bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diet Associated with Exercise Training Improves Heart Rate Recovery and Autonomic Control in Metabolic Syndrome Subjects
Authors: Cepeda Felipe Xerez , Rodrigues Sara , Dutra‐Marques Akothirene C.B. , Toschi‐Dias Edgar , Carvalho Jefferson C. , Carvalho Glauce L. , Rondon Maria Urbana P.B. , Alves Maria Janieire N.N. , Trombetta Ivani C. 
Published: June 2021

PurposePrevious study showed that metabolic syndrome (SMet) subjects have impaired attenuation of heart rate recovery (ΔHRR) after maximal exercise. Autonomic dysfunction is the possible mechanism involved in this alteration. We tested the hypothesis that hypocaloric diet and exercise training (D+ET) improves DHRR, heart rate reserve and autonomic control in MetS subjects.MethodsNever treated patients with MetS (ATP‐III) were assigned into intervention group (MetS/D+ET, n=33) submitted to D (−500 kcal/day) and ET (40 min, 3 times/week of cycle exercise) and control group (MetS/C, n=23) for 4 months. We evaluated pre and post‐intervention or control period, cardiac autonomic control (LF = low frequency, HF = high frequency, LF/HF = sympathovagal balance) by heart rate variability (ECG), muscle sympathetic nervous activity (MSNA ‐ microneurography) and we calculated the ΔHRR (maximal HR minus HR in the 1st, 2nd and 4th min of recovery) and the heart rate reserve (maximal HR minus resting HR) after cardiopulmonary exercise test.ResultsSMet/D+ET improved metabolic profile, functional capacity and reduce body weight. Compared with pre‐intervention, MetS/D+ET increased HF n.u. (33±3 vs. 39±3 bpm, P=0.01) and decreased MSNA (30±1 vs. 25±2 bpm, P<0.001), LF n.u. (67±3 vs. 61±3 bpm, P=0.02) and LF/HF (3.0±0.3 vs. 2.2±0.4 bpm, P=0.02). Furthermore, MetS/D+ET increased ΔHRR at 1st min (16±1 vs. 21±2 bpm, P=0.02), ΔHRR at 2nd min (28±1 vs. 36±2 bpm, P<0.001), ΔHRR at 4th min (46±2 vs. 56±2 bpm, P<0.001) and heart rate reserve (76±3 vs. 86±3 bpm, P <0.001). No significant change was observed in SMet/C.ConclusionThe intervention by hypocaloric diet and exercise training improves the autonomic control, heart rate reserve and heart rate recovery after maximal exercise in subjects with MetS.Support or Funding InformationGrant #2011/17533‐6, #2015/17533‐6 and #2016/16831‐7, São Paulo Research Foundation (FAPESP) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Functional Interaction Between NMDA Receptors and SK Channels in Hypothalamic Magnocellular Neurons: Role in Heart Failure
Authors: Ferreira‐Neto Hildebrando Candido , Stern Javier Eduardo 
Published: June 2021

