bluuebunny/crossref_metadata_2025 huggingface dataset:
Ion Regulation, Acid/Base Balance and Gas Exchange Interactions in Salmon Across Salinities
Authors: Damsgaard Christian , McGrath Monica , Wood Chris M. , Richards Jeffrey G. , Brauner Colin J.
Published: June 2021

Migration between freshwater and sea water in diadromous fishes requires substantial changes in branchial, renal and intestinal regulation. Since little is known about osmoregulation in fishes in brackish water, where the gradients for water and ion movements are reduced, we investigated the organ‐specific transitions in osmoregulation across salinities, and how these may impose tradeoffs with brachial gas‐exchange and organismal acid/base‐balance. We acclimated Coho salmon to fresh‐, brackish‐, and seawater for a full year, and then measured ion‐ and acid/base‐regulation and gas‐exchange in fishes instrumented with vascular and urinary bladder cannulas. We show that glomerular filtration rate and urine production gradually decrease with increases in salinity, while drinking rates do not increase until salinities exceed isosmotic, showing that transitions in osmoregulatory function of the kidneys and gastrointestinal tract are not initiated at the same salinity. Further, we show that arterial blood gas status is identical across salinities, suggesting that branchial remodeling during salinity acclimation does not affect gas‐exchange. Lastly, we show that plasma ion composition differs across salinities and is associated with different set‐points for intra‐ and extracellular pH‐regulation. These data provide insight into compromises between ion regulation, acid/base balance and gas‐exchange in euryhaline animals across salinities.

Support or Funding Information

CD is supported by the Carlsberg Foundation and the research was funded by a Natural Sciences and Engineering Research Council of Canada, Strategic Partnership Grant.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Reconstructing Connective Tissue Lineage Diversification at the Single Cell Level in the Zebrafish Face
Authors: Crump Gage
Published: June 2021

Assembly of the vertebrate face requires the precisely regulated differentiation of neural crest‐derived cells into a diversity of connective tissue fates, including cartilage, bone, and tendon/ligament cells. In order to better understand spatiotemporal regulation of this process, we are conducting a single‐cell transcriptomic analysis of neural crest‐derived cells from embryonic through adult stages. Our preliminary data reveal different trajectories for permanent cartilage, replacement cartilage, bone, and tendon/ligament cells, as well as diverse populations of undifferentiated cells in the adult face that may represent distinct progenitor populations. In the embryo, we have confirmed the presence of both multipotent and lineage‐committed cells through clonal labeling of sox10:CreER animals treated with a limiting dose of tamoxifen. We have also uncovered novel genes implicated in early lineage decisions. In particular, we find that the nuclear receptor transcription factor Nr5a2 marks cells destined to become lower jaw tendons, which we show by generating an nr5a2:GFP knock‐in transgenic reporter and performing time‐lapse microscopy. In nr5a2 mutants, tendon precursors marked by nr5a2:GFP inappropriately become cartilage cells, which results in an enlarged lower jaw cartilage that fails to properly attach to lower jaw musculature due to loss of tendons. These ongoing studies validate genomics approaches in identifying new regulators of connective tissue fates in the developing face.

Support or Funding Information

NIDCR R35 DE027550

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Apolipoprotein E modulates respiratory motor plasticity following cervical spinal cord injury
Authors: Hager Lydia , Stoltz Daimen , Calulot Chris , Ritter Kyle , Silverstein Aaron , Huffman Emily , Alilain Warren
Published: June 2021

Each year, 17,700 Americans suffer a spinal cord injury, over half of which occur at the cervical level. These high level injuries can interrupt bulbospinal neurons that innervate the phrenic motornucleus, the origin of the phrenic nerve. Loss of these descending inputs to the phrenic nerve paralyzes the ipsilateral diaphragm, leading to breathing impairments. One approach to promote recovery of breathing function is by enhancing plasticity through strengthening of synapses or activating spared but latent pathways in the spinal cord. Activation of the latent crossed phrenic pathway can lead to a form of respiratory motor plasticity known as long term facilitation (LTF), which is characterized by a prolonged increase in breathing motor output. LTF can be induced through exposure to intermittent hypoxia (IH) or by intermittently dosing the spinal cord with serotonin (5‐HT). While a portion of the spinal cord injured population responds to IH therapy with the expected increase in respiratory output, others remain non‐responders. This inconsistency indicates that variability in the human population may influence how individuals respond to treatments that aim to enhance plasticity. Therefore, we propose that genetic diversity among the SCI population could be a key factor in determining an individual's propensity for plasticity. Apolipoprotein E (apoE) is a promising candidate gene that could be responsible for this variability because one of the apoE alleles, E4, has previously been shown to reduce synaptic plasticity by decreasing expression of glutamate receptors when compared to the E2 or E3 alleles. The present study investigates the influence of human apoE4 on respiratory motor plasticity in rats following C2 hemisection. 20 weeks after injury, rats were dosed with one isoform of the human apoE protein, E3 or E4, prior to receiving intermittent 5‐HT to induce LTF. Diaphragmatic EMG recordings demonstrated that animals exposed to human apoE3 protein exhibited an increase in diaphragmatic activity ipsilateral to the injury, but this increase was abolished in E4 dosed animals. Analysis of tissue dosed with human apoE protein indicated that apoE also modulates synaptic expression of glutamate receptors, a crucial component of LTF induction. Collectively, these experiments demonstrate ApoE4's potential to inhibit plasticity following spinal cord injury, emphasizing the importance of considering genetic diversity while developing SCI therapeutics for the human population.

