bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermoregulatory Changes in Obese Mexican Young Women Performing Aerobic Exercise
Authors: GARCIA‐PELAGIO KARLA , AMBROSIO NATALIA , FERNANDEZMELGAREJO ERIKA , GALICIA EUGENIO , MILLAN‐SIERRA AURORA , SEGURAALEGRIA BERTHA 
Published: June 2021

Mexico has the highest rate of obesity worldwide. This pandemic is defined as an abnormal and excessive accumulation of adipose tissue providing an insulating layer that impedes heat loss, thus affecting body homeostasis. To maintain normothermia, obese individuals must increase heat dissipation. Here, we explore the potential role of thermoregulation in obese young Mexican women performing aerobic exercise in order to determine how thermoregulation mechanisms act in such conditions. A group of 60 obese (O), overweight (OW) and normal (N) women, with 20 in each group, performed a 15 min test on the cycle‐ergometer at a 65% heart rate (HR) at room temperature (21.0±0.5) °C and under extreme temperature (38.5±0.5) °C conditions. Body mass index (BMI) and % body fat were calculated. HR, blood pressure (Bp), and core (Tc) and external (Te) temperatures were measured during and after the test. We observed a difference in Tc within subjects and within groups. At room and extreme temperatures, OW and O subjects presented higher Tc compared to N ones by about 30%, adding that the initial Tc of O was higher (15%) compared to the other two groups. N women tended to reach their initial temperature faster than the other groups at room and extreme temperatures. A 45% increment of HR was observed in O compared to OW and N women. From our results we concluded that there exists a direct relation between BMI and the thermoregulatory capacity in the human body, suggesting a failure in homeostasis processes in obese women. This experiment gives us the first insight of an active indicator of a metabolic decompensation in young Mexican women and compelling evidence for a thermogenic handicap in the same population. Further analyses have to be done.Support or Funding InformationSupported partially by UNAM (PAPIIT RA207818) to KPGPThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effects of Remote Ischemic Preconditioning on Cognitive Function and Exercise Hyperemia in Isocapnic Hypoxia
Authors: Sorensen Jenna N , Crecelius Anne R 
Published: June 2021

Impairments in neurological and skeletal muscle function can occur in conditions of decreased oxygen delivery and vascular dysfunction can exacerbate any impairments. Remote ischemic preconditioning (RIPC) has been used to improve vascular functioning during exercise and cognitive tasks, but this intervention has yet to be tested in hypoxic conditions. Here, we test the hypothesis that RIPC can attenuate the hypoxia‐induced decline in cognitive function and also impact forearm blood flow during hypoxic exercise. Healthy, young men and women participated in two counterbalanced experimental sessions, consisting of two trials of rhythmic dynamic handgrip exercise (4 min, 10% maximal voluntary contraction) followed by computerized cognitive testing, once in normoxia (21% inspired O2), and once in isocapnic hypoxia (target O2 saturation ~85% via pulse oximetry). The cognitive tests (CNS Vital Signs) measured composite memory, verbal memory, visual memory, and processing speed. During rest and handgrip exercise, forearm blood flow (FBF) responses were determined via Doppler ultrasound and muscle oxygenation was assessed using near infrared spectroscopy (Moxy). Systemic hemodynamics [heart rate (ECG) and non‐invasive beat‐to‐beat blood pressure (Finometer)] were collected throughout. One experimental session consisted of RIPC (4 × 5 min thigh cuff inflation; 200 mmHg) between the normoxic and hypoxic trials whereas the other was a sham (~10 mmHg cuff pressure) intervention. Percent change (%Δ) from normoxia to hypoxia was determined for cognitive test scores. Preliminary results (n=6, mean±sem) demonstrate modest hypoxia‐induced declines in composite, verbal, and visual memory (−8.6±4.4%, −11.2±6.6%, −5.2±3.8%) but not processing speed in sham conditions. The RIPC intervention had no consistent impact on these hypoxia‐induced changes. Exercise hyperemia was increased in hypoxia vs normoxia (177±12 vs 163±6 ml/min in hypoxia vs normoxia, respectively) and RIPC modestly increased exercise hyperemia in hypoxia (191±10 ml/min) but had little effect during normoxia (167±12 ml/min). We conclude that RIPC has a minimal effect on the impact of hypoxia on cognitive function and can augment hypoxic exercise hyperemia in young, healthy humans.Support or Funding InformationUniversity of Dayton University Honors Program, Berry Summer Thesis Institute (JNS)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Repetitive Transcranial Magnetic Stimulation (rTMS) Elicits Long Lasting Phrenic Motoneuron Excitability Increase in the Rat: Possible Treatment for Respiratory Insufficiency?
Authors: Vinit Stéphane , Michel‐Flutot Pauline , Zholudeva Lyandysha V , Randelman Margo L , Mansart Arnaud , Deramaudt Thérèse B , Lane Michael A , Petitjean Michel , Bonay Marcel 
Published: June 2021