Neurohumoral activation, which includes elevated plasma levels of vasopressin, is a hallmark of heart failure (HF). However, the precise mechanisms that regulate hypothalamic magnocellular neurosecretory cells (MNCs) neuronal excitability during HF remains incompletely understood. Here, we evaluated whether an increase in intracellular Ca2+ induced by NMDA receptor activation would evoke a compensatory feedback inhibitory mechanism via activation of Ca2+‐dependent K+ channels, and whether this mechanism would contribute to the regulation of MNCs excitability in HF rats. Whole‐cell patch clamp recordings obtained from MNCs (holding potential: −50 mV) in slices from Sham and HF rats showed that focal application of NMDA (50 mM, 300 ms) evoked an inward NMDAR‐mediated current (INMDAR) whose magnitude was similar in Sham and HF rats (amplitude: Sham 0.16±0.02 vs HF 0.20±0.02 nA, p>0.05; area: Sham 94±24 vs HF 77±15 nA.ms, p>0.05). INMDAR was immediately followed by an outward current, whose magnitude was larger in MNCs from HF than Sham rats (amplitude: Sham 0.9±0.1 vs HF 1.6±0.3 nA, p<0.05; area: Sham 215±19 vs HF 410±76 nA.ms, p<0.01). Blockade of K+ currents with Cs+ revealed that the INMDAR was in fact significantly larger in MNCs from HF than Sham rats (amplitude: Sham 0.18±0.04 vs HF 0.86±0.02 nA, p<0.05; area: Sham 111±24 vs HF 263±54 nA.ms, p<0.05). Intracellular dialysis of MNCs with the Ca2+ chelator BAPTA significantly reduced the outward current triggered by NMDAR activation in both groups to the same extent (amplitude: Sham 0.17±0.05 vs HF 0.22±0.07 nA, p>0.05; area: Sham 18±9 vs HF 42±19 nA.ms, p>0.05). Bath application of the SK channel blocker apamin significantly decreased the outward current triggered by INMDAR in MNCs from HF rats (p<0.05), but this effect was minimal in Sham rats (p>0.05). Finally, current clamp recording showed that focal application of NMDA after SK channel blockade increased the number of evoked spikes both in Sham and HF rats compared to control conditions (Sham 168±25%, p<0.001 vs control; HF 311±71%, p<0.01 vs control), but this effect was exacerbated in HF rats (p=0.06 vs Sham). Taken together, our data supports the presence of a functional coupling between excitatory NMDAR and inhibitory SK channels in MNCs. This interaction is enhanced in HF rats contributing to dampening the NMDAR‐mediated hyperexcitability observed in MNCs during this condition.Support or Funding InformationR01HL090948This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Blockade of central angiotensin II AT1 receptors attenuates acute intermittent hypoxia‐induced sympathetic long‐term facilitation (S‐LTF)
Authors: Shimoura Caroline Gusson , Andrade Mary Ann , Toney Glenn M. 
Published: June 2021

After exposure to acute intermittent hypoxia (AIH) and while undergoing continuous normoxic ventilation, a progressive increase of sympathetic nerve discharge (SND) is observed in the anesthetized rat. This phenomenon, referred to as post‐AIH sympathetic long‐term facilitation (S‐LTF), involves neuroplasticity resulting, at least in part, from repetitive arterial chemoreceptor activation, but the underlying mechanisms remain to be determined. Evidence indicates that post‐AIH S‐LTF is largely unaffected by intravenous injection of the angiotensin II (AngII) AT1 receptor antagonist losartan. Because AIH repetitively increases renal SNA in associated with large amplitude reductions of arterial pressure and thus renal perfusion pressure, both of which potently stimulate the renin‐AngII system, we hypothesized that central AngII actions contribute to post‐AIH S‐LTF. Anesthetized male rats received an injection (2 μl) of losartan (40 pmol) or vehicle (aCSF) into a lateral cerebral ventricle 20 minutes before exposure to a 1 hour AIH protocol, which consisted of 10 cycles of changing FiO2 from 100% to 15% every 3 minutes. Losartan significantly attenuated (p<0.001) the increase of splanchnic SND caused by AIH (vehicle: 112±34%, n=4 vs losartan: 27±7%, n=7). These data indicate that AngII acting at central AT1 receptors contributes to post‐AIH S‐LTF. When considered together with literature evidence, we conclude that the AngII signal of AIH is generated centrally, not peripherally.Support or Funding InformationNIH HL088052 & AHA 25710176 (GMT)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Central Fractalkine Induces Systemic Inflammation Independently of Hypothalamic Prostaglandin E2
Authors: Mota Clarissa Maria Dias , da Rocha Maria José Alves , Antunes‐Rodrigues José , de Siqueira Branco Luiz Guilherme 
Published: June 2021

