bluuebunny/crossref_metadata_2025_split huggingface dataset:
PVN neuropeptide neurons may modulate nTS activation and cardiorespiratory responses to peripheral chemoreflex stimulation
Authors: Ruyle Brian C , Heesch Cheryl M , Hasser Eileen M 
Published: November 2023

The paraventricular nucleus of the hypothalamus (PVN) is required for full expression of cardiorespiratory responses evoked by peripheral chemoreflex stimulation, but the efferent pathways have not been fully elucidated. We previously reported that hypoxia activates (Fos‐immunoreactivity; IR) PVN neurons that project to the nucleus tractus solitarii (nTS). The majority of hypoxia‐activated nTS‐projecting neurons are CRH‐IR. These findings suggest that the PVN may influence chemoreflex‐evoked cardiorespiratory function via CRH actions in the nTS. CRFR2 is the predominant CRH receptor in the nTS. Previous studies indicate that selective activation of nTS CRFR2s produces cardiovascular responses consistent with excitation. CRFR2 co‐localizes extensively with oxytocin‐IR fibers, likely from the PVN, and nTS oxytocin enhances baroreflex function. We hypothesized that interactions between PVN neuropeptide neurons, including CRH binding to CRFR2s located on oxytocin fibers, modulates nTS neuronal activation and thus may augment cardiorespiratory responses to peripheral chemoreflex stimulation. An AAV viral vector expressing mCherry under the CAMKII promoter was injected into the PVN, and mCherry‐expressing fibers were evaluated in the nTS. Immunohistochemical evaluation revealed that mCherry‐expressing fibers formed close appositions with nTS neurons (indicated by HUC/D‐IR), including neurons activated by acute hypoxia (2 hr 10% O2). These findings suggest that PVN inputs to the nTS may modulate the activation of nTS neurons that respond to hypoxia. A separate group of animals received bilateral injections of the retrograde tracer CTB into either the PVN or the RVLM. Immunohistochemistry examined the extent to which CRFR2 fibers contact CTB‐labeled neurons in the nTS. CRFR2 fibers made close appositions with specific populations of nTS neurons activated by acute hypoxia, including catecholaminergic (tyrosine hydroxylase, TH‐IR), RVLM‐projecting and PVN‐projecting cells. Together, these data suggest that PVN neuropeptide projections to the nTS may modulate the activation of subpopulations of nTS neurons in response to hypoxia. We suggest that PVN neuropeptide neurons projecting to the nTS may shape the cardiorespiratory responses evoked by peripheral chemoreflex stimulation. Future in vivo experiments will determine the physiological relevance of PVN neuropeptide projections to the nTS, including the extent to which nTS CRH and/or oxytocin influence basal and chemoreflex‐evoked cardiorespiratory output.Support or Funding InformationNIH RO1 HL98602
Blockade of Brain Sodium Channels or Electroneutral Transporters Attenuates the Hypertensive Response to Central NaCl Stimulation
Authors: King Jesse L , Kinsman Brian J , Stocker Sean D 
Published: November 2023

