bluuebunny/crossref_metadata_2025_split huggingface dataset:
Purinergic signaling contributes to CO2‐sensitivity of neurons in the retrotrapezoid nucleus but not nucleus of the solitary tract or medullary raphe (872.6)
Authors: Wenker Ian , Poss Erin , Sobrinho Cleyton , Ana Takakura , Moreira Thiago , Mulkey Daniel 
Published: June 2021

Central chemoreception is the mechanism by which the brain controls breathing in response to changes in tissue CO2/H+. Several brainstem regions are thought to contribute to chemoreception including the caudal nucleus of the solitary tract (cNTS), medullary raphe and retrotrapezoid nucleus (RTN). Although the molecular basis of chemoreception remains unclear, evidence suggests that RTN chemoreception involves intrinsic H+ sensing by an unidentified K+ channel and purinergic signaling possibly from CO2‐sensitive astrocytes. However, it is not clear whether purinergic signaling influences CO2‐responsiveness of other putative chemoreceptors. The goal of this study is to determine whether purinergic signaling modulates basal activity or CO2‐responsivness of neurons in the cNTS or medullary raphe. We use cell‐attached current clamp techniques to characterize firing rate responses to 15% CO2 and focal application of ATP (1mM) under control conditions and in the presence of a P2‐receptor blocker (PPADS, 100 µM). Chemosensitive neurons in the cNTS or medullary raphe were identified in brain slices (300 µm thick) from neonatal rat pups (P7‐12) bases on a 蠅 0.5 Hz firing rate response to 15% CO2. We found that CO2‐sensitive neurons in the cNTS, but not the medullary raphe, respond to focal ATP application with ~3 fold increase in firing rate. However, bath application of PPADS had no effect on baseline activity or CO2‐responsivness of neurons in either region. Immunohistochemical analysis using an astrocyte‐specific marker (aldehyde dehydrogenase 1L1) suggests that the RTN has a higher density of astrocytes compared to the cNTS or medullary raphe. Together, these results suggest that purinergic signaling is a unique feature of RTN chemoreception.Grant Funding Source: Supported by NLBI (HL 104101) and AHA (11PRE7580037)
Arterial pressure and gene expression in the nucleus of the solitary tract in rats fed with high‐fat diet (874.4)
Authors: Speretta Guilherme , Bassi Mirian , Ruchaya Prashant , Sumners Colin , Menani José , Colombari Eduardo , Colombari Débora 
Published: June 2021

The aim of this study was to evaluate the mean arterial pressure (MAP) and gene expression of components of the renin‐angiotensin system (RAS) and pro‐inflammatory cytokines in the nucleus of the solitary tract (NTS) in rats fed with high‐fat diet (HFD). Male Holtzman rats (300‐320 g, n = 6/group) were fed with either standard chow diet (SCD; 5.4% total fat) or HFD (26.4% total fat) for 3 or 6 weeks before MAP recording, baroreflex tests and brains being harvested for RT‐PCR. HFD for 3 (HFD3) or 6 weeks (HFD6) increased MAP (HFD3: 114 ± 2, vs. SCD3: 105 ± 1 mmHg; HFD6: 116 ± 2, vs. SCD6: 107 ± 1 mmHg, p < 0.05). HFD6 also impaired the baroreflex (HFD6: ‐2.27 ± 0.32, vs. SCD6: ‐2.90 ± 0.15 bpm/mmHg, p < 0.05). HFD3 increased ACE mRNA expression in the NTS (HFD3: 2.78 ± 0.33, vs. SCD3: 1.00 ± 0.26, p < 0.05), without changing the levels of AT1R, TNF‐α and IL‐6 mRNAs. Conversely, HFD6 decreased ACE mRNA levels in the NTS (HFD6: 0.27 ± 0.06, vs. SCD6: 1.11 ± 0.12, p < 0.05), and increased the levels of mRNAs for AT1R (HFD6: 2.74 ± 0.35, vs. SCD6: 1.07 ± 0.25, p < 0.05), TNF‐α (HFD6: 3.00 ± 0.90, vs. SCD6: 1.10 ± 0.17, p < 0.05) and IL‐6 (HFD6: 2.73 ± 0.76, vs. SCD6: 1.08 ± 0.10, p < 0.05) in the NTS. These results suggest that HFD may activate pro‐inflammatory cytokines and modify RAS components in the NTS, whose expression differs based on the period of the HFD. These factors may contribute to the increase in MAP and the impairment of the baroreflex produced by HFD.Grant Funding Source: CAPES, FAPESP, FAPESP/PRONEX
Synaptic plasticity of GABAergic circuitry in the RVLM during Ang II‐dependent malignant hypertension (874.6)
Authors: Derbenev Andrei , Gao Hong , Miyata Kayoko , Mitchell Kenneth , Zsombok Andrea 
Published: June 2021

