bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thyroid hormone supplementation dampens GABAergic inhibition of the brainstem respiratory network in newborn rat
Authors: Rousseau Jean‐Philippe , Kinkead Richard 
Published: June 2021

We previously showed that thyroid hormones (THs) deficiency potentiates GABAergic inhibition in the core elements of the respiratory control circuit. To understand the underlying mechanisms, we tested the hypotheses that 1) cellular mechanisms including K+/Cl− co‐transporters contribute to the delay of GABAergic system development in TH deficient newborn rats and 2) TH supplementation following birth can reverse this enhanced inhibition. Thyroid hormone deficiency in the foetus was recreated by administrating an antithyroid susbstance (Methimazole; MMI) in drinking water of the pregnant dam at concentration of 0,02% (weight per volume; w/v) from the first day of pregnancy (gestational day 1; GD1) to the day of experiment with the newborn. TH supplementation was performed by injecting newborn rats (1 day old) intraperitoneally with Levothyroxine (L‐T4). Experiments were done on Sprague Dawley rats aged of 4 days. Protein levels of newborn co‐transporters were evaluated by western blot analysis. Each brainstem lysate samples were migrated on SDS acrylamide gel under denaturing conditions. Gel was then transferred on nitrocellulose membrane and blocked in 5% non‐fat dry milk in TBS tween. Membranes were incubated overnight with primary antibody for NKCC1 (Cell signaling) or KCC2 (Cell signaling) followed by 1h exposure to secondary antibody (Licor IRDye 800CW). Fictive breathing was measured by extracting the brainstem with a part of the spinal cord and placing it in a chamber where it was superfused with an artificial cerebrospinal fluid (aCSF). The output signal from the respiratory network was recorded by a suction electrode placed on the fourth ventral root representing the inspiratory signal sent to the diaphragm via the phrenic nerve. Brainstems were then exposed to GABAA receptor agonist (muscimol) or antagonist (bicuculline) for 20 minutes and respiratory frequency response was observed. Data show that NKCC1 and KCC2 protein expressions were similar between MMI‐treated and control groups (MMI vs Control: NKCC1 p=0.5260; KCC2 p=0.3309), but L‐T4 supplementation in TH deficient pups increased both co‐transporters protein expression (MMI/L‐T4 vs MMI: NKCC1 p=0.0044; KCC2 p<0.0001). In agreement with these results, L‐T4 supplementation decreased respiratory frequency response to muscimol in MMI‐treated pups (MMI/L‐T4 vs MMI: p<0.0001). This suggests the involvement of different mechanisms in the potentiation of GABAergic inhibition by TH deficiency with a specific action of TH supplementation on GABAergic system development. These results provide new hypotheses regarding the origins of respiratory disorders of the newborn involving reduced respiratory drive such as apnea of prematurity.Support or Funding InformationSupported by NSERCThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Consequences of Microglial Depletion on the Hypercapnic Ventilatory Response of Female Rats
Authors: Kinkead Richard , Jiao Belinda , Fournier Stéphanie , Bretzner Frédéric 
Published: June 2021

Panic disorder (PD) is a neurological disorder associated with an abnormally high hypercapnic ventilatory response. In humans and rodents, early life stress is a significant risk factor for PD. Based on recent data indicating that CO2/H+ sensing by microglia is an important mechanism in the translation of hypercapnic stimulation into physiological responses, we tested the hypothesis that depletion of microglia by pharmacological treatment can decrease the hypercapnic ventilatory response. We also proposed that this effect is greater in stressed rats than controls. The prevalence of PD being ~2 times greater in women than men, experiments were performed on female rats. Following birth, rats were either raised under control conditions or subjected to neonatal maternal separation (NMS; 3h/day, postnatal days 3 to 12). At 8 weeks, females were fed a palatable treat containing either vehicle (DMSO) or PLX3397 (40mg/kg). Treatment was performed daily for 10 consecutive days. 1 day after completion of the treatment, rats were placed in a plethysmography chamber to measure ventilatory activity at rest (room air) followed by hypercapnic exposure (FiCO2 = 0.05; 10 min). Iba‐1 immunohistochemistry was used to quantify microglial density; measurements performed in hypothalamic structures containing orexin neurons showed that PLX3397 treatment educed microglial density by 31%; this effect did not differ between the structures quantified. Furthermore, our preliminary results suggest that oestrus cycle influences the impact of microglial depletion on the CO2 response. During the estrus phase, PLX3397 attenuated the hypercapnic ventilatory response of controls but augmented the response of NMS females. These data suggest that microglia contribute to the abnormal effects that ovarian hormones exert on the neural networks regulating CO2/H+ chemoreflex respiratory regulation in NMS rats. These data provide the basis for the exploration of new treatment for respiratory manifestations of PD.Support or Funding InformationSupported by the Canadian Institutes of Health Research (RK & FB).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Spinal Adenosine 2A Receptor Activation is Necessary for Phrenic Long‐Term Facilitation in Carotid‐Denervated Rats
Authors: Perim Raphael R , Kubilis Paul S , Mitchell Gordon S 
Published: June 2021

