bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intercalation of swallow and breathing recorded optically in the sagittally‐sectioned rat hindbrain
Authors: Huff Alyssa D , Pitts Teresa , Gourévitch Boris , Mellen Nicholas 
Published: June 2021

The ventral respiratory column (VRC) contains heterogeneous neurons that generate and regulate respiration as well as other orofacial behaviors. In neonate SD rat, the VRC extends over 2 mm from the rostral margin of the facial nucleus (VIIn). In addition, networks that modulate breathing on a cycle‐to‐cycle basis are distributed along the dorsomedial margin of brainstem in or near the nucleus tractus solitaries (NTS): these include central networks that intercalate swallow into the respiratory pattern, and the first synapse of lung mechanoreceptors responsible for the Breuer‐Hering (BH) reflex. Both the VRC and NTS are exposed at the surface of the sagittaly‐sectioned rat hindbrain preparation (SSRH), enabling the induction of swallowing, as well as BH via bipolar electrode stimulation. Using previously‐described methods, coupling relations between VRC respiratory neurons before and during induced swallow and BH were obtained via high‐speed optical recordings along the entire VRC. Fluctuations in [Ca2+]I were detected using the medium‐affinity membrane permeant indicator fluo‐8L (KD=1.86 □M, AAT labs). Datasets were aligned using the caudal pole of the VIIn (VIIc) and the minimum of the concavity of the ventral surface at VIIc as rostrocaudal and ventrodorsal landmarks. Importantly this preparation allows for experimental conditions, which can directly test hypothesis related to swallow‐breathing coordination, and identify novel populations of neurons not currently recognized in the swallow central pattern generator.Support or Funding InformationThis work was supported by NIH grants HL 111215, HL 103415 and OT20D001983, the Craig F. Neilson Foundation Pilot Research Grant 546714, Kentucky Spinal Cord and Head Injury Research Trust, and the Commonwealth of Kentucky Challenge for Excellence.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cluster Analysis of Neuronal Discharge Patterns During Breathing and the Laryngeal Adductor Reflex with Computer Simulations and Dynamic Visualizations
Authors: Morris Kendall F. , Shuman H. Dale , O'Connor Russell , Nuding Sarah C. , Horton Kofi‐Kermit , Alencar Pierina Ashley , Bolser Donald C. , Davenport Paul W. , Gestreau Christian , Pitts Teresa G. , Lindsey Bruce G. , Segers Lauren S. 
Published: June 2021

The laryngeal adductor reflex (LAR) is a simple airway protective behavior that closes the vocal folds in response to mechanical or chemical stimulation of sensory afferents in the larynx. Previous work suggested that the intra‐medullary pathway that is responsible for activating laryngeal motoneurons is composed of as little as two synapses. We speculated that the central pathways supporting this behavior are more complex and involve neurons of several different phenotypes. Breathing and non‐breathing modulated neurons (n=632) were recorded with multiple electrode arrays in the ventral respiratory column (ventral respiratory group, pre‐Bötzinger, Bötzinger), pons, raphé, dorsal lateral medulla and spinal cord of decerebrate, paralyzed, vagus‐intact cats (n=13). The LAR was induced by electrical stimulation of the superior laryngeal nerve. We classified brainstem neuron activity phenotypes using a quantitative, reproducible clustering routine during baseline breathing and the LAR. We identified 25 breathing phenotypes that were mapped onto 16 LAR phenotypes. These results were used to produce a simplified model and simulations of the LAR. A 3‐D brainstem atlas displayed neuronal firing rates during periods of baseline breathing and/or the LAR, illuminated in proportion to firing rate. These data support distinct rather than a continuum of phenotypes based on discharge patterns during breathing as well as during the LAR.Support or Funding InformationSupport: OT2OD023854‐01, HL109025, HL131716This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Neuronal Correlates Mediating the Pontine Modulation of the Hering‐Breuer Expiratory Facilitatory (HBEF) Reflex
Authors: Zuperku Edward J , Stucke Astrid G. , Tomlinson Jack , Krolikowski John G. , Hopp Francis A. , Stuth Eckehard A. 
Published: June 2021