The rostral ventrolateral medulla (RVLM) is a critical component of the sympathetic nervous system (SNS) mediating regulation of cardiovascular function, including arterial blood pressure (ABP). It has been shown that decreased inhibition of RVLM neurons increases SNS activity and thereby elevates ABP. However, very little is known about the control of this region of the brain in hypertensive states; in particular, in transgenic rats [TGR(Cyp1a1Ren2)] with inducible Ang II‐dependent malignant hypertension. In the present study we used the transsynaptic retrograde viral tracer, PRV‐152 to identify preautonomic neurons in the RVLM. We found that chronically (8 days) increased plasma Ang II levels significantly potentiate glutamatergic and decrease GABAergic synaptic transmission. Moreover, our data revealed significantly reduced amplitude of inhibitory GABAA‐mediated extrasynaptic tonic current in the RVLM neurons. The results of our study demonstrate that GABAergic activity is decreased in the RVLM of Cyp1a1‐Ren2 transgenic rats with Ang II‐dependent malignant hypertension. These compelling data demonstrate synaptic plasticity in the RVLM in Ang II‐dependent hypertension.Grant Funding Source: NIH P30GM103337
Effect of beta‐adrenergic blockade on coronary blood flow during isometric exercise in older adults (875.7)
Authors: Ross Amanda , Gao Zhaohui , Heffernan Matthew , Leuenberger Urs , Sinoway Lawrence , Muller Matthew 
Published: June 2021

The rise in heart rate (HR) and cardiac contractility during exercise is due to activation of myocardial β‐adrenergic receptors. In animals, β‐adrenergic receptors in the coronary vasculature also mediate a parallel increase in coronary blood flow. However, the role of β‐ adrenergic receptors in the human coronary circulation is unknown. We hypothesized that β‐adrenergic blockade with propranolol would attenuate reflex tachycardia and coronary hyperemia in response to isometric handgrip in healthy older adults. Six men (66 ± 2 yrs) performed isometric handgrip exercise at 40% of maximal voluntary contraction for 2 minutes after receiving intravenous propranolol or no treatment. HR and blood pressure were monitored continuously and rate‐pressure product (RPP) was calculated as an index of myocardial oxygen demand. Coronary blood flow velocity (CBV) was measured by transthoracic Doppler echocardiography and coronary vascular resistance (CVR) was calculated. The coronary supply to demand ratio was calculated as CVR/RPP. Propranolol decreased the HR (8 ± 3 vs. 4 ± 1) and RPP (2580 ± 612 vs. 1520 ± 163) responses to exercise but augmented the CVR/RPP response (‐0.24 ± .09 vs. ‐0.49 ± 0.15). Mean arterial pressure, CVR and CBV were unaltered. β‐adrenergic blockade not only decreased myocardial oxygen demand in response to exercise, it also improved oxygen supply.Grant Funding Source: Supported by NIH P01 HL096570 and UL1 TR000127
Central administration of IL‐1 receptor antagonist increases vasopressin secretion in late phase of sepsis in rats (876.7)
Authors: Wahab Fazal , Tazinafo Lucas , Batalhão Marcelo , Carnio Evelin , Rocha Maria 
Published: June 2021

Clinical and experimental studies have reported that the initial phase of sepsis is characterized by elevated plasma vasopressin (AVP) concentrations. However, in the late phase, despite of the significant decrease in the arterial pressure, the AVP secretion decrease and the plasma concentrations remain unusually low, contributing to the hypotension, vasodilator shock, and death. Considering the role of AVP in the vasopressor response, the elucidation of the mechanisms of this deficient hormone secretion may contribute to therapy during sepsis.The aim of this study was to analyze the effect of IL‐1ra (an Interleukin‐1 receptor antagonist) on sepsis‐induced alterations in plasma AVP and NO, and cerebrospinal fluid (CSF) NO levels. After Wistar rats were intracerebroventricullary injected with 2 ul of IL‐1ra (9 nmol/ or vehicle (PBS 0.01M) sepsis was induced by cecal ligation and puncture (CLP). Blood samples were collected from different groups of rats (n=6‐8/group) by decapitation after 4‐, 6‐ and 24‐h. Specific ELISA and Chemiluminescence assays were used for measurement of AVP and NO concentrations, respectively. All experiments were carried out according to an institutional ethical committee approved protocol.IL‐1ra administration did not alter plasma vasopressin after 4‐ and 6‐h as compared to vehicle in CLP animals. In contrast, after 24‐h AVP levels were significantly (P<0.01) higher in IL‐1ra treated animals as compared to vehicle treated animals. IL‐1ra administration significantly (P<0.01) decreased NO concentration in CSF but not in plasma. Moreover, the survival rate of IL‐1ra treated rats increased by 38% in comparison to vehicle administered animals.In conclusion, the central administration of IL‐1ra increases AVP secretion in the late phase of sepsis which was beneficial for survival. We believe that one of the mechanisms for this effect of IL‐1ra is through reduction of NO concentration in CSF of the septic rats.
Recovery of neural signaling following oxygen glucose deprivation is greater in Syrian hamster hippocampi than in rat hippocampi (877.10)
Authors: Mack Jacob , Mikhailova Alexandra , Hamilton Jock , Horowitz John , Horwitz Barbara 
Published: June 2021

