bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does cAMP‐signaling regulate atrogenes expression in skeletal muscle upon motor denervation? (1162.9)
Authors: Lustrino Danilo , Gonçalves Dawit , Zanom Neusa , Kettelhut Ísis , Navegantes Luiz Carlos 
Published: June 2021

Recent studies have focusing on the role of cAMP‐signaling in modulating the protein degradation via de ubiquitin‐proteasome pathway during muscle wasting. Decreases in this proteolytic system during chronic muscle disuse are thought to prevent the excessive loss of muscle mass. However, the intracellular pathways that elicit this response are elusive. In turn, this study was performed to shed light on the molecular mechanisms involved in this process. For this, C57/BL6 male mice (~30g) were anesthetized and submitted to motor denervation (DEN) by unilateral sciatic nerve section. After 3, 7 and 14 days, tibialis anterior muscles were harvested to examine: mRNA and protein levels of atrophy‐related genes (i.e atrogenes; MuRF1 and atrogin‐1) and different components of cAMP‐signaling, including muscle cAMP levels, the PKA activity (estimated by phospho‐PKA substrates) and the phospho‐CREB and mRNA levels of Sik1, a CREB‐target gene. Sham‐operated and denervated animals were treated with either saline or clenbuterol (CB, 3mg/kg/day; s.c.) during 14 days. The loss of muscle mass induced by DEN started on 7th day (13%) and reached 34% at 14 days after DEN. Skeletal muscles from 3‐days denervated mice showed an increase in the gene expression of atrogin‐1 (243%) and MuRF1 (553%). However, after the 7th day of DEN, atrogenes expression was normalized. This effect was associated with an increase of muscle cAMP content (25% in relation to innervated muscles), phospho‐PKA substrates (~2.2 fold), Sik1 mRNA expression (~5.2 fold) and phospho‐CREB (~4 fold) content. Furthermore, CB treatment for 3 days increased muscle cAMP content (16%) and blunted the up‐regulation of both atrogin‐1 and MuRF1 mRNAs. These results suggest the existence of an adaptive mechanism responsible to restrain the activation of atrogenes during motor denervation that seems to be mediated by activation of cAMP/PKA/CREB signaling.Grant Funding Source: FAPESP (2012/05697‐7; 2012/24524‐6)
Reductions in REDD1 expression correspond to enhanced rates of protein synthesis following eccentric contractions (1163.16)
Authors: Gordon Bradley , Steiner Jennifer , Lang Charles , Kimball Scot , Jefferson Leonard 
Published: June 2021

Resistance exercise induces skeletal muscle hypertrophy due to enhanced rates of protein synthesis. Signaling through mTORC1 plays a vital role in integrating signals generated by resistance exercise to control skeletal muscle growth. REDD1 is a negative regulator of mTORC1 signaling whose mRNA expression is reduced in human skeletal muscle following resistance exercise. The purpose of the present study was to determine how changes in REDD1 protein expression correspond with changes in mTORC1 signaling and protein synthesis, following electrical stimulation of the sciatic nerve to induce contraction of the tibialis anterior in mice. Thirty min post stimulation, phosphorylation of p70S6K1 (T389) was increased 146% while rates of protein synthesis and REDD1 expression were unchanged compared to control. Four h post stimulation, phosphorylation of p70S6K1 (T389) was further elevated 4.5‐fold and rates of protein synthesis were increased compared to control. At this time point, REDD1 expression was reduced 40%, which was accompanied by a 71% increase in Akt (T308) phosphorylation. These data demonstrate that a reduction in REDD1 expression is not necessary for the initial, weak contraction‐induced stimulation of mTORC1 signaling. However, a subsequent fall in REDD1 expression leads to a more dramatic stimulation of mTORC1 signaling resulting in elevated rates of protein synthesis.Grant Funding Source: NIH Grants DK‐15658, GM38032
Growth hormone influences atrophy pathways in skeletal muscle of heart failure rats (1163.3)
Authors: Lima Aline , Damatto Ricardo , Pagan Luana , Bonomo Camila , Martinez Paula , Cezar Marcelo , Damatto Felipe , Zanati Silmeia , Okoshi Katashi , Okoshi Marina 
Published: June 2021