Support or Funding Information

National Science Foundation Graduate Research Fellowship, University of Kentucky College of Medicine Fellowship for Excellence in Graduate Research, University of Kentucky Startup Funds

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ventilatory effects of long‐term nitrite supplementation in a rat model of obesity
Authors: Delloro Derick J , Sindler Amy L. , Van Schaeffer G. , Barnard Chris , Kadel Jacob , Bates Melissa L.
Published: June 2021

Nitrate supplementation improves endothelial function, blood pressure, ejection fraction and overall weight. It also may attenuate the hypoxic ventilatory response (HVR) in healthy individuals. Hypoxic ventilatory response is increased in obese humans when compared to healthy individuals. Therefore, we hypothesize that HVR increases in a rat model of obesity and this increase is mitigated by nitrite supplementation. Two experiments were conducted. In the first, 12 Fischer 344 rats were broken into two groups: Rats fed a standard diet with additional nitrite supplementation (Nitrite) and rats fed a standard diet with no additional supplementation. After 2 months of nitrite supplementation, plethysmography was used to measure ventilation at oxygen levels of 21%, 15%, 12%, and 9%. In the second experiment, 21 Fischer 344 rats were divided into 3 groups: rats fed a high fat diet (HFD), rats fed a high fat diet with nitrite supplementation in their drinking water (HFD‐N), and rats fed a standard diet (Control). After 14 months of diet and nitrite supplementation, all three groups underwent identical plethysmographic measurements to the first cohort. In the first group, as expected, nitrite supplementation significantly reduced HVR. In the second group, contrary to data in humans, the obesity rat model presented a decreased HVR when compared to controls. Nitrite did not alter this obesity induced decrease in ventilation. Nitrite did cause a significant increase in VO2 when compared to both groups. Future studies are needed to determine the mechanisms behind the impact of these interventions on HVR.

Support or Funding Information

This project was funded by the College of Liberal Arts and Sciences and the Health and Human Physiology department at the university of Iowa

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Role of Raphe‐derived Neuromodulation of the Retrotrapezoid Nucleus (RTN) in Ventilatory Chemoreflexes
Authors: Dillard Matt , Mouradian Gary C. , Hodges Matthew R.
Published: June 2021

Excitatory neuromodulators such as serotonin (5‐HT) and Substance P are synthesized in and released from raphe 5‐HT neurons and increase the excitability of neurons within the brainstem nuclei responsible for controlling breathing. These neuromodulators have also been shown to increase the excitability of respiratory chemoreceptors, including the CO2‐sensitive Phox2b‐expressing (Phox2b+) neurons in the retrotrapezoid nucleus (RTN). However, the importance of this raphe‐derived neuromodulation of the RTN for the hypoxic and hypercapnic ventilatory chemoreflexes has not been tested in vivo. We hypothesize that unilateral ablation of serotonergic terminals within the RTN will attenuate the ventilatory chemoreflexes in vivo. To test this hypothesis, 8 week‐old female Sprague‐Dawley rats received stereotaxic injections of 5,7‐Dihydroxytryptamine (5,7‐DHT; 2 mg/ml, 2 μl vol.) unilaterally targeting the RTN to selectively lesion axon terminals from serotonergic neurons under anesthesia. Desipramine (30mg/kg, intraperitoneal) was administered 30 min prior to toxin injection to prevent axon terminal lesions of other aminergic neurons and limit the off‐target effects of 5,7‐DHT. Breathing was measured in room air, hypercapnia (7% CO2 challenge), and hypoxia (12% O2 challenge) before the lesions and then 3, 5, 7, 10, and 14 days after injection. Three days after injection, we observed a 41% decrease in the ventilatory response to hypercapnia and a 45% decrease in the ventilatory response to hypoxia, driven by a decrease in breathing frequency in both cases (N=4). However, the reduced chemoreflexes normalized over the two weeks after injection. There was no consistent effect following sham injection (N=2) of saline (2 μl vol.). These preliminary data suggest that the serotonergic terminals surrounding the RTN play a vital role in facilitating both hypercapnic and hypoxic ventilatory chemoreflexes in vivo, and support our overall hypothesis that raphe‐derived excitatory neuromodulation of the RTN is essential for ventilatory chemoreflexes in vivo.

