bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of rotenone induced Parkinson’s disease on respiration and swallowing rate in drinking rats
Authors: Good Taylor , Wojtas Ireneusz , Gould Francois 
Published: May 2024

Parkinson’s disease is a neurodegenerative disorder known to cause dysphagia, the major contributor to mortality via aspiration pneumonia. The neurological basis of swallowing dysfunction in Parkinson patients is poorly understood. To explore the mechanisms of swallowing dysfunction, we studied the impact of rotenone treatment on respiration rate and swallowing rate in liquid-drinking rats. We hypothesized that rotenone treatment will cause a decrease in respiratory and swallowing rate compared to untreated liquid-drinking rats. Six rats were injected with 2.75 mg/kg/day intraperitoneal rotenone for 16 days to create the parkinsonian phenotype and subsequently recorded with 200fps video fluoroscopy during barium-infused liquid drinking. Before the first injection and on day 4, 7, 10 and 16, the number of swallows and number of breaths in a ten second period of continuous drinking were scored. The data was then analyzed using Analysis of Variance to determine whether the rotenone injections impacted the respiration or swallowing rate. Rotenone injections led to a decrease in respiration rate (p=0.03), but no change in swallowing rate over a 16-day period (p>0.05). Immunohistochemistry of the dorsolateral striatum of rats that received rotenone treatment for 8 days and 16 days showed significant reduction in tyrosine hydroxylase (TH) immunofluorescence with increased impact due to prolonged treatment (Kruskal Wallis test, p<0.001). TH is the rate limiting step of catecholamine synthesis from tyrosine, confirming that rotenone is affecting dopamine production in this model of Parkinson’s disease. These results indicated that rotenone induced parkinsonian treatment has differential impacts on different brainstem mediated processes, swallowing and respiration. Thus, swallow-respiration coordination is likely impacted in these animals, potentially increasing risk of airway protection failure. Internal Rowan funding to F. Gould supported this work. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Sulfonylureas Compromise Microvascular Flow in Mouse Skeletal Muscle
Authors: El-Lakany Mohammed A. , Kowalewska Paulina M. , Ellis Christopher G. , Welsh Donald G. 
Published: May 2024

Sulfonylureas are among the most prescribed oral anti-hyperglycaemics, particularly in low- and middle-income countries. Sulfonylureas are insulin secretagogues through blocking ATP-sensitive potassium channels (KATP) in β-cells of the pancreas. Despite wide usage, sulfonylureas are associated with increased cardiovascular disease morbidity and all-cause mortality, with ill-defined mechanisms. We tested the hypothesis that glyburide could block KATP channels in the microvasculature, thereby disrupting tissue oxygen demand-supply balance. We further investigated the contribution of other potassium channels to capillary-to-arteriole signalling. Experiments were conducted using an in-vivo anesthetized mouse skeletal muscle preparation (extensor digitorum longus, EDL); exteriorized and situated at in-situ length, overtop an oxygen-permeable membrane covering a gas chamber, and bathed in PlasmaLyte. C57BL/6 mice were employed (n=6-8). Brightfield images were captured at two wavelengths: oxygen-dependent and oxygen-independent, enabling the simultaneous determination of capillary hemodynamics and RBC oxygen content. Low oxygen challenges were achieved by dropping oxygen levels in the gas chamber from 7% to 2% for 3 minutes. Challenges were conducted before (control) and after drugs were added to bathing solution. Parameters were obtained before the challenge (baseline), during the challenge (2 regions) and after the challenge (recovery). Statistical significance was determined using a paired Student’s t-test. Target channels localization was investigated using immunofluorescence in formalin-fixed EDL. Oxygen challenges augmented EDL surface capillary hematocrit and RBC velocity and supply rate, while reducing RBC oxygen saturation. Incubation of the EDL with 10 μM glyburide decreased the baseline RBC supply rate (p<0.05 vs control) and blunted the magnitude of capillary responses to the oxygen challenge (p<0.05 vs control). Immunofluorescence confirmed the localization of KATP channels in EDL capillaries. Normal capillary responses were obtained when small and intermediate conductance or inward rectifier potassium channels were neutralized. This implies minimal or no contribution of these channels in oxygen signaling in the microvasculature. This data begins to elucidate the acute and direct effects of systemic KATP blockers on capillary-to-arteriole conducted signaling, which is likely key to optimal tissue oxygen regulation. Further experiments are warranted to confirm this conclusion. This work was supported by the Natural Science and Engineering Research Council of Canada (NSERC, RGPIN/04659-2017), an Ontario Graduate Scholarship (M.A.E) and a CIHR doctoral award (M.A.E). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
The Role of Renal Medullary Bilirubin and Biliverdin Reductase in Ang II Induced Hypertension
Authors: Arthur Gertrude , Stec David 
Published: May 2024

