scholarly journals Altered Regulation of adipomiR Editing with Aging

2020 ◽  
Vol 21 (18) ◽  
pp. 6899
Author(s):  
Sabel Meadows ◽  
Abbagael Seidler ◽  
Madison Wall ◽  
Jamika Page ◽  
Cara Taylor ◽  
...  
Keyword(s):  
Adipocyte Differentiation ◽  
Metabolic Diseases ◽  
Splice Variants ◽  
Male Rats ◽  
Brown Norway ◽  
Mirna Biogenesis ◽  
Small Rna Sequencing ◽  
Functional Changes ◽  
Altered Regulation ◽  
Adipose Dysfunction

Adipose dysfunction with aging increases risk to insulin resistance and other chronic metabolic diseases. We previously showed functional changes in microRNAs involved in pre-adipocyte differentiation with aging resulting in adipose dysfunction. However, the mechanisms leading to this dysfunction in microRNAs in adipose tissue (adipomiRs) during aging are not well understood. We determined the longitudinal changes in expression of adipomiRs and studied their regulatory mechanisms, such as miRNA biogenesis and editing, in an aging rodent model, with Fischer344 × Brown-Norway hybrid rats at ages ranging from 3 to 30 months (male/females, n > 8). Expression of adipomiRs and their edited forms were determined by small-RNA sequencing. RT-qPCR was used to measure the mRNA expression of biogenesis and editing enzymes. Sanger sequencing was used to validate editing with aging. Differential expression of adipomiRs involved in adipocyte differentiation and insulin signaling was altered with aging. Sex- and age-specific changes in edited adipomiRs were observed. An increase in miRNA biogenesis and editing enzymes (ADARs and their splice variants) were observed with increasing age, more so in female than male rats. The adipose dysfunction observed with age is attributed to differences in editing of adipomiRs, suggesting a novel regulatory pathway in aging.

scholarly journals Extensive Analysis of miRNA Trimming and Tailing Indicates that AGO1 Has a Complex Role in miRNA Turnover

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 267
Author(s):  
Axel J. Giudicatti ◽  
Ariel H. Tomassi ◽  
Pablo A. Manavella ◽  
Agustin L. Arce
Keyword(s):  
Small Rna ◽  
Stress Responses ◽  
Cellular Localization ◽  
Mirna Biogenesis ◽  
Small Rna Sequencing ◽  
Sequencing Data ◽  
Extensive Analysis ◽  
Small Regulatory Rnas ◽  
Regulatory Rnas ◽  
Argonaute 1

MicroRNAs are small regulatory RNAs involved in several processes in plants ranging from development and stress responses to defense against pathogens. In order to accomplish their molecular functions, miRNAs are methylated and loaded into one ARGONAUTE (AGO) protein, commonly known as AGO1, to stabilize and protect the molecule and to assemble a functional RNA-induced silencing complex (RISC). A specific machinery controls miRNA turnover to ensure the silencing release of targeted-genes in given circumstances. The trimming and tailing of miRNAs are fundamental modifications related to their turnover and, hence, to their action. In order to gain a better understanding of these modifications, we analyzed Arabidopsis thaliana small RNA sequencing data from a diversity of mutants, related to miRNA biogenesis, action, and turnover, and from different cellular fractions and immunoprecipitations. Besides confirming the effects of known players in these pathways, we found increased trimming and tailing in miRNA biogenesis mutants. More importantly, our analysis allowed us to reveal the importance of ARGONAUTE 1 (AGO1) loading, slicing activity, and cellular localization in trimming and tailing of miRNAs.