Support or Funding Information

This work was supported by NIH HL122358.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of TNFα on Mitochondrial Function and Mitochondrial Biogenesis in Human Airway Smooth Muscle
Authors: Mathieu Natalia Marin , Sekar Preethiya , Chen Xujiao , Delmotte Philippe , Sieck Gary C.
Published: June 2021

Airway inflammation is a key aspect of asthma and is associated with airway smooth muscle (ASM) hyperreactivity as well as airway remodeling. Proinflammatory cytokines, such as TNFα mediate this airway inflammatory response. Previously, we found that TNFα induces an increase airway smooth muscle (ASM) force and ATP hydrolysis. In response, TNFα may also induce an increase in ATP production in ASM. This could be achieved by either an increase in mitochondrial function and/or mitochondrial biogenesis. We previously found that TNFα decreases mitochondrial Ca2+ influx. Since dehydrogenase enzymes in the TCA cycle are Ca2+ dependent, this would tend to reduce mitochondrial function in response to agonist stimulation. We also found that TNFα increases mitochondrial fragmentation, an initial step in mitochondrial biogenesis. We hypothesized that TNFα increases mitochondrial biogenesis and decreases mitochondrial function in human ASM.

Human ASM cells were isolated from lung specimens incidental to patient surgery. The patients were normal as evaluated by a clinical pathologist (no history of asthma or COPD). hASM cells were exposed to TNFα (20 ng/ml) for 24 h. To examine mitochondrial biogenesis, protein expression of porin (an indicator of mitochondrial density) and PGC1α (a regulator of mitochondria biogenesis) were determined by Western blot analysis. In addition, the relative number of copies of human mitochondrial DNA (mtDNA) was determined by PCR and normalized to nuclear DNA. Mitochondrial function was assessed by measuring O2 Consumption Rate (OCR – using a Seahorse Bioscience XF24 Analyzer), succinate dehydrogenase (SDH) activity (using a quantitative histochemical technique) and mitochondrial membrane potential – (DYm – using TMRM and confocal microscopy). OCR and SDH activity measurements were normalized to mitochondrial volume density. Results were analyzed by one‐way ANOVA with post hoc analysis when justified.

We found that TNFα increases mitochondrial biogenesis as indicated by an increase in porin and PGC1α protein expression in hASM and an increase in mtDNA copy numbers. We also found that TNFα decreases mitochondrial membrane potential in hASM cells, and also decreases OCR and SDH activity when normalized for the increase in mitochondrial volume density induced by TNFα. In a normal homeostatic response, an increase in hASM force and ATP hydrolysis (energy demand) would be met by increased mitochondrial ATP production. Our results indicate that TNFα disrupts this normal homeostatic response by reducing mitochondrial Ca2+ influx and thereby reducing mitochondrial TCA activity. However, TNFα increase the number of mitochondria to compensate the decrease in mitochondrial TCA activity.

Support or Funding Information

Supported by NIH grant HL126451

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Propagation and Coordination of Intercellular Astrocyte Ca2+ Waves by Glutamatergic Signaling
Authors: Munoz Manuel , Figueroa Xavier
Published: June 2021

Brain functions are highly dependent on a fine regulation of cerebral blood flow by a mechanism known as neurovascular coupling. This mechanism is mediated by astrocytes, which are located between neurons and parenchymal arterioles. Neurotransmitters released during an increase in synaptic activity activate receptors located on astrocytes, which initiates Ca2+ waves that are propagated to the astrocytic endfeet and neighboring astrocytes through gap junctions and activation of a purinergic signaling by ATP release via connexin (Cx)‐formed hemichannels. However, Cx hemichannels may also participate in the astrocyte signaling by providing the pathway for the release of D‐serine and glutamate. However, the relevance of this process in the astrocytic Ca2+ signaling has not been determined. We evaluated if activation of metabotropic glutamate receptors (mGluR) and NMDA receptors (NMDAR) contribute to the propagation of astrocytic Ca2+ signals in primary cultures of rat cortex astrocytes loaded with the Ca2+ indicator Fluo‐4. Ca2+ waves were initiated in a single astrocyte by applying a controlled mechanical stimulation (MS) using a micropipette. Stimulation with glutamate or t‐ACPD, a mGluR agonist, induced a rapid increase in astrocyte [Ca2+]i, which was abolished by MPEP, a mGluR5 antagonist, but, in addition, this response was attenuated by DL‐AP5, a NMDAR antagonist; phenazine methosulfate (Phen‐Meth), a serine racemase inhibitor; or D‐amino acid oxidase (DAOX), an enzyme that deaminates D‐serine. As expected, stimulation with NMDA plus D‐serine evoked an increase in astrocyte [Ca2+]i, but, interestingly, this NMDAR‐mediated Ca2+ signal was abolished by MPEP. On the other hand, blockade of connexin‐based hemichannels with the Cx blocking peptide 37,43Gap27 also attenuated the glutamate‐elicited increase in [Ca2+]i. Consistent with the involvement of hemichannels in the astrocyte communication, the intercellular propagation of the Ca2+ signaling initiated by MS was inhibited by MPEP, DL‐AP5 or Phen‐Meth. These results suggest that glutamate and D‐serine release through hemichannels coordinates the Ca2+ signal initiated by NMDAR and mGluR, which contributes to enhance the propagation of astrocytic Ca2+ waves.

