bluuebunny/crossref_metadata_2025_split huggingface dataset:
EXCESSIVE DIETARY SALT PROMOTES AORTIC STIFFNESS IN 2K1C HYPERTENSION
Authors: DeLalio Leon , Katayama Pedro , Hahn Scott , Straub Adam , Wenner Megan , Farquhar William , Stocker Sean 
Published: June 2021

Renal artery stenosis is the most common cause of secondary hypertension. The 2‐kidney‐1‐clip (2K1C) model of renal stenosis is associated with elevated arterial blood pressure (ABP), activation of the sympathetic nervous system, and blunted reno‐renal reflexes and natriuretic responses. Excess dietary salt intake has multiple actions on the cardiovascular system and exacerbates ABP in some models of hypertension. The present study tested the hypothesis that 2K1C mice exhibit salt sensitive hypertension and worsening cardiovascular responses to high salt feeding. Male C57Bl6 mice (8–12 weeks) were fed 0.1% NaCl or 4% NaCl diets and ABP was continuously monitored using telemetry. 2K1C hypertension was produced by placing a 0.5mm length of PTFE tubing around the right renal artery. Baseline 24‐h mean ABP was not different between 0.1% versus 4.0% NaCl fed mice (101±1 vs 99±1 mmHg, respectively; n=8/group). 2K1C significantly increased ABP in both groups; however, 24‐h mean ABP at 3 weeks post‐renal clipping was not different between mice fed 0.1% vs 4.0% NaCl (122±3 vs. 124±6 mmHg, respectively; n=8/group). In addition, renal artery stenosis significantly increased arterial pulse pressure (systolic‐diastolic) in 0.1% NaCl (Day 0: 35±1 vs Day 21: 42±1 mmHg, P<0.05) and 4.0% NaCl (Day 0: 36±1 vs Day 21: 49±3 mmHg, P<0.05). Interestingly, the magnitude of the increase in arterial pulse pressure was significantly greater in mice fed 4.0% vs 0.1% NaCl (Δ14±3 vs Δ7±2 mmHg, P<0.05). This suggests dietary salt intake promotes aortic stiffness in the 2K1C model. To test this, endothelial‐dependent vasodilatory responses were measured using myography in sham and 2K1C mice fed 0.1% and 4.0% NaCl diets for 3 weeks. 4.0% NaCl 2K1C mice exhibited significantly blunted aortic vasodilation responses versus 2K1C mice fed 0.1% NaCl or sham mice fed 0.1% or 4.0% NaCl. These effects were not observed in the mesenteric arteries of the same animal. In vivo, pulse wave velocity (PWV) measurements revealed a significantly higher PWV value in 2K1C mice fed 4.0% NaCl versus 2K1C fed 0.1% NaCl (3.97±0.19; n=7 vs. 3.18±0.19; n=8, P<0.01) or sham fed 0.1% or 4.0% NaCl (3.21±0.19; n=7 vs. 3.01±0.19; n=7). We conclude that high dietary salt does not exaggerate the chronic hypertension in 2K1C mice but produces a specific endothelial‐dependent aortic stiffness.Support or Funding InformationRO1 HL128388This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Age‐associated Alterations of Microglia in the Rostral Ventrolateral Medulla of F344 rats
Authors: Balivada Sivasai , Artalejo Adriana , Ortiz Richard J , Kenney Michael J 
Published: June 2021