The gain of the HBEF is controlled by neurons in the medial parabrachial (PB) region (1). However, the mechanism is unknown. Responses of E decrementing (Edec) neurons to inputs from slowly adapting pulmonary stretch receptors (PSRs) suggest that they may mediate the HBEF reflex (2). This study analyzed the responses of E‐neurons in the pre‐Bötzinger/Bötzinger (preBC/BC) region to inputs from both the PSRs and PB neurons in a decerebrate vagotomized dog model. Neurons were recorded with a 16‐electrode probe. Weak electrical stimulation (~100 μA & 100 μs duration) of the central end of a desheathed cervical vagus nerve was used to activate PSR afferents and a concentric bipolar microelectrode was used to activate the PB region neurons. Post‐stimulus time histograms triggered by stimulus sync pulses (10 Hz for 10 min) were used to detect the presence of synaptic inputs to E‐neurons by either or both of these inputs. Cycle‐triggered histograms triggered from the phrenic neurogram (PNG) were used to analyze induced‐changes in average discharge (Fn) patterns. The data from this study and a previous study (2) show that the decrementing rate of ~all Edec neurons decreases and the discharge duration increases with the PSR‐induced increases in expiratory duration (TE). About 60% (11/18) of the Edec neurons received an inhibitory input from the PB region (3). CTHs show that concurrent PB and PSR stimulation depress the PSR‐mediated increase in TE and depress Edec discharge patterns (e.g., see figure). This finding suggests that gain modulation of the HBEF reflex by the PB region may be mediated by inhibitory inputs to Edec neurons in the preBC/BC region.Support or Funding InformationSupported by VA grant 2 I01BX000721‐08 (Zuperku) & R01GM112960‐01A1 (Stucke)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Endogenous mechanism of right ventricular repair in pulmonary hypertension
Authors: Shults Nataliia , Rybka Vladyslava , Suzuki Yuichiro J. 
Published: June 2021

IntroductionRight‐sided heart failure is the major cause of death among patients with pulmonary hypertension (PH) as well as children who suffer from various forms of congenital heart disease. Thus, agents that repair the damaged right ventricle (RV) have therapeutic potential to treat right‐sided heart failure. The biology of RV, however, is not well understood. The present study describes an endogenous mechanism for RV repair that was discovered in an experimental animal model of PH.Methods & ResultsThe treatment of Sprague‐Dawley (SD) rats with the injection of SU5416 (VEGF inhibitor) and 3 weeks of chronic hypoxia, followed by the maintenance in normoxia, resulted in progressive PH and RV remodeling. At 17 weeks after the initiation of the treatment, RV cardiomyocytes were damaged and the fibrotic region was found to be 12% of the total RV. However, at 35 weeks, RV fibrosis was significantly reduced and new cardiomyocytes were regenerated, despite RV pressure remained elevated. Before the RV repair occurs, α‐smooth muscle actin (αSMA) was found to be expressed in myofibroblasts. In addition, we noted the expression of αSMA in some of RV cardiomyocytes. Normal terminally differentiated cardiomyocytes do not express αSMA, but induced cardiomyocytes (iCMs) derived from induced pluripotent stem cells (iPSCs) do. Thus, we hypothesized that the damaged RV is repaired by activating the cellular reprogramming process that converts resident cardiac fibroblasts into iCMs perhaps through an iPSC‐like mechanism. This hypothesis was substantiated by our observations that Sox2, stem cell‐specific transcription factor, was also expressed in RV cardiomyocytes being repaired. Further, transmission electron microscopy observations revealed that extracellular matrix contains fibroblast‐line cells with myofilaments, which are organized into myofibrils and formed into the sarcomere‐like structure similar to iCMs.ConclusionsThe RV damage promoted by PAH can be repaired through a naturally occurring process that may involve cardiomyocyte regeneration through cell reprogramming. Understanding such an endogenous repair mechanism should contribute to the development of therapeutic strategies to treat right‐sided heart failure.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
H2S Contributes to Carotid Body Response to Hypoxia but Not Anoxia
Authors: Peng Ying‐Jie , Makarenko Vladislav , Nanduri Jayasri , Chupikova Irina , Girdina Anna , Zhang Xiuli , Kumar Ganesh , Fox Aaron , Prabhakar Nanduri R 
Published: June 2021

