bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequential effects of aerobic training upon muscular and renal arteries in hypertensive rats (706.8)
Authors: Alves Tatiana , Batista Junior Alvaro , Al Chaar Laiali , Barboza Tatiane , Oliveira Thais Cristina , Michelini Lisete , Lacchini Silvia
Published: June 2021

This study evaluated if aerobic training determine an arteriolar remodeling in locomotor and non‐locomotor skeletal muscle, heart and kidney of hypertensive (SHR) and normotensive (WKY) rats.

Were used SHR and WKY male rats 10 weeks‐age submitted or not to aerobic training (AT, 1hr, 5 times/week, in treadmill). Rats were trained for 1, 2, 4, 8 and 12 weeks (55% of maximal capacity) or kept sedentary for 0 and 12 weeks (n=8/group). At the end of each time, mean arterial pressure (MAP) and heart rate (HR) were measured. Heart and locomotor (soleus, gastrocnemius) and non‐locomotor (temporalis) skeletal muscles (SM), heart and kidneys were harvested for arteriolar wall/lumen ratio measurements. Results were compared by ANOVA, using Bonferroni as post‐test. p蠄0.05 was considered as significant.

Both SHR and WKY improved physical performance after 6 and 12 weeks of AT (S0:1.02±0.3 vs 1.62±0.4, T6:1.32±0.2 vs 2.09±0.3, T12:1.92±0.4 vs 2.40±0.4 km/h, WKY vs SHR). AT induced a rest bradycardia in WKY (326±4 to 294±3bpm), and in SHR (385±7 to 357±2bpm). Only SHR reduced MAP after AT (174±2 to 164±1mmHg). SHR showed increased arteriolar wall/lumen ratio compared to WKY (soleus: 0.19±0.02 vs 0.10±0.01µm; gastrocnemius red fibers (GRF): 0.20±0.02 vs 0.10±0.01µm; gastrocnemius white fibers (GWF): 0.21±0.01 vs 0.11±0.01µm; and temporalis: 0.19±0.01 vs 0.13±0.01µm; heart: 0.22±0.02 vs 0.12±0.02µm; kidney: 0.26±0.03 vs 0.15±0.01µm). On the other hands, AT decreased arteriolar wall/lumen ratio in SHR in locomotor SM (soleus: ‐47%; GRF: ‐50%; GWF: ‐52%), non‐locomotor SM (temporalis: ‐32%), and in heart ‐45%), with no changes in Kidney arterioles.

The data indicates that AT induced beneficial vascular remodeling after hemodynamic adjusts, improving arteriolar wall/lumen ratio of SHR, and these modifications seems to be depending also of metabolic and systemic (hemodynamic and sympathetic) mechanisms.

Grant Funding Source: Supported by FAPESP
Drinking patterns in relation to hydration status in children (707.10)
Authors: Kavouras Stavros , Bougatsas Dimitrios , Arnaoutis Giannis , Tsipouridi Spiridoula , Panagiotakos Demosthenes
Published: June 2021

Children are known to consume various fluids in order to cover their water needs. However the contribution of the different fluid categories to hydration is still unknown in children. PURPOSE: To examine whether various drinking patterns are associated with different hydration levels. METHODS: Two hundred and ten Greek healthy children, 105 girls (height: 1.49±0.13 m, weight: 44.1±12.9 kg, fat: 27.7±7.1%) and 105 boys (height: 1.49±0.14 m, weight: 42.6±12.3 kg, fat: 22.8 ± 7.7%) were asked to collect their urine for 24 hours while conducting normal daily activities during autumn and winter months. They were also instructed to record the fluids they consumed in a diary specially designed for children, for two consecutive days. Urine samples were analyzed for color (Ucol) via an eight‐point scale, urine specific gravity (USG) via a hand‐held refractometer, and urine osmolality (Uosm) via freezing point depression osmometry. Principal components analysis was applied to extract dietary patterns from 9 drinks or drinking groups. Multivariate regression analysis evaluated the associations between the extracted dietary patterns and hydration levels deriving from 24h urine osmolality. RESULTS: Six principal components were extracted from the analysis. Component 1 was mainly characterized by consumption of milk, but not water, component 2 by packaged juice and sugar sweetened drinks (SSD) but not Natural Juice, component 3 by natural juice and rest drinks, component 4 by packaged juice, component 5 by water and milk and component 6 by natural juice and SSDs. Component 5 was inversely correlated with hypohydration (P=0.006), whereas none of the other components was associated with the outcomes. CONCLUSION: A drinking pattern that includes water and milk seems to promote better hydration.

Grant Funding Source: Danone Research
Respiratory pump contributes to increased physiological reserve for compensation during reductions in central blood volume (707.4)
Authors: Poh Paula , Carter Robert , Hinojosa‐Laborde Carmen , Mulligan Jane , Grudic Gregory , Convertino Victor
Published: June 2021

The impedance threshold device (ITD) represents a therapy for increasing systemic circulation through creation of negative intrathoracic pressure. PURPOSE: To evaluate the respiratory pump effect on the diminution of compensatory responses during progressive reductions in central blood volume. METHODS: The Compensatory Reserve Index (CRI) algorithm measured compensation capacity to reduced central blood volume. Continuous analog recordings of arterial waveforms were extracted from data files of 7 volunteers. Subjects had previously participated in experiments designed to induce hemodynamic decompensation by application of graded lower body negative pressure (LBNP). The LBNP protocol was completed while spontaneously breathing through a standard medical facemask without (sham ITD) and with (active ITD) a resistance (~‐7cmH2O). RESULTS: At the onset of pre‐syncope in the sham ITD, CRI (0.08±0.02) was smaller (P=0.05) than CRI at the same time point in the active ITD (0.09±0.01). CRI at pre‐syncope in the active ITD (0.08±0.01) was similar (P=0.19) to CRI at pre‐syncope in the sham ITD. Kaplan‐Meier and log rank tests indicated that CRI survival curves shifted to the right (P=0.04) by the active ITD. CONCLUSIONS: Optimizing the respiratory pump contributed a small but significant effect of increasing tolerance to progressive reductions in central blood volume by extending the compensatory reserve.