Accumulating evidence suggests excess dietary salt intake elevates plasma or cerebrospinal fluid NaCl concentrations to increase sympathetic nerve activity (SNA) and arterial blood pressure (ABP) in salt‐sensitive hypertension. Both acute and chronic infusion of hypertonic NaCl into the lateral cerebral ventricle produces a sympathetically mediated increase in ABP that depends on the integrity of forebrain hypothalamic structures that contain NaCl‐sensing neurons. However, the mechanism by which these neurons detect changes in NaCl concentrations to alter ABP is not known; however, there are two possibilities. First, prior studies have suggested that the epithelial sodium channel (ENaC) mediates central pressor actions of hypertonic NaCl. Second, electroneutral transporters are expressed in hypothalamic regions involved in body fluid homeostasis including vasopressin neuroendocrine neurons. Thus, the purpose of this study was to test the hypothesis that the ENaC or electroneutral transporters mediate the hypertensive effect of central NaCl. This hypothesis was tested by pharmacological blockade of ENaC or electroneutral transporters via pretreatment with central infusion of benzamil or furosemide, respectively. At least 3 days before experiments, Male Sprague‐Dawley rats (300–450g) were anesthetized with isoflurane and instrumented with a femoral arterial catheter and intracerebroventicular (ICV) brain cannula to measure ABP and infuse drugs, respectively. On the day of the experiment, rats were pretreated with aCSF (2μL per 1 min), benzamil (5nmol) or furosemide (10 nmol) through an ICV infusion at 10 min before a second ICV infusion of 0.5M NaCl (5μL per 10 min). ICV infusion of 0.5M NaCl in aCSF‐treated rats produced a significant increase in mean ABP (Δ9±1 mmHg, n=10; P<0.01) but not heart rate (Δ−6±10 bpm, n=10). Pretreatment with the ENaC antagonist benzamil attenuated the pressor response (Δ3±1 mmHg, n=7; P<0.01) and decreased heart rate (Δ−17±5 bpm, n=7; P<0.05). Interestingly, pretreatment of the electroneutral transporter antagonist furosemide completely attenuated the pressor (Δ−1±1 mmHg, n=6, P<0.01) and tachycardic (Δ−11±7 bpm, n=6; P<0.05) response to ICV infusion of 0.5M NaCl. ICV infusion of furosemide alone did not alter baseline ABP (Δ1±1 mmHg, n=3; P<0.05) or heart rate (Δ12±7 bpm, n=3; P<0.05). These findings suggest that ENaC and electroneutral transporters play a critical role in sympathetic activation and pressor effect during central NaCl stimulation.Support or Funding InformationAHA Established Investigator Award (SDS), NIH R01 HL113270, AHA Predoctoral Fellowship (BJK), and NIH F30 HL131269 (BJK)
The Effects of Imidacloprid on Danio rerio (Zebrafish) Ocular and Osteological Development
Authors: Babcock Hailey , Cochran Kelly , Daggett Melissa A. F. 
Published: November 2023

Imidacloprid is a common insecticide that acts as a neurotoxin. The application of this pesticide may have long‐term effects on ecosystems, especially aquatic biomes. Imidacloprid has a lower toxicity to mammals, but neurotoxic effects have been recorded in zebrafish (Danio rerio). The purpose of this study was to determine the potential neurological and osteological effects of imidacloprid on zebrafish ocular and osteological development. Ocular diameters and ceratohyal cartilage lengths were expected to decrease with increasing imidacloprid concentration. Zebrafish embryos were treated with a low‐dose (LD) or high‐dose (HD) of imidacloprid starting at 24 hours post‐fertilization. After seven days, a relationship was seen between imidacloprid concentration and 1) ocular diameter and 2) ceratohyal cartilage lengths. Imidacloprid exposure delayed both ocular and osteological development during embryonic development in zebrafish.Support or Funding InformationMissouri Western State University
Alterations of a Nigro‐Vagal Pathway in a Rodent Model of Parkinson's Disease
Authors: Hampton Jessica , Anselmi Laura , Travagli R. Alberto 
Published: November 2023

Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive motor impairment resulting from the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Prodromal to the classic motor symptoms, a majority of PD patients experience gastrointestinal (GI) dysfunction such as reduced gastric motility, dysphagia, and severe constipation. Upper GI tract functions are modulated by vago‐vagal reflexes originating in the dorsal vagal complex (DVC) of the brainstem. We have recently described a novel nigro‐vagal connection that, when activated in response to NMDA microinjections in the SNpc, increases gastric tone and motility via vagal brainstem pathways.The aim of the present study was to elucidate the functions of the nigro‐vagal connection in a rodent model of Parkinson's disease.Male Sprague Dawley rats received 3 once‐weekly intraperitoneal injections of 10mg/kg paraquat (10P, n=4) or saline (control, n=3). Motor function was assessed following the second and third injections, as well as 2 weeks after the end of treatment.Two‐four weeks after the end of treatment, rats were anesthetized and gastric motility and tone were recorded via strain gauges surgically affixed to the anterior corpus and antrum of the stomach. Modulation of gastric activity via the nigro‐vagal pathway and by direct vagal pathways was assessed upon microinjection of NMDA (5.25 nmoles/210nl) in the SNpc and thyrotropin‐releasing‐hormone (TRH; 1‐3‐10pmol/60nl) in the DVC, respectively. Rats were then perfused‐fixed and the stomachs were collected for analysis of the neurochemical phenotype of SNpc, DVC and myenteric plexus neurons.Rats treated with paraquat showed a significant motor impairment compared to controls (stepping test, p<0.05). Moreover immunohistochemistry results showed presence of misfolded α‐synuclein (a hallmark for PD) in DVC and SNpc, confirming the validity of the PD model used in the present study. The gastric motility response to NMDA microinjection in the SNpc was decreased (p<0.05), while gastric responses to microinjections of TRH in the DVC were not significantly reduced. NOS immunoreactivity in myenteric plexus neurons was similar across all groups, suggesting that changes in gastric responses were likely due to alterations in the nigro‐vagal pathway, rather than alterations in neurochemical phenotype of the gastric myenteric neurons.These data indicate that the nigro‐vagal pathway is compromised in an established rodent model of Parkinson's disease, offering further insight into the etiology and neuropathophysiology of Parkinson's disease.Support or Funding InformationNIH DK 55530
Brain Region Specific Association of Microtubule‐Associated Protein 2 with Inflammatory and Growth Factor Gene Expression
Authors: Maxi John , Oberhelman Sarah , Mercante Donald E , Bagby Gregory J , Nelson Steve , Molina Patricia 
Published: November 2023