Previous studies have demonstrated the importance of renal medullary heme oxygenase-1 (HO-1) in blood pressure response to angiotensin II. However, the role of the HO metabolite, bilirubin, in this response remains unknown. The goal of the present study was to test the hypothesis that generation of bilirubin in the renal medulla plays an important role in the regulation of blood pressure in response to angiotensin II. Twenty-week-old male C57Bl/6J mice were implanted with intrarenal medullary interstitial (IRMI) catheters following unilateral nephrectomy. After this time, biliverdin IXα was specifically infused into the kidney (3.6 mg/day) for 3 days prior to implantation with an osmotic minipump delivering angiotensin II (1000 ng/kg/min). Blood pressure was recorded for 3 days, 1 week after minipump infusion, in conscious mice. IRMI infusion of biliverdin significantly decreased blood pressure as compared to mice infused with vehicle (118 ± 4 vs. 158 ± 2 mmHg, p<0.05). To further explore the antihypertensive role of renal medullary bilirubin generation, mice with specific deletion of biliverdin reductase-A (BVRA) in the thick ascending loop of Henle (TALH) were generated by crossing BVRAflox/flox mice with Tamm-Horsfall Cre (THP-Cre) mice. THP-Cre/BVRAflox/flox mice exhibited specific deletion of BVRA in the TALH by co-immunostaining with endogenous THP protein. THP-Cre/BVRAflox/flox mice did not exhibit any differences in baseline blood pressure as compared to BVRAflox/flox mice (108 ± 2 vs. 108 ± 2 mmHg). However, angiotensin-II infusion resulted in significantly higher blood pressure measured in conscious mice 7 days after implantation in THP-Cre/BVRAflox/flox as compared to BVRAflox/flox mice (152 ± 2 vs. 140 ± 3 mmHg, p<0.05). These results demonstrate an important role for renal medullary bilirubin and biliverdin reductase in the blood pressure response to angiotensin II. Strategies which increase renal medullary bilirubin/biliverdin reductase levels could be novel antihypertensive therapies. Future studies will examine the mechanistic link between bilirubin and electrolyte transporters in the kidney, specifically, the Na+-K+-2Cl2 cotransporter (NKCC2), which is a major transporter of electrolyte in the thick ascending limb and is known to play a role in Ang II-induced hypertension. This work was supported by National Institutes of Health grants (RO1-HL088421 to DS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Age-Related Loss of Phrenic Motor Neurons in Rats
Authors: Alabdulqadar Aliyah , Fogarty Matthew , Dasgupta Debanjali , Mantilla Carlos B. , Sieck Gary C. 
Published: May 2024