Previous studies showed that neurons in mammalian obligatory hibernators are less damaged by oxygen glucose deprivation (OGD) than those of non‐hibernating species. But it is unknown if recovery of hippocampal signal processing after transient OGD is greater in facultative hibernators (e.g., Syrian hamsters) than in rats (non‐hibernators). We tested the hypotheses that 30 min after OGD exposure, recovery would be greater: (1) at low vs. high temperatures in both species and (2) in hamsters vs. rats. Following Schaffer collateral stimulation, evoked responses from CA1 neurons were measured at 25oC, 30oC, and 35oC. A 15 min baseline response was recorded for slices perfused in oxygenated artificial cerebrospinal fluid (O2aCSF). Perfusate was then switched to aCSF minus glucose and gassed with nitrogen (OGD) for 10 min, after which it was returned to O2aCSF for 30 min. Degree of recovery from OGD was significantly greater (P<0.05) at lower temperatures in hamster and rat slices, supporting hypothesis 1. Additionally, at 25oC, hamster slice recovery (108%; n=19 slices) was significantly greater (P<0.05) than that of rat slices (80%; n= 16). The same was true at 30oC (93% for 19 hamster slices vs. 49% for 18 rat slices), consistent with hypothesis 2. No significant species differences were seen at 35oC. Understanding naturally occurring tolerance to OGD in hibernators may lead to new strategies mitigating stroke damage.Grant Funding Source: JM was supported by an American Physiological Society UGSRF award.
Recovery of synaptic transmission from oxygen glucose deprivation in Syrian hamster hippocampi is temperature dependent and enhanced in hibernation (877.11)
Authors: Mikhailova Alexandra , Hamilton Jock , Horowitz John , Horwitz Barbara 
Published: June 2021

It is not known if recovery of signal processing following transient oxygen glucose deprivation (OGD) is greater in hippocampal slices from hibernating hamsters (HH) than in slices from nonhibernating euthermic hamsters (EU). We hypothesized that HH slices recover synaptic transmission more completely than do EU slices, and that decreased temperature further enhances recovery. To test these two hypotheses, evoked response amplitudes (ERAs) of CA1 neurons to afferent stimulation were measured during a 15 min control period [slices perfused with oxygenated artificial cerebrospinal fluid (O2 aCSF, 10 mM glucose)], followed by OGD treatment (perfusate switched to aCSF gassed with nitrogen and no glucose) for 10 min, and a 30 min recovery period (slices returned to O2 aCSF, 10 mM glucose). At 35°C, 10 min after OGD treatment, HH ERAs had recovered to 65.7 ± 12.6% (n=9) of control while EU ERAs had recovered to 22.9 ± 8.0% (n=17; P<0.05). Lower slice temperatures (25°C and 30°C) were neuroprotective for both HH and EU, while the hibernating state afforded no additional neuroprotection. These data support our hypotheses that HH slices are more tolerant to OGD than are EH slices, that decreased temperatures further enhance protection in both HH and EH slices, and suggest that preparation for hibernation induces neuroprotective mechanisms in this facultative hibernator.Grant Funding Source: Supported by UC Davis Provost's Undergraduate Fellowship to AM
Can cold‐induced cardiac activity prevent cardiac pathologies caused by obesity? (881.12)
Authors: Barnhill Spencer , Schaeffer Paul 
Published: June 2021

