bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arcuate Nucleus Angiotensin II Increases Arterial Pressure and Sympathetic Nerve Activity in Part via Inhibition of Neuropeptide Y Projections to the Hypothalamic Paraventricular Nucleus
Authors: Shi Zhigang , Brooks Virginia L. 
Published: June 2021

Angiotensin II (AngII) acts centrally to increase arterial pressure (AP) and sympathetic nerve activity (SNA) mainly via AngII type 1 receptors (AT1R). Multiple brain areas have been identified as targets of AngII, including the arcuate nucleus (ArcN). However, the neural pathway that mediates AngII actions in the ArcN remains unknown. Recent studies suggest that AT1R expression in the ArcN is restricted to Neuropeptide Y (NPY) neurons, which project to the hypothalamic paraventricular nucleus (PVN). Therefore, we hypothesized that, in the ArcN, AngII increases AP and SNA in part by suppressing the activity of tonically sympathoinhibitory NPY neurons that innervate the PVN. To test this hypothesis, in α‐chloralose anesthetized male SD rats, we determined if blockade of PVN NPY Y1 receptors (Y1R) with bilateral nanoinjections of BIBO3304 (60 pmol/60nL) elicits smaller increases in AP and SNA 60 min after nanoinjection of exogenous AngII into the ArcN, compared to 60 min after ArcN injections of artificial cerebrospinal fluid (aCSF). As we reported before, after ArcN aCSF, blockade of PVN Y1R increased (n=3; all P<0.05) mean AP (MAP, 99±4 to 111± 4 mmHg), lumbar SNA (LSNA, 99±9 to 130±12 % control) and splanchnic SNA (SSNA, 105±9 to 142±10 % control). Bilateral nanoinjection of AngII into the ArcN slowly increased (n=4; all P<0.05) MAP (101±4 to 116±3 mmHg), LSNA (100 to 153±10 % control) and SSNA (100 to 151±6 % control). However, 60 min after ArcN AngII, blockade of PVN Y1R did not further increase MAP (to 122±2 mmHg), LSNA (to 174±17 % control), and SSNA (to 176±22 % control), compared to the changes observed after PVN aCSF injections (ArcN AngII+PVN aCSF: n=5; MAP, 120±4 to 123±3 mmHg; LSNA, 160±20 to 174±22 % control; SSNA, 172±21 to 193±20 % control). In summary, ArcN injections of AngII markedly attenuated the pressor and sympathoexcitatory effects of blockade of PVN NPY Y1R. Therefore, we conclude that ArcN AngII increases MAP, LSNA, and SSNA, in part, via inhibition of NPY neuronal projections to the PVN.Support or Funding InformationSupported in part by NIH HL128181.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of Suppressor of Cytokine Signaling 3 (SOCS3) in POMC Neurons in Metabolic and Cardiovascular Regulation during Chronic Leptin Infusion
Authors: Wang Zhen , Moak Sydney P. , do Carmo Jussara M. , Bailey Kandice C. , Hall John E. 
Published: June 2021

Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of leptin signaling and is expressed in proopiomelanocortin (POMC) neurons. We previously showed that activation of leptin receptors in POMC neurons mediates the chronic effects of leptin on blood pressure (BP). In this study, we examined whether deletion of SOCS3 specifically in POMC neurons amplifies the chronic metabolic and cardiovascular responses to leptin. 28‐week old male (n=5) and female (n=7) SOCS3flox/flox‐POMC/cre mice in which SOCS3 was selectively deleted in POMC neurons and control SOCS3flox/flox male (n=5) and female (n=7) mice were implanted with BP telemetry probes. After recovery, 24‐hr mean arterial pressure (MAP), heart rate (HR), body weight, and daily food intake were recorded for 5 consecutive days at baseline. Then leptin was infused (2 mg/kg/day, i.p) via osmotic minipumps for 14 days followed by 6‐days of recovery.Compared to SOCS3flox/flox controls, SOCS3flox/flox‐POMC/cre mice had similar body weight (36.5 ± 2.4 vs 38.5 ± 5.0 g in males and 24.7 ± 0.7 vs 25.2 ± 0.8 g in females) during baseline and consumed similar amounts of food (3.2 ± 0.3 vs 3.3 ± 0.4 g/day in males and 2.6 ± 0.2 vs 2.7 ± 0.1 g/day in females). MAP and HR were similar in SOCS3flox/flox‐POMC/cre and control mice in males (111 ± 5 vs 113 ± 2 mmHg; 546 ± 24 vs 543 ± 26 bpm) and females (105 ± 3 vs 106 ± 2 mmHg; 562 ± 20 vs 573 ± 25 bpm). Leptin infusion reduced body weight by 7–8% in male and female SOCS3flox/flox‐POMC/cre and control mice. Reductions of food intake were similar in SOCS3flox/flox‐POMC/cre and control mice in males (2.5 ± 0.4 vs 2.5 ± 0.7 g/day) and females (2.3 ± 0.3 vs 2.2 ± 0.4 g/day) when calculated as average daily food intake during 10 days of leptin infusion. Leptin infusion transiently increased MAP in male and female SOCS3flox/flox‐POMC/cre and control mice despite decreasing body weight and food intake. Increases of MAP and HR during leptin infusion were similar in male and female SOCS3flox/flox‐POMC/cre mice compared to control mice. Chronic leptin infusion produced similar reductions in fasting blood glucose concentration in SOCS3flox/flox‐POMC/cre and control mice.These results provide no evidence that SOCS3 deletion specifically in POMC neurons amplified the chronic effects of leptin to reduce food intake, body weight, and fasting glucose concentration in male or female mice. Deletion of SOCS3 in POMC neurons also did not substantially amplify the chronic effects of leptin on MAP and HR.Support or Funding InformationFunded by NHLBI PO1HL51971, NIGMS P20GM104357This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A NOVEL ROLE OF THE DESCENDING ANALGESIA SYSTEM IN THE REGULATION OF VAGAL REFLEXES
Authors: McGovern Alice , Kerr Nicole , Farrell Michael , Mazzone Stuart 
Published: June 2021

The submedius nucleus of the thalamus (SubM), ventrolateral orbital cortex (VLO) and periaqueductal grey (PAG) constitute a well‐described pain modulatory pathway. Activation leads to depression of nociceptive inputs in the spinal cord via the rostromedial medulla and brainstem descending inhibitory systems. Using transynaptic anterograde viral tracing we noted a neural circuit derived from jugular ganglia vagal afferents innervating the respiratory tree projecting to the SubM, suggestive that vagal afferent pathways may be regulated by SubM‐VLO‐PAG descending modulatory system. In functional studies using urethane anesthetized Sprague Dawley rats, electrical stimulation of the larynx to activate vagal afferent fibres evoked respiratory slowing in a stimulus frequency dependent manner. Concomitant SubM activation via microinjections of 5 ug serotonin significantly inhibited reflex reductions in respiration when compared to vehicle controls (e.g., baseline respiratory rate of 117±4.7 breaths per minute (bpm), to 12±2.2 bpm and 69±5.9 bpm in vehicle and serotonin animals, respectively; p=0.0001, n=9/group). Chemogenetic activation of the SubM with the Gq‐DREADD demonstrated a similar inhibitory effect on respiratory slowing (86±7.6 bpm and 15±62.4 bpm in +m3D+1 mg/kg CNO and –m3D+1 mg/kg CNO animals, respectively; p=0.0001, n=3/group). This inhibitory effect was absent in animals receiving prior electrolytic lesion of the VLO. Moreover, lesion of the VLO facilitated respiratory slowing caused by laryngeal stimulation (6±6.6 bpm and 73.5±6.7 bpm in lesion and sham animals, respectively; p=0.0001, n=5/group), consistent with a tonic descending inhibitory influence over respiratory vagal afferent processing. Taken together, these data support the notion that the SubM‐VLO‐PAG descending modulatory system plays an import role in the regulation of bulbar visceral afferent processing.Support or Funding InformationA McGovern a a current recipient of a Peter Doherty Fellowship (National Health and Medical Research Council, Australia).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Chronic effects of Inflammatory Cytokines on the Protein Expression of Voltage‐gated Potassium Channels in a Dorsal Root Ganglion Cell line
Authors: Hong Juan , Adam Ryan J. , Xia Zhiqiu , Rozanski George J. , Zuker Irving H. , Wang Hanjun 
Published: June 2021