Skeletal muscle atrophy is usually observed in heart failure. Growth hormone (GH) increases muscular mass in several clinical settings. Objective: To evaluate GH administration effects on myogenin, MyoD, MRF4, myostatin, follistatin, PI3K, Akt, atrogin‐1 and MuRF‐1 protein expression, in the gastrocnemius muscle of rats with aortic stenosis‐induced heart failure. Methods: Male Wistar rats were subjected to thoracotomy for ascending aortic stenosis induction. After developing tachypnea, rats were evaluated by echocardiogram and subdivided into three groups (n=8): Sham, aortic stenosis (AS) and AS treated with GH (AS‐GH, 2mg/kg/day for 14 days). At the end of treatment, animals were subjected to echocardiogram and euthanized. Protein expression was analized by Western‐Blot. Statistical analysis: Anova and Tukey. Results: Before treatment, cardiac variables did not differ between AS and AS‐GH groups. GH administration preserved body weight (BW, Sham 492±32; AS 420±32; AS‐GH 486±69 g; p<0.05 AS vs Sham and AS‐GH). Left ventricular posterior wall thickness (Sham 3.22±0.20; AS 3.80±0.36; AS‐GH 4.37±0.67 mm) and right ventricle weight/BW ratio (Sham 0.55±0.03; AS 1.15±0.25; AS‐GH 1.18±0.15 mg/g) were higher in AS and AS‐GH than Sham. MyoD expression was higher in AS group than Sham and unchanged in AS‐GH and Sham (Sham 1.00±1.28; AS 1.71±1.37; AS‐GH 1.21±1.21 arbitrary units). MRF4 levels were higher in AS‐GH than Sham and similar in AS and Sham (Sham 1.00±0.73; AS 1.58±0.42; AS‐GH 3.14±1.61 arbitrary units). Atrogin‐1 was lower decreased in AS‐GH than Sham and AS (Sham 1.00±0.58; AS 1.14±0.87; AS‐GH 0.31±0.16 arbitrary units). Protein expression of myostatin, follistatin, myogenin, PI3K, Akt and MuRF‐1 did not differ between groups. Conclusion: Growth hormone administration modulates myogenic regulatory factors and atrogin‐1 expression in the gastrocnemius muscle of heart failure rats.Grant Funding Source: Supported by Fapesp
The preventive effects of middle frequency electrical stimulation combined with eccentric contraction on disuse atrophy in deep portion of calf muscles (1163.5)
Authors: Tanaka Minoru , Murakami Shinichiro , Fujita Naoto , Fujino Hidemi 
Published: June 2021

The purpose of the present study is to evaluate the combined effect of electrical stimulation using middle frequency (ES) and eccentric contraction on disuse atrophy in deep portion of calf muscles induced by hindlimb unloading . Rats were randomly divided into the control, hindlimb unloading for 2 weeks (HU), HU plus ES combined concentric (HU+cES), isometric (HU+iES), and eccentric (HU+eES) contraction groups. The animals in the ES groups were stimulated electrically using middle frequency current twice a day during the unloading period. Animals undergoing HU for 2 weeks exhibited the significant loss of muscle mass, decreased cross‐sectional area of muscle fibers, and overexpression of ubiquitinated protein in the soleus muscles compared with the control animals. HU+eES inhibited the HU‐induced loss of muscle mass, decreased cross‐sectional area of muscle fibers in the soleus muscles. In addition, the HU+eES inhibited the overexpression of ubiquitinated protein in the soleus muscles. Furthermore, the HU+eES inhibited the HU‐induced above factors in the soleus muscles compared with ES combined using other types of contraction groups. These results suggested that the combination of electrical stimulation with eccentric contraction might contribute to higher preventive effects on muscle atrophy in the deep portion of calf muscle.Grant Funding Source: Supported by The Japanese Society of Physio Therapeutics
Muscle slow to fast fiber plasticity is triggered by low frequency stimulation, membrane depolarization and ATP (1164.11)
Authors: Casas Mariana , Llanos Paola , Jorquera Gonzalo , Jaimovich Enrique 
Published: June 2021

An important pending question in neuromuscular biology is how skeletal muscle cells decipher the stimulation pattern coming from motoneurons to define their phenotype as slow or fast twitch muscle fibers; we realized that the muscle fiber signals through extracellular ATP to regulate important cellular processes, including regulating fast to slow muscle fiber phenotype changes. In adult muscle fibers, 20 Hz electrical stimulation activates a signaling cascade that starts with Cav1.1 activation, ATP release trough pannexin channels, purinergic receptors activation and IP3‐dependent calcium signals, to finally lead to gene transcription related to fast to slow muscle fiber type transition. ATP release plays a key role in this process, being able to activate, in the absence of electrical stimulation, most of the transcriptional changes observed after 20 Hz stimulation. In fibers depolarized to using external K+, we documented calcium signals and transcriptional changes similar to those observed after 20 Hz stimulation.Addition of 100‐500 µM external ATP induced muscle fiber depolarization and that transcriptional changes observed after stimulation of fibers with 30 µM external ATP, were abolished by 25 µM nifedipine, a Cav1.1 inhibitor. These two events were completely inhibited by the IP3R blocker Xestospongin B, suggesting that IP3‐dependent events are triggered at these membrane depolarization values.Grant Funding Source: Supported by Fondecyt 1110467, ACT 1111
Upstream activators of PGC‐1α transcription with acute contractile activity (1164.4)
Authors: Carter Heather , Shuen Michael , Hood David 
Published: June 2021