Fractalkine (FKN; CX3CL1) belongs to the gamma‐chemokine family and binds to CX3CR1 receptors. Currently, the mechanisms involving FKN‐induced inflammatory mediators are research targets in an attempt to study immune diseases mechanisms. Besides, FKN seems to modulate inflammation in the nervous system by inducing the secretion of pro‐inflammatory mediators such as prostaglandin E2 (PGE2). PGE2 is a classic and important mediator of fever that activates warm‐responsive neurons in the anteroventral preoptic region of the hypothalamus (AVPO). Here, we tested the hypothesis that central FKN modulates febrigenic signaling both centrally and peripherally. Thus, male Wistar rats (280–350 g, n=5/group) were obtained from the Central Animal Facility at the University of São Paulo in Ribeirão Preto and all the experiments were performed according to the Brazilian society of laboratory animals science and in conformance with the FASEB Statement of Principles for the use of animals in research and education. We performed intracerebroventricular (icv) microinjections of saline (1 μL) and FKN (doses of 5, 50, 500 pg/μL) and measured body temperature (Tb), besides assessing tail skin temperature (Tsk) as a thermoeffector indicator. We also measured AVPO PGE2, plasma corticosterone (CORT) and interleukin‐6 (IL‐6) levels. FKN induced a long lasting febrile response in which the highest dose (500 pg/μL) induced a marked rise on Tb that was accompanied by a reduced Tsk. FKN had no effect on AVPO PGE2 production, whereas caused increases in plasma CORT and IL‐6 levels. Our data consistently indicate that FKN induces fever (reducing Tsk) in a PGE2 independent way probably by increasing plasma IL‐6 levels.Support or Funding InformationThe São Paulo Research Foundation (FAPESP) grant numbers #16/17681‐9 and #17/01633‐8 and the National Council for Scientific and Technological Development (CNPq), Brazil.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Glucoprivic sensitivity of hindbrain catecholamine neurons is astrocyte‐dependent
Authors: Rogers Richard C. , McDougal David , Ritter Sue , Qualls‐Creekmore Emily , Hermann Gerlinda E. 
Published: June 2021

Hypoglycemia poses a threat to survival. Endocrine, metabolic, and behavioral counter‐regulatory responses (CRRs) act to correct blood glucose deficit. These responses require sensor, integrator, and effector elements to restore glucose homeostasis. Groups of hindbrain catecholamine (CA) neurons are essential for implementation of different CRRs which include activation of descending sympathetic pathways controlling epinephrine and glucagon release and ascending pathways controlling feeding behavior and glucocorticoids (3, 4). Hindbrain astrocytes respond to low glucose (1, 2, 5). Therefore, we postulated that CA neurons are activated by astrocytes during glucose deficit. To directly test the proposition that CA neuron responses to glucoprivic challenges are astrocyte dependent, we utilized male and female transgenic mice in which the calcium reporter construct (GCaMP5) was expressed selectively in tyrosine hydroxylase neurons (TH‐GCaMP5; TH+). We conducted live‐cell calcium imaging studies on tissue slices containing the nucleus of the solitary tract (NST) and the ventrolateral medulla (VLM); loci of glucoregulatory circuitry (4). Results show that hindbrain TH+ neurons are robustly activated by a glucoprivic challenge and that this response is dependent on functional astrocytes. Pretreatment of hindbrain slices with fluorocitrate (an astrocytic metabolic suppressor) abolished TH+ neuronal responses to glucoprivation, but not to glutamate stimulation. Pharmacologic results suggest that the astrocytic connection with TH+ neurons is purinergic via P2 receptors. Parallel imaging studies on hindbrain slices of NST from wild type C57BL/6J mice (astrocytes and neurons were prelabeled with a calcium reporter dye and an astrocytic vital dye) show that both cell types are activated by glucoprivation but astrocytes responded nearly a minute sooner than neurons. Pretreatment of these hindbrain slices with fluorocitrate eliminated both astrocytic and neuronal responses to glucoprivation; pretreatment with P2 antagonists only abolished neuronal responses to glucoprivation without interruption of astrocyte responses. These results support earlier work suggesting that the primary detection of glucoprivic signals by the hindbrain is mediated by astrocytes which utilize purinergic gliotransmission to activate critical effector neurons.Support or Funding InformationNIH NIDDK 108765, U54 GM 104940, ADA‐1‐15‐JF‐37,This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Influence of GABA Receptor Antagonists on the Biphasic Hypoxic Ventilatory Response of Newborn Rats
Authors: Cottingham Peter L. , March Ryan J. , Bavis Ryan W. 
Published: June 2021