Grant Funding Source: U.S. Army MRMC Combat Casualty Care Research Program
Effect of acute hypoxia on the time course change in flow‐mediated dilation: effect of sympathetic nerve activity (708.4)
Authors: Lewis Nia , Messinger Laura , Ainslie Philip
Published: June 2021

Endothelium‐dependent flow‐mediated dilation (FMD) is impaired during exposure to high altitude. Although the time course and mechanism(s) governing this impairment are undefined, hypoxic‐induced elevations in sympathetic outflow may attenuate FMD. We examined the hypothesis that acute exposure to normobaric hypoxia would lead to reductions in FMD that could be reversed via adrenergic blockade. In a placebo‐controlled crossover experiment, brachial FMD, arterial oxygen saturation, blood pressure and heart rate (HR) were assessed in 11 healthy participants (aged 32±7 y) in normobaric normoxia and following 60 min, 210 min and 330 min of normobaric hypoxia (FIO2=0.11). At 210 min, participants ingested an α1‐adrenoreceptor blocker (Prazosin; 1 mg/20 kg body mass) or an identical placebo. Compared to normoxic baseline, FMD was reduced following 60 min, 210, and 330 min of hypoxia by 1.6 ± 0.2% (relative change 28%), 2.5 ± 0.1% and 2.8 ± 0.2% (36%), respectively (P蠄0.003). Following α1‐blockade, FMD and HR at 330 min were 5 ± 2 beats∙min‐1 and 1.8 ± 1.4% (35%) higher compared with the placebo trial (P蠄0.03). In summary, sustained reductions in FMD occur within 60 min of exposure to normobaric hypoxia and are largely mediated via the α1‐adrenoceptor pathway.
Role of carotid bodies in glucose counterregulation in type 1 diabetes (709.2)
Authors: Dube Simmi , Shonkwiler Cheryl , McConahey Brent , Joyner Michael , Basu Ananda , Basu Rita
Published: June 2021

Carotid bodies (CB) are desensitized by hyperoxia/hyperglycemia and sensitized by hypoxia/hypoglycemia. We have reported in healthy humans that CB chemoreceptors secrete counterregulatory hormones in response to normoxia and hypoglycemia. While the role of central nervous system in glucose counterregulation is known, it is unknown whether alteration in CB response to glucose contributes to the pathogenesis of hypoglycema in T1D. We hypothesized that glucose counterregulation is impaired in T1D due to reduced sensitization of CB. 10 T1D and 12 healthy subjects (ND), matched for BMI (23 ± 3 vs 26 ± 5 kg/m2) underwent a 180 min hyperinsulinemic (2 mU/kg TBW/min), hypoglycemic clamp (~3.3mM) under normoxic conditions (SpO2 98 ± 1%). T1D subjects did not report autonomic symptoms. [3‐3H] glucose was infused to measure glucose turnover. Results were compared using means of last forty minutes of clamp data. Statistical analyses were done using unpaired t‐tests and p<0.05 was considered significant.

In the presence of matched glucose (3.3±0.1 vs.3.3±0.1 mM) and insulin concentrations (783±106 vs. 812±185 pM;p=0.66), counterregulatory hormonal responses epinephrine (274 ± 165 vs. 742 ± 279 pg/ml) and glucagon (30 ± 11 vs 105 ± 31pg/ml) to hypoglycemia were significantly lower (p<0.001) in T1D vs. ND respectively. The glucose infusion rate required to maintain hypoglycemia was significantly higher (36 ± 1 vs.28 ± 0 µmol/kg/min, p <0.001) and endogenous glucose production was significantly lower (10 ± 3 vs.14 ± 4 µmol/kg/min, p<0.05) in T1D vs. ND with unchanged insulin stimulated glucose uptake. We conclude that in T1D the CB sensitivity to hypoglycemia is impaired and may contribute to increased risk of hypoglycemia in these individuals. Future studies are required to evaluate CB response in hypoglycemia unaware individuals with T1D.

Grant Funding Source: DK90541
The effects of moderate hypoxia on circadian rhythm: implications in disease and treatment options (710.1)
Authors: Allwood Melissa , Foster Andrew , Huber Jason , Simpson Jeremy
Published: June 2021

Impairments in O2 delivery are a common feature of many chronic diseases (e.g., COPD, diabetes, and anemia). It reduces quality of life and increases morbidity, mortality and hospitalizations in patients. Circadian rhythms in mammals, including humans, are essential to health whereas disruptions exacerbate disease pathogenesis. While severe hypoxia can abolish circadian rhythm, moderate hypoxia is more clinically relevant but its effects on circadian rhythm are unknown. Our objective was to investigate the effects of moderate hypoxia on circadian rhythm. Methods: Mice were implanted with telemetry devices to measure heart rate (HR) and body temperature (Tb). Baseline measurements were obtained and animals subjected to 24 hours of moderate hypoxia (O2 = 15%) followed by 24 hours of normoxic recovery. Results: Moderate hypoxia disrupted, but did not abolish, the circadian rhythm of HR and Tb. Amplitude of circadian rhythm for HR was altered during both sleep and active states whereas Tb amplitude was altered only during sleep. Importantly, these disruptions persisted following 24 hours of normoxic recovery. Conclusions: A single 24 hour exposure of moderate hypoxia is sufficient to alter HR and Tb circadian rhythm, which does not recover within 24 hours of reoxygenation. This suggests that moderate hypoxia may have a critical role in disease pathogenesis.