Support or Funding Information

Grants: FONDECYT 1150530 and CONICYT 21160646.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Age‐Related Dysregulation of Neuronal Activity in Single Dopaminergic Neurons
Authors: Parikh Ishita , Lopez Sergio Dominguez , Howell Rebecca D. , Beckstead Michael J.
Published: June 2021

Aging is a known risk factor for neurodegenerative diseases, including Parkinson's disease (PD) and Alzheimer's disease. Dopamine neurotransmission has been implicated in the etiology of PD and age‐related decline of motor control, motivation, and cognitive functions. Few studies have pursued cellular and synaptic mechanisms to explain the decline in midbrain dopamine neurotransmission with age. Here, we used in vivo single‐cell electrophysiological recordings in anesthetized mice to characterize changes in dopamine neurotransmission related to age. We used mice of 4, 12, 24, 30 months of age to record midbrain dopamine neuronal firing activity. Our preliminary data indicates a steady decrease of dopamine neuron firing activity with age, particularly in 30 month‐old mice. In a parallel experiment, using ex vivo whole cell patch clamp electrophysiology, we assessed excitability and firing pattern in midbrain dopamine neurons. To evaluate excitability, spontaneous firing was measured and step current injections from 20pA up to 400pA were also applied to induce firing. Our results show an increase in firing rate frequency and a decrease in the number of spikes with higher current injections, starting with 18 months of age, possibly indicating increased sensitivity to depolarization block. We are currently studying synaptic transmission by assessing glutamate receptor‐mediated burst firing in dopamine neurons in young and old mice. These results will provide a comprehensive assessment of the effects of age on firing induced by both intrinsic conductances and external synaptic input.

Support or Funding Information

R01 from NIA (R01 AG052606) and T32 training grant from NIA (T32 AG052363)

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Do Female Prairie Voles Prefer Stressed Males?
Authors: McGlothlin Stephanie , Curtis Tom
Published: June 2021

The prairie vole (Microtus ochrogaster) is a monogamous rodent that can be used to study the development of social bonds. Stress is known to have an effect on the formation of monogamous pair‐bonds in this species. The purpose of this experiment was to examine the relationship between stress and pair‐bond formation. Specifically, we wanted to test the effect of stress in males on mate choice by females, and also test the effects of pair‐bond formation on stress levels in males over a period of time following the mate choice test. “Stressed” males were exposed to a resident‐intruder paradigm immediately prior to a 120‐minute mate choice test. During the test, females were allowed the choice of spending time with a stressed male or a male that had not been exposed to a stressor. Following the mate choice procedure, females were paired with the preferred male or, if they did not make a choice, were paired with one of the two males at random. Fecal samples were collected from the paired male periodically over a 14‐day period for corticosterone measurement. Contrary to expectations, only a small number of females preferred the stressed male, while the majority of subjects either preferred the male that had not been exposed to a stressor, or did not make a choice. We conclude that female prairie voles do not prefer stressed males.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Acute Kidney Injury during pregnancy decreases pup size and sensorimotor development
Authors: Bowles Teylor , Dixon Sellena , Szczepanski Jamie , Spencer Shauna‐Kay , Wallace Kedra
Published: June 2021

BACKGROUND

Acute kidney injury during pregnancy (NP+AKI) leads to growth restriction and a delay in neurodevelopment in the resulting babies. As the incidence of AKI during pregnancy has been increasing over the last few years it is important to examine the consequences of this disorder during pregnancy. We hypothesize that similar to what is seen in humans with intrauterine growth restriction, there will be a sex difference in sensorimotor development between NP and NP+AKI rat pups.

METHODS

To induce AKI, on gestational day (GD) 18, normal pregnant (NP) rats (n=4) had their renal pedicles isolated and occluded with microvascular clamps for 45 minutes under anesthesia. NP control rats (n=4) that received no surgical interventions served as controls and all rats delivered on GD21. 2–3 pups/litter were placed with a separate set of SHAM rats. Beginning on postnatal day (PND) 4 rat pups underwent the standard Irwin battery of developmental milestones: Surface righting, negative geotaxis, cliff avoidance, open circle. All pups were sexed and euthanized between PND32‐35.

