bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non‐uniform myostatin transcription in the acute response to a myocardial infarction (699.7)
Authors: Romanova Nadya , Platt Mathew , Simpson Jeremy 
Published: June 2021

Myostatin, a negative regulator of skeletal muscle growth, is transcriptionally upregulated in the heart following myocardial infarction (MI). Investigations have largely focused on myostatin production in the left ventricle (LV) during development of LV dysfunction. However, MI causes significant right ventricle (RV) dysfunction along with greater re‐expression of fetal genes as compared to LV. Our objective was to examine relative RV and LV myostatin expression following MI. Methods. Mice were sacrificed following MI and the infarct, peri‐infarct and RV were separated. Myostatin mRNA levels were determined via qPCR. Results. Baseline myostatin expression was statistically similar between the LV and RV. One‐hour post‐MI, a 10 and 2.3 fold increase in myostatin mRNA was observed in the RV and peri‐infarct tissue, respectively. Myostatin mRNA levels peaked 12h post‐MI with a 30 and 7.5 fold increase in RV and peri‐infarct regions, respectively. Out to 1 week, myostatin levels remain significantly higher in the RV than in the peri‐infarct tissue. Conclusion. Myostatin transcription in response to a MI is 4‐5 times greater in the RV than in other regions of the heart. Determining the mechanism behind this region specific increase in myostatin transcription may provide key details in understanding the role of myostatin expression in cardiac pathology.Grant Funding Source: Canadian Institute of Health and Research
Role of the angiotensin II blockade on glycemic and cardiovascular profile in rats with diet‐induced obesity (701.7)
Authors: Oliveira Junior Silvio , Pagan L , Vieira L , Martins F , Martinez P , Campos D , Okoshi M , Okoshi K , Cicogna A 
Published: June 2021

Mitogen‐activated protein kinases (MAPKs) have been involved in heart damage in obesity. However, their role remains controversial. This study tested the hypothesis that angiotensin II blockade attenuates metabolic and cardiovascular disorders in rats with diet‐induced obesity. Wistar rats were subjected to control and hypercaloric diets for 20 weeks. After this period, rats were assigned to four groups: C, LC; OB, and LOB. L‐groups received Losartan (30mg/kg/day) in drinking water during four weeks. Glucose levels were determined in serum samples. Cardiovascular analysis included systolic blood pressure and echocardiography; collagen interstitial fraction and p38 MAPK protein levels were assessed in the left ventricle. Results are presented in the table.

Variables
C
OB
LC
LOB

Glucose (mg/dL)
88.4 ± 7.7
97.9 ± 10.7 *
83.1 ± 7.0
99.1 ± 8.9 â€

SBP (mmHg)
115.0 ± 7
121 ± 18
98 ± 8 *
94 ± 6 â€

Left atrium weight (g)
0.847±0.178
0.918±0.128
0.779±0.093
0.795±0.090

Ejection Fraction
0.879±0.023
0.869±0.038
0.879±0.027
0.851±0.028

E/A
1.48 ± 0.21
1.40 ± 0.17
1.63 ± 0.36
1.48 ± 0.29

CIF (%)
1.90 ± 1.30
4.01 ± 2.60 *
2.48 ± 0.49
1.14 ± 0.73#

p38 MAPK (AU)
1.00 ± 0.69
1.15 ± 0.68
1.42 ± 1.22
0.70 ± 0.34

Mean ± standard deviation. SBP: systolic blood pressure; AU: arbitrary units; *p<0.05 vs. C; #p<0.05 vs. OB; â€ p<0.05 vs. LC; ANOVA and Tukeyâ€™s test.