Grant Funding Source: Supported by Canadian Institute of Health Research
Regulation of HIF‐alpha isoform expression and redox state by carotid body chemosensory reflex (710.5)
Authors: Kumar Ganesh , Peng Ying‐Jie , Yuan Guoxiang , Khan Shakil , Nanduri Jayasri , Semenza Gregg , Prabhakar Nanduri
Published: June 2021

The carotid body (CB) chemosensory reflex regulates breathing and sympathetic activity during hypoxia. Here, we determined mechanisms underlying regulation of cardio‐vascular function by chemosensory reflex using a rat model of chronic intermittent hypoxia (CIH). Rats exposed to CIH exhibited hypertension and elevated sympathetic activity; these effects were associated with increased HIF‐1α, decreased HIF‐2α expression, and oxidative stress in brainstem regions that regulate sympathetic nervous system.

Systemic, cellular and molecular effects of CIH in brainstem were abolished by selective ablation of the CB. CIH exposed adrenal medulla (AM), a major end organ of the sympathetic nervous system also exhibited imbalanced expressions of HIF‐α isoforms and oxidative stress. Selective ablation of CB or sympathetic innervation to the AM abolished these effects. Analysis of the mechanisms in the AM revealed that activation of mTOR pathway and Ca2+ activated calpain proteases by Ca2+ signaling coupled to muscarinic acetylcholine receptors (mAChR) contribute to increased HIF‐1α and decreased HIF‐2α expression, respectively. These observations demonstrate a novel reflex regulation of HIF‐α isoforms expression and redox state by the CB, which contributes to regulation of cardio‐vascular function during CIH (Supported by NIH‐HLBI PO1 NIH‐HL‐090554).

Grant Funding Source: NIH‐HLBI‐P01HL‐090554
Time course of changes in glutamatergic transmission within NTS during CIH exposure and the role of ΔFosB (710.6)
Authors: Wu Qiong , Mifflin Steve
Published: June 2021

ΔFosB is a transcription factor induced by chronic intermittent hypoxia (CIH), a model of the arterial hypoxemia seen in sleep apnea patients. We reported that 7 days of CIH increases the amplitude of mEPSCs recorded in 2nd order arterial chemoreceptor NTS neurons. We hypothesize that NTS injection of a dominant‐negative construct of ΔFosB (provided by Dr. E. Nestler) to block the function of ΔFosB will block the CIH increase in mEPSC. A brain slice preparation was used to record mEPSCs by whole cell patch clamp in a normoxia group and in rats exposed to CIH of differing durations. mEPSC amplitude in normoxia group and after 1, 3, 5, and 7 days CIH exposure averaged 12.3±0.8 pA (n=12), 19.6±1.3 pA (n=11), 17.5±1.6 pA (n=11), 16.7±1.2 pA (n=21), 18.2±0.8 pA (n=7), respectively (all p<.05 vs. normoxia). 1 day after a 7 day exposure, mEPSC amplitude remained increased (17.5±1.6 pA, n=4), after 3 day recovery mEPSC amplitude was similar to normoxia (12.9±1.0 pA, n=7). AAV‐GFP‐ΔJunD construct was microinjected into NTS to block the function of ΔFosB, then GFP labeled second order NTS neurons were recorded after 1 day and 7 days CIH exposure. ΔFosB inhibition decreased the amplitudes of mEPSCs to normoxia levels in both groups, 13.9±0.6 pA (n=10), 13.0±0.6 pA (n=19), respectively. CIH rapidly enhances the post‐synaptic response to glutamatergic synaptic transmission within the NTS and ΔFosB plays a role in mediating this enhancement.

Grant Funding Source: HL088052
Long non‐coding RNA changed in expression in tumors growing on EP2 knockout mice (711.4)
Authors: Asting Annika , Iresjö Britt‐Marie , Nilsberth Camilla , Blomqvist Anders , Lundholm Kent
Published: June 2021

Cyclooxygenase‐2 and prostaglandin E2 (PGE2) displayed increased expression in tumor tissue and promotes tumor progression. PGE2 exerts its action via four membrane receptors, EP1‐4, and patients with high EP2 receptor expression have worse prognosis. Accordingly, tumors growing on EP2 knockout mice display reduced tumor weight compared to wild type mice. Therefore, our aim was to evaluate the effect of EP2 on tumor growth by analyses of differences in RNA expression between tumors in EP2 knockout and wild type mice with gene expression arrays (Sureprint, Agilent). Results displayed that several long non‐coding RNA (lncRNA) had a more than 5‐fold decreased expression in tumor tissue at host EP2 knockout and more than 100 had a 2‐fold change. Many lncRNAs are not characterized and their function is unknown. However, lncRNAs are known to regulate transcription and expression of genes. Therefore, our observations on lncRNA expression may be involved in tumor growth regulation.

Grant Funding Source: Supported by the Swedish Cancer Society (CAN 2010/255) and the Assar Gabrielsson foundation
Blood tissue expresses a molecular signature of endurance exercise training (711.9)
Authors: Silva Michelle , Dias Rodrigo , Bolani Wladimir , Alves Cleber , Junior Jose , Silva Jeferson , Oliveira Patricia , Oliveira Edilamar , Rocha Cristiane , Marsiglia Julia , Negrao Carlos , Krieger Eduardo , Krieger Jose , Pereira Alexandre
Published: June 2021

Aim: The purpose of this study was to identify a PBMC gene expression signature in response to endurance training. We also aimed to identify transcripts associated with changes in peak oxygen uptake (VO2peak). Methods: Healthy untrained policemen recruits (n=13; 25 ± 3 yrs; BMI 27.0 ± 2.8 kg∙m‐2) were selected. VO2peak (cardiopulmonary exercise test) and total RNA were obtained before and after 18 weeks of running endurance training (3 times/wk; 60min), for whole‐genome expression analysis (GeneChip® Human Gene 1.0 ST). Results: Training induced changes (Δ) in VO2peak (0.27±0.28 l∙min‐1, P=0.09) and a differential regulation of 211 transcripts (P<0.05; fold change>1.3). Baseline expression levels of 98 transcripts were strongly correlated with absolute ΔVO2peak (r>0.75; P<0.01). Differentially regulated transcripts were mostly represented in immune response of heat shock proteins and cytokines (HSPA1A, IL‐1), cell cycle regulation of differentiation and post‐translational modification processes (Histone H1, PLK1, SUMO‐1) and growth factors (EGR1, GH) activation and signalling. Conclusions: We describe a transcriptional map regulated by endurance training, ocurring in easily accessed PBMCs. Future research will focus on establishing transcriptional markers of trainability.