The diaphragm muscle (DIAm) is the major inspiratory muscle. Neural control of DIAm activation involves recruitment of phrenic motor neurons. Activation of the DIAm during breathing involes recruitment of fatigue resistant motor units comprising smaller PhMNs and type I and IIa muscle fibers. More force, but infrequent non-ventilatory behaviors of the DIAm involes the recruitment of fatigable motor units comprising larger PhMNs and type IIx/IIb fibers. This study investigated the role of brain derived neurotrophic factor (BDNF) signaling, through its high-affnity receptor, tropomyosin receptor kinase B (TrkB.FL), in the survival of PhMNs in young (6 months old) and old (24 months old) Sprague Dawley rats. Previous research in Fischer 344 rats revealed an age-related loss of larger PhMNs. We hypothesize that both BDNF/TrkB signaling and PhMN activity are crucial for PhMN survival, but that the influence of BDNF/TrkB decreases with age due to reduced TrkB.FL expression. PhMNs were retrogradely labeled and imaged using 3D confocal microscopy in both young and old rats. We found a similar reduction in larger PhMNs in Sprague Dawley rats as previously observed in Fischer 344 rats. In contrast to younger rats, intrathecal BDNF treatment did not induce phosphorylation of the transcription factor CREB at Serine133 in older rats, consistent with reduced TrkB.FL expression and signaling in older rats. In both old age and following TrkB kinase inhibition, smaller PhMNs survived perhaps due to the continued activation driving pCREB, while larger PhMNs may require BDNF/TrkB signaling to maintain pCREB and survival. Research Supported by NIH R01 grants AG44615, HL146114 and R56-HL166204. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Exploration of the Propagation of Hippocampal Theta Oscillations in Freely Moving Rats
Authors: Lovett Sarah , Qin Yu , Zhao Ben , Kochis Sam , Hershkowitz Sean , Kennedy Jack , Besosa Cristina 
Published: May 2024

Comprehending the mechanisms by which theta waves propagate across the hippocampus is of utmost importance in understanding various aspects of cognition in rodent models. A popular argument made by those studying hippocampal rhythms is that they are synchronous throughout the medial temporal lobe. However, recent studies have concluded that theta oscillations travel as waves along the septotemporal axis of the hippocampus. Our experimental goal was to derive a relationship between theta oscillations in the anterior and posterior regions of the hippocampus by examining local field potential in freely moving rats. We trained a mixed-sex cohort of five Fisher Brown Norway hybrid rats to run on a circular track for a food reward and implanted them with an intracranial silicon probe in the CA1 region of the anterior dorsal hippocampus (AP: -2.8 ML: 1.5 DV: 4.0) and the CA1 region of the posterior parietal hippocampus (AP: -5.6 ML: 4.2 DV: 4.5). After a recovery period, the rats were reintroduced to the circular track where data was collected from each site. This poster presents the activity of traveling dentate spikes, ripples, theta, and gamma within these hippocampal regions. R01MH126236 1R01MH109548-01A1. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Sex Differences in Alcohol-related Cardiomyopathy
Authors: Harris Nicholas , Edavettal Joshua , Bysani Chandrasekar , Gardner Jason D. 
Published: May 2024