Conclusion: Losartan attenuates obesity‐induced cardiovascular changes.Grant Funding Source: CNPq
Exercise training improves neuronal nitric oxide synthase mediated inhibition of sympathetic vasoconstriction (706.20)
Authors: DeLorey Darren , Jendzjowsky Nicholas 
Published: June 2021

We hypothesized that exercise training (ET) would increase neuronal nitric oxide synthase (nNOS) mediated inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle. Sprague‐Dawley rats were randomly assigned to sedentary (S, n=8) or ET (n=10; 40m/min, 5° grade; 15 min/d, 5d/wk for 4 wks) groups. Rats were anesthetised and instrumented for lumbar sympathetic chain stimulation and measurement of femoral vascular conductance (FVC) at rest and during contraction of the triceps surae muscles. The percentage decrease in FVC to sympathetic stimulation (2 and 5 Hz) was determined at rest and during contraction before and after selective nNOS (SMTC) and non‐selective NOS blockade (L‐NAME). At rest, SMTC increased (p<0.05) vasoconstriction by a similar magnitude (p>0.05) in ET (2Hz: 7±2%; 5Hz: 7±2%) and S (2Hz: 5±2%; 5Hz: 6±2%). L‐NAME further increased (p<0.05) vasoconstriction by a similar amount (p>0.05) in ET (2Hz: 11±4%; 5Hz: 8±5%) and S (2Hz: 10±5%; 5Hz: 10±3%). During contraction, SMTC caused a larger (p<0.05) increase in the constrictor response in ET (2Hz:16±2%; 5Hz: 19±5%) compared to S (2Hz :9±4%; 5Hz: 9±4%), whereas the increase in the constrictor response with L‐NAME was not different (p>0.05) between ET (2Hz: 5±3%; 5Hz: 9±5%) and S (2Hz: 10±4%; 5Hz: 10±3%). These data demonstrate that ET improved nNOS‐mediated inhibition of sympathetic vasoconstriction in contracting muscle.Grant Funding Source: Supported by NSERC Canada and CFI
Enhanced whole body maximal aerobic capacity following 12‐weeks of alternating single‐leg knee extension training (706.4)
Authors: Wolff Christopher , Suer Miranda , Konopka Adam , Trappe Todd , Harber Matthew 
Published: June 2021

Maximal aerobic capacity (VO2max) is primarily limited by the delivery of oxygen to active tissue, however the role of the peripheral tissues in limiting VO2max is unclear. The cardiovascular system and the skeletal muscle both respond favorably to aerobic exercise training, but it is unknown to what extent an improved skeletal muscle phenotype in the absence of altered cardiovascular function enhances VO2max. Thus, we employed an alternating single‐leg knee extension exercise training protocol to limit training adaptations to the skeletal muscle and assessed the skeletal muscle phenotype and whole body aerobic capacity. Eight sedentary volunteers (20±1 y; VO2max: 2.5±0.3 L.min‐1) completed the 12‐week progressive alternating single‐leg training. Subjects underwent testing to determine whole body VO2max, single‐leg peak workload, muscle function and a DXA scan before and after training. Skeletal muscle biopsies were obtained to assess muscle fiber type and fiber size. Following training there were increases (P<0.05) in VO2max (9±3%), single‐leg peak workload (43±8%), skeletal muscle size (3±1%) and slow and fast myofiber size (13±4% and 14±4%, respectively) while there was a decrease (P<0.05) in hybrid fiber content (‐33±8%). These data suggest that isolating aerobic training adaptations to the skeletal muscle may improve whole body aerobic capacity independent of altered cardiovascular physiology.Grant Funding Source: Supported by a pilot grant from the National Skeletal Muscle Research Center
Comparison of effective body water and body mass changes at three ground speeds during a 164‐km cycling event (707.9)
Authors: Armstrong Lawrence , Johnson Evan , Ganio Matthew , Judelson Daniel , Vingren Jakob , Kupchak Brian , Kunces Laura , Muñoz Colleen , McKenzie Amy , Williamson Keith 
Published: June 2021