We previously reported that cystathionine‐γ‐lyase (CSE)‐derived H2S mediates carotid body (CB) response to hypoxia (Hx) (Peng et al., PNAS, 2010). A recent study showed that CB Type I cell responses to anoxia (Ax) were unaffected by CSE inhibitors (Kim et al. Respir Physiology, 2015). We re‐examined the role of CSE‐derived H2S in CB sensory and Type I cell responses to Hx and Ax in adult Sprague‐Dawley rats, wild‐type and CSE knockout (KO) mice. Hx (pO2=37± 3mmHg) produced robust sensory excitation, and increased H2S levels in the CB; whereas Ax (pO2 =5±4 mmHg) produced only a weak sensory excitation and had no effect on H2S levels. Ax evoked a robust [Ca2+]i response of Type I cells as compared to hypoxia. CSE inhibitor DL‐propargylglycine (DL‐PAG, 50μM) inhibited Hx but not Ax‐evoked sensory and Type I responses. Higher concentration (300μM) of DL‐PAG alone, or in combination with aminooxyacetic acid (300μM), non‐selectively blocked [Ca2+]i responses of Type I cells to Ax and decreased cell viability. CB sensory excitation and [Ca2+]i elevation in Type I cells were unaffected in CSE null mice as compared to wild‐type (Wt) mice. Breathing stimulation by Hx was absent in CSE KO mice, whereas depressed breathing by Ax was unaffected. These observations suggest that CSE‐derived H2S contributes to carotid body response to “physiologically” relevant hypoxia but not to anoxia.Support or Funding InformationSupported by National Institutes of Health grants P01‐HL‐90554This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hippocampal neural stem cells undergo fate switch following intermittent hypoxia
Authors: Khuu Maggie A. , Nallamothu Thara , Garcia Alfredo J. 
Published: June 2021

Adult neurogenesis is a phenomenon widely recognized as a process supporting neurophysiology of the hippocampus. We recently reported that 30 days of intermittent hypoxia (IH), a principal consequence for sleep apnea, stimulates the expansion of hippocampal neural stem cells (NSCs), yet suppresses the generation of adult‐born neurons. This study investigates how IH impacts NSCs by using a shorter duration of IH. We hypothesize that 10 days of IH (IH10) redirects the course of development of NSCs. We examined how NSCs in the neurogenic niche of the dentate gyrus are affected by IH10. Immunohistochemical analysis revealed that the number of NSCs (Sox2+ cells) was not increased following IH10, yet appears to increase in quiescent NSCs (i.e., Sox2+ cells that co‐express the astrocytic marker, S100b, and do not develop into adult‐born neurons). Fewer NSCs were observed transitioning into intermediate neuronal progenitors (INPs, SOX2+/TBR2+ cells) and a reduction in the total number of INPs (TBR2+ cells) was also noted. These experiments suggest that the impact of IH on cells involved with adult neurogenesis is cell‐type specific. Our findings provide further support that untreated sleep apnea may impact the fate of pluripotent cellular constituents in the central nervous system.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.
Duration‐dependent effects of IH‐stimulated Hif1a signaling on adult hippocampal neurogenesis
Authors: Nallamothu Thara , Khuu Maggie A. , Garcia Alfredo J. 
Published: June 2021