Grant Funding Source: Supported by FAPESP #2005/59740‐7; CNPq #482863/2011‐0
Endogenous opioids in the pre‐Bötzinger complex via action on mu opioid receptors are critical in maintaining normal breathing by preventing and/or depressing sighs (712.12)
Authors: Zhuang Jianguo , Zhang Zhenxiong , Zhang Cancan , Xu Fadi , Frazier Donald
Published: June 2021

The PBC is pivotal in generating augmented breathings (sighs), but local endogenous neurotransmitters responsible for control of sigh are not fully understood. Owing to the abundant presence of MORs in the PBC and centrally inhibitory effect of opioids on VT, we hypothesized that endogenous PBC opioids, via action on local MORs, would play an important role in maintaining normal respiration by preventing and/or depressing sighs. In anesthetized and spontaneously breathing rats, we recorded the cardiorespiratory activities before and after microinjection of naloxone methiodide, a MOR antagonist (10 mM, ~15 nl), into the PBC (PBCNLX). PBCNLX triggered sighs or if present, enhanced the frequency of sighs (from 0.7 ± 0.3 to 13.6 ± 1.6 sighs/10 min, P < 0.001). We further defined the effect of intravenous (5 μg/kg) and intracisternal injection of fentanyl (1 μg/kg), a MOR agonist, on the PBCNLX‐induced sighs. The sighs were abolished by intravenous injection of fentanyl and largely suppressed by intracisternal injection. In conclusion, endogenous PBC opioids via action on MORs are essential in maintaining normal respiration by preventing and/or suppressing sighs, consistent with centrally inhibitory effect of exogenous MOR agent on sighs.

Grant Funding Source: Supported by HL 107462 and ALA Grant RG‐191095‐N
The pontine respiratory group is involved in opioid‐induced respiratory depression in adult rabbits (712.6)
Authors: Miller Justin , Zuperku Edward , Stuth Eckehard , Hopp Francis , Stucke Astrid
Published: June 2021

Recent studies in adult dogs suggest that the parabrachial nucleus plays an important role in the respiratory depression by clinical concentrations of intravenous (IV) opioids (Prkic et al, 2012). This study investigated whether a similar area could be identified in adult rabbits. Each rabbit (2.2 ‐ 4.0 kg) was anesthetized with 1‐1.5 MAC sevoflurane, tracheotomized, ventilated and decerebrated. α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA, 50 µM, 70 nl) was injected in a grid‐wise fashion from 1‐3 mm caudal of the inferior colliculi and 1‐4 mm lateral of midline into the dorso‐ventral center of neuronal activity. The area of maximal tachypnea as determined from the phrenic neurogram was on average 1.4 mm caudal to the inferior collicle, 2.4 mm lateral and 6.3 mm from the dorsal surface (n=5). Microinjection of the mu‐opioid agonist [D‐Ala2, N‐MePhe4, Gly‐ol]‐enkephalin (DAMGO, 100 µM, 700 nl) into this region led to significant respiratory slowing without decrease in amplitude. Local injection of the opioid‐antagonist naloxone (1mM, 350 nl) partially reversed the respiratory depression caused by IV remifentanil (0.5 mcg/kg/min). These early studies suggest that lateral pontine mu‐opioid receptors in rabbits are responsible for bradypnea induced by systemically administered opioids at clinically relevant doses. Future studies will establish the magnitude of this effect.
Comparison of the neurochemical response to atropine dialysis in pontine and medullary nuclei in goats (712.9)
Authors: Langer Thomas , Bonis Josh , Neumueller Suzanne , Olesiak Samantha , Miller Justin , Muere Clarissa , Pan Lawrence , Hodges Matthew , Forster Hubert
Published: June 2021

To gain insight into neuromodulatory role of cholinergic signaling in different brainstem regions, we dialyzed atropine (50mM), a non‐specific muscarinic receptor blocker, into the brainstems of chronically cannulated goats. Atropine dialysis into the pontine Kölliker‐Fuse nucleus (KFN) at night decreased breathing (J. Appl. Physiol. 109: 159‐170, 2010). Atropine dialysis into the medullary pre‐Bötzinger complex (preBötC) increased breathing both at night and during the day (J. Appl. Physiol 114: 694‐704, 2013) with increases observed in substance P and glycine in the effluent mock cerebral spinal fluid (mCSF). Herein we report levels of neurochemicals in effluent mCSF during 50mM atropine dialysis into the KFN and lateral and medial parabrachial nuclei. There were no pontine site‐related differences in levels of tested neurochemicals; thus the data were pooled. In all pontine cannulated goats, during the day and at night, atropine dialysis increased substance P to the same level as atropine dialysis into the medulla (preBötC). In contrast, atropine dialysis into the pontine nuclei did not change levels of glutamine, glycine, or GABA in the effluent mCSF. These findings suggest that the site specific differences in the respiratory response to atropine dialysis are not due to alterations in substance P levels.

Grant Funding Source: Supported by NIH HL007852, NIH HL25739, NIH HL112996, and the Department of Veteran Affairs
Systemic inflammation impairs phrenic long‐term facilitation following moderate, but not severe acute intermittent hypoxia (713.3)
Authors: Agosto Ibis , Nichols Nicole , Mitchell Gordon
Published: June 2021