The Rostral ventrolateral medulla (RVLM) is a part of the medullary reticular formation and plays a critical role in the regulation of several physiological responses, including cardiovascular and sympathetic neural function. Although aging alters the responsiveness of the cardiovascular and sympathetic nervous systems, the role of the RVLM in age‐related physiological dysregulation remains unclear. Aging is associated with alterations in immune system‐related genes in various brain areas and our recent microarray analysis of the RVLM in young and aged rats revealed an increase in immune system‐related gene expression in the aged RVLM. Activation of immune system‐related genes implies changes in neuro‐immune interactions, suggesting brain resident immune cells, such as microglia, might be altered in the RVLM of aged F344 rats. In the present line of inquiry, we hypothesized that aging alters microglia in the RVLM of F344 rats. To test this hypothesis, the RVLM of young, middle‐aged, and aged F344 rats were analyzed for differences in microglia at molecular and cellular levels. First, whole rat genome microarrays of RVLM RNA samples were examined using gene ontology and pathway analysis to assess microglial phenotype in the aged RVLM. Second, age‐associated changes in microglia‐related gene expression in the RVLM was evaluated using qPCR. The microarray analysis indicated that molecular pathways involved in the regulation of microglia/macrophage phenotype, such as CXCR4, Toll‐like receptor, and inflammatory cytokine‐related signaling pathways were altered in the RVLM of aged rats (p<0.05, FDR<0.3). In addition, the RVLM of aged rats showed upregulation of microglia‐related genes, such as CD68, Tlr2, Trem2, and Fcrl2 (p<0.05, FDR<0.1). Our present experiments are characterizing RVLM microglia using IBA1 and MHC class ii immunohistochemistry. These preliminary results suggest that the microglial phenotype is altered in the RVLM of aged rats, providing an important foundation for age‐associated changes in neuro‐immune interactions in the RVLM and its effect on physiological responses.Support or Funding InformationNIH grant AG‐041948, Minority Institutions program grant 5G12MD007592‐24 from the National Institute on Minority Health and Health Disparities (NIMHD).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Influence of Heat Stress on Monocyte Chemoattractant Protein‐1 Expression by Satellite Cells after Rat Skeletal Muscle Injury
Authors: Sugiyama Megumi , Kawashima Masato , Miyakawa Motoi , Taniguchi Kaho , Arakawa Takamitsu 
Published: June 2021

Heat stress could promote skeletal muscle regeneration via early recruitment and invasion of macrophages into the necrotic muscle fibers (e.g., Takeuchi et al., 2014; Hatade et al., 2014). Macrophages play important roles in myoblasts proliferation, differentiation and fusion by producing some cytokines and be involved in muscle regeneration (e.g., Tidball, 2005; Arnold et al., 2007). But in the regeneration process, the mechanisms for the macrophages recruitment via the heat stress is unclear. Monocyte Chemoattractant Protein‐1 (MCP‐1) is involved in the migration, and this chemokine is produced by the satellite cells (e.g., Chazaud et al., 2003). Spatial distributions and chronological changes of the MCP‐1, Pax7 (a specific marker of satellite cells) and CD68 (a pan‐macrophages marker) were examined by using the immunohistochemistry via heat stress after crush injury to the extensor digitorum longus muscle of rats. In the present study, 8‐week old male Wistar rats weighing 180–200g were used. According to the crush method described by Furuta (2001) and our earlier reports (Takeuchi et al., 2014; Hatade et al., 2014), animals were anesthetized by an isoflurane and exposed the muscle. Next, the middle part of the muscle belly was crushed for 30s using forceps, to which a weight (500g) was attached. After the muscle crush injury, animals were randomly divided into heat and non‐heat groups. In the heat group, packs filled with hot water (42 degrees C) were percutaneously applied to the muscle for 20 min soon after the injury and in the non‐heat group were not. At 6, 12 and 24 h (n = 1, respectively) after the injury, animals were sacrificed, muscles were harvested and frozen cross sections (10 μm) of the injured muscle were prepared by cutting with a cryostat. Some sections were used for hematoxylin and eosin staining, the others were used for immunohistochemistry. At 6 h after the injury, macrophages were recruited around the degenerating muscle fibers in the non‐heat group. In the heat group, recruitment of the macrophages was higher than the non‐heat group. Similarly, recruitment and infiltration of macrophages in the heat group were higher than those in the non‐heat group at 12 h and 24 h after the injury. In addition, at 6 h after the injury of the heat group, the MCP‐1 was expressed in the satellite cells, whereas in the non‐heat group it was seen after 12 h, suggesting that the heat stress soon after the skeletal muscle injury might promote more rapid MCP‐1 expression of the satellite cells.Support or Funding InformationNoneThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Fidelity of Reinnervation Modulates Susceptibility to Aging Muscle Impact and Frailty in Elderly Women
Authors: Sonjak Vita , Jacob Kathryn , Morais Jose , Spendiff Sally , Spake Carole , Rivera‐Zengotita Marie , Taivassalo Tanja , Chevalier Stéphanie , Hepple Russell 
Published: June 2021

