The role of the cardiac opioidergic system in cardiac morphogenesis and cardioprotection

During heart morphogenesis, cardiac chambers arise by differential expansion of regions of the primitive cardiac tube. This process is under the control of specific transcription factors such as Tbx5 and dHAND. To gain insight into the cellular mechanisms that underlie cardiogenesis, we have used a retrospective clonal approach based on the spontaneous recombination of an nlaacZ reporter gene targeted to the murine α-cardiac actin locus. We show that clonal growth of myocardial cells is oriented. At embryonic day (E) 10.5, the shape of clones is characteristic of a given cardiac region and reflects its morphology. This is already detectable in the primitive cardiac tube at E8.5, and is maintained after septation at E14.5 with additional modulations. The clonal analysis reveals new subdivisions of the myocardium, including an interventricular boundary region. Our results show that the myocardium, from the time of its formation, is a polarized and regionalized tissue and point to the role of oriented clonal cell growth in cardiac chamber morphogenesis.

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Inactivation of erythropoietin leads to defects in cardiac morphogenesis

Development ◽

10.1242/dev.126.16.3597 ◽

1999 ◽

Vol 126 (16) ◽

pp. 3597-3605

Author(s):

H. Wu ◽

S.H. Lee ◽

J. Gao ◽

X. Liu ◽

M.L. Iruela-Arispe

Keyword(s):

Cardiac Development ◽

Fetal Liver ◽

Ventricular Myocardium ◽

Erythropoietin Receptor ◽

Erythroid Progenitor ◽

Cardiac Morphogenesis ◽

Proliferation And Differentiation ◽

Proliferation Assays

Erythropoietin is an essential growth factor that promotes survival, proliferation, and differentiation of mammalian erythroid progenitor cells. Erythropoietin(−/−) and erythropoietin receptor(−/−) mouse embryos die around embryonic day 13.5 due, in part, to failure of erythropoiesis in the fetal liver. In this study, we demonstrated a novel role of erythropoietin and erythropoietin receptor in cardiac development in vivo. We found that erythropoietin receptor is expressed in the developing murine heart in a temporal and cell type-specific manner: it is initially detected by embryonic day 10.5 and persists until day 14.5. Both erythropoietin(−/−) and erythropoietin receptor(−/−) embryos suffered from ventricular hypoplasia at day 12–13 of gestation. This defect appears to be independent from the general state of hypoxia and is likely due to a reduction in the number of proliferating cardiac myocytes in the ventricular myocardium. Cell proliferation assays revealed that erythropoietin acts as a mitogen in cells isolated from erythropoietin(−/−) mice, while it has no effect in hearts from erythropoietin receptor(−/−) animals. Erythropoietin(−/−) and erythropoietin receptor(−/−) embryos also suffered from epicardium detachment and abnormalities in the vascular network. Finally, through a series of chimeric analysis, we provided evidence that erythropoietin acts in a manner which is non-cell-autonomous. Our results elucidate a novel role of erythropoietin in cardiac morphogenesis and suggest a combination of anemia and cardiac failure as the cause of embryonic lethality in the erythropoietin(−/−) and erythropoietin receptor(−/−) animals.

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The role of satellite glia and opioidergic system in the peripheral mechanisms of orofacial neuropathic pain

Brazilian Journal Of Pain ◽

10.5935/2595-0118.20200061 ◽

2020 ◽

Vol 3 ◽

Author(s):

Carla Pires Veríssimo ◽

Juliana Coelho Aguiar ◽

Lionete Gall Acosta Filha ◽

Marcos Fabio Dos Santos ◽

Natália dos Reis Ferreira

Keyword(s):

Neuropathic Pain ◽

Opioidergic System ◽

Satellite Glia

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The Role of Prenatal Melatonin in the Regulation of Childhood Obesity

Biology ◽

10.3390/biology9040072 ◽

2020 ◽

Vol 9 (4) ◽

pp. 72 ◽

Cited By ~ 1

Author(s):

Dmitry O. Ivanov ◽

Inna I. Evsyukova ◽

Gianluigi Mazzoccoli ◽

George Anderson ◽

Victoria O. Polyakova ◽

...