The purpose of this study is to investigate the idea that prolonged cold exposure, which mimics the increased demand of exercise, can prevent the early effects of pathological cardiac hypertrophy caused by obesity in mice. Given that exercise has reduced detrimental effects of hypertrophic cardiomyopathy, we hypothesized that prolonged cold exposure may act similarly. We investigated three groups of mice at three months of age. The groups were wild‐type mice fed a standard chow diet (CON), transgenic UCP‐dta mice fed a high‐fat diet (Obese), and cold exposed transgenic UCP‐dta mice fed a high‐fat diet (Cold‐Obese). Both Obese and Cold‐Obese mice showed higher cardiac weight compared to CON. Gene expression analysis showed little to no up‐regulation of pathological hypertrophy markers in Obese and Cold‐Obese mice. Further analysis showed down‐regulation of several metabolic genes in Obese mice and maintenance or up‐regulation of those genes in Cold‐Obese mice. Echocardiography and cardiac catheterization suggested healthy left ventricular pressures but mild diastolic dysfunction in the Cold‐Obese mice. Metabolic profiles suggested improvements in cardiac metabolism while functional analyses showed cold exposure may lead to cardiac dysfunction in Cold‐Obese mice.Grant Funding Source: Supported by NIH #1R15DK085497–01A1 to PJS
Combined strength and endurance training does not improve left ventricular systolic function in response to a high‐intensity exercise in females (881.7)
Authors: Dumanoir Greg , Haykowsky Mark , Taylor Dylan , Syrotuik Dan , Bell Gordon 
Published: June 2021

The acute effect of high‐intensity exercise combined with strength and endurance training on left ventricular (LV) systolic function in female rowers is not well known. The objective of this study was to evaluate the effects of 10‐weeks of endurance and strength training on maximal oxygen uptake (VO2max), endurance performance, strength, and LV morphology and systolic function in eight female rowers (mean age: 25 ± 9 years). LV systolic function was also assessed before and immediately after completing a high‐intensity endurance performance test (2000m of rowing). Ten‐weeks of combined strength and endurance training significantly improved VO2max (before vs. after; 2.7 ± 0.4 vs. 3.0 ± 0.3 L/min), endurance performance time (510 ± 41 vs. 491 ± 24 sec), leg press (163 ± 45 vs. 235 ± 86 kg) and bench press (40 ± 4 vs. 46 ± 5 kg) one repetition maximum strength. Combined training did not change end‐diastolic cavity area (19 ± 3 vs. 19 ± 4 cm2), end‐systolic cavity area (9 ± 2 vs. 8 ± 2 cm2), fractional area change (51 ± 6 vs. 55 ± 3%) or mass (160 ± 34 vs. 159 ± 17 g). High‐intensity exercise was associated with an increase in contractility and fractional area change from before to after training. In conclusion, 10 weeks of rowing and strength training in female rowers improves exercise capacity, endurance performance and muscle strength without altering LV morphology. In addition, combined strength and endurance training was not associated with an increase in LV systolic function but contractility and fractional area was significantly increased with high intensity exercise.Grant Funding Source: Supported by the Sport Science Association of Alberta
Genome‐wide detection of oxidized base products in guanine quadruplex (G4) sequences by ChIP‐Seq analysis in hypoxic cells (887.1)
Authors: Pastukh Viktor , Borchert Glen , Gillespie Mark 
Published: June 2021

Reactive oxygen species (ROS) generated in hypoxic signaling cause a nuclear oxidant stress accompanied by oxidative DNA modifications. Detailed studies on a few genes show that these modifications are prominent in hypoxic responsive promoters (Al‐Mehdi et al, 2012) and G4 sequences in growth regulatory genes (Clark et al., 2012). The G4 damage in hypoxia was interesting because it did not relate to the transcriptional state of the gene, was often localized close to transcription start sites, and because mutations in G4 sequences have been linked to genomic instability and carcinogenesis. To gain more insight into the impact of hypoxia‐generated ROS on genomic integrity, we used ChIP‐Seq analysis to determine if G4 sequences immunoprecipitated by an antibody to the base damage product 8‐oxoguanine were enriched on a genome‐wide scale in pulmonary artery endothelial cells cultured in hypoxia for 3h. We found two notable differences between normoxic and hypoxic cells. First, DNA contigs from hypoxic cells were ≍1/3 the size of those from normoxic cells. Second, the number of 8‐oxoG harboring G4 sequences was enriched by ≍30 fold in hypoxia compared to normoxia. These findings suggest that ROS generated during hypoxic signaling cause widespread base damage in G4 sequences and thereby point to new mechanisms of disease‐causing mutations in this enigmatic gene regulatory region.Grant Funding Source: Supported by the NIH R01HL58234
Hypoxia reduces the function and expression of hERG potassium channels (887.2)
Authors: Lamothe Shawn , Song WonJu , Guo Jun , Zhang Shetuan 
Published: June 2021