BackgroundStudies in aging rodent models and elderly men have recognized skeletal muscle denervation as an important factor contributing to age‐related muscle atrophy. This has not yet been assessed in octogenarian women, a population that is at a greater risk of becoming physically frail. On this basis we determined the presence of muscle denervation in prefrail/frail elderly women and its contribution to aging muscle phenotypes compared to a population with high function in advanced age, world class octogenarian track and field athletes.MethodsMuscle biopsies were obtained from vastus lateralis muscle from prefrail/frail elderly women (FE, n=17, 77.9±1.5y), master athletes (MA, n=7, 80.9±2.2y) and young inactive (YI, n=12, 24.0±1.0y) controls, to assess denervation‐induced morphological and transcriptional markers.ResultsThe FE group displayed a high abundance of grouped slow fibers, accumulation of very small myofibers, a severe reduction in type IIa to type I size ratio, and an accumulation of neural cell adhesion molecule‐positive myofibers and pyknotic nuclei, consistent with recurring cycles of denervation/reinnervation with a sporadic occurrence of failed reinnervation in prefrail/frail subjects. The MA group exhibited a smaller decline in type IIa/I size ratio, but not attenuated fiber atrophy relative to FE, and this was associated with a higher degree of fiber type I grouping in MA vs FE, suggesting a greater reinnervation of denervated fibers in MA. Consistent with this interpretation, MA had higher mRNA levels of the reinnervation promoting cytokine Fibroblast Growth Factor Binding Protein 1 than FE.ConclusionOur results indicate that the muscle of prefrail/frail elderly women undergoes significant neurogenic atrophy, whereas MA exhibit evidence of superior reinnervation capacity that attenuates functional decline with aging by attenuating aging muscle atrophy through better retention of muscle fiber number.Support or Funding InformationThis work was supported by Canadian Institute of Health Research (MOP 125986 and MOP 119583 to R.T. Hepple). Part of the expenses involving older participants was supported by an Internal Grant from the Helen McCall Hutchison Family Foundation of the Montreal General Hospital. V. Sonjak was supported by the Bloomberg Manulife Fellowship. K.J. Jacob was supported by a PhD scholarship from the Fonds de recherche du Quebec – Sante (FRQS).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Neuromuscular Junction Plasticity Confers Atrophy Resilience of Aging Muscle
Authors: Burke Sarah Skinner , Fenton Andrew , Goddard Yana , Anagnostou Maria‐Eleni , Hepple Russell T 
Published: June 2021

INTRODUCTIONAging is associated with progressive muscle atrophy that contributes to weakness and increased risk of falls in advanced age. Our previous work has highlighted the importance of persistent denervation of muscle fibers (Rowan et al. PLoS One 2012), associated with a failed reinnervation response (Aare et al. Skeletal Muscle 2016), as a primary cause of muscle fiber atrophy in advanced age. We have also noted previously (Picard et al. Aging Cell 2011) that there is considerable heterogeneity between different muscles in severity of atrophy with aging that is unrelated to muscle fiber type composition per se. Most notably, in a comparison of two hindlimb muscles predominately composed of type I fibers in young adulthood, the soleus (Sol) exhibits a 30–40% decline in muscle mass while the adductor longus (AL) exhibits a remarkable 47% increase in muscle mass in advanced age rats. In view of the importance of denervation to aging muscle atrophy, we compared age‐related changes in neuromuscular junction (NMJ) morphology in the Sol and AL muscles to test the hypothesis that vulnerability to aging muscle atrophy parallels adaptive plasticity of the NMJ with aging.FINDINGSAL and Sol muscles were collected from 9‐mo old (YA) and 34‐mo old (VO) male Fischer 344 × Brown Norway F1‐hybrid (F344BN) rats (n=6; 3 YA) obtained from the colony maintained by the National Institute on Aging. NMJs in each muscle were immunofluorescently labelled and imaged by confocal microscopy (Leica SP8). Images were quantitatively assessed using NMJ‐Morph, an Image‐J based package designed for characterization and analysis of NMJ morphology. Interestingly, whereas for several parameters of NMJ morphology the AL exhibited changes with aging that were either not seen in the Sol or of greater magnitude in the AL, the majority of these parameters were already altered in the YA Sol versus the YA AL in the same direction as occurred with aging in the AL. As such, this suggests that NMJ morphological plasticity may be initiated much earlier in the lifespan in the Sol and that exhaustion of this plasticity may account for the atrophy susceptibility of the Sol in advanced age. Further to this, our data suggest that a substantial reserve of NMJ plasticity in the AL is amongst the factors responsible for its resilience to aging muscle atrophy in advanced age.CONCLUSIONOur results are consistent with the hypothesis that vulnerability to aging muscle atrophy parallels adaptive plasticity of the NMJ with aging.Support or Funding InformationSSB is supported by a T32 from the National Institute of Child Health and Human Development Grant T32HD043730.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Characterizing mu Opioid Receptor Splice Variants Using Gene Targeting Rat Models Generated by Easi‐CRISPR
Authors: Rossi Grace , Xu Jin , Le Rouzic Valerie P , Pasternak Gavril W , Yoshiki Miyasaka , Mashimo Tomoji , Saunders Thom , Gurumurthy Channabasavaiah B , Pan Ying‐Xian 
Published: June 2021