Intermittent hypoxia (IH), is a hallmark consequence of sleep apnea, a common untreated disorder associated with impaired neurological health. We have recently demonstrated that thirty days of IH impairs long term potentiation and reduced the proportion of neurons generated during adult neurogenesis. Hypoxia Inducible Factor 1a (HIF1a) is a transcription factor important to stem cell development that is regulated by the state of oxygenation. The objective of this on‐going study is to characterize how the duration of IH exposure influences the generation of adult‐born neurons and to determine the role of IH‐dependent HIF1a signaling in the generation of adult‐born neurons in the hippocampus. We hypothesize that IH has duration dependent influence over neurons generated through adult neurogenesis and involves HIF1a dependent signaling. We used a cre‐loxP transgenic strategy to birth label a discrete cohort of stem cells that experience room air for 30 days (control), 10 days of IH +20 days of recovery in room air (IH10+20RA), or 30 days of IH (IH30) in wild‐type reporter mice (Ai27) and in Ai27‐HIF1a+/flox mice. In wild‐type mice, exposure to IH10+20RA led to higher proportion of birth‐labelled neurons compared to the control (+19% ± 5%, n=6) while the proportion of neurons following IH30 decreased (−40% ± 10%, n=4). In Ai27‐HIF1a+/− mice, the proportion of birth‐labeled neurons was similar between control and IH10+20RA groups. However, following IH30 the proportion of birth‐labeled neurons was markedly decreased when compared to control in Ai27‐Hif1a+/− and to the IH30 wild‐type group. Dendritic complexity, as determined by Sholl analysis, was similar among labeled neurons in both wild‐type and Ai27‐HIF1a+/− groups suggesting that neither IH nor IH‐dependent HIF1a signaling influences dendritic complexity. These findings indicate that exposure duration is factor impacting how IH affects the generation of adult‐born neurons through a HIF1a signaling shaping how IH influences, associated with sleep apnea affects the generation of adult‐born neurons.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.
Environmental Enrichment Dampens the Increase in Glucocorticoid Receptors in the Hippocampus Caused by Endometriosis
Authors: Rivera‐Lopez Leslie , Appleyard Caroline B. , Torres‐Reveron Annelyn 
Published: June 2021

Endometriosis is a disorder in which the development of uterine‐lining tissue is found outside the uterine cavity causing infertility, pain and stress. Previous studies have shown that stress can negatively affect the progression of the disease. Under the control of the hypothalamic pituitary adrenal (HPA) axis, circulating glucocorticoids regulate immune and stress responses by binding to the glucocorticoid receptors (GR). Our objective was to determine if GR is altered in the brain hippocampal area of rats with endometriosis. We focused on the hippocampus as this is one of the main brain areas that display GR. In addition, hippocampal GR play a significant role in HPA axis hyperactivity. Endometriosis was induced in female rats (n=16) by suturing uterine horn tissue next to the intestinal mesentery and the disease was allowed to progress for 60 days, during which rats were exposed to either environmental enriched conditions (increased social groups, larger enclosures, toys and nesting) or normal housing conditions. Sham rats (n=8) had only sutures in the intestinal mesentery and were exposed to normal housing conditions. At the time of sacrifice, endometriotic vesicles, uterus and brains were collected. A single labeling with DAB immunohistochemistry was performed to analyze the levels of GR in the Cornus amon (CA1 and CA3) and Dental Gyrus (DG) of the hippocampus. We have previously documented that environmental enrichment can significantly reduce the progression of endometriosis resulting also in decreased GR expression within endometriotic vesicles compared to nonenriched rats. Results show that rats with endometriosis had 60% increased GR integrated density in CA1 and DG regions of the rat hippocampus compared to sham controls. Non‐enriched animals had double the integrated density of GR in the dorsal CA3 compared to sham controls and this increase was dampened by environmental enrichment. Our data suggest that interventions that decrease stress can provide some benefit to return GR activity to baseline levels in both, peripheral tissues and also in brain structures involved in stress regulation.Support or Funding InformationNIH‐K07AT008027This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Immune System Changes in a Rat Model of Maternal Vertical Sleeve Gastrectomy
Authors: Spann Redin A , Taylor Erin B , Himel Alexandra R , Grayson Bernadette E 
Published: June 2021

