bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disrupted spatial learning and memory is unaffected by training prior to intermittent hypoxia exposure
Authors: Nwakudu Chinwendu U. , Arias‐Cavieres Alejandra , Khuu Maggie A. , Garcia Alfredo J. 
Published: June 2021

Intermittent hypoxia (IH) is a common event occurring with untreated sleep apnea, a clinical condition commonly associated with cognitive deficits in learning and memory. Rodents exposed to IH, as a model for sleep apnea, exhibit impairments in spatial learning and memory. However, performance on spatial learning and memory tasks show individual variance. The objective of this ongoing study is to determine whether training prior to IH exposure influences performance on spatial learning tasks following IH. We hypothesize that while IH impairs spatial learning and memory through an oxidative stress mediated mechanism, training prior to exposure will improve performance on spatial memory tasks following IH. To test this, we developed a Barnes maze protocol to assess spatial learning and memory in mice preceding and after exposure to 10 days of IH (IH10). Before IH10, variance among individual mice was evident during the probe trial in the latency to initial entry into the exit zone. However, during the second maze session (10 days after the first probe trial), the latency in initial entry into the exit zone was increased in IH10 treated mice (n=4). Conversely, mice naive to IH10 exhibited decreased latency in initial entry into the exit zone during the second maze session (n=4). LTP measured in area CA1 was suppressed in hippocampal brain slices from mice exposed to IH (control 162%±12% (n=7) vs. IH 122±7% (n=11)). This suppression of LTP was only partially mitigated by antioxidant treatment during IH10. These results indicate that IH disrupts learning and memory independent of prior training and impaired spatial learning and memory corresponds with suppressed LTP following IH.Support or Funding InformationThis work was supported by NIH R01 NS10742101 (AJG)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Erythropoietin Secretion to Hypoxia Is Enhanced with an Expanded Plasma Volume after a Bout of Exercise in Warm Environment
Authors: Okazaki Kazunobu , Takeda Ryosuke , Imai Daiki , Kawai Eriko , Ota Akemi , Saho Kosuke , Morita Emiko , Suzuki Yuta , Goto Kazushige , Yokoyama Hisayo 
Published: June 2021

BACKGROUNDErythropoietin (EPO) secretion is a critical determinant for hematological adaptation to hypoxia, which is associated with the level of hypoxemia. Plasma volume (PV) expansion and the resultant hemodilution is observed even after a bout of exercise especially in warm conditions. With these as background, we tested the hypothesis that EPO secretion to hypoxia was enhanced with an expanded PV after a bout of exercise in a warm condition.METHODSEight healthy young men underwent two identical trials which differs only ambient temperature (Ta) during exercise. In a thermoneutral condition, baseline blood sample was taken, then subjects performed a 72‐min intense‐intermittent exercise (8 sets of 4 min at 80% VO2max ‐5 min at 20% VO2max) under cool (Ta, 20°C) and warm (Ta, 30°C) conditions. Twenty‐three hours after exercise, they exposed to hypoxia (14.4%) for 3 hours and blood sample was taken at the middle and the end of exposure. We determined percent change in PV (%ΔPV) from baseline and serum EPO. Also, esophageal (Tes) and mean skin temperature (Tsk) were measured during exercise.RESULTSDuring exercise, Tsk was significantly (p < 0.05) higher in warm than cool trial while Tes was comparable between trials. %ΔPV at 23 hours after excise was significantly higher in warm than cool trial. Serum EPO during exposure significantly increased from baseline in both trials and we found significant effects of interaction (trial x time) in serum EPO, indicating that EPO response to hypoxia was enhanced during warm trial.CONCLUSIONSEPO release to hypoxia was enhanced with expanded PV after a bout of exercise especially in a warm condition.Support or Funding InformationThis study was supported in part by a Grant‐in‐Aid for Scientific Research (17H03741) and a Grant‐in‐Aid for challenging Exploratory Research (16K13020), from Japan Society for the Promotion of Science for Kazunobu OkazakiThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Higher metabolic capacity in mice in comparison to rats during acclimation to chronic hypoxia
Authors: Reyes Christian Arias , Losantos Karen , Soliz Jorge , Joseph Vincent 
Published: June 2021