Microtubule‐associated protein 2 (MAP2) expression is directly correlated with neurocognitive impairment in subjects with HIV‐associated neurocognitive disorder (HAND). Our previous microarray analysis of hippocampal tissue, identified alterations in immune response and neurogenesis as potential mechanisms contributing to cognitive deficits in chronic binge alcohol (CBA)‐administered, simian immunodeficiency virus (SIV)‐infected macaques. The aim of this study was to determine whether expression of inflammatory genes and growth factor genes were associated with differential MAP2 expression in brain regions associated with HAND. Adult, male rhesus macaques were fitted with intra‐gastric catheters for chronic binge alcohol (CBA, 13–14 g EtOH/kg/week, n = 8) or sucrose (SUC, n = 7) administration beginning three months prior to SIV infection and continuing through the duration of the study until animals reached end‐stage disease criteria (range from 3 to 24 months post‐inoculation). Following euthanasia, brains were excised and pre‐frontal cortex (PFC), caudate (CD), and hippocampus (HP) tissue were isolated and used for qPCR quantification of inflammatory and growth factor genes, and viral loads. We utilized R statistical software to build regression models using the all‐subsets technique with gene expression, viral load, CBA, and time to end‐stage as predictor variables for MAP2 expression. In the PFC, growth factors BDNF and IGFBP5, along with time to end‐stage by CBA interaction were significantly associated with MAP2 expression. In the CD, growth factors IGFBP5 and MAPK1, inflammatory cytokines ISG15, IL6, and TNF, and time to end‐stage were significantly associated with MAP2 expression. In the HP, the growth factor MAPK1, inflammatory cytokine IL6, and brain viral load were significantly associated with MAP2 expression. These results indicate brain region specific relationships between growth factor and inflammatory cytokine expression with MAP2, a molecular marker of cognitive impairment. PFC MAP2 associated with growth factors and showed greater susceptibility to an alcohol‐SIV interaction. In the subcortical structures, CD and HP, MAP2 expression associated with inflammation. Different treatments may be necessary for HAND subjects with cortical compared to subcortical cognitive impairments.Support or Funding InformationP60AA09803, T32AA07577, F31AA024365
Highly palatable food during adolescence and youth increased anxiety‐/depression‐like behaviors in males, but not in females
Authors: Jahng Jeong Won , Kim Jin Young , Lee Jong‐Ho 
Published: November 2023

This study was conducted to examine sexual dimorphic effects of highly palatable food access during adolescence and youth on psycho‐emotional behaviors of rats and its underlying neural mechanism. Male and female Sprague‐Dawley pups had free access to chocolate cookie rich in fat (highly palatable food) from postnatal day 28 in addition to ad libitum chow, and the control groups received chow only. The food conditions were continued though out the entire experimental period, and the neurochemical and behavioral measurements were performed during young adulthood. Corticosterone levels during 2 h of restraint stress were analyzed with radioimmunoassay, and ΔFosB and brain‐derived neurotrophic factor (BDNF) expression in the nucleus accumbens (NAc) with Western blot analysis. Cookie access did not affect body weight gain and total caloric intake in both sexes; however, it increased retroperitoneal fat depot only in males. The time spent in open arms during elevated plus maze test was decreased and immobility during forced swim test was increased in cookie‐fed males, but not in cookie‐fed females. Main effect of food condition on the stress‐induced corticosterone increase was observed in males, but not in females, and cookie access increased BDNF expression in the NAc only in males. Increased BDNF expression in the NAc and fat depot, in addition to the stress axis dysfunction, may play roles in the pathophysiology of depression‐ and/or anxiety‐like behaviors induced by cookie access.Support or Funding InformationSupported by a grant from the Oromaxillofacial Dysfunction Research Center for the Elderly at Seoul National University in Korea (2015048003) funded by the Ministry of Science, ICT and future Planning
Liposomal miR‐29b Delivery Attenuates Increased Expression of Matrix Proteins and Improves Alveolarization in Mice Exposed to Maternal Inflammation and Neonatal Hyperoxia
Authors: Sugar Sophia S , Heyob Kathryn M , Tipple Trent E , Rogers Lynette K 
Published: November 2023