Systemic inflammation impairs phrenic long‐term facilitation following moderate, but not severe acute intermittent hypoxia Ibis M. Agosto, Nicole L. Nichols and Gordon S. Mitchell Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706 Phrenic long‐term facilitation (pLTF) is a form of respiratory motor plasticity elicited by acute intermittent hypoxia (AIH). When elicited by moderate AIH (mAIH, 35‐45mmHg), pLTF is serotonin‐dependent; in contrast, pLTF is adenosine‐dependent (serotonin‐independent) when the same AIH protocol is used, but with more severe hypoxic episodes (sAIH, 25‐30mmHg). Systemic inflammation induced by lipopolysaccharide (LPS) blocks mAIH induced, serotonin‐dependent pLTF (Huxtable et al. 2013). Here, we tested the hypothesis that sAIH induced pLTF is inflammation resistant, since sAIH elicits pLTF through a distinct adenosine‐dependent mechanism. mAIH and sAIH induced pLTF were assessed in anesthetized Sprague Dawley rats 24 hrs post‐LPS (100ug/kg, i.p.) or saline injections. Whereas mAIH induced pLTF was reduced by LPS (LPS: 25±3%, n=5; control: 54±2%, n=5; p0.05). Thus, systemic inflammation undermines serotonin‐, but not adenosine‐dependent pLTF. Our results give insight concerning the functional significance of multiple cellular mechanisms that give rise to respiratory motor plasticity. Specifically, inflammation resistance of adenosine‐dependent pLTF may provide a “back up” as animals regulate breathing in conditions where normal regulatory mechanism have been lost.

[Supported by: NIH HL111598, and Francis Families Foundation (NLN)]

Grant Funding Source: Supported by: NIH HL111598, and Francis Families Foundation (NLN)
Repetitive acute intermittent hypoxia differentially affects CD11b+ cell phenotypes after C2 spinal hemisection (713.6)
Authors: Small Alissa , Nikodemova Maria , Dougherty Brendan , Mitchell Gordon , Watters Jyoti
Published: June 2021

Inflammation is a hallmark of spinal cord injury (SCI), mediated in part by CD11b+ resident microglia (MG) and infiltrating macrophages (MP). Although neuroinflammation is well‐characterized at the lesion site, little is known about MG/MP activities above or below the injury. Repetitive acute intermittent hypoxia (rAIH) elicits somatic motor plasticity following chronic spinal injury, and this plasticity is undermined by neuroinflammation. Since recent microarray data suggest that rAIH (4 weeks) suppresses spinal inflammation, we tested the hypothesis that rAIH shifts the MG/MP phenotype following C2 spinal hemisection (C2HS), decreasing inflammatory (M1) and increasing reparative/trophic (M2) activities. We further posited that these effects would differ above vs. below the injury site. mRNAs for molecular markers of M1 and M2 phenotype were assessed (qRT‐PCR) on immunomagnetically isolated MG/MP from sham‐ and C2HS‐operated rats exposed to normoxia or rAIH (10 episodes per day, 3 x per week, 4 wks) beginning 3 days post‐surgery. In normoxia, whereas M1 genes were unaffected by C2HS above the injury site (brainstem), M2 genes were increased. In contrast, below the injury (C4‐C6), M2 genes were unaffected, and there was little indication of increased M1 expression. Treatment with rAIH decreased both M1 and M2 gene expression in brainstem MG/MP, but increased M2 and decreased M1 gene expression below the injury, suggesting a switch to a supportive phenotype below the injury. Thus, rAIH elicits differential effects on MG/MP activities above and below the injury, and its beneficial effects on spinal plasticity and functional recovery following SCI may involve alterations in CD11b+ cell phenotypes.

Grant Funding Source: Supported by NIH R01 HL111598, The Craig H. Neilsen Foundation, and Wisconsin Hilldale Fellowship
Dopamine receptor blockade improves pulmonary gas exchange during exercise in healthy humans (717.1)
Authors: Tedjasaputra Vince , Bryan Tracey , Moore Linn , van Diepen Sean , Bouwsema Melissa , Petersen Stewart , Welsh Robert , Stickland Michael
Published: June 2021

Impaired pulmonary gas exchange during heavy exercise, manifested as an increase in the alveolar‐arterial oxygen difference (A‐aDO2), may be due to anatomical intrapulmonary (IP) shunt recruitment. Dopamine (DA) has been shown to recruit IP shunts at rest and circulating DA increases with exercise, and thus may contribute to the increased A‐aDO2 during exercise. We hypothesized that gas exchange impairment during exercise will decrease with DA receptor blockade. Ten healthy males (Age: 25±6 yrs, VO2max: 56.3±6.6 ml∙kg‐1∙min‐1) performed two incremental staged cycling exercise sessions after ingestion of either placebo (P) or DA blockade (B) (Metoclopramide 20mg). Arterial blood gas sampling and cardiorespiratory data were obtained at rest and during 4 exercise intensities (30%, 50%, 75% and 90% of previously determined VO2max). At 90% VO2max, DA blockade decreased A‐aDO2 (P: 19.3±8.5 torr, B: 14.8±6.8 torr, p=0.038 and increased arterial O2 saturation (P: 95.4±1.0%, B: 96.2±0.9%, p=0.004). Blood gases were similar between the two groups at rest, 30%, 50% and 75% of VO2max. Compared to placebo, DA blockade did not change O2 consumption, CO2 production, or respiratory exchange ratio at any intensity. Administration of a DA receptor blockade decreased A‐aDO2 during near‐maximal exercise, suggesting that endogenous DA affects affects pulmonary gas exchange during exercise.

Grant Funding Source: Supported by The National Sciences and Engineering Research Council of Canada
Hypothalamic control of pulmonary renal reflex (718.3)
Authors: Choudhary Rishabh , Gulati Kavita , Ravi Krishnan
Published: June 2021

Pulmonary lymphatic obstruction (PLO) is associated with a reflex increase in urine flow. The central integration of this reflex termed PRR is not known. Thus the aim of the present study is to observe the role of paraventricular nucleus (PVN) on PRR.

Experiments were performed on anesthetized, artificially ventilated adult New Zealand white rabbits. After routine cannulations, an isolated venous pouch was created in the right external jugular vein in the neck region. A cannula was positioned in this pouch and the other end of it was connected to a saline reservoir. To cause PLO, the reservoir was raised to a height of 30 cm. The urinary bladder was cannulated for collecting urine. Each rabbit was hydrated by giving saline infusion (rate ‐ 12 ml/10 min). The rabbit was then fixed to a stereotaxic apparatus. A dorsal incision was made and activity from right renal sympathetic nerve (RSN) was recorded. Electrodes were placed on either PVN. Urine was collected every 10 min during the initial control period, during PLO and after releasing PLO each for a period of 20 min. The study was repeated after electrolytic lesion of PVN bilaterally. The significant increases in urine flow and RSN activity observed before lesion were abolished after the lesion.