Alcohol-related Cardiomyopathy (ACM) manifests in humans with a significant history of alcohol use and is characterized by ventricular dilation and cardiac function impairment. Although the most common age group for ACM is males between the ages of 30-55, women require a lesser lifetime alcohol exposure to develop ACM than men. The objective of this study is to assess sexual differences in a mouse model of chronic plus binge alcohol consumption. We hypothesize that female mice exposed to chronic plus binge alcohol will not develop as severe cardiac dysfunction as their male counterparts. In this study, male (n=19) and female (n=14) C57BL/6J mice were provided chronic plus binge alcohol feeding. After 5 days of acclimation to the liquid diet, mice are fed ad libitum 5% ethanol (EtOH) liquid or isocaloric control liquid diet for 30 days. At 10 and 30 days, mice received an oral binge dose of EtOH (5 g/kg body weight), or isocaloric maltose dextrin solution (9 g/kg body weight). Noninvasive cardiac structural and functional data were obtained via echocardiography at baseline and following binges. After 30 days, cardiac hemodynamics was measured by open chest left ventricle catheterization. Two-way ANOVA with Tukey’s post hoc analysis was performed for each cardiac parameter, and significance was defined as p<0.05. Male EtOH mice exhibited a significant decrease in stroke work (1119 ± 297 mmHg/mL when compared to male controls, 1622 ± 365 mmHg/mL; p= 0.03). Female EtOH mice had a nonsignificant decrease in stroke work (1242 ± 374 mmHg/mL when compared to female controls, 1423 ± 469 mmHg/mL; p= 0.80). Maximum left ventricular pressure was decreased 20% in male EtOH mice (p=0.003) but increased 10% in female EtOH mice (p=0.46). The maximum rate of pressure change within the ventricle was 24% lower in the male EtOH mice (p=0.02) and 9% higher in female EtOH mice (p=0.87). The minimum rate of pressure change within the ventricle was 24% higher in male EtOH mice (p=0.02) and 17% lower in female ETOH mice (p=0.44). After 30 days of EtOH exposure, male mice showed significant systolic and diastolic dysfunction. Female mice on the other hand, did not show substantial cardiac dysfunction after chronic plus binge ethanol exposure. Further experiments involving qPCR of proinflammatory and profibrotic markers will elucidate the molecular mechanism of sex differences in ACM development. R21AA029747 (JG & CB) & T32AA007577. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Theta Phase Precession and the Dynamics of Spatiotemporal Asymmetry in Hippocampal Place Fields
Authors: Qin Yu , Zhao Ben , Lovett Sarah , Besosa Cristina , Kennedy Jack , Burke Sara , Maurer Andrew 
Published: May 2024

A consistently observed characteristic of hippocampal place fields is the shifting of the field's center of mass and the subsequent development of asymmetry. This is evidenced by the expansion of the place field in an asymmetric manner over repeated traversals, wherein a rat's initial entry into the field prompts a low firing rate that substantially increases as it exits. Our study delves deeper into these spatiotemporal asymmetries of place field spiking, specifically examining their relationship with theta oscillations and disentangling the effects from environmental factors. Analysis of neuronal data from a T-maze alternation task revealed a distinct non-uniform firing pattern of place cells. This pattern was markedly skewed in relation to the phases of theta cycles, indicating a phase precession effect. We found that as the rat navigates through the place field, there is a systematic advancement of spike timing, with action potentials tending to cluster in the early phases of theta during the exit phase of the field. Such temporal coordination of spikes suggests that the timing of neural activity within theta cycles is as integral as spatial location, influencing the dynamics of place field expansion and potentially affecting the hippocampal local field potential. This discovery underscores the role of theta phase precession in spatial encoding, proposing a novel temporal component that could underpin the cognitive map within the hippocampus. R01 MH126236 R01 AG055544. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Effect of Intravenous Delivery of N,N Dimethyltryptamine on Sleep-Wake States in Rat
Authors: Summerfield Rachel , Groenhout Trent , Liu Tiecheng , Vanini Giancarlo , Mashour George A. , Pal Dinesh 
Published: May 2024