PGC‐1α is a potent transcriptional coactivator of numerous genes involved in contractile activity‐induced mitochondrial biogenesis. We sought to describe the role of transcription factors that regulate the PGC‐1α promoter in the context of acute contractile activity along with established downstream targets. A 1.5kb upstream region of the PGC‐1α promoter fused to a luciferase reporter was injected and electroporated into the rat tibialis anterior (TA) muscle bilaterally. Five days after injection the left TA was subjected to in situ contractile activity for 15 mins (5 mins at 1 Hz, 10 mins at 10Hz) while the right TA served as a resting control. Animals were allowed to recover for 2 hours, and then tissues were extracted. During stimulation, muscle force declined to 40% of initial tension. Transcriptional activity of the PGC‐1α promoter was elevated 3.6‐fold in the stimulated TA, while PGC‐1α mRNA was increased by 1.4‐fold. COX IV and NRF‐1, transcriptional targets of PGC‐1α, were each elevated by 1.2‐fold. NF‐E2 related factor 2 (Nrf2), a transcription factor with a putative binding site on the PGC‐1α promoter was increased by 1.4‐fold at the mRNA level, while GATA4, previously identified as a transcriptional regulator of PGC‐1α, remained unchanged. Thus, contractile activity signals lead to large increases in PGC‐1α transcription along with smaller increments in upstream activators, and downstream targets.Grant Funding Source: Supported By NSERC.
Ambulatory moderate plus vigorous physical activity is associated with greater bone mineral density in the hip in children with Prader‐Willi syndrome (1166.2)
Authors: Duran Andrea , Castner Diobel , Tucker Jared , Rubin Daniela 
Published: June 2021

Individuals with Prader‐Willi Syndrome (PWS) present hypotonia, low lean mass and a fairly low amount of spontaneous ambulatory physical activity (PA), possibly influencing bone mineral density (BMD). This study explored the differences in BMD between more and less active children with PWS. Twenty five children with PWS participated (age: 10.8±2.0 y, height: 141.4±11.7 cm, lean mass [LM]: 28.32±10.31 kg). Moderate plus vigorous PA (MVPA) was assessed via accelerometry. Participants were categorized into more active (n=13, MVPA: 44±3 min/day) and less active (n=12, MVPA: 23±2 min/day) groups based on a MVPA median split of 33 min/day. LM, bone mineral content (BMC), BMD and BMD z‐score (BMDz) of the hip, spine and total body minus the head were measured by dual energy x‐ray absorptiometry. Group differences were assessed using analyses of covariance, controlling for age, height and LM depending on the model. More active children had a significantly greater hip BMD (0.86±0.03 vs. 0.76±0.03 g/cm2), BMDz (0.28±0.28 vs. ‐0.86±0.29) and BMC (19.37±0.72 vs. 17.20±0.75 g) than their less active peers (p<0.05). There were no significant group differences for any spine or total body bone parameters. Children with PWS should incorporate moderate plus vigorous weight‐bearing activities as a critical component of their daily routine.Grant Funding Source: Supported by USAMRAA Award W81XWH‐08‐1‐0025
Cardiovascular responses to orthostatic stress after 90 minutes head‐down bed rest and artificial gravity exposure in hypovolemic men and women (1169.18)
Authors: Zhang Qingguang , Knapp Charles , Smith Jeffrey , Evans Joyce 
Published: June 2021