The aptitude of mammals to colonize high altitude (HA) environments is limited by their ability to tolerate decreased oxygen availability. While rats are not found under natural conditions above 2500 meters of altitude, mice are common in such habitats. Previous research in our lab showed that rats and mice display divergent physiological and molecular responses after acute (short‐term) exposure to hypoxia. As the response to hypoxia and metabolism control are tightly linked, in this work we aimed to identify the strategies underlying the metabolic response of mice and rats along the process of acclimation to short and long‐term hypoxia.Male FVB mice and Sprague – Dawley rats were exposed to hypoxia (12% O2) for 0 hours (normoxic controls), 6 hours, 1, 7 and 21 days. During the last hour of the exposure, the whole‐body oxygen consumption (VO2) and CO2 production (VCO2) were measured by indirect calorimetry. In following, samples of brain cortex were collected to evaluate the mitochondrial O2 consumption rate with the high‐resolution respirometer Oxygraph‐2k (Oroboros Inc.).Our results in mice showed increased VO2 and VCO2 (25% and 41% compared to controls) starting at 7 days of exposure to hypoxia. At the cellular level, mitochondrial O2 consumption in brain cortex increased after one day of hypoxia and then returned to control levels. A mild uncoupling was also observed in the cerebral mitochondria of mice. Contrastingly, no change was observed in rats.These results show that mice, are able to increase their aerobic metabolism during acclimatization to chronic hypoxia, while rats are not. Given that this phenotype is also present in other rodent species adapted to high altitude, our findings support hypothesis that mice, but not rats, are pre‐adapted to high altitude hypoxia due to early events in their phylogeographic history.Support or Funding InformationThis research is conducted with the funds granted by the Natural Sciences and Engineering Research Council of Canada.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of Calcium‐Sensor in bromine‐induced lung hyper‐reactivity
Authors: Lazrak Ahmed , Creighton Judy , Laube Mandy , Yu Zhihong , Matalon Sadis 
Published: June 2021

Exposure to bromine causes major injuries to skin and internal organs. In the lung, the exposure to bromine causes symptoms similar to asthma. When mice were exposed to 600 ppm bromine for 30 minutes, they developed lung hyper‐reactivity. 50% of the exposed animals died when treated with 5 mg/kg of L‐type calcium channel inhibitor nifedipine compared to controls. In contrast, treatement with 5mg/kg of diltiazem, a non dihydropyridine L‐type calcium channel blocker, protected animals from the injury induced by bromine. Exposure of human or murine Airway Smooth Muscle Cells (ASMC) to 100 ppm bromine for 10 minutes caused membrane potential (Vm) depolarization from −62±3 mV to −45±5 mV, p <0.001. Nifedipine exacerbated Vm depolarization to −15±10 mV, p<0.001; however diltiazem helped Vm recovery to −55±5 mV, p< 0.001. Using Fura‐2 AM, we found bromine injury to increase intracellular calcium (Cai) in human and murine ASMC. Cai was reduced by diltiazem but not nifedipine. the nifedipine caused Cai increase was dose dependent with an EC50 of 200 nM. Western blot studies showed an increase of Calcium Sensor (CaSR) expression in human and murine ASMC exposed to bromine and to Low Molecular Weight Hyaluronic Acid (LMW‐HA). LMW‐HA is formed by the breakdown of high molecular weight hyaluronic acid by bromine. The knockdown of the CaSR with siRNA significantly reduced nifedipine induced Vm depolarization, and Cai increase in both human and murine ASMC exposed to bromine or LMW‐HA. In conclusion, lung hyper‐reactivity induced by bromine is caused by an increase in CaSR expression in ASMC mediated by LMW‐HA.Support or Funding InformationGrants: 1U01ES027697‐01, 5U01ES026458‐02, and SAB100322373This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
cAMP‐dependent modulation of Ih underlies the P2Y1 receptor‐mediated excitation of the preBötzinger Complex inspiratory network in vitro
Authors: Zhang Yong , Biancardi Vivian , Tapia Ana Miranda , Jaib Toka Abu , Gourine Alexander , Kasparov Sergey , Funk Gregory Douglas 
Published: June 2021