An exaggerated exercise pressor reflex (EPR) causes excessive sympatho‐excitation and exercise intolerance in the chronic heart failure (CHF) state. A recent preliminary study from our laboratory suggested that a functional loss of voltage‐gated potassium (Kv) channels in muscle afferent neurons plays a critical role in mediating the exaggerated EPR and afferent sensitization in CHF. However, the molecular mechanisms underlying the Kv channel dysfunction in muscle afferent neurons in CHF remains unclear. Since CHF is associated with chronic inflammation, we investigated the potential effects of chronic inflammation on protein expression of Kv channels in the 50B11 DRG cell line. We used pro‐inflammatory cytokines Interleukin‐6 (IL‐6), Interleukin‐1b (IL‐1β) and tumor necrosis factor alpha (TNFα) to create an inflammatory environment. We investigated the effects of TNFα, IL‐1β and IL‐6 on multiple Kv channel isoforms (Kv1.4, Kv3.4, Kv4.2 and Kv4.3), respectively. Three day exposure of TNFα (10 ng/ml) decreased protein expression of Kv3.4, but increased Kv1.4 protein expression without any change in the protein expression of Kv4.2 and Kv4.3. Similarly, 3‐day exposure of of IL‐1β (10 ng/ml) decreased the protein expression of Kv3.4, but had no effect on protein expression of Kv1.4, Kv4.2 and Kv4.3 in 50B11 cells. Finally, 3‐day exposure of IL‐6 (10 ng/ml) decreased the protein expression of Kv3.4, Kv4.2 and Kv4.3 without any effect on Kv1.4 (Table 1). These data suggest that chronic exposure of inflammatory cytokines cause the reduction of Kv channels in DRG neurons. However, each cytokine may have a slightly different impact on individual Kv channel isoforms.Support or Funding InformationThis work was supported by grants from the National Heart, Lung, and Blood Institute (R01HL121012‐A1 to HJW and in part, by R01HL126796‐A1 to HJW and IHZ).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Neurogenic CGRP on Renal Afferent Peptidergic Neurons
Authors: Rodionova Kristina , Raschke Giulia , Ditting Tilmann , Hindermann Martin , Ott Christian , Schmieder Roland , Amann Kerstin , Veelken Roland 
Published: June 2021

Although release of the proinflammatory vasodilator CGRP from peptidergic afferent nerves is generally unquestioned the matter is far less investigated with respect to afferent renal innvervation that is said to be involved in sympathetic control and blood pressure regulation. Furthermore, it is not known in how far released neurogenic CGRP will affect renal afferent innervation in return. Hence we wanted to test the hypothesis that CGRP elicits action potential production related to TRPV1 receptor stimulation in cultured neurons with afferent projections from the kidney in vivo.Cultured dorsal root ganglion neurons (Th11‐L2) of rats with renal afferents in vivo were investigated in current clamp mode to asses action potential generation or in voltage clamp mode to investigate inward currents during stimulation of TRPV1 receptors with acid of pH 6 (−80 mV holding voltage) and/or administration of CGRP (0,5 μmol). Furthermore, renal slices were incubated during baseline, experimental stimulation period and recovery to study CGRP release due to TRPV1 receptor stimulation (capsaicin 10−6 M, increased proton concentrations). CGRP concentrations in the organ bath were assessed with a commercial kit. Capsazepine was used for TRPV1 receptor blockadeMore than 90 DRG neurons with renal afferents were tested. Addition of CGRP did not change action potential generation nor inward currents. Proton stimulation (ph 6) of TRPV1 markedly increased long‐term inward currents (baseline −361,7 +/− 89,6 pA vs. −1393,3+/−337,3 pA, p<0,05, mean +/− SEM). The co‐stimulation of renal neurons with protons (pH 6) and CGRP led to an impairment of sustained inward current as compared to proton stimulation alone (baseline − 478,2 +/−54,4 pA vs. −767,6+/−89,6 pA, p<0,05, mean +/− SEM). Baseline CGRP release of renal slices (2.5 to 6 pg/ml) increased significantly after TRPV1 receptor stimulation (on average: 21+4 pg/ml CGRP).In contrast to our hypothesis CGRP could not elicit action potentials in afferent neurons related to the kidney but even impaired electric currents in general after TRPV1 receptor stimulation. Hence, renal CGRP secretion from peptidergic afferent nerves might decrease further neuronal CGRP release.Support or Funding InformationDFG Deutsche Forschungsgemeinschaft VE 104/4‐1This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
ALTERATIONS IN THE ENDOCANNABINOID SYSTEM IN ASTROCYTES RELATED TO COMMERCIAL SWEETENER INTAKE
Authors: Aguirre‐Fuerte María , Contreras Irazú , Estrada José Antonio 
Published: June 2021