Intermittent artificial gravity (AG) training was proved to improve orthostatic tolerance limit (OTL) and alter cardiovascular regulations in response to orthostatic stress. The effect of short duration AG was not determined, especially in deconditioned subjects. To test the hypothesis that cardiovascular responses to orthostatic stress would be altered by a short bout of AG compared with head‐down bed rest (HDBR), nine men and seven women were studied during combined 70º head‐up tilt (HUT) and progressive lower body negative pressure (LBNP) until the onset of presyncope after 90‐min HDBR and AG exposure in hypovolemic condition (20 mg intravenous furosemide). To assess associated changes in cardiovascular regulation, blood pressure and heart rate variability were analyzed by spectral analysis and spontaneous baroreflex activity was evaluated by cross‐spectral analysis. Orthostatic tolerance limit was significantly increased after AG compared with HDBR. Women and men had similar responses to orthostasis for most of the cardiovascular parameters following short duration AG compared with HDBR. Following AG, women and men had a greater low frequency (0.04‐0.15 Hz) phase delay between systolic blood pressure and RR intervals at supine and did not change in response to orthostasis. Following HDBR, the supine phase delay increased in response to orthostatic stress. We conclude that a short bout AG alters some cardiovascular responses to orthostatic stress.Grant Funding Source: Supported by KY NASA EPSCoR Grant #NNX07AT58A, KY State Matching Grants, the NASA Johnson Space Cent
Interactive effects of trigeminal nerve stimulation and muscle metaboreflex activation on muscle sympathetic nerve activity in healthy humans (1170.5)
Authors: Fisher James , Fernandes Igor , Barbosa Thales , Coote John , Nóbrega Antonio , Vianna Lauro 
Published: June 2021

We investigated the independent and interactive effects of trigeminal cutaneous receptor stimulation and activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex) on muscle sympathetic nerve activity (MSNA). Heart rate (HR; ECG), blood pressure (BP; Finometer) and MSNA (microneurography) were continuously recorded in eight healthy men (29±2 yr) during three experimental conditions; 1) facial cooling [0°C, trigeminal stimulation, TGS], 2) muscle metaboreflex activation by post‐exercise ischemia [PEI] following isometric handgrip at 30% maximum voluntary contraction, and 3) simultaneous TGS and PEI. Trials were counterbalanced and respiratory rate and tidal volume controlled at baseline, TGS, PEI and TGS+PEI. TGS produced a significant decrease in HR (Δ‐5±2 bpm; mean±SE), and increase in mean BP (Δ14±3 mmHg) and MSNA total activity (Δ353±118% AU). During PEI, HR remained at resting levels (Δ3±2 bpm; mean±SE), while mean BP (Δ25±3 mmHg) and MSNA total activity (Δ234±83% AU) increased. Finally, during combined TGS and PEI, HR was unchanged (Δ0±2 bpm; mean±SE), while mean BP (Δ30±3 mmHg) and MSNA total activity (Δ331±100% AU) were increased. Thus, excitatory inputs from the trigeminal nerve and metabolically sensitive skeletal muscle afferents do not appear to summate algebraically in determining a MSNA response, but rather exhibit neural occlusion.Grant Funding Source: Supported by CAPES, CNPq, FAPERJ.
Effect of sub‐occipital release on steady‐state and dynamic oscillatory features of the cardiovascular system (1170.7)
Authors: Wilson Thad , Wagler Josiah , LePorte Andrew , Vijayakumar Amirtha , Kaya Ryan , Metzler‐Wilson Kristen , Walkowski Stevan 
Published: June 2021

To determine if sub‐occipital release (SOR) modulates sympathetic control during basal conditions and in conditions with acutely increased activity, 9 healthy subjects (5 male, 4 female) participated in 2 protocols: 1) cold stress (15°C water perfused through a high‐density tube‐lined suit for 20 min) to increase sympathetic tone and 2) normothermia (34°C). In each thermal condition, subjects received in random order, SOR and yaw sham (30 cycles/min) for 2 min. Measurements included: heart rate (HR; ECG); mean arterial blood pressure (MAP; photoplethysmography); cutaneous vascular conductance (CVC; laser‐Doppler flux/MAP); stroke volume (SV; Modelflow); systemic vascular resistance (SVR; Modelflow); and low frequency (LF; 0.04‐0.15 Hz) spectral power (Fast‐Fourier Transform). Cold stress increased MAP (SOR: 90±2 to 98±2; yaw: 87±2 to 99±2 mmHg) and SVR (SOR: 15±2 to 17±2; yaw: 15±2 to 17±2 units), decreased CVC (SOR: 0.52±0.22 to 0.26±0.14; yaw: 0.46±0.15 to 0.24±0.11 units, normothermia to cold stress, respectively), and did not significantly change HR or SV. Blood pressure and laser‐Doppler flux LF spectral power also increased during cold stress. No significant differences were observed between SOR and yaw during normothermia or cold stress. These data indicate that cold stress increases sympathetic noradrenergic tone but SOR does not have the capability to modulate these variables.Grant Funding Source: Supported by a grant from the American Osteopathic Association
Increased ATP delivery to contracting skeletal muscle blunts sympathetic vasoconstriction in humans (1172.5)
Authors: Hearon Christopher , Racine Matthew , Richards Jennifer , Luckasen Gary , Larson Dennis , Dinenno Frank 
Published: June 2021