BackgroundA single‐copy mu opioid receptor (OPRM1) gene generates a vast array of mu opioid receptor splice variants through extensive alternative splicing that is conserved from rodent to human. These variants can be divided into two sets: exon 11 (E11) and exon 1 (E1) associated variants. The functional differences between the E1 and E11 sets of variants have been demonstrated using gene targeted mouse models.Rationale/SignificanceWhile mouse models are valuable, rats have many advantages both in behavioral modeling and in vivo manipulation.HypothesisE11‐ and E1‐associated splice variants play important and distinct roles In opioid pharmacology.ResultsWe have generated two conditional Oprm1 knockout (KO) models, E11‐KO and E1‐KO, in Sprague Dawley rats using a novel Easi‐CRISPR approach. Cre‐mediated E11 and E1 deletions was confirmed through breeding a CAG‐Cre rat. Initial behavioral studies showed that in both E11 and E1 KO rats, buprenorphine analgesia was lost. Buprenorphine CPP was significantly reduced in E11 KO rats. Morphine analgesia was completely lost in the E1‐KO rat, but intact in the E11‐KO rat.DiscussionOur results suggest that buprenorphine analgesia is dependent on both E11 and E1‐associated variants, a similar scenario seen in the E11‐KO and E1‐KO mouse models. E11‐associated variants also involved in buprenorphine reward in rat. These conditional Oprm1 KO rat models will provide valuable resources for the research community and would expand our ability explore mu opioid pharmacology with approaches and techniques not feasible in mice.Support or Funding InformationSupported by grants from NIH (DA40858, DA06241, DA042888 and CA08748)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Antidepressant Effects of Crocin‐1 from Saffron in Mice with Chronic Unpredictable Mild Stress‐Induced Depression
Authors: Wang Ping , Lin Susu , Chen Zhuoyi , Jiang Yu , Jiang Jinyan , Liu Ling 
Published: June 2021

AimDepression is a severe disorder that has enormous consequences for the individual's quality of life, and it is among the most prevalent forms of mental illness. Saffron, a famous herb medicine and spice in the world, has been suggested as a potential efficacious and tolerable treatment for depression and anxiety, while there is no study about the effect of crocin‐1 on depression and a few studies about the mechanism of saffron. So the aim of this study was to investigate the effects of crocin‐1, one of the most important active compounds in saffron, on chronic unpredictable mild stress (CUMS) induced depression in mice.MethodsThe effects of crocin‐1 were examined using CUMS induced depression ICR mice and factors including depressant‐like behaviors, neurotransmitters, the expression of MKP‐1, CREB and BDNF.ResultsOur data showed that crocin‐1 significantly prevented reduction of body weight induced by CUMS. Oral administration of crocin‐1 (10, 20, and 40mg/kg) markedly improved depressant‐like behaviors, increasing the latency and reducing the immobility time in both the tail suspension test and forced swimming tests, compared with the CUMS mice. Enzyme‐linked immunosorbent (Elisa) assay were performed on serum and it showed that crocin‐1 treatment not only restored the decreased neurotransmitter concentrations of dopamine (DA) and serotonin (5‐HT), but also increased the level of mBDNF and decreased proBDNF. The results of reverse transcription‐polymerase chain reaction and Elisa assay showed that crocin‐1 decreased the level of MKP‐1 mRNA and MKP‐1 expression in hippocampus, moreover, it also increased the level of BDNF mRNA expression and CREB mRNA expression.ConclusionTaken together, our study confirmed that crocin‐1 might have an antidepressant‐like effect in the CUMS model of depression in mice, and suggest it might be mediated by regulation of neurotransmitters, activation MKP‐1/CREB/BDNF pathway and balanced the ratio of proBDNF and mBDNF.Support or Funding InformationThis work was supported by Natural Science Foundation of China (81703688), China Postdoctoral Science Foundation (2016M592016) and Key Project of Science and Technology Department of Zhejiang Province (2015C02032).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of Cortical Catecholamines in the Paradoxical Action of Psychostimulants
Authors: Harris Sharonda , Green Sara 
Published: June 2021