Repetitive transcranial magnetic stimulation (rTMS) is a cortical neuromodulatory technique shown to be effective in a clinical setting. However, the underlying mechanisms are poorly understood, thus emphasizing the need to reverse translate the technique to prelinical animal models. We have recently demonstrated the feasibility of using TMS to evaluate diaphragmatic corticomotor pathways by recording specific motor evoked potentials from the diaphragm (MEPdia) in naïve rats as well as in a preclinical rat model of neurological respiratory deficit (C2 hemisection, Vinit et al., PLoS One 2014, 2016). Based on these encouraging preliminary results, we evaluated the evolution of the phrenic motoneuron excitability (by assessing MEPdia) following acute high frequency rTMS protocol applied to the cortical and subcortical areas in a respiratory neurobiology animal model. In an anesthetized adult rat preparation, we applied a repetitive high frequency rTMS protocol (9 trains of 100 biphasic pulses at 10Hz, with 30s intervals, under the motor threshold stimulation of the animal) and evaluated the phrenic motoneuron excitability by recording MEPdia before and up to 60 min post‐rTMS session. This acute high frequency rTMS protocol led to a robust and long lasting increase in phrenic motoneuron excitability (89.9 ± 21 % increase from baseline compared to time control animals 12.6 ± 14.6 %; p<0.002) at 60 min post rTMS protocol. Interestingly, pretreatment with Clonazepam (GABAA agonist) or Baclofen (GABAB agonist) before rTMS blocked this increase in respiratory excitability (9.1 ± 9.2 % and −2.3 ± 10.6 % respectively; p<0.001). Trans‐synaptic retrograde labeling with pseudorabies virus from the diaphragm revealed pre‐phrenic interneurons with GABAA and GABAB receptors, supporting the notion that GABAergic modulation of respiratory excitability could be induced by rTMS. To conclude, one single rTMS protocol induces a long‐lasting increase in respiratory excitability in naïve animals, by disinhibiting GABAergic receptors. Ongoing experiments investigating whether chronic daily rTMS might extend this acute effect. These data serve as foundations for future applications of rTMS to further enhance functional recovery of respiration after high cervical injury.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Distribution of brain derived neurotrophic factor (BDNF) immunostaining along the C2–C5 spinal cord in adult rats
Authors: Benevides Ethan S , Sunshine Michael D , Wollman Lila B , Jorgensen Marda L , Fuller David D 
Published: June 2021