Although body mass change (ΔMb) before and after exercise often is measured to assess dehydration, ΔMb does not represent all water losses and gains. The present field investigation was designed to determine if (a) ΔMb equaled net effective body water change during ultra‐endurance exercise, and (b) ground speed and exercise duration influenced these variables. Thirty‐two experienced male cyclists (35 ‐ 52y) completed a 164‐km event in a hot environment (35ºC), were retrospectively triplet‐matched, and were placed into one of three participant groups (C4.8, C6.3, C9.6; named to match their mean exercise duration, h). Net effective body water loss was computed from measurements (body mass, total fluid intake, urine excreted) and calculations (water evolved and mass loss due to substrate oxidation, solid food mass, respiratory water loss, and sweat loss), including and excluding water bound to glycogen (ΔEBWgly and ΔEBW, respectively). With all cyclists combined, the mean ΔMb (i.e., loss) was greater than that of ΔEBWgly by 1194 ± 213 g (P<.001), was similar to ΔEBW (difference, 0 ± 200 g; P = .21), and was strongly and linearly correlated with both (r2 = .98). Analysis of variance detected no effect of group between C4.8, C6.3 and C9.6 for ΔMb, ΔEBWgly, and ΔEBW. Due to complexity of calculations, we conclude (a) athletes likely will not utilize ΔEBWgly and ΔEBW routinely during training due to their complexity, and (b) ΔMb remains a field‐expedient estimate of net effective body water change.Grant Funding Source: University and Department Internal Funds
Role of cyclooxygenase in sex‐specific cerebrovascular responses to hypoxia (708.2)
Authors: Harrell John , Peltonen Garrett , Rousseau Cameron , Schrage William 
Published: June 2021

Animal data suggest females rely more on cyclooxygenase (COX) than males to achieve increases in cerebral blood flow. Our aim was to determine the contribution of COX to hypoxia‐mediated increases in cerebral blood flow in young, healthy female and male humans. We hypothesized females would exhibit greater hypoxia‐mediated increases in cerebral blood flow due to increased COX signaling. We measured middle cerebral artery velocity (MCAv) with transcranial Doppler ultrasound in young (24±1 yr) females (n=12) and males (n=17). Females were studied during early follicular phase (cycle day 1 ‐ 5) to minimize the effects of female hormones. Inspired air was titrated to lower arterial O2 saturation to 80% for 5 minutes while end‐tidal CO2 was maintained at basal levels. MCAv was normalized for blood pressure as cerebrovascular conductance index (CVCi). Hypoxia was conducted on twice after ingestion of placebo or COX inhibitor (100mg indomethacin). Hypoxia increased CVCi (ΔCVCi) but ΔCVCi was not different between groups (females: 13±2 vs. males: 10±2 cm/s/mmHg, p=0.55). Indomethacin reduced ΔCVCi 4±3 cm/s/mmHg in females and increased ΔCVCi 0.5±2 cm/s/mmHg in males; however, the indomethacin‐mediated change in ΔCVCi was not statistically significant (p=0.15). Our data indicate males and females respond similarly to hypoxia, but COX may play a relatively larger role in females to mediate cerebral vasodilation.Grant Funding Source: AHA PRE7390038 & NIH HL105820
Cortocotropin releasing hormone neurons in the paraventricular nucleus of the hypothalamus co‐labeled with nNOS are activated by acute hypoxia (710.8)
Authors: Coldren K. Max , Berka Charles , Kline David , Hasser Eileen , Heesch Cheryl 
Published: June 2021