Chronic non‐communicable diseases (NCDs) have prevalence rates of up to 60% in some countries, with obesity and diabetes corresponding to the highest number of cases worldwide. Presently, non‐nutritive sweeteners are used as a therapeutic alternative for these pathologies, as well as being commonly used by the healthy population. Recent studies have shown that human health can be impacted by frequent intake of non‐nutritive sweeteners, so it is important to determine the molecular mechanisms involved. The endocannabinoid system (ECS) has gained relevance due to its roles in the regulation of homeostasis, energy metabolism and behavior, through effects on a variety of tissues, including the central nervous system (CNS). Although in the CNS these processes are governed primarily by neurons, astrocytes play an important role in their regulation by modulating neuronal function, in part through the ECS. The objective of this project is to evaluate the effect of frequent intake of non‐nutritive sweeteners on the expression of endocannabinoid CB1 receptors in astrocytes in vivo. Adult Balb/C male and female mice were supplemented with commercially available sucralose, steviol glycosides or sucrose in their drinking water, daily, for 8 weeks. After treatment, their brains and spinal cords were dissected and analyzed for CB1 expression in astrocytes by immunofluorescence. Preliminary results show increased CB1 expression in astrocytes from mice supplemented with sucralose, whereas there was a decrease in CB1 expression in astrocytes from mice supplemented with either steviol glycosides or sucrose, compared to controls without sweetener supplementation. Our results suggest the presence of alterations in CB1 expression in astrocytes related to frequent intake of commercial sweeteners, which in turn may be related to changes in feeding behavior that may be relevant to human health.Support or Funding InformationThis project is funded by grant 4320/2017/CI from the Autonomous University of the State of Mexico (UAEM).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
MASP‐3 aggregation and its blood to cerebrospinal fluid diffusion.
Authors: Padrón‐González Alexander Ariel , González‐Losada Cristobal , Lumpuy‐Castillo Jairo , Rodriguez‐Pérez Jose Alejandro , Ramos‐Robledo Alejandro , Castillo‐González William , Dorta‐Contreras Alberto Juan 
Published: June 2021

IntroducctionMASP‐3 functions are not clarified totally, in spite of that it is a regulatory protein from the lectin pathway. It can be found as complexes and its molecular weight is around 105 KDa.Materials and methodsMASP‐3 and albumin from serum and cerebrospinal fluid were quantified by immune‐enzimatic test in a 60 control group without inflammatory process. Q (cerebrospinal fluid/serum) ratio was performed. QMASP‐3 was order and its relative frequency was calculated.ResultsFrom the different inflexion points of the relative frequency was found five different molecular orders and it's identified with a same number of aggregation forms. Blood‐cerebrospinal fluid allows the protein diffusion according to it molecular size and its relationship with their molecular flow.This five aggregation forms was associated with the molecular flow of this structures throughout blood‐cerebrospinal barrier. It takes into account that the structure that diffuses more rapidly should be the 105 KDa native structure y it is possible to associate this aggregation with native multiple structures and its molecular flow.
Developmental changes in hypoglossal motoneuron morphology in neonatal rat
Authors: Williams Paul Allen , Bellinger Denise , Wilson Christopher G. 
Published: June 2021

The autonomic brainstem generates and modifies breathing rhythm by integrating inputs from chemo‐ and mechanosensors in the viscera while coordinating descending outputs from higher CNS structures. Hypoglossal motoneurons (XII MNs) receive inputs from respiratory premotor neurons in the medulla. Previous studies in rodents have demonstrated significant changes in breathing control during the first three weeks of life, with a putative sensitive period at 10 to 13 days post‐birth (P10–P13) characterized by pronounced changes in neurotransmitters, receptors, excitation‐inhibition balance, and breathing physiology [Li et al., J Physiol, 577:957–770, 2006]. However, age‐dependent morphological changes of XII MNs during the first three weeks post‐birth and especially during this sensitive period, have not been thoroughly studied. In this study, we comprehensively characterize and quantify the postnatal morphological changes in rat XII MNs. We hypothesized that morphological changes occur in XII MN morphology and arbor complexity corresponding to the functionally‐defined sensitive period observed at P10–P13. To test this hypothesis, we used innovative statistical approaches to quantify and compare developmental changes in Golgi‐Cox stained XII MNs at nine postnatal ages between P1–P21. Soma size increased ~40% from P1 to P21, with no significant change in shape. However, dendritic arborization increased in extent and complexity. Dendritic branching of developing neurons significantly increased from P1 through P13, with the greatest increase at P10–P13 based on the Sholl method. For many parameters, three age groups 1) P1–P5, 2) P7–P12, and 3) P13–P21 were used as possible windows of development. We also found that at specific ages certain parameters such as soma size and dendrite distance were non‐normally distributed. Our detailed characterization of XII MN morphological development establishes a foundation for the study and elucidation of morphological changes caused by maternal and perinatal conditions using a rigorous statistical approach.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Lipid raft uptake at diaphragm muscle axon terminals
Authors: Gonzalez Porras Maria A. , Fogarty Matthew J. , Sieck Gary C. , Mantilla Carlos B. 
Published: June 2021