Newborn mammals exhibit a characteristically biphasic hypoxic ventilatory response (HVR) in which an initial increase in ventilation is followed by a progressive decline toward (or below) baseline values. Studies in anesthetized, newborn piglets suggest that the secondary hypoxic depression is partially attributable to γ‐aminobutyric acid (GABA) signaling through GABAA and GABAB receptors (Huang et al. J Appl Physiol 77:1006–1010, 1994). To determine whether GABAA and GABAB receptors similarly contribute to the biphasic HVR of newborn rats, we measured normoxic (21% O2) and hypoxic (12% O2) ventilation of newborn (P3–5) rats by head‐body plethysmography 30 minutes after intraperitoneal injection with vehicle or a GABA receptor antagonist. Two different GABAB receptor antagonists, CGP‐35348 (200 mg kg−1) and CGP‐46381 (50 or 100 mg kg−1), were found to have no effect on normoxic ventilation or the HVR (all P>0.05). Similar results were obtained for the GABAA receptor antagonist (+)‐bicuculline (2 or 3 mg kg−1). Collectively, these data do not support a role for GABAergic signaling in the biphasic HVR of newborn rats.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Aging Effects on Diaphragm Muscle Sarcopenia
Authors: Vang Pangdra , Zhan Wen Zhi , Gransee Heather , Sieck Gary , Mantilla Carlos 
Published: June 2021

The population at very old age is increasing dramatically throughout the world. Aging adults experience increased health and medical needs associated with debility and sarcopenia (i.e., muscle atrophy and force loss). Respiratory complications and diseases are common causes of morbidity and mortality in the elderly. Sarcopenia of respiratory muscles such as the diaphragm muscle (DIAm) may contribute to respiratory complications since the DIAm, the main inspiratory muscle in mammals, plays an important role in ventilation and generating the forces necessary to maintain airway clearance. Presently, there is limited information about aging effects into very old age. Specifically, whether DIAm sarcopenia is exacerbated in old age and if it will effect ventilation into very old age are presently unknown. We hypothesized that DIAm sarcopenia in very old mice (>30 mo; ~30% survival) will result in reduced DIAm force generation across motor behaviors, exhibit impaired ventilation, decreased isometric force, and reduced fiber cross‐sectional area compared to old (24 mo; ~80% survival), and young (6 mo, 100% survival). C57BL/6 × 129 female and male mice (n = 30) at 6 mo, 24 mo, and >30 mo were used to examine transdiaphragmatic pressure (Pdi) generation during eupnea, exposure to hypoxia‐hypercapnia, as well as higher force behaviors in airway occlusion, and/or bilateral phrenic stimulation. Ventilation was assessed using whole body plethysmography and venous blood gases. Isometric force was examined via physiological muscle force testing, and fiber cross‐sectional area was determined in immunohistochemically labeled sections across fiber types. There was a significant reduction in Pdi between young and old mice for higher force behaviors – tracheal occlusion and bilateral phrenic nerve stimulation, (p < 0.001); however, there was no further decline in Pdi for all behaviors between old and very old mice. There was no evidence of impaired ventilation (ventilatory parameters – respiratory rate, minute ventilation, or tidal volume) across age groups, and no evidence of differences between sex in any of the measurements. A loss of ability to generate higher levels of force necessary to maintain airway clearance may predispose older individuals to recurrent infection. Understanding the mechanisms of sarcopenia in old age will be important in mitigating the effects of aging on quality of life and maintaining the health span.Support or Funding InformationThis work was supported by grants R25‐GM075148, R01‐AG044615, and R01‐AG057052 from the National Institutes of Health.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Phrenic‐to‐Intercostal Reflex Activity in Response to High Frequency Spinal Cord Stimulation (HF‐SCS)
Authors: Kowalski Krzysztof E. , DiMarco Anthony F. 
Published: June 2021