Keyword(s):

Gut Microbiome ◽

Developmental Regulation ◽

Night Shift ◽

Medical Conditions ◽

Negative Consequences ◽

Opioidergic System ◽

Metabolic Outcomes ◽

Alpha 7 ◽

Early Developmental

There is a growing awareness that pregnancy can set the foundations for an array of diverse medical conditions in the offspring, including obesity. A wide assortment of factors, including genetic, epigenetic, lifestyle, and diet can influence foetal outcomes. This article reviews the role of melatonin in the prenatal modulation of offspring obesity. A growing number of studies show that many prenatal risk factors for poor foetal metabolic outcomes, including gestational diabetes and night-shift work, are associated with a decrease in pineal gland-derived melatonin and associated alterations in the circadian rhythm. An important aspect of circadian melatonin’s effects is mediated via the circadian gene, BMAL1, including in the regulation of mitochondrial metabolism and the mitochondrial melatoninergic pathway. Alterations in the regulation of mitochondrial metabolic shifts between glycolysis and oxidative phosphorylation in immune and glia cells seem crucial to a host of human medical conditions, including in the development of obesity and the association of obesity with the risk of other medical conditions. The gut microbiome is another important hub in the pathoetiology and pathophysiology of many medical conditions, with negative consequences mediated by a decrease in the short-chain fatty acid, butyrate. The effects of butyrate are partly mediated via an increase in the melatoninergic pathway, indicating interactions of the gut microbiome with melatonin. Some of the effects of melatonin seem mediated via the alpha 7 nicotinic receptor, whilst both melatonin and butyrate may regulate obesity through the opioidergic system. Oxytocin, a recently recognized inhibitor of obesity, may also be acting via the opioidergic system. The early developmental regulation of these processes and factors by melatonin are crucial to the development of obesity and many diverse comorbidities.

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Essential Role of Developmentally Activated Hypoxia-Inducible Factor 1α for Cardiac Morphogenesis and Function

Circulation Research ◽

10.1161/01.res.0000338613.89841.c1 ◽

2008 ◽

Vol 103 (10) ◽

pp. 1139-1146 ◽

Cited By ~ 75

Author(s):

Jaya Krishnan ◽

Preeti Ahuja ◽

Sereina Bodenmann ◽

Don Knapik ◽

Evelyne Perriard ◽

...

Keyword(s):

Essential Role ◽

Hypoxia Inducible Factor ◽

Cardiac Morphogenesis ◽

Hypoxia Inducible Factor 1Α ◽

And Function

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THE ROLE OF THE OPIOIDERGIC SYSTEM IN A FAMILIAL MODEL OF DILATED CARDIOMYOPATHY

The FASEB Journal ◽

10.1096/fasebj.20.4.a251-a ◽

2006 ◽

Vol 20 (4) ◽

Author(s):

Craig Steven Bolte ◽

Gilbert Newman ◽

Jo El Schultz

Keyword(s):

Dilated Cardiomyopathy ◽

Opioidergic System

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Protagonist Role of Opioidergic System on Post-Traumatic Stress Disorder and Associated Pain

Psychiatry Investigation ◽

10.30773/pi.2020.0002 ◽

2020 ◽

Vol 17 (6) ◽

pp. 506-516

Author(s):

Marjan Nikbakhtzadeh ◽

Fatemeh Mohtashami Borzadaran ◽

Elham Zamani ◽

Mohammad Shabani

Keyword(s):

Chronic Pain ◽

Post Traumatic Stress Disorder ◽

Traumatic Stress ◽

Stress Disorder ◽

Pain Reduction ◽

Ptsd Symptoms ◽

Post Traumatic Stress ◽

Opioidergic System ◽

Post Traumatic

Objective Post-traumatic stress disorder (PTSD) and chronic pain often co-occur. Studies have shown an interaction between pain and PTSD. In this narrative review, we aim to support conducting comprehensive studies by describing PTSD, pain and determining whether opioidergic system, its agonist and antagonist manipulation could positively or negatively affect PTSD symptoms and concurrent pain.Methods Term searches was done in Google Scholar, Scopus, ScienceDirect, Web of Science and PubMed databases as well as hand searching in key resource journals from 1979–2019.Results There are a lot of contradictions and disputes when endogenous opioidergic system and opioidergic antagonist system are studied in PTSD patients. Exogenous morphine administration in PTSD patients can decrease the symptoms of PTSD but it doesn’t have a pain reduction effect to an acceptable level. Beta-endorphin as an endogenous opioid is effective in pain reduction in the moment of events but after minutes to hours, the endorphins withdrawal syndrome leads to exaggerated intrusive thoughts and flashbacks of PTSD, which exacerbate the pain. It has also been shown that naloxone, as an opioidergic antagonist, can reduce or increase the PTSD symptoms and its associated pain.Conclusion Data suggest different roles of opioidergic system and their antagonist in pain control and mood in PTSD. However, further investigations need to be done in order to reveal the role of endogenous opioidergic system and opioidergic antagonist system as a mediator in PTSD patients suffering from acute or chronic pain.

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