Effect of fluoxetine treatment on mitochondrial bioenergetics in central and peripheral rat tissues

2015 ◽  
Vol 40 (6) ◽  
pp. 565-574 ◽  
Author(s):  
Aline Isabel da Silva ◽  
Glauber Ruda Feitoza Braz ◽  
Reginaldo Silva-Filho ◽  
Anderson Apolonio Pedroza ◽  
Diorginis Soares Ferreira ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Diseases ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Wistar Rat ◽  
Male Rats ◽  
Mitochondrial Activity ◽  
Rat Tissues ◽  
Transferase Activity ◽  
Mitochondrial Bioenergetics

Recent investigations have focused on the mitochondrion as a direct drug target in the treatment of metabolic diseases (obesity, metabolic syndrome). Relatively few studies, however, have explicitly investigated whether drug therapies aimed at changing behavior by altering central nervous system (CNS) function affect mitochondrial bioenergetics, and none has explored their effect during early neonatal development. The present study was designed to evaluate the effects of chronic treatment of newborn male rats with the selective serotonin reuptake inhibitor fluoxetine on the mitochondrial bioenergetics of the hypothalamus and skeletal muscle during the critical nursing period of development. Male Wistar rat pups received either fluoxetine (Fx group) or vehicle solution (Ct group) from the day of birth until 21 days of age. At 60 days of age, mitochondrial bioenergetics were evaluated. The Fx group showed increased oxygen consumption in several different respiratory states and reduced production of reactive oxygen species, but there was no change in mitochondrial permeability transition pore opening or oxidative stress in either the hypothalamus or skeletal muscle. We observed an increase in glutathione S-transferase activity only in the hypothalamus of the Fx group. Taken together, our results suggest that chronic exposure to fluoxetine during the nursing phase of early rat development results in a positive modulation of mitochondrial respiration in the hypothalamus and skeletal muscle that persists into adulthood. Such long-lasting alterations in mitochondrial activity in the CNS, especially in areas regulating appetite, may contribute to permanent changes in energy balance in treated animals.

Mechanisms involved in developmental programming of hypertension and renal diseases. Gender differences

2014 ◽  
Vol 18 (2) ◽  
Author(s):  
Analia Lorena Tomat ◽  
Francisco Javier Salazar
Keyword(s):  
Metabolic Diseases ◽  
Current Knowledge ◽  
Adult Life ◽  
Developmental Programming ◽  
Renal Diseases ◽  
Future Studies ◽  
Functional Changes ◽  
Regulatory Systems ◽  
Increased Risk ◽  
Renal Changes

AbstractA substantial body of epidemiological and experimental evidence suggests that a poor fetal and neonatal environment may “program” susceptibility in the offspring to later development of cardiovascular, renal and metabolic diseases.This review focuses on current knowledge from the available literature regarding the mechanisms linking an adverse developmental environment with an increased risk for cardiovascular, renal and metabolic diseases in adult life. Moreover, this review highlights important sex-dependent differences in the adaptation to developmental insults.Developmental programming of several diseases is secondary to changes in different mechanisms inducing important alterations in the normal development of several organs that lead to significant changes in birth weight. The different diseases occurring as a consequence of an adverse environment during development are secondary to morphological and functional cardiovascular and renal changes, to epigenetic changes and to an activation of several hormonal and regulatory systems, such as angiotensin II, sympathetic activity, nitric oxide, COX2-derived metabolites, oxidative stress and inflammation. The important sex-dependent differences in the developmental programming of diseases seem to be partly secondary to the effects of sex hormones. Recent studies have shown that the progression of these diseases is accelerated during aging in both sexes.The cardiovascular, renal and metabolic diseases during adult life that occur as a consequence of several insults during fetal and postnatal periods are secondary to multiple structural and functional changes. Future studies are needed in order to prevent the origin and reduce the incidence and consequences of developmental programmed diseases.

Time course of hemodynamic changes in rats with healed severe myocardial infarction

1989 ◽  
Vol 257 (1) ◽  
pp. H289-H296 ◽  
Author(s):  
A. DeFelice ◽  
R. Frering ◽  
P. Horan
Keyword(s):  
Myocardial Infarction ◽  
Blood Flow ◽  
Cardiac Output ◽  
Diastolic Pressure ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Male Rats ◽  
Coronary Artery Ligation ◽  
Sham Operation ◽  
Functional Changes