BackgroundChronic lung disease or bronchopulmonary dysplasia (BPD) continues to be a significant pulmonary complication for preterm infants. In addition to decreased alveolarization, these infants can develop obstructive and/or restrictive lung function due to increases in or dysregulation of extracellular matrix proteins. Our mouse model mimics the pathophysiology observed in infants with severe BPD and we have previously reported decreased pulmonary miR‐29b expression in this model. The current studies tested the hypothesis that liposomal mediated restoration of miR‐29b in the developing lung will improve lung alveolarization and minimize the pulmonary fibrosis.MethodsMiR‐29 levels were measured in the plasma of preterm infants by PCR. Pregnant C3H/HeN mice received an intraperitoneal LPS injection on E16 and newborn pups were exposed in 85% oxygen from birth to 14 days of life. On postnatal day 3, PBS containing a liposomal preparation of miR‐29b or an empty liposome was administered intranasally. On postnatal day 14 or 28, mouse lung tissues were analyzed for changes in miR‐29 expression, alveolarization, and matrix protein expression.ResultsAnalyses of plasma obtained from preterm infants during the first week of life indicate that circulating miR‐29b levels are suppressed and the levels are inversely correlated to severity in infants later diagnosed with BPD. In our mouse model, modest improvements in alveolarization were detected in the miR‐29b‐treated mice. MiR‐29b treatment completely attenuated the LPS/O2‐associated increases in aSMA, MMP‐9, and SMAD 2/3 and restored PDGFa levels in lung tissues.ConclusionOur data suggest that miR‐29b restoration may represent a novel therapeutic strategy to treat or prevent severe BPD in prematurely born infants.
Maternal High Fat Diet Causes Decreased Alveolarization and Persistent Pulmonary Inflammation in the Offspring
Authors: Heyob Kathryn M , Trask Aaron J , Thompson Michael , Rogers Lynette K 
Published: November 2023

BackgroundThe incidence of asthma and obesity continue to rise throughout the world. Past research has shown that obesity can cause numerous complications in asthma patients, including increased severity of symptoms, treatment non‐responsiveness, and required increased dosage of treatments. In addition, maternal obesity has been associated with multiple complications for both the mother and the child, including hypertensive disorders and gestational diabetes for the mother, and macrosomia and congenital abnormalities for the child.We tested the hypothesis that maternal obesity would impair lung growth through the presence of a persistent inflammatory state.MethodsFemale mice were fed high fat diets (HFD) or control diets (CD) for 8 weeks prior to mating and through weaning. Mouse pups were sacrificed at 21 days for inflammation analysis using PCR and western blot. An additional group of mouse pups were placed on CD at weaning and maintained on CD until sacrifice at 3 months. Lungs were inflation fixed and morphometric analyses were performed on H&E stained tissue sections.ResultsAt 3 months, mice exposed to maternal HFD had fewer and larger alveoli than mice exposed to maternal CD. At 21 days, no differences were observed in IL‐6, IL‐5, TNF‐alpha gene expression in lung tissues. There were also no significant differences found in pSMAD 2/3 or IkBa protein levels. There were significantly lower protein levels of p65 and IKKb in HFD mice.ConclusionsMaternal HFD results in decreases in alveolariztion in the offspring. Inflammatory responses and changes in matrix regulation are not evident at 21 days but ongoing chronic inflammation was observed.
Postnatal Growth Restriction Alters Lung Function and Structure In Juvenile Rats
Authors: Ballard Craig R , Zhou James , Zuspan Katie , Rebentisch Andrew , Wang Haimei , Joss‐Moore Lisa 
Published: November 2023