RESULTS

Rat pups born to NP+AKI dams weighed significantly less compared to NP pups (p<0.0001). AKI pups were significantly smaller compared to NP pups (p<0.0001). This trend remained true for female AKI pups through PND9 (p<0.05); after which time both NP and NP+AKI females were significantly smaller than male pups. On PND3 NP+AKI females took longer to complete surface righting (23.5±12.7sec) compared to rat pups in the groups. Similar results were seen in cliff avoidance between groups (30.5±16.5 vs. 48.7±11.3sec; respectively). On PND5 NP+AKI pups (55.7±4.3sec) take longer to complete the negative geotaxis task compared to NP pups (17±1sec). There was a statistically significant difference in kidney size between female and male NP rats (p=0.02). There was not a statistically significant sex differences between groups in brain size (p=0.06), however NP+AKI pups had significantly smaller brains compared to NP pups (p=0.03).

CONCLUSION

NP+AKI pups are smaller compared to NP pups and have delays in surface righting. AKI during pregnancy did not affect kidney size in offspring, however both male and female NP+AKI pups had smaller brains more than 30 days post‐birth compared to NP pups. The results from this study suggest that AKI during pregnancy leads to a significant delay in growth and sensorimotor development.

Support or Funding Information

Research reported in this publication was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under Award Number P20GM121334. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A Motor Response Offset Score Mitigates Apparent Differences in Cognitive Function between People with and without Spinal Cord Injury
Authors: Lee Jinhyun A , Dudley‐Javoroski Shauna A , McCue Patrick M , Johnson Kristin A , Petrie Michael A , Shields Richard K
Published: June 2021

Objective

Cognitive impairment is a common secondary health condition of spinal cord injury (SCI) that may limit rapid attainment of complex new skills in rehabilitation. Standardized cognitive test batteries often include a reaction time‐based score vector that may impose a cognitive score penalty upon patients who have reduced upper extremity function. The purpose of this study was to determine whether differences in cognitive function exist for participants with and without SCI using cognitive tests with and without motor demands.

Methods

68 individuals without SCI (“NON”) and 22 individuals with motor complete SCI (“SCI”) completed NIH Toolbox cognitive assessments, including two with motor demands and reaction‐time based scoring (Dimensional Change Card Sort (DCCS), Flanker Inhibitory Control and Attention (Flanker) and two without timed scoring (List Sorting Working Memory (List Sorting), Picture Sequence Memory Test (Picture Sequence). Tests were administered with and without the assistance of a proctor on two days (>24 hr interval). For DCCS and Flanker, the motor‐task score offset was estimated as the difference between the proctored and non‐proctored scores.

Results

For demographically‐corrected data, proctoring reduced DCCS and Flanker scores (p < 0.001) and mitigated apparent differences between SCI and NON (all p > 0.403). SCI and NON did not differ for List Sorting (p > 0.072) but did differ significantly for Picture Sequence (p < 0.001). Significant practice effects existed for memory‐based tests (List Sorting and Picture Sequence); all p < 0.015, effect size > 0.645.

Conclusions

DCCS and Flanker scores for individuals with SCI may be artificially reduced consequent to secondary motor demands of the tests. Proctoring and computation of a motor‐response score offset enables comparisons to be made between individuals with SCI and a Non‐SCI control cohort; however, further work is needed to determine whether offset‐adjusted scores can be compared to standardized normative values.

Support or Funding Information

Research Support: This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development: R01HD084645, R01HD082109

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects That Sleep has on Mental Health in College Science Students
Authors: Herring Heather , Daft Joseph M , Hobbs Pamela M
Published: June 2021

College students can suffer from lack of sleep for reasons such as sleep deprivation (psychological or behavioral) or sleep disorders (most common being insomnia, obstructive sleep apnea, or restless leg syndrome). Psychological disorders are becoming more common in our society‐with college campuses being adversely affected. This study investigated the correlation between sleep and mental health in science students at Lee University. Anonymous surveys were used to measure a student's mental health and sleep patterns. Surveys were distributed to several classes within the Natural Sciences and Mathematics Department at Lee University.

Support or Funding Information

McNair Scholars Program

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Nandrolone Use During Adolescence Increases Cocaine Sensitization and Impairs Reproductive Function in Adult Female Rats
Authors: Rivero Carlos J. , Freire Jaime A. , Segarra Annabell C.
Published: June 2021

Anabolic androgenic steroids (AAS) are known to affect mood and motivational behaviors. One of the AAS most commonly used by young adults is nandrolone. In 2017, prevalence of cocaine use in this population was approximately 33% compared to 4.9% in the rest of this population. Cocaine and AAS increase risk taking behaviors. However, the link between the use of AAS during adolescence and propensity to use other drugs of abuse has not been clearly established. In this study, adolescent female rats were administered nandrolone decanoate (20mg/kg/sc) or vehicle for 10 successive days starting on day 28, the rats were then divided into 4 groups; Oil‐Saline, ND‐Saline, Oil‐cocaine and ND‐cocaine. Beginning on day 40, they were tested for locomotor sensitization to cocaine. From days 1–5 and at days 13 and 23 rats received an injection of cocaine (15 mg/kg/ip). Their locomotor response to cocaine was measured at days 1, 5, 13 and 23. Our data show that nandrolone enhances cocaine sensitization in female rats. In ovarian tissue, it reduced weight and induced cysts formation. These data show that exposure to supra‐physiological levels of androgens during adolescence modifies the brain circuitry that regulates addictive behaviors increasing the psychoactive properties of cocaine. AAS also have detrimental effects on the female reproductive system and on fertility.