BDNF is a powerful modulator of neuroplasticity and can be found across the rostral‐caudal extent of the spinal neuroaxis in neurons, astrocytes and microglia. BDNF is necessary and sufficient to drive plasticity in the phrenic motor system, likely through either pre‐ and/or post‐synaptic actions on phrenic motoneurons. To our knowledge, the relative distribution of BDNF expression across this region of the mid‐cervical spinal cord has not been systematically “mapped”. Accordingly, in ongoing experiments, we are quantitatively evaluating the distribution of BDNF positive neurons in the C2–C5 spinal cord in adult Sprague‐Dawley rats. The guiding hypothesis is that BDNF will be most prevalent in the C3‐5 ventral horn in the region of the phrenic motor nucleus. Tissues were harvested from adult male rats and processed with standard immunochemistry methods using a BDNF antibody (Alomone, 1:500 dilution). Control experiments showed an absence of spinal cord staining when tissues were incubated without the primary antibody and while keeping all other aspects constant. A custom MATLAB code was used to quantify the number of BDNF positive cells throughout C2–C5. Specifically, BDNF expressing soma were identified as areas with fluorescent intensity above a common threshold. To separate putative neurons, identified regions were sorted by size and only regions with an area of 250–1500 μm2 were included for further analysis. We observed BDNF expression within neurons in laminae I, II, VII, VIII, and IX across the mid‐cervical spinal cord. Further, the number of BDNF positive neurons increased in a rostral to caudal manner from C2 to C5 (P<0.05). There were more BDNF expressing neurons located in the ventral horn when compared to the dorsal horn across C2–C5 (p< 0.01). Finally, smaller BDNF positive cells were evident throughout the gray and white matter which is consistent with microglial distribution in the spinal cord, however, this staining has not been verified at this time. These initial results suggest that naturally occurring levels of BDNF vary across the cervical spinal cord, and are greatest in the region of the phrenic motor nucleus.Support or Funding Information1R01HL139708‐01A1 (DDF), T32‐HD043730 (MDS).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Acute Impact of Disrupting BDNF/TrkB Signaling on Diaphragm Muscle Force Generation across Motor Behaviors
Authors: Pareja‐Cajiao Miguel , Cole Naomi A. , Gransee Heather M. , Sieck Gary C. , Mantilla Carlos B. 
Published: June 2021

Brain‐derived neurotrophic factor (BDNF) binds with high affinity to tropomyosin‐related kinase receptor subtype B (TrkB), and plays an important role in neuromuscular junction (NMJ) function (regulating neuromuscular transmission and muscle innervation). We previously showed impaired neuromuscular transmission following acute inhibition of TrkB kinase activity in TrkBF616A mice harboring a point mutation that renders the kinase domain susceptible to inhibition by 1NMPP1 treatment. Neuromuscular transmission failure is expected to predominantly affect the ability of more fatigable motor units to generate force and thus primarily impair higher force motor behaviors. Accordingly, we hypothesized that acute administration of 1NMPP1 will impair the ability of the diaphragm muscle to accomplish higher force behaviors in adult, 6‐month old TrkBF616A mice. Transdiaphragmatic pressure (Pdi) measurements were conducted across a range of motor behaviors in lightly anesthetized mice during eupnea, exposure to hypoxia (10% O2)/hypercapnia (5% CO2), tracheal occlusion, spontaneous deep breaths (“sighs”) and during maximal activation elicited by bilateral phrenic nerve stimulation. Adult male and female TrkBF616A mice at 6 months were injected with 1NMPP1 or vehicle (DMSO) one hour prior to Pdi measurements. The Pdi generated during eupnea and hypoxia/hypercapnia was ~8 cm H20 compared to ~70 cm H20 during maximal stimulation. There was a significant reduction in Pdi during maximal force with bilateral phrenic nerve stimulation in the 1NMPP1 group compared to the vehicle control (p=0.01). There was no effect of 1NMPP1 on Pdi during eupnea, hypoxia/hypercapnia, tracheal occlusion, or sigh behaviors. The reduction in Pdi is generally similar to the impairment in neuromuscular transmission consistent with a predominant effect on motor units innervating fast‐twitch fatigable muscle fibers in the diaphragm muscle. Thus, impaired trophic BDNF/TrkB signaling can be expected to limit the range of motor behaviors accomplished by the diaphragm muscle and may be an important contributor to neuromuscular dysfunction.Support or Funding InformationThis study was supported by NIH grant R01 AG057052.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Adenosine 2A Receptor Inhibition Promotes Neuroprotection Following Toxic Insult to Phrenic Motor Neurons
Authors: Sajjadi Elaheh , Seven Yasin B , Simon Alec K , Zwick Amanda , Satriotomo Irawan , Mitchell Gordon S 
Published: June 2021