Women undergoing metabolic surgery for weight loss see many improvements in health, including reduced adiposity and treatment of type 2 diabetes. Fertility is also improved by bariatric surgery and the number of large for gestational day births are reduced. Unfortunately, fetal demise and low birth weights are more prevalent following bariatric surgery, and children born small for gestational age are at an increased risk of obesity as adults. We have replicated these findings in a rat model of vertical sleeve gastrectomy (VSG), however, the origin of these poor outcomes in offspring remains unknown. We have previously reported a reduction in plasma T lymphocytes in pregnant female VSG rats compared to pregnant Sham surgery rats, and increased circulating Immunoglobulin G (IgG) protein. We also reported in the placenta increased mRNA levels of interleukin 1 β (IL1B), interleukin 1 receptor antagonist, and matrix metalloproteinase 9 in VSG animals compared to Shams as well as increased TUNEL positive cells indicating apoptosis. We have currently expanded our work in the placenta, finding that mRNA for B cell marker, PTPRC, and cytotoxic T cell marker, CD8A, is elevated in VSG dams. In postnatal day 21 (PND21) pups, we measure lower circulating B lymphocytes in both males and females born to VSG dams compared to pups born to Sham dams, as well as elevated total IgG, while T cells and monocytes were not altered. In the pup hypothalamus at PND21, IL1B mRNA is elevated and this persists until PND120 in males fed chow diet. Transcription of other pro‐inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha, is not altered in the hypothalamus. These data suggest that VSG surgery alters the immune system in utero and these changes may affect immune health postnatally. Future work will determine what signalling pathways transduce this immune response and if they contribute to low birth weight and metabolic syndrome in offspring.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Contribution of basolateral amygdala‐dorsal striatum pathway in stress
Authors: Kondev Veronika , Patel Sachin 
Published: June 2021

While the dorsal striatum (DS) has been historically heavily implicated in habit formation and goal‐directed learning, the role of the DS in stress‐induced effects remains unknown. It has been shown that stress biases rodents towards using a DS‐dependent form of memory. We hypothesize that an understudied input from the basolateral amygdala (BLA) to the DS may play a role in stress‐induced changes in habit and fear learning. Using optogenetics, we analyzed BLA inputs to the DS with whole‐cell patch clamp, focusing specifically on the endocannabinoid system due to the abundant expression of the endocannabinoid receptor (CB1) in the DS. We showed that the pre‐pulse ratio was significantly increased in stressed mice, suggesting decreased activity twenty‐four hours after stress. In vivo fibre photometry data was also collected to further explore the role of the DS before and after stress. Furthermore, endocannabinoid agonists and antagonists were administered to behaviorally and molecularly assess the contribution of endocannabinoid signaling in the DS.Support or Funding InformationT32 Training Grant ‐ Veronika KondevMH107435This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of 1% Mouse Serum on the Catalase‐ and Superoxide Dismutase‐Mimetic Activity of Custom‐Synthesized Cerium Oxide Nanoparticles
Authors: Estevez Ana Y. , Stadler Brad , Erlichman Joseph S. 
Published: June 2021

Due to their potent antioxidant activity, cerium oxide nanoparticles (CeNPs) are being investigated as a potential therapeutic for neurodegenerative diseases. CeNPs are small, regenerative and display both catalase‐ and superoxide dismutase‐mimetic activity. However, toxic effects of CeNPs in biological systems have also been reported. Our working hypothesis is that the synthetic and/or biological identity of CeNPs could account for these disparate reports. In particular, the biological identity of CeNPs can be influenced by serum proteins that adsorb onto the nanoparticle surface. This can then impact the catalytic activity as well as pharmacokinetics properties of CeNPs, potentially contributing to toxic effects in an organism. The aim of the present study was to investigate the effects of serum on the catalytic activity of CeNPs. Custom‐synthesized CeNPs were incubated with or without 1% mouse serum for 30 minutes. CeNPs were then spun in an ultracentrifuge at 434, 513 x g for one hour in order to separate the supernatant (SUP) and pellet (PEL) fractions. We used commercially available enzymatic assay kits to assess the catalase‐ and superoxide dismutase (SOD)‐mimetic activity of each fraction. We also assayed oxidase activity, which could be indicative of promiscuous toxic activity. We observed that pre‐incubation with 1% serum did not significantly impact the catalase‐ or SOD‐mimetic activity of the CeNPs. On the other hand, serum pre‐incubation resulted in significantly enhanced oxidase activity that, upon further analysis, was revealed to be an artifact of the serum rather than attributable to promiscuous CeNP activity. In summary, we demonstrate that pre‐incubation with serum does not negatively affect the antioxidant activity of CeNPs, an important step in continuing to develop CeNPs as neuroprotective agents in oxidative stress diseases.Support or Funding InformationSupported by St. Lawrence University and Cerion, LLC.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.