Male rats were monitored for 8 mo after severe myocardial infarction (MI) to chronicle hemodynamic and left ventricular (LV) functional changes. Blood pressure (BP), heart rate (HR), cardiac output index (CO), regional blood flow, and systemic vascular resistance (SVR) were measured with catheters and radiolabeled microspheres at 4, 7, 10, 20, and 35 wk after coronary artery ligation (n = 10–16/group) or sham operation (control; n = 9–14/group). At 4 wk, 43 +/- 1% of the LV circumference was scarred, peak LV BP, LV dP/dtmax, mean BP, SVR, and HR were 11–38% less than control (P less than 0.05), and LV end-diastolic pressure (LVEDP) was increased by 313% (P less than 0.05). Mean BP, LVEDP, LVBP, and LV dP/dtmax did not further deviate after 4 wk. However, CO and SVR changed progressively and were 67 and 33%, respectively, of control by 35 wk (P less than 0.05) when blood flow to stomach, small intestine, and kidney was 55, 38, and 27% of control. Lung and heart weights were significantly increased by 148 and 22% at 4 wk, and remained elevated, and lung dry weight-to-wet weight ratio was reduced at 7 and 10 wk. Thus the trajectory of rats with healed severe MI reflects progressive cardiac decompensation, cardiac output redistribution, and terminal heart failure.

scholarly journals Altered regulation of the rostral ventrolateral medulla in hypertensive obese Zucker rats

2011 ◽  
Vol 301 (1) ◽  
pp. H230-H240 ◽  
Author(s):  
Domitila A. Huber ◽  
Ann M. Schreihofer
Keyword(s):  
Sympathetic Nerve Activity ◽  
Nucleus Tractus Solitarius ◽  
Excitatory Input ◽  
Rostral Ventrolateral Medulla ◽  
Male Rats ◽  
Ventrolateral Medulla ◽  
Zucker Rats ◽  
Caudal Ventrolateral Medulla ◽  
Obese Zucker Rats ◽  
Altered Regulation

Obese Zucker rats (OZR) have elevated sympathetic nerve activity (SNA) and mean arterial pressure (MAP) compared with lean Zucker rats (LZR). We examined whether altered tonic glutamatergic, angiotensinergic, or GABAergic inputs to the rostral ventrolateral medulla (RVLM) contribute to elevated SNA and MAP in OZR. Male rats (14–18 wk) were anesthetized with urethane (1.5 g/kg iv), ventilated, and paralyzed to record splanchnic SNA, heart rate (HR), and MAP. Inhibition of the RVLM by microinjections of muscimol eliminated SNA and evoked greater decreases in MAP in OZR vs. LZR ( P < 0.05). Antagonism of angiotensin AT1 receptors in RVLM with losartan yielded modest decreases in SNA and MAP in OZR but not LZR ( P < 0.05). However, antagonism of ionotropic glutamate receptors in RVLM with kynurenate produced comparable decreases in SNA, HR, and MAP in OZR and LZR. Antagonism of GABAA receptors in RVLM with gabazine evoked smaller rises in SNA, HR, and MAP in OZR vs. LZR ( P < 0.05), whereas responses to microinjections of GABA into RVLM were comparable. Inhibition of the caudal ventrolateral medulla, a major source of GABA to the RVLM, evoked attenuated rises in SNA and HR in OZR ( P <0.05). Likewise, inhibition of nucleus tractus solitarius, the major excitatory input to caudal ventrolateral medulla, produced smaller rises in SNA and HR in OZR. These results suggest the elevated SNA and MAP in OZR is derived from the RVLM and that enhanced angiotensinergic activation and reduced GABAergic inhibition of the RVLM may contribute to the elevated SNA and MAP in the OZR.

scholarly journals Region-specific maladaptive gray matter myelination is associated with differential susceptibility to stress-induced behavior in male rodents and humans

2021 ◽  
Author(s):  
Kimberly L. P. Long ◽  
Linda L. Chao ◽  
Yurika Kazama ◽  
Anjile An ◽  
Kelsey Y. Hu ◽  
...  
Keyword(s):  
Gray Matter ◽  
Traumatic Stress ◽  
Adult Brain ◽  
Fear Learning ◽  
Male Rats ◽  
Adult Rats ◽  
Behavioral Variation ◽  
Weighted Estimates ◽  
Functional Changes ◽  
Symptom Profiles