BackgroundPreterm infants receiving respiratory support often experience extrauterine growth restriction (EUGR). EUGR in preterm infants occurs secondary to feeding intolerance and clinically indicated feeding volume restrictions. EUGR increases the severity and incidence of the chronic lung disease of infancy, bronchopulmonary dysplasia (BPD). BPD is characterized by impaired lung development, with decreased lung compliance, and increased lung resistance. Animal models demonstrate the importance of EUGR to lung development in the context of respiratory support. However, the isolated contribution of EUGR to lung development and function is unknown. We hypothesize that, in the juvenile rats, EUGR will impair alveolar development, decrease lung compliance, and increase lung resistance.MethodsWe induced EUGR in a rat model by cross fostering newborn rat pups to rat dams with litter sizes of 16 (EUGR) or 8 (control). Rat pup weight was measured every other day from birth to day of life 21 (d21). At postnatal d24, we measured alveolar wall thickness, second crest septal volume, and radial alveolar count (RAC) using ImageQuant software. At postnatal d24 we also measured lung compliance and resistance of the parenchyma (RPar) and airway (RAir) using a Flexivent System.ResultsResults are EUGR values as a percentage of control±SD (*=p<0.05). Rat pups in the EUGR group weighed significantly less (75±3%*) than control by postnatal d5 and continued to weigh less through d21 (70±5%*). Structural analysis of rat lungs revealed that EUGR rats had thicker alveolar walls than control in male (136±20%*) and female (134±32%*) rats, but no change in sepal density or RAC. EUGR decreased compliance in male (67±26%*) and female (66±25%*) rats. EUGR significantly increased RPar in both male (153±70%*) and female (157±56%*) rats and significantly increased RAir in male (111±25%*) and female (166±148%*) rats.ConclusionEUGR alters lung structure and function in juvenile rats. Given the role of elastin and elastic fiber formation in lung structure and function, we speculate that EUGR may disrupt elastin expression and fiber deposition. Ongoing studies are evaluating expression of elastin isoforms in the EUGR lung.Support or Funding InformationSpecial thanks to the American Physiological Society for the Undergraduate Summer Research Fellowship that funded this research, and to Lisa Joss‐Moore and the University of Utah for hosting me in their lab. In addition, thanks you to James Zhou and Haimei Wang for help with collection of mechanics data, as well as Katie Zuspan and Andrew Rebentisch for conducting image analysis for structural data.
Diaphragm and Intercostal Muscle Activity following Unilateral Mid‐cervical Spinal Cord Contusion in the Rat
Authors: Wen Ming‐Han , Lee Kun‐Ze 
Published: November 2023

The present study was designed to investigate the diaphragm and intercostal muscle activity following unilateral mid‐cervical spinal cord contusion in rats. Adult male rats were received laminectomy or unilateral contusion at C3–C4 spinal cord using the MASCIS Impactor (height: 6.25 mm). The respiratory airflow and bilateral diaphragm and T2 intercostal muscle electromyogram (EMG) activity were measured during hyperoxia (50 % O2 and 50 % N2) and hypoxia (12.5 % O2) at 3 day, 2 weeks and 8 weeks following spinal surgery. The respiratory frequency was similar between uninjured and contused animals; however, the tidal volume was significant lower in contused animals than uninjured animals at three time points post‐injury. At 3 days post‐injury, the burst amplitude of the contralateral diaphragm EMG was enhanced in contused animals. When the data were normalized by the maximal response during the hypoxic challenge, the ipsilateral diaphragm EMG value of contused animals was greater than that of uninjured animalsat 3 days and 2 weeks post‐injury. At 8 weeks post‐injury, there were no significant differences in the diaphragm EMG activity between uninjured and contused animals. Notably, the intercostal muscle activity was not substantially influenced by mid‐cervical contusion from acute to chronic injury state. These results suggested that mid‐cervical spinal contusion induced a compensatory increase in contralateral diaphragmatic activity and resulted in greater utilization of percentage of maximal inspiratory activity of the ipsilateral diaphragm. The maintenance of intercostal activity may enable the animal to sustain the essential breathing capacity following injury.Support or Funding InformationNHRI‐EX105‐10223NC, MOST 105‐2628‐B‐110‐002‐MY3