Motor neuron death is the hallmark of certain diseases, such as amyotrophic lateral sclerosis (ALS). Neuroprotective strategies promoting respiratory motor neuron survival are critical to avoid respiratory insufficiency and improper airway clearance. Adenosine 2A (A2A) receptors contribute to excitotoxic motor neuron death in vitro. Since different motor neuronal populations have differential susceptibilities in neurodegenerative disorders, we explored the role of A2A receptors in phrenic motor neuron cell death in vivo. We used an experimental model of phrenic motor neuron death developed in our laboratory (CtB conjugated Saporin; CtB‐Sap) injected into the intrapleural space. We tested the hypothesis that A2A receptor expression is upregulated in phrenic motor neurons under toxic insult. We also tested the hypothesis that A2A receptor inhibition promotes phrenic motor neuron survival and preserves diaphragm activity. Rats were randomly assigned to control, CtB‐Sap + Vehicle and CtB‐Sap + Istradefylline (A2A receptor antagonist) groups. CtB and CtB‐Sap were injected intrapleuraly bilaterally. Following transcardial perfusion, spinal cords were fixed, cryoprotected, and sectioned. Immunohistochemistry was performed to count CtB‐labeled phrenic motor neurons and assess A2A receptor expression within these motor neurons. Diaphragm EMG activity was recorded via intramuscular electrodes during normoxia, hypoxia (10.5%) – hypercapnia (7%), and spontaneous sighs during hypoxia‐hypercapnia. A2A receptors were upregulated in the spared phrenic motor neurons of CTB‐Sap treated rats (p<0.05). CtB‐Sap selectively killed nearly all phrenic motor neurons within a week and caused diaphragm paralysis (p<0.01). With A2A receptor inhibition, phrenic motor neuron loss was reduced (p<0.05) and diaphragm EMG activity partially preserved (p<0.05). A2A receptors, which contribute to motor neuron death during toxic insults, are upregulated in spared phrenic motor neurons of CTB‐Sap treated rats. This is an important finding since A2A receptor upregulation may accelerate motor neuron death in neurodegenerative diseases like ALS.Support or Funding InformationNIH HL69064 and the McKnight Brain InstituteThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Respiratory Deficiency in the Optn−/−Mouse, A Novel Model of Amyotrophic Lateral Sclerosis
Authors: McCall Angela L , Strickland Laura M , Pucci Logan , Dhindsa Justin , Tseng Henry , ElMallah Mai K 
Published: June 2021

Amyotrophic Lateral Sclerosis (ALS) is a devastating and fatal neurodegenerative disease with no current cure. Patients with ALS die 3–5 years after diagnosis when they ultimately succumb to inadequate ventilation, hypoxia, and respiratory failure. Several genes associated with ALS have recently been discovered. One of these genes encodes optineurin (OPTN) which is associated with neurodegeneration in both ALS and glaucoma. Optineurin has multiple roles in various biochemical pathways such as regulation of inflammation and autophagy. Through these functions, OPTN appears to be neuroprotective but the exact mechanism by which loss of OPTN results in progressive neural degeneration and respiratory failure in ALS is still unclear.Since respiratory pathology is a significant cause of morbidity and mortality in ALS, this study sought to characterize the respiratory pathology in a novel ALS mouse model – the Optn−/− mouse. The hypothesis driving this work is that the Optn−/− mouse has respiratory insufficiency due to degeneration of the respiratory motor unit – motor neuron, nerve, neuromuscular junction and muscle. Whole body plethysmography (WBP) was used to assess breathing at baseline and during a respiratory challenge with hypercapnic and hypoxic conditions (FiCO2: 0.07, FiO2: 0.10; nitrogen balance). During the respiratory challenge, compared to the WT mice, Optn−/− mice had significantly lower peak inspiratory flow and peak expiratory flow. Peak inspiratory flow and peak expiratory flow are indirect measures of inspiratory and expiratory muscle strength. Furthermore, throughout the challenge period Optn−/− mice spent a greater amount of time in apnea indicating pathology in the respiratory control centers. The weakness and pathology in control of breathing during the respiratory challenge progresses as the mice age. Post mortem immunohistochemical studies of the neuromuscular junctions within the diaphragm showed that Optn−/− mice had fragmented synaptotagmin staining indicating presynaptic degeneration. Finally, the hypoglossal nerves of Optn−/− mice had significantly reduced g‐ratio which indicates pathology and decompaction of myelin sheaths. In conclusion, the Optn−/− ALS mouse model displays respiratory insufficiency, aberrant control of breathing, and increased nerve demyelination.Support or Funding InformationR21 NS098131‐02 (MKE) and K08HD077040‐07 (MKE)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
PHD2 Deficiency Induces Nitrative Stress via Suppression of Caveolin‐1 in Pulmonary Arterial Hypertension
Authors: Dai Zhiyu , Zhao Youyang 
Published: June 2021