AbstractBackgroundIndividual reactions to traumatic stress vary dramatically, yet the biological basis of this variation remains poorly understood. Recent studies have demonstrated surprising plasticity of oligodendrocytes and myelin in the adult brain, providing a potential mechanism by which aberrant structural and functional changes arise in the brain following trauma exposure.MethodsWe tested the hypothesis that gray matter myelin contributes to traumatic stress-induced behavioral variation. We exposed adult rats to a single, severe stressor and used a multimodal approach to characterize avoidance, startle, and fear-learning behavior. We quantified oligodendrocyte and myelin content in multiple brain areas and compared these measures to behavioral metrics. We then induced overexpression of the oligodendrogenic transcription factor Olig1 in the adult rat dentate gyrus (DG) to test the potential, causal role of oligodendrogenesis in behavioral variation. Lastly, T1-/T2-weighted estimates of myelin were compared to trauma-induced symptom profiles in humans.ResultsOligodendrocytes and myelin in the DG of the hippocampus positively correlated with stress-induced avoidance behaviors in male rats. In contrast, myelin levels in the amygdala positively correlated with contextual fear learning. Olig1 overexpression increased place avoidance compared to control virus animals, indicating that increased oligodendrocyte drive in the DG is sufficient to induce an avoidance behavioral phenotype. Finally, variation in myelin correlated with trauma-induced symptom profiles in humans in a region-specific manner that mirrored our rodent findings.ConclusionsThese results demonstrate a species-independent relationship between region-specific, gray matter oligodendrocytes and myelin and differential behavioral phenotypes following traumatic stress exposure. This study provides a novel biological framework for understanding the mechanisms that underlie individual variance in sensitivity to traumatic stress.

Abstract 595: Genomic, Transcriptomic and MiRNomic Analysis of Triglyceride and Cholesterol Distribution into Lipoprotein Fractions in the Rat

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Miloslava Hodúlová
Keyword(s):  
Genome Wide Association Study ◽  
Recombinant Inbred Strain ◽  
Cholesterol Biosynthesis ◽  
Single Gene ◽  
Male Rats ◽  
Brown Norway ◽  
Ldl Particles ◽  
Genome Wide ◽  
Definition Of ◽  
Hepatic Transcriptome

Background: Dyslipidemia is central to the definition of metabolic syndrome (MS), one of most prevalent human diseases worldwide. We preformed genome-wide association study (GWAS) of triacylglycerols (TG) and cholesterol (C) distribution into lipoprotein fractions in the recombinant inbred strain panel PXO (segregating alleles of two MS models, SHR and PD strains, together with those of normolipidemic Brown Norway strain origin), followed by transcriptomic and miRNomic (microRNA profiling) analyses. Methods: We established morphometric and metabolic profile in adult male rats of 14 PXO strains and two progenitor strains (n=183) including glucose tolerance and TG and C concentrations in 20 lipoprotein fractions. GWAS utilizing >20,000 SNPs was performed using MapManager, the significance validated by 2000 permutations per trait. The hepatic transcriptome and miRNome profiles of the most contrasting strains were generated using Affymetrix GeneAtlas system followed by network analysis (Ingenuity Pathway Analysis). Results: We have identified 14 haplotype blocks showing suggestive or significant linkage to studied traits. Except for LDL-TG loci on chromosomes 3 and 12, PXO strains carrying the SHR allele displayed significantly higher values of the lipid linked traits, e.g. LDL-C (21.2±0.4 vs. 12.5±0.4 mg/dl in PXO strains with SHR allele vs. BXH2 allele). C concentrations in large, medium and very small LDL particles were significantly associated to a single gene ( Lrp1b ). Subsequent transcriptomic comparison of phenotypically most contrasting identified series of dysregulated metabolic and signaling pathways including cholesterol biosynthesis and the key upstream regulators such as HNF1 , HNF4 and PPARA . Conclusion: We identified several novel variants associated to TG and C concentrations in lipoprotein fractions together with their transcriptomic and biological network correlates.

scholarly journals Functional Changes Of Fetal Muscle Acetylcholine Receptor During Mouse Development

Physiology ◽  
1998 ◽  
Vol 13 (5) ◽  
pp. 247-251
Author(s):  
Francesca Grassi ◽  
Fabrizio Eusebi
Keyword(s):  
Acetylcholine Receptor ◽  
Single Channel ◽  
Splice Variants ◽  
Mouse Development ◽  
Functional Changes ◽  
Γ Subunit ◽  
Muscle Innervation ◽  
Fetal Muscle

In developing muscles in vivo and in vitro, the acetylcholine receptor γ-subunit exists in two splice variants, conferring different single-channel open durations (τop) to reconstituted receptors. In mouse muscles, τop changes around birth, possibly as receptors incorporate either variant of γ-subunit. This might be relevant to the concomitant maturation of muscle innervation.