Acute hypoxia (AH) increases vasopressin (AVP) and corticosteroid secretion through a peripheral chemoreceptor pathway including the PVN. Previously we found that AH activates ~ 6% of AVP and 15% of nNOS cells in the PVN, but the activated nNOS cells were neither AVP nor spinally projecting (pre‐sympathetic) (McCalmon et al, 2013). In the current study conscious rats were normoxic (N, 21% O2, n = 4) or AH (10% O2, n = 5) for 2 hrs, followed by immunohistochemical evaluation of Fos‐ , CRH‐, and nNOS‐IR. Spinally‐projecting neurons were identified by prior retrograde tracer labeling. nNOS cells in the PVN contained CRH in both N (46 ±6%) and AH rats (39 ±4%). More nNOS cells were activated in AH (nNOS + Fos; 16 ±2%) compared to N rats (5±1%) . AH did not activate spinal neurons, but resulted in greater activation of CRH neurons (15 ±2%) compared to N rats (5 ±2%). Of the activated nNOS cells in AH rats, half also co‐labeled with CRH (50 ± 5%). Nitric oxide is generally inhibitory in the PVN due to enhanced GABA release and CRH, AVP, and presympathetic neurons receive robust GABAergic innervation. Thus, activation of CRH cells which contain nNOS might serve as an early compensatory mechanism to increase NO and limit increases in CRH and downstream secretion of ACTH and corticosteroids. Since NO is highly diffusible, increased NO in the PVN may also prevent activation of spinal, and limit activation of AVP neurons during AH.Grant Funding Source: NIH R01 HL98602
Decreased adipocyte size and lipid of high aerobic capacity rats is associated with protection from steatosis following a 3‐day high fat diet (711.10)
Authors: Morris E. Matthew , Jackman Matthew , Johnson Ginger , Meers Grace , Lopez Jordan , Koch Lauren , Britton Stephen , MacLean Paul , Thyfault John 
Published: June 2021

In obese individuals, 60 ‐ 80% possesses hepatic steatosis. We assessed if intrinsic aerobic capacity influences adipose cellularity and hepatic steatosis following an acute high fat diet (HFD). High capacity runner (HCR)/low capacity runner (LCR) rats (n=8), divergent for aerobic capacity, were fed a 45% HFD for days followed by measures of body composition, adipose cellularity/lipid content and liver steatosis. LCR rats have higher percent body fat (%BF), greater average adipocyte size and lipid content, and greater steatosis on control diet compared to HCR. Acute HFD resulted in increased %BF and steatosis in the LCR, while HCR were protected. The HFD increased adipocyte size and lipid in both strains; however, LCR remained higher than HCR. Interestingly, LCR demonstrated a greater distribution of large adipocytes compared to HCR on control diet. HFD resulted in a shift to larger adipocytes in both groups, with LCR demonstrating greater total lipid in this large adipocyte fraction. In conclusion, high aerobic capacity in the HCR results in protection from HFD‐induced hepatic steatosis, which is associated with smaller adipocytes and less lipid per adipocyte than the low aerobic capacity LCR.Grant Funding Source: Supported by NIH DK‐088940 & T32 AR048523
Mu opioid receptors hyperpolarize respiratory‐controlling Kölliker‐Fuse neurons (712.1)
Authors: Levitt Erica , Abdala Ana , Paton Julian , Bissonnette John , Williams John 
Published: June 2021

Respiratory depression is the primary cause of death from opioid overdose, yet little is known about the cellular mechanisms of opioids on respiratory‐controlling neurons. The pontine Kölliker‐Fuse (KF) regulates respiration, especially the inspiratory/expiratory phase transition. In the in situ arterially perfused working heart‐brainstem preparation of rat, injection of the mu opioid agonist DAMGO into the KF caused robust apneusis that was similar to complete silencing of the KF. The apneusis was rapidly reversed by perfusion of the opioid antagonist naloxone. In whole‐cell recordings from KF neurons contained in rat brain slices, activation of mu opioid receptors hyperpolarized a majority (75%) of KF neurons. The hyperpolarizing current produced by [Met5]enkephalin (ME) was concentration‐dependent, reversed at the potassium equilibrium potential and was blocked by BaCl2, characteristics of a GIRK conductance. Unexpectedly, the partial agonist morphine produced the same amplitude current as full agonists DAMGO or ME, indicating a large receptor reserve. The presence of many spare receptors could reduce the degree of desensitization induced by prolonged application of ME. Indeed, only minimal acute desensitization of the ME‐mediated GIRK current was observed. This lack of desensitization correlates with the lack of tolerance to the respiratory depressant effects of opioids.Grant Funding Source: Supported by DA08163 (JTW) and DA33036 (ESL)
Examining the role of inhibition in establishing the three respiratory phases in a horizontal slice (712.14)
Authors: Anderson Tatiana , Garcia Alfredo , Ramirez Jan‐Marino 
Published: June 2021