Human ether‐a‐go‐go‐related gene (hERG) encodes the pore‐forming subunit of the IKr channel which is important for cardiac repolarization. Loss of function of the hERG channel due to mutations or drugs causes long QT syndrome, a cardiac disorder with high risk of cardiac arrhythmias and sudden death. Obstructive Sleep Apnea (OSA) patients who experience intermittent hypoxia display an increased incidence of cardiac arrhythmias. We recently found that OSA patients display a trend of reduced hERG expression in atrial tissues. In the present study, we demonstrate that hypoxic culture (0.5% O2) of neonatal rat cardiomyocytes for 24 h reduced IKr by 80%. However, the same treatment did not affect the amplitudes of Na+ current, Ca2+ current, the transient outward K+ current (Ito) and the inward rectifier K+ current (IK1). Hypoxic culture (0.5% O2) decreased the abundance of hERG channels expressed in HEK 293 cells along with an enhanced expression of HIF1‐ (Hypoxia‐Inducible Factor) which is known to up‐regulate various proteins including proteolytic enzymes. Chemically inducing HIF1‐ by using cobalt chloride also decreased hERG expression. Protease inhibitors including leupeptin (100µM) completely abolished the hypoxic‐induced reduction in hERG expression. Our data raised the possibility that hypoxia decreases hERG expression by activating certain proteases, which degrade the channel protein.Supported by the Canadian Institutes of Health Research ‐ CIHRGrant Funding Source: supported by: CIHR
Can you believe what you see: evaluation of choline acetyl transferase (ChAT) expression in the ChAT‐eGFP transgenic mouse (89.1)
Authors: Gyengesi Erika , Münch Gerald , Paxinos George , Zaborszky Laszlo 
Published: June 2021

The creation of the BAC transgenic mice expressing promoter‐specific enhanced‐ green fluorescent protein (eGFP) in the cholinergic cells provided an enormous advantage for numerous experimental methods. However, the exact distribution of the eGFP expressing, presumably cholinergic neurons in the brain was not compared with the expression of choline acetyl transferase (ChAT), the specific marker for cholinergic neurons. Here we report the comparison and discrepancies found between the distribution of ChAT‐eGFP neurons and the goat‐α‐ChAT immunoreactive neurons by using immunohistochemistry and 3D mapping with Neurolucida. We found complete overlap between the two markers in the areas of the medial septum, the ventral, horizontal and lateral nuclei of the diagonal band, the ventral pallidum, the extension of the amygdala, the globus pallidus, the caudate putamen and the striatum. Special attention was paid to areas where the expression was not overlapping, such as the cortex, the striatum, the thalamus, the hypothalamus and the mesopontine tegmentum in the brainstem. We also compared our results with those of the Allan Brain Institute maps of mRNA expression of ChAT. Weather these differences between the two technical approaches are due to the insufficient sensitivity of the antibody in areas where the level of ChAT is lower, or due to genetic default, for example gene leaking is yet to be confirmed.Grant Funding Source: Supported by NIH grant NS023945 to LZ and Australia Fellowship awarded to GP (466028)
Morphology of Golgi stained neurons in spinal cord of African giant pouched rat (Cricetomys gambianus Waterhouse) (89.2)
Authors: Alawa Judith , Salaudeen Rukayya , Adetiba Bamidele , Alawa Clement 
Published: June 2021

The spinal cord of the adult African Giant Pouched rat was studied using the rapid Golgi technique in order to get further clarification on the morphology of the neuronal cell types based on soma size, shape, dendritic density and aborization. Two main types of cells were observed to characterize the dorsal grey horn: Type 1 cells are the islet cells which were distinguished by triangulated or globular‐ shaped soma with one thick “axoniform” primary dendrite bifurcating into a Y or T secondary branches indicative of local integrating functions. They resembled the pseudounipolar cells of the dorsal root ganglion and were predominant in the cervical segments. Type 2 cells were stalked cells with several dendrites and round or polygonal soma and these were predominant in the thoracic and lumbosacral segments. The ventral grey horn demonstrated multipolar neurons with dendritic arborization arranged in a radiating or tuft‐like manner. Some cells had sparse dendrites while some other cells demonstrated unique features of a double‐pyramidal cell (conjoined neurons) joined at their apical dendrites with sparse dendritic arborization. These cells were predominant in the thoracic segment and have not been previously described. These findings give some new insight on the morphology of neurons in the spinal cord of one of the largest and unique muroids in the world.Grant Funding Source: Supported by Grant from Ahmadu Bello University, Zaria Kaduna State. Nigeria