ObjectiveHF‐SCS is a novel technique of inspiratory muscle activation which results in coincident activation of the diaphragm and inspiratory intercostal muscles via spinal cord pathways and has the potential to provide respiratory support in ventilator dependent persons with spinal cord injury. The purpose of the present study was to examine the phrenic to intercostal reflex during HF‐SCS.MethodsIn 3 anesthetized and C2 spinalized dogs, electrical stimulation was applied via a stimulating electrode located on the ventral surface of the upper thoracic spinal cord at the T2 level before and after cervical phrenicotomy. Fine wire recording electrodes were used to assess single motor unit (SMU) activity of the external intercostal muscles before and after phrenicotomy.ResultsFollowing unilateral phrenic nerve section, mean peak SMU firing frequency of EI ipsilateral to the section was significantly greater when compared to control (15.9±0.7 vs. 12.1±0.5 Hz, p<0.05). However, mean peak SMU firing frequency of the contralateral EI was unchanged (11.1±0.4 vs. 12±0.4 Hz, NS). Section of the contralateral phrenic nerve results in significantly higher mean peak SMU firing frequency of the contralateral EI (15.9±0.7 Hz, p<0.05) when compared to before section.ConclusionThis study demonstrates that during HF‐SCS after C2 spinalization: 1) diaphragmatic afferents reflexly inhibit motor activity to the ipsilateral external intercostal muscles, and 2) the neural circuitry mediating the phrenic‐to‐intercostal reflex is preserved at a spinal level. Consequently, HF‐SCS applied to support ventilation in high tetraplegics with unilateral phrenic nerve injury may elicit increased activity of ipsilateral inspiratory intercostal muscles.Support or Funding InformationSupport: NIH‐NINDS (R01NS064157) and MetroHeath FoundationDisclosure: Dr. DiMarco is a Founder of and has a significant financial interest in Synapse BioMedical, Inc, a manufacturer of diaphragm pacing systems.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Slc26a3 (DRA) Deficient Mice Display an Acidic Colonic pH‐microclimate, Develop a Strongly Altered Microbiome and Colonic Inflammation
Authors: Kini Archana , Basic Marijana , Singh Anurag Kumar , Riederer Brigette , Römermann Dorothee , Suerbaum Sebastian , Bleich André , Strowig Till , Seidler Ursula 
Published: June 2021

BackgroundThe anion transporter Slc26a3 (DRA‐Down Regulated in Adenoma) is localized on the apical membrane of the colonic mucosa and is functionally involved in the absorption of luminal chloride (Cl−) in exchange for bicarbonate ions (HCO3−). Mutations in the dra gene result in congenital chloride diarrhoea (CLD) which is characterized by secretory diarrhoea, loss of Cl− in the stool, dehydration and metabolic alkalosis. These patients also have a higher risk of incidence of acute as well chronic intestinal inflammation (Wedenoja et al. Hum. Mut 2011). We previously reported low colonic HCO3− output rates and an increased susceptibility to Dextran Sodium Sulfate (DSS) damage in slc26a3−/− mice (Xiao, F. et al. Acta Phys. 2015).AimThe present study was undertaken to explore whether the slc26a3−/− mice develop spontaneous intestinal inflammation, and whether an altered microbiome composition may be the underlying molecular mechanism for inflammation.MethodsColonic surface pH was measured in vivo by two photon microscopy, the inflammatory state of the mucosa by Quantitative PCR (qPCR) and immunohistochemistry, the intestinal microbiome by 16S rRNA sequencing, and the effect of the microbiome of the slc26a3−/− colon on the development of inflammation in germ‐free mice by fecal crossing experiments.ResultsThe slc26a3−/− mice developed distal colonic inflammation evidenced by an increase in proinflammatory cytokine expression and the number of inflammatory cells in the colonic mucosa/submucosa at the time of sacrifice. The slc26a3−/− microbiome was significantly different from that of cohoused wild type (WT) littermates, with a strongly decreased diversity, and an increased percentage of several proinflammatory species. Transmission of this dysbiotic microbiome into germ free mice did not lead to a development of inflammation in the recipient mice. Instead, the species richness in the germ free mice gavaged with slc26a3−/− microbiome had increased, and the percentage of proinflammatory species decreased, in comparison to its donor microbiome.ConclusionsSlc26a3−/− mice display a very low colonic pH microclimate and develop spontaneous intestinal inflammation. The microbiome of slc26a3−/− colon is “dysbiotic” with strongly reduced diversity. However, transmission of this microbiome into germ‐free mice does not result in inflammation, but does result in microbiome normalization, suggesting that the reduced pH microclimate and reduced colonic transit time is necessary for the development of intestinal dysbiosis.Support or Funding InformationVolkswagen Foundation VW Vorab, DFG project SE460/17‐1 and 19‐1 and SFB621/C9This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.