It is concluded that along with an increase in urine flow, there is an increase in RSN activity also during PLO and PVN functions as an integrating centre in PRR.

Grant Funding Source: Supported by: CSIR,UGC India
A comparative approach to temporal bone laboratory dissections for teaching middle and inner ear anatomy (721.2)
Authors: Master Terrel , Glover Mitzi , Hedgepeth Krystle , Desha David , Bazer Gary
Published: June 2021

The goal of this study was to identify an improved approach for visualization and identification of the components of the middle/inner ear. Traditional dissection on fixed cadavers by students tends to lead to less than ideal specimens for learning the material. The students in the first year medical school class currently enrolled in Head and Neck Anatomy were divided into three groups, 40 students per group. Group 1 was instructed to perform a traditional dissection on their fixed cadaver (calcified bones) following instructions in the laboratory dissector [Grant’s Dissector, 15th edition]. Group 2 was to perform dissections following the dissector on decalcified, undissected temporal bones. Group 3 was to study previously dissected temporal bones. The three groups were tested on middle ear anatomy through an identification practical immediately following the lab period. Students were also asked to complete a survey to evaluate their perceived use of time, grasp of the material, and ease of dissection/study. The results of this study can be used to amend the current course for the most effective teaching method for middle/inner ear anatomy.
Teaching healthy eating and cooking helps Polynesian and Pacific Islander participants make nutritious food choices (721.26)
Authors: Vogelsang David , Clayton Craig , Frampton S , Ray Gaye , Brown Laura , Lassetter Jane , Wisco Jonathan
Published: June 2021

According to the Centers for Disease Control (CDC) and Prevention (2013), more than one‐third of U.S. adults (35.7%) are obese, and since 1980, obesity among adolescents has risen from 5% to 18%. To prevent obesity the National Heart, Lung and Blood Institute suggests healthy eating. Cooking Anatomy Academy (CAA) teaches anatomy, physiology, and nutrition, and promotes healthy eating and cooking among parents and students in the Polynesian and Pacific Islander communities. CAA is composed of seven, one hour cooking lessons offered as an afterschool program at Mana Academy Charter School (West Valley, UT). The CAA curriculum incorporates nutrition guidelines on MyPlate.gov, and focuses on moderation, variety, and raw/unrefined foods. We studied the impact of CAA using a qualitative analysis of journal entries responding to questions about how participants' experiences in CAA have influenced how they prepare meals at home, and feedback received during the lessons. Preliminary data shows that CAA is helping participants make healthy food choices. Several parents have indicated that their kids are asking to eat healthier foods at home because of the foods they ate in class.

Grant Funding Source: Mentoring Research Grant, College of Life Sciences, Brigham Young University
The low‐level laser and natural latex protein applied on the sciatic nerve crushed: morphometric and scanning electron microscopy study (726.11)
Authors: Dias Fernando , Issa Joao Paulo , Coutinho‐Netto Joaquim , Fazan Valeria , Iyomasa Mamie , Watanabe Ii‐sei
Published: June 2021

This study evaluated the effects of low‐level laser (LLL 15J/cm2, 780nm) and F1 protein (natural latex ‐ 0,1%) on the sciatic nerve crushed (15 kgf, axonotmesis). We used 72 rats (♂, 200‐250g) divided into 6 groups (n = 12): GC ‐ control; EG ‐ exposed nerve; IG ‐ injured nerve; LG ‐ LLL; PG ‐ F1; LPG ‐ LLL and F1. After 4 or 8 weeks, the animals were euthanized, the sciatic nerve was processed for morphometric (nerve fibers minimum diameter, myelin thickness and G‐ratio) and scanning electron microscope (SEM) analyzes.

The morphometric data after 4 weeks showed improvements with the applied treatments, PG showed better results. After 8 weeks it was observed greater homogeneity among the groups. The G‐ratio showed no tendency to change (4 or 8 weeks), the values were closer after 8 weeks.

The SEM data showed normal features in CG and EG, the IG (4 weeks) revealed a huge loss of nerve fibers and endoneurial collagen synthesis, the LG and PG (4 weeks) showed small clusters of nerve fibers. PG and LPG (8 weeks) revealed larger and more juxtaposed fibers in comparison to the injured groups discussed at 4 weeks.

The treatment with the F1 and LLL suggest an improvement in the recovery of crushed peripheral nerve (4 and 8 weeks). After 8 weeks, the treated groups were more similar to each other, revealing the time‐dependency. The groups that received F1 associated or not to LLL showed the better results.

Grant Funding Source: FAPESP 2010/12018‐3
IMP2 expression in the mouse nervous system (727.4)
Authors: Vinarsky Victoria , Chmielewski Sarah , Wiens Naomi , Cho Ellen , Lau Kelly , Park Irene , Xu Mei
Published: June 2021