Support or Funding Information

Financial assistance was provided by the Office of International Science and Engineering (OISE) of NSF through the Partnerships for Research and Education (PIRE) program (OISE #1545803).

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Relationship Between Heart Rate Variability and Perceived Stress in Healthy College‐Aged Adults
Authors: Lombardo Danielle Michelle , Vick Robert Stephen
Published: June 2021

Heart rate variability (HRV) is a measurement of how well the heart can adapt to change and is a function of the autonomic nervous system (ANS). HRV is determined by measuring the variations between each heartbeat; sympathetic input decreases HRV (less beat‐to‐beat variation) while parasympathetic input increases HRV (more beat‐to‐beat variation). We examined the relationship of HRV to the perceived amount of self‐reported stress in healthy college‐aged students (n=11) once a week over a 5‐week period (Elon IRB 17‐222). This population routinely vacillate between stressed and non‐stressed states. Students completed a Perceived Stress Scale followed by a 5 min ECG. The ECG was analyzed using AD Instruments software (Colorado Springs, CO). HRV data was generated for each individual and was compared to the perceived stress data. Chi‐square test of independence concluded that HRV and perceived stress are related factors (p= 0.03). These results indicate that HRV could be a valuable biological indicator of stress levels in young healthy individuals; however, multiple regression analysis of each individual generated R squared values ranging from 0.05–0.92 indicating a large degree of variability. Future research would examine the use of HRV as a biomarker for stress, as well as the lasting effects of stress on HRV.

Support or Funding Information

Elon Undergraduate Research Program

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Thermoregulation through the glutamatergic neurons in vestibular nucleus complex
Authors: Abe Chikara , Yamaoka Yusuke , Morita Hironobu
Published: June 2021

The vestibular system is one of the sensory systems which contributes to the sense of balance and spatial orientation. This also participates in the autonomic nervous response, which stimulation of the peripheral vestibular organs induces sympathoexcitation. This response is observed in both rodents and human beings, and we have reported that vestibular system contributes to the arterial pressure response during postural change as one of the feedforward control system (Morita, Abe et al., Sci Rep, 2016). In the other autonomic nervous responses, stimulation of the otolith organs in the inner ear induces hypothermia; exposure to the hypergravity environment decreases body temperature by 8 degree Celsius in mice. This response was attenuated by vestibular lesion or genetic deletion of otolith. In order to elucidate the central mechanism of hypergravity‐induced hypothermia, we examined the role of Vglut2, Vgat and ChAT neurons in vestibular nucleus complex (VNC) on thermoregulation in mice. We used Vglut2‐cre, Vgat‐cre, and ChAT‐cre mice to manipulate each neuron in VNC. Based on the previous work (Abe et al., Nat Neurosci, 2017), AAV‐DIO type viral vector was injected in VNC to express photo sensors (channelrhodopsin or archaerhodopsin) for optogenetics or hM3D(Gq) for chemogenetics. Unilateral photostimulation of the Vglut2 neurons in VNC induced body tilt to the ipsilateral side, while photoinhibition induced body tilt to the contralateral side. In Vgat‐cre mice, opposite response was observed compared with Vglut2‐cre mouse. Photostimulation of ChAT neurons did not show any responses. Chemogenetics stimulation of Vglut2 neurons showed hypothermia with increasing in activity, while Vgat stimulation increased body temperature with decreasing in activity. Deletion of Vglut2 neurons in VNC using AAV2–DIO–taCasp3–TEVp attenuated hypothermia induced by hypergravity exposure. On the other hand, hypothermia was still observed by deletion of Vgat neurons in VNC. Interestingly, chemogenetics stimulation of Vglut2 neurons in VNC 2 days before hypergravity exposure, the hypothermia was attenuated. Taken together, hypothermia induced by hypergravity exposure is due to activation of Vglut2 neurons in VNC.

Support or Funding Information

Grant‐in‐Aid for Scientific Research on Innovative Areas 15H05940 (HM) and 18H04974 (CA), Grant‐in‐Aid for Scientific Research (C) 18K06850 (HM), The Takeda Science Foundation (CA), The Uehara Memorial Foundation (CA), Kato Memorial Bioscience Foundation (CA), The Nakatomi Foundation (CA)

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Investigating Single‐cell Transcriptome Dynamics of the Dorsal Motor Nucleus of the Vagus (DMV) in a Rat Model of Remote Ischemic‐Reperfusion Cardioprotection (RIPC)
Authors: Chong Weelic , Balycheva Marina , Schwaber James , Vadigepalli Rajanikanth
Published: June 2021