Lipid rafts are structurally unique components of plasma membranes, crucial for neural development and function. The uptake and transport of lipid raft associated molecules in motor neurons is poorly characterized under normal and pathologic conditions, including advanced aging effects. Lipid rafts are particularly important for motor neurons as they shuttle cargo between peripheral and central compartments. The cholera toxin subunit B (CTB) binds the cell‐surface ganglioside GM1, which is internalized and transported via lipid rafts in motor neurons, and thus is commonly used to investigate lipid rafts. We hypothesized firstly, that axon terminal cargo loading into lipid rafts will be different across fiber types and secondly, that uptake at axon terminals is not affected by activity at the neuromuscular junction (NMJ).Ex vivo diaphragm muscle and phrenic nerve preparations from 6‐month old female and male Fischer 344 rats were harvested. Morphological analyses of pre‐ and post‐synaptic structures at the NMJ were conducted using confocal imaging of fluorescently labeled anti‐synaptophysin and alpha‐bungarotoxin, respectively. NMJs were identified at type I or IIa vs. type IIx and/or IIb fibers using validated morphological characteristics. Quantitative analyses of CTB fluorescence at each type‐identified NMJ were conducted. CTB fluorescence was identified in all NMJs, and there were no fiber type differences in CTB uptake. Phrenic nerve stimulation had no effect on any parameters of CTB uptake, consistent with the exclusive involvement of lipid rafts rather than synaptic vesicle membrane uptake. Taken together, we conclude that lipid rafts are an important constituent of axon terminal membranes, that there are no differences in lipid raft uptake across motor unit types, and that lipid raft uptake is not affected by motor unit activity.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of BDNF on Mitochondrial Morphology and Protein Expression in NSC‐34 Cells
Authors: Duffey Christopher Aaron , Nicholls Shannon , Mantilla Carlos Bernardo , Fogarty Matthew Joseph , Sieck Gary Charles 
Published: June 2021

Age related loss of larger phrenic motor neurons (PhMNs) may underlie diaphragm muscle sarcopenia. We found increased mitochondrial fragmentation in larger PhMNs, similar to that reported to be associated with motor neuron loss in amyotrophic lateral sclerosis (ALS). In rodents, we observed diminished brain‐derived neurotrophic factor (BDNF) signaling via its high affinity TrkB.FL receptor in older animals. TrkB.FL is expressed on the outer mitochondrial membrane, and in ALS models, BDNF/TrkB.FL signaling promotes motor neuron survival and mitochondrial fusion. In the present study, we hypothesized that enhancing BDNF/TrkB.FL signaling increases Mfn2 expression, thereby promoting mitochondrial fusion. Studies were conducted using a mouse motor neuron‐like cell line (NSC‐34), which were differentiated by serum depletion until neurite structures were observed. The differentiated NSC‐34 cells were treated with BDNF (12.5 ng/ml for 1 h) and then loaded with MitoTracker Green to image mitochondria using a Nikon A1R confocal microscope (60× oil immersion 1.4 NA). BDNF treatment increased both form factor and aspect ratio of mitochondria by ~ 20% and 15%, respectively, while also causing a threefold increase in expression of Mfn2, indicating mitochondrial fusion. These experiments were performed in six different trials with two replicates each. The observed relationship between BDNF/TrkB.FL signaling and mitochondrial fusion/fragmentation proteins supports our hypothesis. These results are consistent with diminished BDNF/TrkB.FL signaling underlying mitochondrial fragmentation and dysfunction in age‐related PhMN loss.Support or Funding InformationSupported by NIH grant AG44615This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.