Sympathetic stimulation of postjunctional α‐adrenergic receptors elicits vasoconstriction in resting skeletal muscle that is blunted during exercise in an intensity dependent manner. This ‘sympatholysis’ is hypothesized to occur due to increased circulating ATP. We tested the hypothesis that infusion of a non‐sympatholytic low dose of ATP during mild exercise will evoke sympatholysis in humans. In young adults (n=8), we measured forearm blood flow (Doppler Ultrasound) and calculated vascular conductance (FVC) to local intra‐arterial infusion of phenylephrine (PE; α1‐agonist) during: 1) control vasodilator infusion (low dose adenosine triphosphate, ATP; sodium nitroprusside, SNP), 2) mild (5% maximum voluntary contraction; MVC) or moderate (15% MVC) intensity handgrip exercise, and 3) combined ATP or SNP + 5% exercise. Vasoconstriction to PE during mild exercise (ΔFVC: ‐30±1%) was similar to that observed during ATP and SNP (ΔFVC: ‐30±3 and ‐35±3%; NS), however this was blunted during moderate exercise (ΔFVC: ‐17±3%; P<0.05). ATP + 5% exercise blunted PE mediated vasoconstriction similar to that seen during moderate intensity exercise (ΔFVC: ‐18±3%). In contrast, SNP + 5% exercise did not blunt PE mediated vasoconstriction (ΔFVC: ‐34±5%). These data suggest that increasing ATP delivery to contracting muscle during exercise can blunt sympathetic vasoconstriction in humans.Grant Funding Source: Supported by: H HL102720L
K252a inhibits carotid body growth but not oxygen sensitivity (1177.2)
Authors: Bavis Ryan , Logan Sarah , Blegen Halward , Fallon Sarah 
Published: June 2021

Brain‐derived neurotrophic factor (BDNF) supports innervation of the carotid body by afferent neurons (Hertzberg et al., Dev. Biol. 166:801‐811, 1994). Carotid body glomus cells express TrkB receptors as well, but the role of BDNF in carotid body growth and O2 sensitivity has not been studied. Neonatal rats were injected with the TrkB antagonist K252a (100 µg kg‐1, i.p.) or vehicle (25% DMSO) twice daily on postnatal days P0‐P6 and studied on P7. Carotid body volume was decreased by 35% after chronic K252a (P<0.001). However, single‐unit chemoafferent responses to 5% O2, measured in vitro, were unaffected by K252a administration. Ventilatory responses to 12% O2, measured by head‐body plethysmography, were also normal. Similar results were obtained for hypoxic chemoafferent and ventilatory responses after acute K252a administration. These data suggest that BDNF regulates carotid body growth but does not modulate glomus cell O2 sensitivity.Grant Funding Source: Supported by NIH grant P20 GM‐103423 (Maine INBRE)
Spinal cord injury and disruption of extrinsic sympathetic control of cerebral vasculature does not significantly alter cerebrovascular reactivity to carbon dioxide (1183.10)
Authors: Inskip Jessica , Ravensbergen Rianne , O'Connor Shawn , Claydon Victoria 
Published: June 2021

The role of the autonomic nervous system in the control of the cerebral circulation has been widely debated. Individuals with spinal cord injury (SCI), who have damage to sympathetic pathways, provide a unique opportunity to study cerebrovascular control in the absence of extrinsic sympathetic control. Here we studied cerebrovascular reactivity to CO2 in individuals with chronic SCI (both with and without damage to sympathetic pathways) and neurologically intact controls.A range of CO2 levels was obtained by voluntary hyperventilation and hypoventilation, with increased inspired CO2, during normoxia (controlled on a breath‐by‐breath basis using dynamic end‐tidal forcing). Supine middle cerebral artery velocity (MCAv), inspired and expired O2 and CO2 were recorded continuously.Compared to controls, individuals with autonomically complete SCI had reduced supine end‐tidal CO2 (36.6 ± 1.5 mmHg) and MCAv (53.4 ± 3.3 cm/s) compared to controls (40.5 ± 0.9 mmHg, p=0.05; 76.8 ± 6.0 cm/s, p<0.05). However, no significant difference in cerebrovascular reactivity to CO2 were observed between groups: disruption of extrinsic sympathetic neural control of the cerebral vasculature in individuals with complete autonomic SCI did not significantly alter the sensitivity or operating point of cerebrovascular reactivity to CO2.Grant Funding Source: Supported by the Heart and Stroke Foundation of B.C. and Yukon (V.E.C.)