Nitrative stress is evident in human pulmonary arterial hypertension (PAH) patients. However, the role of nitrative stress in the pathogenesis of obliterative vascular remolding and severe PAH remains unclear. Our recent studies identified a novel mouse model (Egln1Tie2Cre) with obliterative vascular remodeling and right heart failure, which provides us an excellent model to study nitrative stress in PAH. We found that nitrative stress was elevated whereas endothelial Caveolin‐1 (Cav1) was suppressed in the lung of Egln1Tie2Cre mice in HIF‐2 a dependent manner. Genetically overexpression of endothelial Cav1 restored nitrative stress and inhibited right ventricular (RV) systolic pressure and RV hypertrophy, as well as improved right heart function Egln1Tie2Cre mice. ROS scavenger MnTmPyp treatment also suppressed severe PAH in Egln1Tie2Cre mice. These data suggest that suppression of endothelial Cav1 expression depended on PHD2 deficiency and HIF‐2 a activation mediated upregulation of nitrative stress, which leading to elevation of pulmonary pressure and severe vascular remodeling in PAH. Our studies provide evidences that restoration of Cav1 and ROS scavenger might be therapeutic potentials for the inhibition of obliterative vascular remodeling and severe PAH.Support or Funding InformationThis work was supported in part by NIH grants R01HL123957, R01HL125350, R01HL133951, and P01HL077806 (Project 3) to Y.Y.Z, and K99HL138278 to Z.D.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
DDAH1 siRNA Knockdown in a Human Pulmonary Vascular Co‐Culture Cell Model
Authors: Milton Avante D , Almazroue Hanadi , Nelin Leif D , Trittmann Jennifer K 
Published: June 2021

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of premature infants. Pulmonary hypertension (PH) develops in 25–40% of BPD patients, contributing to morbidity and mortality. Nitric oxide (NO) is a potent vasodilator and apoptotic mediator made in the pulmonary endothelium by nitric oxide synthase (eNOS). Asymmetric dimethylarginine (ADMA) is an endogenous competitive NOS inhibitor. Dimethylarginine dimethylaminohydrolase (DDAH) hydrolyzes ADMA and DDAH1 is the most important for ADMA metabolism in vivo. Translational studies from our group have identified DDAH1 single nucleotide polymorphisms that are differentially expressed in BPD‐PH patients compared to BPD patients. We hypothesized that inhibiting DDAH1 in human pulmonary microvascular endothelial cells (hPMVECs) will lead to decreased apoptosis and increased proliferation of human pulmonary artery smooth muscle cells (hPASMCs) via effects in hPMVECs. We utilized a co‐culture model where hPMVECs were transfected with DDAH1 siRNA or scramble for 24h and then incubated in co‐culture with hPASMCs for 24h. Analysis included 1) trypan blue exclusion for viable cell numbers and 2) western blot analysis for cleaved caspase‐3 and 8, total caspase‐3 and 8, PCNA, and β‐actin. After DDAH1 siRNA transfection of hPMVECs and co‐culture with hPASMCs, we found greater hPASMC viable cell numbers compared to scramble hPASMC controls (N=3, p<0.05). After DDAH1 siRNA transfection of hPMVECs and co‐culture with hPASMCs, we found lower hPASMC levels of cleaved caspase‐3 protein (N=3, p<0.05) and cleaved caspase‐8 (N=3, p<0.05), with greater hPASMC protein levels of PCNA (N=3, p<0.05) compared to scramble. DDAH1 siRNA knockdown in hPMVEC results in greater hPASMC proliferation and less cleaved caspase‐3 mediated apoptosis. We speculate that DDAH1 is a potential therapeutic target for BPD‐PH. We speculate that these findings support the concept that DDAH1 regulates vascular remodeling by minimizing ADMA‐inhibition of eNOS, resulting in maintained NO production which would support angiogenesis and prevent/attenuate vascular remodeling. Future studies would include in vivo experiments in transgenic neonatal mice exposed to a BPD‐like lung injury.Support or Funding InformationThis work was funded by NIH‐K08 HL129080This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.