The three homologs of insulin like growth factor‐II (IGF‐II) mRNA binding protein (IMP) play an essential role in the posttranscriptional regulation of gene expression in nervous tissue. IMP1/ZBP1 (zipcode binding protein) regulates the localization and translation of specific mRNAs allowing for axon guidance and regeneration. Additionally, previous studies show that IMP1 and IMP3 expression decreases dramatically after birth, whereas IMP2 is sustained in in brain, liver and other organs throughout life (Leeds et al., 1997; Mueller‐Pillasch et al., 1999; Nielsen et al., 1999; Hansen et al., 2004; Gu et al., 2004; Hammer et al., 2005). Of the three homologs, IMP2 is least understood. Our pilot data implicates that IMP2 may play a role in axon regeneration by localizing specific mRNAs. Understanding IMP2 expression pattern is fundamental to further investigation of its functions. We hypothesized that IMP2 is present in both the central and peripheral nervous systems throughout life. Using a custom made IMP2‐specific antibody, along with immunohistochemistry, Western Blot, and primary dorsal root ganglion (DRG) culture we examined the expression of IMP2 in the spinal cord and DRG of the mouse at embryonic, postnatal, and adult stages of life. We found that IMP2 expression is present in both the spinal cord and DRG through all developmental stages of life. Ongoing experiments are focused on the role of IMP2 in axon regeneration in the adult nervous system.
Effect of dietary supplementation of pomegranate fruit grown in Oman on the memory, anxiety and learning skills in a transgenic mice model of Alzheimer's disease (728.10)
Authors: Subash Selvaraju , Essa Musthafa , Al‐Buraiki Zayana , Al‐Asmi Abdullah , Al‐Adawi Samir , Vaishnav Ragini , Lakhtatika Ritu , Al‐Senawi Hamad , Awlad‐Thani Kathiya , Al‐Jabri Ahood , Samuoi Maha
Published: June 2021

Several reports have suggested neurotoxic effects of Aβ and role of oxidative stress in AD. Oman grown fruit; Pomegranates contain very high levels of antioxidants and several medicinal properties. We studied the effect of dietary supplementation of pomegranate on the memory, anxiety and learning skills in double Swedish APP mutation (APPsw/Tg2576) AD mouse model. Animals were divided into 3 groups; group 1 was wild type non‐transgenic; group 2 and 3‐ transgenic mice. Group 1and 2 fed with normal diet and group 3 were fed custom‐mix diets (pellets) containing 4% pomegranate. At age of 4‐5 months and 14‐15 months the behaviors of the animals were analyzed for memory, learning and anxiety. APPsw/Tg2576 at the age of 4‐5 months and 14‐15 months that were fed control diet without pomegranates showed memory deficit, anxiety‐related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination compared to the wild type mice on the same diet. Diets rich in 4% pomegranate fed tg mice showed a significant improvement above behavior abnormalities compared to AD tg mice on normal diet. Our results suggest that dietary supplementation of pomegranate grown in Oman may have the beneficial effect in reducing the risk, delaying the onset or slowing the progression of Alzheimer's disease. Further studies needed to validate and determine the mechanism of action of Omani pomegranates against AD. Financial support came from The Research Council, Oman (RC/AGR/FOOD/11/01).

Grant Funding Source: Supported by The Research Council, Oman (RC/AGR/FOOD/11/01).
Neutrophil gelatinase‐associated lipocalin in rats with myocardial infarction: expression in the brain related to depression? (728.13)
Authors: Gouweleeuw Leonie , Liu Hui , Eisel Ulrich , Schoemaker Regien
Published: June 2021

Heart failure increases the risk to develop depression, which worsens prognosis. Plasma Neutrophil Gelatinase‐Associated Lipocalin (NGAL), associated with heart failure as well as with depression, is found increased in cardiomyocytes weeks after myocardial infarction (MI) in rats. This study was aimed to investigate the role of NGAL in depressive symptoms in MI rats.

Male Wistar rats were subjected to coronary artery ligation (MI) or sham surgery. Three weeks later, depressive symptoms were obtained from the open field test. Plasma levels of NGAL were measured with Elisa, and NGAL expression in the brain was obtained using immunohistochemistry.

Plasma NGAL levels were increased related to infarct size (r=0.78, p=0.013, N=9). NGAL expression in the paraventricular nucleus of the hypothalamus was increased in MI compared to sham rats (45±7 vs 26±3 NGAL+ cells per high power field), irrespective of plasma NGAL levels. The increased number of NGAL positive cells in the paraventricular nucleus of the hypothalamus was negatively correlated to exploratory behavior in the open field (r=‐0.77, p=0.006). A decrease in exploratory behavior in the open field can be considered a sign of depressive behavior.

Data indicate that while circulating NGAL may rather represent severity of heart failure, locally expressed NGAL in the brain may be associated with depressive symptoms after myocardial infarction in rats.
Innovative therapies in psychiatric medicine (728.14)
Authors: Cartier Earnestine , Cartier William , Tulp Orien , Einstein George
Published: June 2021

To determine the effectiveness of innovative approaches on behavioural medicine outcomes, a long term two phase study was developed involving using clinical records review and associated parameters in a long term in‐patient population. Phase I of the research has taken 5 years (Psychological Aspect). The second ongoing phase, which will last a duration of 2 years, will consist of medical‐lab testing, bio‐markers, nutritional guidance and usage of pharmaceuticals. Within our research, we wondered what was missing in the treatment of the mentally ill. Phase one of our research has been within the correctional system. The United States and the world at this time are being overwhelmed with mentally ill Offenders. We all must remember, before these individuals became offenders they may have been in our school systems, walking the streets, everywhere within our infrastructure. In this phase of our research we will demonstrate that each case study has presented evidence that each individual was able to exercise some “Independent” control over his/her stressors within society by being taught how to correctly “manage” their own behavior. Phase two of our research, will be outside of the correctional system. We hope to prove again, that utilizing of this form of therapy, along with a group of researchers, researching critical diseases, that there will be measurable metabolic and behavioural changes that will favourably enhance the rehabilitative process.

Grant Funding Source: Institutional Resources
Effects of stress on CRH, CRH‐R1, CRH‐R2 expressions and anxiety‐related behaviors (728.16)
Authors: Eraslan Evren , Akyazi Ibrahim , Ergül Ekiz Elif , Matur Erdal
Published: June 2021

The effects of noise stress on brain corticotrophin‐releasing hormone (CRH), CRH receptors 1and 2 (CRH‐R1, CRH‐R2) mRNA levels and anxiety related behaviors in rats have been investigated.