Breathing is composed of three phases: inspiration (I), post‐inspiration (E1), and active expiration (E2). Essential for the generation of breathing is the preBtzinger complex (preBtC). Isolated in transverse slices (TS) the preBtC generates predominantly inspiratory activity which can be recorded as population activity. Yet, the preBtC is only one part of a wider respiratory network that is distributed along the rostro‐caudal axis of the ventral respiratory column (VRC) in the ventrolateral medulla of the brainstem. The interactions between this extended respiratory network and how it generates different forms of expiration are not entirely understood. We recently developed a novel horizontal slice (HS) preparation (CD1 mice, p5‐8) that preserves the entire VRC bilaterally while maintaining amenability for intracellular manipulation. Inspiratory population bursts from the HS preBtC are broader compared to the TS and appear to consist of two components. Burst durations in the HS decrease in the presence of 1µM strychnine, and we hypothesize that the increased burst durations reflect the glycine‐dependent partial separation of the I and E1 phases. Moreover, we discovered an additional, yet conditional rhythm rostral to the preBtC that is tightly coupled to the inspiratory rhythm. Based on the location, the phase, and the low spontaneous frequency of the rostral rhythm, we hypothesize that it represents the E2 phase. The rostral rhythm can be stimulated with 4uM norepinephrine or hypoxia and can be tightly coupled to fictive sighs in the HS. The addition of 10µM gabazine synchronizes the two rhythms suggesting that the separation of I and E2 is GABA‐dependent. Thus, the horizontal slice offers a novel approach to examining the role of inhibition in generating expiration.Grant Funding Source: Supported by the NIH
Relative contributions of NMDA and AMPA receptor‐mediated excitation to the spontaneous discharge of canine pontine respiratory group neurons (712.5)
Authors: Zuperku Edward , Prkic Ivana , Hopp Francis , Miller Justin , Stucke Astrid , Stuth Eckehard 
Published: June 2021

Neurons within the parabrachial complex appear to play a key role in controlling breathing frequency since local application of opioid receptor agonists produces bradypnea and apnea. To characterize the excitatory neurotransmission underlying the discharge of these PRG neurons, we antagonized glutamatergic inputs to AMPA and NMDA receptors with microejections of 2,3‐dihydroxy‐6‐nitro‐7‐sulfamoylbenzo‐(f)quinoxaline (NBQX) and 2‐amino‐5‐phosphonovalerate (AP5) in a decerebrate, vagotomized, ventilated and paralyzed canine model. Histograms (CTHs) triggered from the phrenic neurogram were used to quantify the activity of simultaneously recorded PRG neurons. NBQX reduced the discharge frequency (Fn) of all subtypes of PRG neurons by 25‐30% while AP5 decreased Fn by an additional 35‐45%, with the greatest depression occurring in non‐respiratory modulated (NRM) and expiratory (E) neurons after AP5. These data suggest that most (~70%) of the excitation of PRG neurons is mediated via AMPA and NMDA receptors with the latter contributing ~33% more drive than the former.Grant Funding Source: Supported by VA Medical Research Funds I01 BX000721‐01
Pontine respiratory group neuronal discharge is modulated by powerful GABAergic tonic inhibition (712.7)
Authors: Zuperku Edward , Prkic Ivana , Hopp Francis , Miller Justin , Stucke Astrid , Stuth Eckehard 
Published: June 2021

