bluuebunny/crossref_metadata_2025_split huggingface dataset:
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 InformationSupported by NIH grant HL126451This 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 InformationGrants: 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 InformationR01 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

BACKGROUNDAcute 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.METHODSTo 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.RESULTSRat 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).CONCLUSIONNP+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 InformationResearch 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

ObjectiveCognitive 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.Methods68 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.ResultsFor 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.ConclusionsDCCS 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 InformationResearch Support: This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development: R01HD084645, R01HD082109This 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 InformationMcNair Scholars ProgramThis 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 InformationFinancial 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 InformationElon Undergraduate Research ProgramThis 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 InformationGrant‐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.