The ventilatory response to hypoxia comprises an initial peripheral chemoreceptor‐mediated increase in ventilation followed by a centrally‐mediated secondary depression that can be life‐threatening in premature infants with apnea. ATP appears to be released from astrocytes in the preBötzinger Complex (preBötC, critical site for inspiratory rhythm generation), during hypoxia where it attenuates the secondary depression via a P2Y1 receptor (R)‐dependent excitation of inspiratory neurons. Here we apply nerve and whole‐cell recording methods to rhythmic medullary slices (700 μM) from neonatal rat to test the hypothesis that the P2Y1R‐mediated excitation of the preBötC network is mediated via cAMP‐dependent modulation of the hyperpolarization‐activated inward current, Ih, in inspiratory neurons. Local application of MRS2365 (P2Y1R agonist, 100 μM) evoked, in a subpopulation of inspiratory neurons (~33%), inward currents that reversed between −40 and −60 mV, consistent with activation of Ih. MRS2365 also potentiated the sag current, characteristic of Ih, that was progressively activated with hyperpolarizing voltage pulses from −50 to −110 mV (10 mV increments; 32 ± 6% potentiation measured at −100 mV). Comparison of Ih activation curves, produced via analysis of tail currents evoked by a series of 10 mV hyperpolarizing steps from −50 mV to −140 mV, in control and MRS2365, revealed a 6.6 mV, MRS2365‐induced depolarizing shift in V1/2 (Vm at which 50% of HCN channels are open). The MRS2365 inward current and its potentiation of Ih were blocked by local pre‐application of ZD 7288 (open channel blocker of Ih, 100 μM). At the network level, pre‐application of ZD 7288 at 100 μM and 25 μM attenuated the MRS2365‐induced frequency increase in inspiratory‐related activity by 94 ± 3% and 70 ± 12%, respectively. 15‐min intracellular dialysis of SQ 22536 (adenylyl cyclase inhibitor, 100 μM) from the whole‐cell pipette significantly attenuated the MRS2365 currents by 60 ± 4%. Similarly, SQ 22536 (1 mM and 100 μM for local and bath application respectively) attenuated the MRS2365‐induced frequency increase by 67 ± 8%. These data suggest that the P2Y1R‐mediated excitation of the preBötC network is produced, at least in part, via a cAMP‐dependent modulation of Ih in a subpopulation of inspiratory neurons.Support or Funding InformationCIHR, AIHS, NSERC, CFI, and WCHRIThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sex Hormone Influence on Nesfatin‐1 Signaling in the Pituitary
Authors: Schnell Abigayle L , Samson Willis K , Yosten Gina LC 
Published: June 2021

The stress response is intimately connected to appetite regulation; indeed, many peptides that modulate feeding behavior play a role in stress‐related behaviors. Nesfatin‐1 is a potent anorectic peptide that participates in the hypothalamo‐pituitary‐adrenal (HPA) axis. While nesfatin‐1 signaling in the hypothalamus is well‐studied, nesfatin‐1 signaling in the pituitary has yet to be investigated. Furthermore, the receptor through which nesfatin‐1 acts is currently unknown, and identification of that receptor would be a vital step toward establishing the physiological relevance of nesfatin‐1. Experiments were conducted in dispersed rat pituitaries to identify a candidate receptor and downstream signaling events elicited by treatment with nesfatin‐1. Our preliminary data indicate that the action and expression of nesfatin‐1 is influenced by female sex hormones; therefore, downstream signaling was investigated in both male and cycled female dispersed pituitaries. These studies suggest that nesfatin‐1 signals through an orphan GPCR to physiologically induce activation of the HPA axis in a sex‐dependent manner. Gaining a fuller understanding of how sex hormones influence nesfatin‐1 signaling in the pituitary will provide key insight into sex differences in stress‐related disorders.Support or Funding InformationNational Institute of HealthThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Possible behavior modulation in Drosophila mediated by the α1T channel
Authors: Iniguez Jorge , Chu Tiarni , Cheung Elwin 
Published: June 2021