The dorsal motor nucleus of the vagus (DMV) is one of the brainstem structures from which arises the vagus nerve, and is responsible for the vagal activity that protects the heart from reperfusion injury during an acute myocardial infarction. Remote ischemic‐reperfusion cardioprotection (RIPC) is a phenomenon known to protect the heart against injury via humoral and vagal mediation (Mastitskaya et al. 2012). It is hypothesized that RIPC cardioprotection may be mediated through changes in the gene expression of DMV neurons. However, the dynamics of gene expression in the DMV following RIPC is not known. Here, we performed RIPC by occluding the femoral artery, and using multiplex qPCR, we examined changes in gene expression of single cells taken from the DMV at several time points following RIPC. We conducted these experiments in both female and male rats and both left and right DMV. We also used a retrograde tracer to identify DMV neurons that travel to the heart and the gut, to identify different transcription profiles between these neuronal subpopulations. Our results show a distinct shift in transcriptomic identity of the neuronal subpopulations in the RIPC group over the sham controls. We conclude that there may be neuronal subpopulations in the DMV that are differentially activated following RIPC, which provides insights for translational applications of RIPC in decreasing reperfusion damage.

Support or Funding Information

We are supported by NIH NHLBI 5U01HL133360‐02 and NIH Director Office 3OT2OD023848. The funding sources played no role in study design, collection nor analysis of the data.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Adrenergic neurotransmission increases in obesity‐associated hypertension
Authors: Alula Kibrom , Fink Gregory , Xu Hui , Galligan James
Published: June 2021

Obesity‐related hypertension (HTN) is a risk factor for cardiovascular disease, stroke, type 2 diabetes, and kidney failure. Adrenergic neurotransmission is mediated by norepinephrine (NE) released from sympathetic nerve terminals onto effector tissues. Neuroeffector junctions on vascular smooth muscle in the mesenteric artery (MA) are an essential site whereby adrenergic neurotransmission regulates vascular tone, blood pressure, and blood flow distribution. The effect of obesity on adrenergic control of blood pressure in the MA is not well established, so our aim was to elucidate if and how adrenergic neurotransmission is altered during the development of obesity. We hypothesized that adrenergic‐mediated arterial constriction increases in obese male Dahl salt‐sensitive (Dahl SS) rats. Male Dahl SS rats were fed control diet (CD; 10% fat) or high‐fat diet (HFD; 60% fat) beginning at 3 weeks (wks) of age. Experiments were conducted after rats were fed for 10, 17, and 24 wks to establish a relationship between adrenergic neurotransmission and HTN development. Body weight (BW) was greater in HFD rats at all time points. Mean arterial pressure (MAP; measured by tail‐cuff) was greater in HFD rats at only 17 and 24 wks. Neurogenic constriction of MA was studied ex vivo using electrical field stimulation, a pressure myograph, and video imaging. Constriction response curves were left‐shifted in MA only from 24‐week HFD rats compared to 10‐ and 17‐week HFD rats. Constriction was similar between CD and HFD rats at all time points. MA reactivity to exogenous NE was decreased in the 24‐week CD and HFD rats compared to younger rats. There was no difference in MA reactivity between CD and HFD rats. Adrenergic nerve density was higher in HFD rats compared to CD rats at 10 and 24 wks. It also increased in a 24‐week CD and HFD rats compared to younger rats. TH (NE marker)‐immunoreactive nerve intensity was similar between CD and HFD rats at all time points. Plasma NE was increased at 24 wks in CD and HFD rats compared to 10 and 17‐week rats. However, plasma NE was similar between CD and HFD at all time points. Tissue NE content (measured by HPLC) was not different between CD and HFD rats, although decreased at the 24‐week CD and HFD rats compared to 10 and 17‐week rats. α2‐adrenergic autoreceptor and NE transporter functions were not altered by the HFD. We conclude that HTN in HFD‐induced obesity is partly mediated by overactivity of adrenergic nerves in a time‐dependent manner.

Support or Funding Information

Michigan State University

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impaired Regulation of Peripheral Blood Flow and Blood Pressure in Adults with Down Syndrome
Authors: Hilgenkamp Thessa , Wee Sang Ouk , Hong Kwangseok , Schroeder Elizabeth , Baynard Tracy , Fernhall Bo
Published: June 2021

Individuals with Down syndrome (DS) exhibit autonomic dysfunction in response to various sympathoexcitatory stimuli, with blunted responses in heart rate and blood pressure (BP). This abnormal central hemodynamic regulation may also affect peripheral blood flow regulation. Preliminary investigations suggest an impairment of brachial blood flow regulation in response to a sympathetic stimulus (−20 mmHg lower body negative pressure (LBNP)), but a larger sample is needed to confirm these findings.

PURPOSE

To investigate differences in brachial blood flow and BP in response to LBNP between individuals with DS and a control group.