Psychedelics, including N, N, Dimethyltryptamine (DMT), are being increasingly explored for therapeutic potential to treat psychiatric disorders such as depression, anxiety, and post-traumatic stress disorder. These and other psychiatric conditions have a bidirectional relationship with sleep patterns but the impact of psychedelics, particularly DMT, on sleep architecture is incompletely understood. Therefore, in this study, we determined the effect of intravenous DMT administration on sleep-wake states in male and female rats. Under surgical isoflurane anesthesia, adult Sprague Dawley rats (n=10, 5 male, 5 female) were instrumented with electrodes to record electroencephalogram (EEG) from across the cortex and electromyogram (EMG) from dorsal nuchal muscles. In addition, a chronic catheter was positioned in jugular vein for the infusion of DMT or 0.9% saline (as vehicle control). Each rat received an intravenous bolus (100 uL/min over 5 min) of either one of two doses of DMT (low dose: 3.75 mg/kg, high dose: 7.5 mg/kg) or 0.9% saline. The DMT and saline infusions were performed 30-minutes after the start of the lights-ON period (8:00 am) after which EEG and EMG data were recorded for 24h across the light and dark cycle. EEG and EMG data were manually scored (SleepSign, Kissei Comtec) in 4-second intervals and classified as wakefulness, slow-wave sleep, or rapid eye movement sleep, then averaged in 3h bins across the 24h recording period. A linear mixed model was used to compare the changes in percent time spent in each state, mean duration per episode for each state, and mean number of episodes for each state, between vehicle control and DMT infusion sessions. There was a statistically significant increase in the time spent in wakefulness in the first 3h bin after DMT infusion (p<0.02 for low dose, p<0.03 for high dose). In the same 3h bin, a significant decrease in slow-wave sleep (p<0.02 for low and high dose DMT) was observed. DMT infusion produced a significant increase in the latency to the onset of rapid eye movement sleep (p<0.01), but no statistical effect was observed on the time spent in rapid eye movement sleep during the light period. Our results with DMT align with previous reports showing an increase in wakefulness after administration of serotonergic psychedelics. Further analysis of neurophysiologic data is needed to understand the neural dynamics associated with DMT-induced increases in wakefulness. Department of Anesthesiology, University of Michigan. RS was partly supported by Magnificent Michigan Summer Undergraduate Research fellowship, University of Michigan. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Technology-Mediated Learning in Higher Education Physiology Classes: The Use of MeGli App to Teach Glycemic Control
Authors: de Gouvêa Fernandes Ana Clara , Magalhães Carneiro Everardo 
Published: May 2024

Glycemic control is a fundamental physiological concept in diabetes and obesity. Proper training of healthcare professionals in this content is essential for disease prevention and management. Active learning methods, including technology-mediated learning (TML), are important for effective education and student engagement. Given the complexity of physiology, educational technology can facilitate the visualization of its dynamic processes. Thus, we've developed the MeGli smartphone application as an educational tool to teach glycemic control and related conditions, aimed at undergraduate students in health and biological courses. Our hypothesis is that the use of MeGli in Physiology classes promotes student learning and satisfaction. MeGli ( https://t.ly/crEwT ) is a didactic simulator for glycemic metabolism, allowing users to observe postprandial and fasting events, interact with objects, and explore cellular processes. The aim of this study was to conduct and evaluate a TML class using the app and its impact on students' outcomes in Biological Sciences Physiology classes at University of Campinas (n = 23). We analyzed pretest-posttest knowledge questionnaires using the Wilcoxon matched-pairs signed rank test (p ≤ 0.05) due to non-normal data (Shapiro-Wilk normality test). Additionally, we applied a Likert scale opinion survey. Prior to the intervention, students provided informed consent, ensuring anonymous participation. The use of MeGli in a non-expository class, where students consulted the app in an active-learning process for answering and discussing questions, led to a significant improvement in their performance on the topic of glucose metabolism and diabetes (pretest mean 5,739± 0,3784 versus 8,652± 0,2142 on posttest; p < 0.0001). In terms of student feedback, opinion questionnaire results were overwhelmingly positive. All students agreed that the app was useful for learning and helped in their understanding of diabetes mechanisms. 87% understood the importance of healthy eating and physical exercise through the app. 91.3% reported a higher acquisition of knowledge due to the app's use and found the app-integrated class more stimulating and engaging. These findings strongly support the effectiveness of the MeGli application in facilitating physiology education, leading to a more motivating educational experience. Consequently, this study is significant in introducing an innovative tool that mediates active learning with technology, enhancing physiology teaching strategies and improving the education of future healthcare professionals. CNPq (441028/2020-9), FAPESP (2018/26080-4), CEPID (2013/07607-8). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.