Rats, which were divided into 4 groups consisting of 8 animals each, were used for gene expression analyses. Basal Level Group (BSG) was sacrificed without exposing to stress. Other groups were exposed to 4 hour long, 100 dB white noise stress every day. Acute Stress Group (ASG) was sacrificed after 30 min stress application. Subacute Stress Group (SSG) and Chronic Stress Group (KSG) were sacrificed at day 16 and at day 31 respectively, 24 hours after stress application. Expression profiles of CRH, CRH‐R1, and CRH‐R2 in amygdala and hypothalamus were analysed by quantitative RT‐ PCR.

The same stress procedure was applied to the experimental group of behavior test. Effects of stress on anxiety‐related behaviors were investigated in defensive withdrawal test. Control and experimental rats were tested on 29th and 30th of the stress application days.

CRH and CRH‐R1 mRNA levels increased in amygdala and hypothalamus of KSG animals comparing to those of control. In amygdala mRNA levels of CRH‐R1 in ASG animals and CRH‐R2 in ASG, SSG and KSG decreased. In hypothalamus, CRH‐R2 mRNA levels in SSG decreased. In the defensive withdrawal test, latency to exit the closed chamber decreased in stressed group.

Chronic white noise stress causes delayed CRF system activation observed as CRH and CRH‐R1 mRNA expression increases in brain . As anxiety related behaviors were measured before this delayed activation, anxiolytic effect observed in stressed animals may be related to decreased CRH‐R2 mRNA levels in amygdala and also the type of the stressor.

Grant Funding Source: This work was supported by Research Fund of Istanbul University (No:4963)
Recurrent laryngeal nerve morphometry in short‐term experimental diabetes (728.21)
Authors: Mendes Vânia Alice , Silva Greice Anne , Castania Jaci , Salgado Helio , Fazan Valéria Paula
Published: June 2021

The recurrent laryngeal nerve (RLN) is responsible for the innervation of most laryngeal muscles, including the vocal muscle. Reports on vocal cord palsy in diabetic patients are increasing in the literature but, to the best of our knowledge, there are no reports on the morphology of the RLN in human or experimental models of diabetes. In the present study, male Wistar rats received a single intravenous streptozotocin (STZ) injection in order to induce diabetes while control rats received vehicle. The diabetic state was confirmed by the high glycemic levels on the 3rd day after STZ injection. On the 15th day after the injections, rats were anesthetized for arterial pressure (AP) and heart rate (HR) recordings, prior to RLN removal. Proximal and distal segments of the right and left RLN were prepared for light microscopy morphometry, by means of a computer software. Both the AP and HR were reduced in the diabetic group, attaining significant difference on the HR values. Fascicle morphometry parameters were not different between groups. Myelinated fiber morphometry showed smaller axonal area and diameter on diabetic animals’ nerves, attaining significance on the distal left segments. Average G ratio values were normal (0.6) in controls with a tendency to smaller values in the diabetic group. These results suggest the presence of axonal atrophy on the RLN of diabetic rats, that show early in the STZ experimental model.

Grant Funding Source: Supported by FAPESP, CAPES, CNPq and FAEPA.
Vagus nerve morphology in elderly spontaneously hypertensive rats (728.23)
Authors: Silva Letícia , Castania Jaci , Salgado Helio , Fazan Valéria Paula
Published: June 2021

Aging affects peripheral nerve function and regeneration in experimental models but few literature reports deal with animals aged one year or more. The vagus nerve is an important branch of the efferent arm of the baroreflex heading to the heart. In adult spontaneously hypertensive rats (SHR), the vagus nerve morphology was compared between genders [1] and no differences were found. However, the effects of aging associated to hypertension were not yet investigated for this nerve. Male SHR aged 20 and 50 weeks had their arterial pressure (AP) and heart rate (HR) recorded by a computerized system. The rats were then systemically perfused with a fixative solution and had their cervical vagi nerves prepared for light microscopy. Proximal and distal segments of the left and right vagi nerves were evaluated for morphometric parameters including fascicle area and diameter. Comparisons were made between sides and segments on the same age as well as between ages. Differences were considered significant when p<0.05. SHR aged 50 weeks were heavier than 20‐week old animals, with no differences on the AP and HR averages. Body weight differences were followed by fascicular area and diameter results, as 50‐week old animals have larger vagus nerve fascicles compared to 20‐week old animals. Also, 50‐week old animals presented a clear reduction of the number of endoneural vessels compared to younger animals. This results deserves further investigations. Our data provide a morphological basis for further studies involving functional investigations of the efferent arm of the baroreflex in hypertension associated with ageing.

[1] Alcântara et al. Brain Res 1197:170, 2008.

Grant Funding Source: FAPESP, CAPES, CNPq and FAEPA
Abnormalities in BDNF/TrkB/PI3K signaling pathways in autism (728.3)
Authors: Fahnestock Margaret , Nicolini Chiara
Published: June 2021

Cortical connectivity and spine abnormalities may account for clinical features of autism. BDNF, a key spine regulator, exhibits altered isoform balance in autism. Here, we investigated whether BDNF receptors and their signaling pathways are disrupted in post‐mortem fusiform gyrus from subjects with autism compared to controls and in the valproic acid (VPA)‐induced rat model of autism.

Protein levels were examined by Western blot in 11 autism vs 13 control subjects and in lateral temporal neocortices of VPA rats vs controls. Reduced TrkB, PI3K, Akt, mTOR, phospho‐mTOR, p70S6K, eIF4B and PSD‐95 and a trend towards increased truncated TrkB and p75NTR, but no changes in 4E‐BP1 or eIF4E, were found in autism subjects versus controls. Similar deficits were observed in VPA rats, although total and phospho‐4E‐BP1 were decreased in these rats.

These findings suggest imbalances in BDNF/TrkB/PI3K and proBDNF/p75NTR signaling in autism which could lead to spine defects. Reduced Akt‐mTOR protein and signaling, suggesting spine protein synthesis deficits, were observed in both autism and VPA rats, despite minor differences in down‐regulated signaling cascades. The resulting spine defects might lead to loss of excitatory synapses/decreased PSD‐95 in autism. Reduced excitatory synapses might perturb cortical circuitry, contributing to autism’s cognitive and behavioral deficits.