Voltage gated calcium channels regulate calcium influx and vesicular release of neurotransmitter at chemical synapses. In Drosophila, there are three genes, Dmca1D, 1A, and α1T encoding Cav1, Cav2 and Cav3‐type channels respectively. Studies have shown that the α1T channels are important in regulation of action potential firing in Drosophila at the neuromuscular junction and the central nervous system. The α1T has been shown to be expressed across the adult fly brain. These include sensory neuropils, motor‐associated neuropils, and neuropils associated with learning and memory. We explored the role the α1T gene in adult Drosophila plays in motor‐associated activity using a locomotor assay. Our data suggests that the α1T gene knockout results in a defect in regulating excitability in adult Drosophila that manifests in altered motor activity.Support or Funding InformationCSUN PODER programThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Synthetic Corticotropin Therapy Reduces Microglial Activation in a Rodent TBI Model
Authors: Siebold Lorraine , Ashwal Stephen , Bartnik‐Olson Brenda , Johnson Rhaya , Tone Beatriz , Figueroa Johnny , Vega‐Torres Julio , Wilson Christopher G. 
Published: June 2021

Traumatic brain injury (TBI) is a leading cause of mortality/morbidity and is associated with chronic neuroinflammation. Melanocortin receptor (MCR) agonists (e.g., ACTH or adrenocorticotropic hormone) that target MC3R/4R ameliorate inflammation and provide a novel therapeutic approach. Following TBI, quiescent microglia become activated resulting in anti and pro‐inflammatory responses and morphological changes. We examined the effect of Cosyntropin (synthetic ACTH) administration on microglial activation through quantification of microglia morphology in a rodent TBI model. We hypothesized that Cosyntropin administration would reduce injury‐induced microglia morphological changes following experimental TBI in rats. We used CCI in adult Sprague‐Dawley rats, randomized to 4 groups: sham‐vehicle (N = 2), sham‐Cosyntropin (N = 2), CCI‐vehicle (N = 4), and CCI‐Cosyntropin (N = 4). Subcutaneous injections of Cosyntropin (120U/kg/day; West Therapeutic Development; Grayslake, IL) were given 30 minutes after CCI and every 12 hours for 7 days thereafter. Microglia activation was quantified based on morphology. Sectioned brains were immunostained (Iba1) and visualized with diaminobenzidine. Image processing and quantification were conducted with FIJI and FracLac for ImageJ resulting in 15 morphological values/cell. Parameters included cell area, fractal dimension, circularity, and cell perimeter and density. CCI animals exhibited increased microglia in the lesion site with no difference in cell count between vehicle and treated. Microglia from CCI animals exhibited no change in cell area, decreased cell perimeter and increased density and circularity compared to sham animals. Cosyntropin treatment altered CCI‐induced microglia changes in cell area, cell perimeter, and cell density. Cosyntropin‐treated CCI animals showed reduced morphological changes in microglia suggesting a reduced activation state. Decreased activation may decrease long‐term deleterious neuroinflammatory effects and may be mediated by Cosyntropin effects on melanocortin receptor signaling.Support or Funding InformationSupported in part by the Pediatric Epilepsy Research Foundation. Cosyntropin was supplied by West Therapeutic Development (Grayslake, IL).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Postpartum Changes in Microglia Density and Activation in a Rat Model of Superimposed Preeclampsia
Authors: Clayton Ahsia M , Shao Qingmei , Maeda Kenji J , Garrett Michael R , Sasser Jennifer M , Warrington Junie Paula 
Published: June 2021