Neurons within the parabrachial (PB) complex appear to play a key role in controlling breathing frequency. Densely labeled GABA‐immunoreactive varicosities have been observed throughout the PB and the Kölliker‐Fuse (KF) nuclei of rats, however, the role of GABAergic control of PRG neurons is inadequately understood. To characterize GABAergic inhibition in the control of PRG discharge frequency (Fn) patterns, we analyzed the effects of microejected GABA‐A receptor antagonists bicuculline and picrotoxin on PRG neuronal activity in a decerebrate, vagotomized, ventilated and paralyzed canine model. Histograms (CTHs) triggered from the phrenic neurogram were used to quantify neuronal unit activity. Both antagonists produced marked increases in Fn (>80%) either alone or combined (sequentially ejected) in 80‐90% of PRG neurons. Activity throughout the cycle of phase spanning PRG neurons was increased and phasic portions of Fn showed gain modulation. Effects of both antagonists appear to be qualitatively and quantitatively similar. The results show that most PRG neurons are under strong endogenous GABAergic inhibition that attenuates their activity and is expected to markedly impact phase‐timing.Grant Funding Source: Supported by VA Medical Research Funds I01 BX000721‐01
Upregulation of substance P, neurokinin‐1 receptor, TRPV1, and adenosine A1R in nodose ganglia of rat pups treated with prenatal nicotinic exposure (713.5)
Authors: Zhao Lei , Zang Na , Zhu Qicheng , Zhuang Jianguo , Lee Lu‐Yuan , Xu Fadi 
Published: June 2021

Bronchopulmonary C‐fibers (PCFs) play a key role in producing central apnea, especially the lethal ventilatory arrest during hypoxia (Xu, JAP 2003). We recently found that PNE sensitized PCFs and promoted central apnea and lethal ventilatory arrest during severe hypoxia (5% O2 for 60 min) in rat pus (EB 2013). Pulmonary SP and AD, and PCFs’ receptors (NK1R, 5‐HT3R, ADA1R, TRPV1, and α7nAChR) are responsible for PCF sensitization/stimulation. Thus, we hypothesized that PNE would upregulate pulmonary SP and AD and these receptors in the nodose ganglia, contributing to the central apnea and lethal ventilatory arrest. In P11‐14 rat pups, we analyzed inflammatory cells, SP, and AD in BALF and SP and gene expressions of NK1R, 5‐HT3AR/3BR, ADA1R, TRPV1, and α7nAChR in the nodose ganglia. SP and AD were detected by ELISA and biosensors, respectively, and others by real‐time PCR. Our results showed that PNE obviously increased total inflammatory cells primarily via raising microphages without change in SP and AD in BALF. PNE significantly increased SP and mRNA of NK1R, TRPV1 (all P < 0.05), and ADA1R (P = 0.06) with 5‐HT3AR/3BR unchanged and α7nAChR undetectable in the nodose ganglia. Our results suggest that PNE is able to enhance inflammatory cells and NK1R, TRPV1, ADA1R and SP expressions in the nodose ganglia, likely contributing to the PNE‐induced PCF sensitization/activation.Grant Funding Source: Supported by HL‐107462
Neuroscience laboratory instruction using a computer‐based neuroanatomical learning tool (720.2)
Authors: Severson Arlen 
Published: June 2021

An interactive computer‐based neuroanatomical learning tool is being used in an integrated neuroscience laboratory to facilitate learning neuroanatomical structures, relationships, significant morphological and functional features of the human central nervous system, and clinical relevance of the neuroanatomical structures. Gross images of intact and dissected brains, thick and stained thin brain sections, thin stained brainstem and spinal cord sections, and MR images are studied. Neural structures to be identified are listed on the right‐hand side of the computer screen. Clicking on the name of a specific structure produces a transparent overlay of that structure. Structures can be identified also by moving the pointer over the image and clicking on a specific structure. With either approach, the structure is identified by a colored overlay and a collapsible dialog box at the bottom on the screen that provides a brief description of the structure and its functional role in the nervous system. In addition, images from the program are incorporated into clinical vignettes to reinforce learning. Data from student surveys and comments indicate that this is an effective way to learn the anatomical and functional aspects of the nervous system that is available at the student’s convenience. The computer‐assisted learning tool accomplishes our laboratory goals and is enthusiastically accepted by the students.Grant Funding Source: Supported by Minnesota Medical Foundation Herz Development Award