Attention deficit hyperactivity disorder (ADHD) affects young children and manifests symptoms such as hyperactivity, impulsivity and cognitive disabilities. The primary line of treatment for ADHD are the psychostimulant class of drugs including amphetamine (Adderall) and methylphenidate (Ritalin). Several theories have been postulated on the paradoxical calming effect of psychostimulants on ADHD patients, but even after decades of research, their exact mechanism of action is unknown. Clinical studies have shown reduced levels of dopamine (DA) receptor and DA transporters (DAT) in ADHD patients, presumably due to elevated caudate DA levels. Studies using the dopamine (DA) transporter (DAT) knockout mice, which have elevated striatal DA levels and are considered an animal model of ADHD, have suggested that the paradoxical calming effect of psychostimulants might be through the parallel actions of other monoamine neurotransmitters. On the other hand, newer non‐stimulant classes of drugs such as atomoxetine and Intuniv suggest that targeting the norepinephrine (NE) system might explain the paradoxical calming effect. Again, the molecular and cellular mechanisms of action for these drugs or neurotransmitters in ADHD therapy is unknown.Previous work has shown that DA levels in the PFC have a reciprocal effect on striatal DA levels and locomotion. Our preliminary data suggest that PFC D2+ pyramidal neurons project to the striatum and midbrain dopamine neurons and that infusion of D2 agonists in the PFC inhibits locomotion. We hypothesize that PFC DA through the action of PFC D2+ pyramidal neurons regulates striatal DA release and locomotion. To test our hypothesis we use ex vivo neurotransmitter release from mouse PFC slices, microdialysis and locomotor measurements, in NET and DAT knockout mice. Our preliminary data suggest that NET and SERT blockers not only increase extracellular levels of NE and 5HT, but also DA. These data suggest a possible role for cortical catecholamines in regulating the paradoxical effects of psychostimulants. Our future studies will not only shed light on the mechanism of psychostimulant action in ADHD therapy, but will facilitate development of newer therapies based on mechanistic evidence.Support or Funding InformationBrain Behavior Research Foundation 27765 to N. UrsThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mechanism of Arsenic Trioxide Inhibition of Cell Growth and Induction of Apoptosis in Triple Negative MDA‐MB‐231 Breast Cancer Cell Line
Authors: Alzuwaidi Sarah , Khalil Rafaat 
Published: June 2021

Arsenic Trioxide ATO exhibits antitumor activities and potent inducer of apoptosis in a variety of cancer types, the exact mechanism of antitumor activity is not clear and its effectiveness in solid cancer remain controversial. Tumor necrosis factor‐alpha (TNF‐alpha) has also been shown to both induce apoptosis and prevent cell proliferation. The present study was designed to further investigate the effect of different concentrations of ATO on the viability of triple negative breast cancer MDA‐MB‐231 cell line, and to investigate apoptosis activated proteins induced by the treatment of ATO, TNF‐alpha, and combination. MDA‐MB‐231 cells exposed to seven different concentrations of ATO from 0 to 12 μM, for 24 hours, cell viability was measured by Alamar blue assay. Results show that ATO treatment effectively caused cell growth inhibition, and induced apoptosis in MDA‐MB‐231 cancer cells in a concentration‐dependent manner. Human apoptosis array is used to evaluate expression of apoptosis‐regulated proteins. Treated cells were labeled as control, ATO (2μM), TNF‐alpha (40 ng/ml) or combinations of ATO and TNF alpha, the arrays were made with dots corresponding to 43 major proteins. The analysis of dot blot intensity indicate that all treatments presented the same 43 proteins with a difference in the intensity of P53, Bcl2, BID, Caspase 3, Caspase 8, Cytochrome C, SMAC, HSP60, HSP70, HTRA2, and surviving proteins. Current results show that arsenic trioxide is useful to treat Breast cancer and apoptosis induced by activation of key regulatory proteins.Support or Funding InformationDepartment of BiologyThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.