Microglia are the primary immune cells of the central nervous system, surveying the microenvironment and responding to cell injury or tissue damage. The Dahl Salt Sensitive (Dahl‐S) rat model of superimposed preeclampsia (PE) has preexisting hypertension and chronic kidney disease and exhibits characteristic symptoms of PE during pregnancy. Preexisting cardiovascular and renal disease increase the risk of superimposed PE, which further increases risk of maternal complications. Recently, we showed that the rat model of placental ischemia (induced preeclampsia) has increased posterior cortical microglia activation 2 months postpartum. However, whether superimposed PE exacerbates postpartum microglia activation is not known. Because the Dahl‐S rat has increased peripheral inflammation (increased circulating TNFα) during pregnancy and exacerbated hypertension and proteinuria with subsequent pregnancies, we hypothesized that the Dahl‐S model has increased microglia activation after two pregnancies. Dahl‐S rats were randomly assigned to virgin (DSV) or postpartum (DSP) groups (n=3 per group). Postpartum rats were mated twice (3 and 5 months of age) and brains were collected at 8 months of age. Posterior cerebrum was cryo‐sectioned and immuno‐stained using ionized calcium binding adapter molecule (Iba1). Microglia density and morphology were analyzed using ImageJ in 3 images per region and averaged per rat. There was no difference in microglia density (number of Iba1+ microglia per image) in the hippocampus (10±2 in DSV vs. 9±1 in DSP) or cortex (7±1 in DSV vs. 7±2 in DSP). DSP rats had higher proportion of hippocampal Type 3 (78% vs. 62% in DSV) and fewer Type 4 (5% vs. 22% in DSV) microglia (p<0.05). DSP had fewer hippocampal amoeboid (activated) microglia and higher cortical ramified (surveying) microglia compared to DSV (Figure). Taken together, history of superimposed preeclampsia symptoms in DSP rats does not induce exacerbated microglia activation suggesting that pregnancy is either protective to the brain or that following damage, microglia fail to activate, contributing to incomplete repair processes. These hypotheses will be tested in future studies. Future studies will also determine cortical and hippocampal cytokine levels and astrocyte activation in the postpartum Dahl‐S rats.Support or Funding InformationNIH R00HL129192, R25HL121042, 5T32HL105324‐09, R01HL134711This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impaired autonomic cardiac regulation due to altered baroreceptor reflex sensitivity in conscious P2rX7 knockout rats
Authors: Kuzmin Vladislav S , Potter D'Anna L , Arkhipov Sergey N , Pavlov Tengis S 
Published: June 2021

IntroductionBaroreceptor (BR) reflex is a central mechanism that underlies autonomic control of the circulation due to tight coordination between heart output and peripheral vasculature resistance. Abnormal and/or pathological sensitivity of the BR reflex (BRRS) is associated with many cardiovascular diseases. ATP acting as a co‐transmitter in sympathetic and parasympathetic terminals regulates excitability of the carotid sinus cells and therefore participates in BRR. The goal of the present study was to reveal the role of P2X7 receptors in the autonomic control of the cardiovascular system and BR reflex sensitivity.MethodWe used a constitutive CRISPR/Cas9‐mediated knockout of P2X7 receptor in the PCK rat background. PCK rats are a model of chronic autosomal recessive polycystic kidney disease which associated with cardiovascular complications. As PCK rats were originally derived from the Sprague Dawley strain, the latter was used as control. BRR was studied in vivo in a series of telemetry‐based subchronic experiments. DSI HD‐S11 transmitters were implanted for direct blood pressure collection from carotid artery in addition to lead II electrode placement for electrocardiogram. After a week‐long recovery period standard approach for BRR testing with bolus intravenous sodium nitroprusside (SNP 10μg/kg) injection was used before and after double autonomic blockade (DAB, atropine plus atenolol). Mean arterial pressure (MAP) and heart rate (HR) were collected from free‐moving conscious animals and BRRS was calculated as ΔMAP/ΔHR relation.ResultsNo significant difference in resting HR was observed in Sprague‐Dawley (SD) and WT or P2X7 KO PCK rats (378±15, n=6; 359±16, n=6 and 365±8, n=6 respectively). After DAB, HR reduction was similar in WT and KO groups (11.3±2.2% and 10.1±2.3%), but SD demonstrated a more pronounced effect (18.2±3.1%). The KO rats demonstrated significantly reduced BRRS in comparison to WT and SD animals (0.43±0.05 and 0.63±0.07, 0.57±0.06, respectively). Moreover, while SD and WT rats are characterized by negative slope of ΔMAP‐ΔHR relation, ΔHR in KO group demonstrates lack of dependence on ΔMAP. In addition, the time from the beginning to maximal HR elevation in response to SNP application was significantly shorter in KO (13.5±2.5 s) vs SD (32.4±3.6s).ConclusionAutonomic control of cardiac function in PCK rats is impaired in comparison to SD rats due to chronic kidney disease. P2X7 deficiency leads to impaired BR reflex sensitivity. P2X7 receptors involved in neurotransmission contribute to the sympathetic/parasympathetic balance of cardiac function control.Support or Funding InformationNIH R00 DK105160, P30 DK090868 via Baltimore PKD Center P&F Grant and APS Dean Franklin AwardThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.