1 enzyme activity, 5-((1R,2R)-2-((cyclopropylmethyl)amino)cyclopropyl)-N-(tetrahydro-2H-pyran-4-yl)thiophene-3-carboxamide hydrochloride (TAK-418), almost completely normalized the dysregulated gene expression in the brain and ameliorated some ASD-like behaviors in these models. The genes modulated by TAK-418 were almost completely different across the models and their ages. These results suggest that LSD1 enzyme activity may stabilize the aberrant epigenetic machinery in neurodevelopmental disorders, and the inhibition of LSD1 enzyme activity may be the master key to recover gene expression homeostasis. TAK-418 may benefit patients with neurodevelopmental disorders.

Abstract 095: CD74 Deficient Mice are Resistant to Toll-Like Receptor-Induced Preeclampsia

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Mohamad Hatahet ◽  
Olga Y Gasheva ◽  
Valorie L Chiasson ◽  
Piyali Chatterjee ◽  
Kelsey R Bounds ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Endothelial Dysfunction ◽  
Mhc Class Ii ◽  
Immune Cells ◽  
Immune Cell ◽  
Class Ii ◽  
Poly I:C ◽  
Hypertensive Disorder ◽  
Toll Like Receptor

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder characterized by vascular endothelial dysfunction and excessive immunity and inflammation. Activation of the dsRNA receptor Toll-like receptor 3 (TLR3) or the ssRNA receptor TLR7 elicits a pregnancy-dependent PE-like syndrome in mice by inducing a pro-inflammatory immune response. CD74 (MHC Class II invariant chain) acts as a chaperone for MHC Class II surface expression on immune cells during antigen presentation and is cleaved into Class II-Associated Invariant Peptide (CLIP) following polyclonal activation of immune cell TLRs. The presence of CLIP in the groove of MHC Class II prevents T cell-dependent death leading to persistent immune cell activation. We hypothesized that genetic deletion of CD74 and subsequent depletion of CLIP on immune cells prevents TLR-induced immune responses and the development of PE in mice. Pregnant WT and CD74 KO mice were given i.p. injections of normal saline (P), poly I:C (TLR3 agonist; P-PIC), or R837 (TLR7 agonist; P-R837) on gestational days 13, 15, and 17 and euthanized on day 18. P-PIC and P-R837 WT mice had significantly increased splenic levels of pro-inflammatory CD3+/gd T cells and plasma levels of the gd T cell-derived cytokines IFNg, TNFa, and IL-17 compared to P WT mice whereas P-PIC and P-R837 CD74 KO mice had significantly increased anti-inflammatory CD3+/gd T cells and no significant increases in plasma IFNg, TNFa, and IL-17 levels. P-PIC and P-R837 CD74 KO mice did not develop the hypertension (gd17 SBP in mmHg: P WT=102±3, P CD74 KO=100±3, P-PIC WT=147±4*, P-PIC CD74 KO=95±3, P-R837 WT=133±2*, P-R837 CD74 KO=97±1; *p<0.05 vs. P WT), endothelial dysfunction, proteinuria, or placental necrosis seen in P-PIC and P-R837 WT mice. In conclusion, CD74 is crucial for the development of TLR-induced PE-like symptoms in mice and CD74/CLIP depletion may be a promising therapeutic target for women with PE.

Long-term alcohol self-administration and alcohol withdrawal differentially modulate microtubule-associated protein 2 (MAP2) gene expression in the rat brain

1998 ◽  
Vol 62 (2) ◽  
pp. 196-205 ◽  
Author(s):  
Jörg Putzke ◽  
René De Beun ◽  
Rudy Schreiber ◽  
Jean De Vry ◽  
Thomas R Tölle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rat Brain ◽  
Alcohol Withdrawal ◽  
Self Administration

scholarly journals Antiviral responses of human Fallopian tube epithelial cells to toll-like receptor 3 agonist poly(I:C)

2008 ◽  
Vol 89 (5) ◽  
pp. 1497-1506 ◽  
Author(s):  
Mimi Ghosh ◽  
Todd M. Schaefer ◽  
John V. Fahey ◽  
Jacqueline A. Wright ◽  
Charles R. Wira
Keyword(s):  
Epithelial Cells ◽  
Fallopian Tube ◽  
Poly I:C ◽  
Toll Like Receptor ◽  
Antiviral Responses ◽  
Human Fallopian Tube
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