METHODS

After 10 min of supine rest, participants with DS (n=19, 13 men, 24.0 ± 4.3 years) and age‐matched controls (n=30, 16 men, 24.2 ± 4.0 years) underwent 5 min of LBNP stimulation (−20 mmHg). Blood pressure and brachial blood flow were obtained for analysis in the last minute of baseline and LBNP. Mean flow velocity and arterial diameters were recorded with ultrasonography to determine brachial blood flow (BBF), forearm vascular conductance (FVC), and shear rate.

RESULTS

Mean arterial pressure (MAP) decreased significantly in the DS group during the LBNP stimulus, with no change in the control group (interaction, p=0.027). The LBNP also produced differential blood flow responses between groups. Mean velocity (p=0.016), FBF (p=0.021), FVC (p=0.012), and shear rate (p=0.013) were different between groups at baseline and only decreased in response to LBNP in the controls (see table).

CONCLUSION

Young adults with DS exhibit reduced peripheral blood flow regulation in response to LBNP compared to controls, with an abnormal response in blood pressure to LBNP. Further research is required to explore the impact of this blunted sympathetic control of blood flow and blood pressure on exercise and work capacity.

Support or Funding Information

This work has been supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIH K99/R00 1 K99 HD092606‐01).

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Renal hypertrophic signaling triggers activation of kidney immune response and accelerates cystogenesis in polycystic kidney disease
Authors: Saigusa Takamitsu , Huang Jifeng , He Lan , Yoder Bradley K , Zimmerman Kurt A , Bell P. Darwin
Published: June 2021

Background

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease with the predominant form resulting from mutations in the gene, PKD1. The disease severity is highly variable even among families with the same PKD1 gene mutation and factors other than genetics may affect cystogenesis. Protein load or unilateral nephrectomy (UNx: 1K) results in glomerular hyperfiltration and renal hypertrophy which both accelerates kidney cyst growth in PKD mice. Children with PKD that exhibit glomerular hyperfiltration were shown to have a higher rate of cyst growth and faster decline in kidney function. Thus, hypertrophic signaling in PKD may clinically be a risk factor to accelerate cystogenesis.

Methods

To test the effect of renal hypertrophy in PKD, we used adult tamoxifen inducible Pkd1flox/flox mice with or without CAGG‐cre. Three weeks after cre induction, first group of mice underwent sham surgery or UNx to accelerate cyst formation and observed for 3 or 6 weeks. The second group of mice were fed with either high protein (60%), normal protein (18%) or low protein diet (6%) for a total of 6 weeks. Mice from both UNx and modified protein diet group were sacrificed at the end of the experiment and kidneys were harvested for RNA‐seq, histology, inflammatory cytokines and flow cytometry for kidney immune cell sorting.

Results

Analysis of RNA sequencing data revealed that 1K compared to intact two kidney (2K) Pkd1 deficient mice show differentially expressed genes involved in activating/recruiting macrophages and production of pro‐inflammatory cytokines during the hypertrophic signaling. 1K compared to 2K Pkd1 mice had increased number of resident macrophage (CD11blo, F4/80 hi) but not infiltrating macrophages (CD11bhi, F4/80lo), increased inflammatory cytokine production, and severe cystic kidneys. Pkd1 deficient mice that were given a high protein diet compared to a low protein diet, resulted in activation of kidney immune cells, recruitment of inflammatory cytokines and worsening kidney cysts.

Conclusions

Renal hypertrophic signaling triggered by either UNx or protein load in adult Pkd1 mice activates kidney immune cells, inflammatory cytokine production and accelerates cyst growth.

Support or Funding Information

NIH K08DK106465, P30 DK074038, T32AI007051

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Intrinsic Circadian Clock in Podocytes Controls the Glomerular Filtration Rate
Authors: Ansermet Camille , Centeno Gabriel , Pradervand Sylvain , Maillard Marc , Firsov Dmitri
Published: June 2021

The circadian clock is a molecular mechanism that allows the kidney to continuously adjust specific glomerular and tubular functions to anticipate dramatic transitions induced in the internal body environment by circadian rhythms in activity and feeding.

The role of the intrinsic renal circadian clocks in renal functions rhythmicity is still not fully understood and remains to be further characterized. In this study, we aimed to investigate the importance of the intrinsic circadian clock of podocytes in the circadian dynamic of the glomerular filtration rate (GFR). We showed that mice devoid of the circadian clock specifically in podocytes (Bmal1lox/lox/Nphs2‐rtTA/LC1 or cKO mice) lose the circadian rhythmicity of the GFR. Moreover, we observed significant alterations in excretion profiles of creatinine, electrolytes as well as in rhythmicity of plasma aldosterone levels in cKO mice. Finally, we demonstrated that the circadian clock in podocytes controls expression of various genes having a critical role in podocyte function and known to be involved in the pathogenesis of diverse glomerular diseases. Altogether, these results demonstrate that circadian clocks located in podocytes play a significant role in circadian rhythmicity of the GFR.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.