Dynamic genetic architecture of metabolic syndrome attributes in the rat

2005 ◽  
Vol 21 (2) ◽  
pp. 243-252 ◽  
Author(s):  
Ondrej Seda ◽  
Frantisek Liska ◽  
Drahomira Krenova ◽  
Ludmila Kazdova ◽  
Lucie Sedova ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Genetic Architecture ◽  
Genetic Model ◽  
Interval Mapping ◽  
Male Rats ◽  
Brown Norway ◽  
Whole Genome ◽  
Morphometric Traits ◽  
Whole Genome Analysis ◽  
Genetic Determination

The polydactylous rat strain (PD/Cub) is a highly inbred (F > 90) genetic model of metabolic syndrome. The aim of this study was to analyze the genetic architecture of the metabolic derangements found in the PD/Cub strain and to assess its dynamics in time and in response to diet and medication. We derived a PD/Cub × BN/Cub (Brown Norway) F2 intercross population of 149 male rats and performed metabolic profiling and genotyping and multiple levels of genetic linkage and statistical analyses at five different stages of ontogenesis and after high-sucrose diet feeding and dexamethasone administration challenges. The interval mapping analysis of 83 metabolic and morphometric traits revealed over 50 regions genomewide with significant or suggestive linkage to one or more of the traits in the segregating PD/Cub × BN/Cub population. The multiple interval mapping showed that, in addition to “single” quantitative train loci, there are more than 30 pairs of loci across the whole genome significantly influencing the variation of particular traits in an epistatic fashion. This study represents the first whole genome analysis of metabolic syndrome in the PD/Cub model and reveals several new loci previously not connected to the genetics of insulin resistance and dyslipidemia. In addition, it attempts to present the concept of “dynamic genetic architecture” of metabolic syndrome attributes, evidenced by shifts in the genetic determination of syndrome features during ontogenesis and during adaptation to the dietary and pharmacological influences.

scholarly journals Effects of Vocal Training on Thyroarytenoid Muscle Neuromuscular Junctions and Myofibers in Young and Older Rats

2020 ◽  
Author(s):  
Adrianna C Shembel ◽  
Charles Lenell ◽  
Sophia Chen ◽  
Aaron M Johnson
Keyword(s):  
Neuromuscular Junction ◽  
Muscle Fiber ◽  
Acoustic Analysis ◽  
Neuromuscular Junctions ◽  
Fiber Type ◽  
Male Rats ◽  
Brown Norway ◽  
Control Group ◽  
Vocal Training ◽  
Thyroarytenoid Muscle

Abstract The purpose of this investigation was to determine the effects of vocal training on neuromuscular junction (NMJ) morphology and muscle fiber size and composition in the thyroarytenoid muscle, the primary muscle in the vocal fold, in younger (9-month) and older (24-month) Fischer 344 × Brown Norway male rats. Over 4 or 8 weeks of vocal training, rats of both ages progressively increased their daily number of ultrasonic vocalizations (USVs) through operant conditioning and were then compared to an untrained control group. Neuromuscular junction morphology and myofiber size and composition were measured from the thyroarytenoid muscle. Acoustic analysis of USVs before and after training quantified the functional effect of training. Both 4- and 8-week training resulted in less NMJ motor endplate dispersion in the lateral portion of the thyroarytenoid muscle in rats of both ages. Vocal training and age had no significant effects on laryngeal myofiber size or type. Vocal training resulted in a greater number of USVs with longer duration and increased intensity. This study demonstrated that vocal training induces laryngeal NMJ morphology and acoustic changes. The lack of significant effects of vocal training on muscle fiber type and size suggests vocal training significantly improves neuromuscular efficiency but does not significantly influence muscle strength changes.

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