Moderate acute intermittent hypoxia (AIH) elicits a long‐lasting increase in phrenic nerve activity, known as phrenic long‐term facilitation (pLTF). pLTF was originally demonstrated by intermittent electrical carotid sinus nerve stimulation, highlighting the pivotal role of carotid chemoafferent neurons in this form of respiratory motor plasticity. Surprisingly, there is still some residual pLTF after carotid body denervation (CBX) through unknown mechanisms. Carotid body‐dependent, serotonin 2 receptor‐induced pLTF is not expected after CBX; thus, a distinct mechanism must account for residual pLTF. Greater hypoxia‐induced hypotension after CBX might further reduce spinal tissue PO2 more during each hypoxic episode, potentially inducing pLTF via an alternate adenosine‐dependent mechanism. Thus, we tested the hypothesis that adenosine 2A (A2A) receptor activation underlies residual pLTF after CBX. Phrenic nerve activity and spinal tissue PO2 were measured in vivo during our standard pLTF protocol in urethane anesthetized, male Sprague Dawley rats. The contribution of severe hypoxic hypotension to residual pLTF after CBX was evaluated by preventing the arterial pressure drop during hypoxic episodes via systemic phenylephrine administration. We demonstrate that severe hypoxia‐induced hypotension diminishes spinal tissue oxygenation (at the same arterial PO2) during hypoxic episodes to an extent sufficient to trigger residual pLTF. Preventing hypoxia‐induced hypotension minimizes tissue hypoxia, and residual pLTF is no longer observed. Spinal A2A receptor (MSX‐3; 12 μL, 10 μM), but not a serotonin 2A receptor (Ketanserin, 500 μM, 15 μL), antagonist abolishes residual pLTF after CBX. We conclude that differences in arterial blood pressure regulation impact expression and mechanisms of phrenic motor plasticity, a finding of importance for conditions characterized by hypotension such as anemia or spinal injury, where sympathetic outflow is disrupted by injury.Support or Funding InformationSupported by: NIH Grants HL69064, SPARC and University of Florida McKnight Brain InstituteThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Respiratory Plasticity in Adult Rats after Exposure to Chronic Hyperoxia
Authors: Pratt Ashley E , Bavis Ryan W 
Published: June 2021

Neonatal rats reared in moderate hyperoxia (60% O2) from birth hypoventilate when acutely returned to room air (e.g., Bavis et al., Respir. Physiol. Neurobiol. 198: 1–12, 2014); this hypoventilation reflects reductions in both respiratory frequency and tidal volume. Since many forms of respiratory plasticity are specific to development, we questioned whether chronic hyperoxia would have similar effects on normoxic ventilation in adult rats. Adult Sprague‐Dawley rats (3–5 months old) were randomly assigned to Control (chronic 21% O2; n=11) or Hyperoxia (chronic 60% O2; n=10) treatment groups. Normoxic ventilation was measured by whole‐body plethysmography prior to exposure, after 4 and 14 days of exposure, and after 4 days of recovery in room air. Chronic hyperoxia altered minute ventilation in adult rats (Treatment × Day, P=0.002), but surprisingly this effect was not apparent during the hyperoxic exposure itself. Instead, Hyperoxia rats exhibited a modest increase in normoxic ventilation when measured during the recovery period (39±2 vs. 33±1 ml min−1 100g−1; P=0.003). Tidal volumes and respiratory frequencies were similar between groups before and during the chronic exposures, but Hyperoxia rats exhibited greater tidal volumes and respiratory frequencies during the recovery period (Treatment × Day, P=0.047 and 0.038, respectively). Neither metabolism nor blood gases were measured during these experiments, so it is unclear whether the increase in ventilation constitutes a true hyperventilation. We conclude that the effects of chronic hyperoxia on normoxic ventilation are age‐specific.Support or Funding InformationSupported by NIH grant P20 GM‐103423 (Maine INBRE).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Acute and chronic changes in the control of breathing in a hyperoxia‐induced model of bronchopulmonary dysplasia
Authors: Mouradian Gary C , Argote‐Alvarez Santiago , Gorzek Ryan , Thuku Gabriel , Michalkiewicz Teresa , Wong‐Riley Margaret , Konduri Girija Ganesh , Hodges Matthew R 
Published: June 2021

Infants born very prematurely (<28 weeks gestation) have immature lungs and often require supplemental oxygen. However, long‐term hyperoxia exposure can arrest lung development leading to bronchopulmonary dysplasia (BPD), which increases acute and long‐term respiratory morbidity and mortality. The neural mechanisms controlling breathing are highly plastic during development. Whether the ventilatory control system adapts to pulmonary disease associated with hyperoxia exposure in infancy remains unclear. Here, we tested the hypothesis that there would be age‐dependent adaptations in the control of breathing in an established rat model of hyperoxia‐induced BPD. Hyperoxia exposure (FIO2: 0.9 from 0–10 days of life) led to a BPD‐like lung phenotype, including sustained reductions in alveolar surface area and counts, and modest increases in airway resistance. Hyperoxia exposure also led to chronic increases in room air and acute hypoxic minute ventilation (VE) and age‐dependent changes in breath‐to‐breath tidal volume and breathing frequency variability. Hyperoxia‐exposed rats had normal hypoxic ventilatory responses, oxygen saturation (SpO2) in room air, but greater reductions in SpO2 during acute hypoxia (12% O2) indicating reduced hypoxic sensitivity and/or hypoventilation due to diseased lungs. However, VE was increased indicating an increase in respiratory drive. Perinatal hyperoxia led to greater glial fibrillary acidic protein expression and an increase in neuron counts within 6 of 8 and 1 of 8 key brainstem regions controlling breathing, respectively, suggesting astrocytic expansion. In conclusion, perinatal hyperoxia in rats induced a BPD‐like phenotype and age‐dependent adaptations in VE that may be mediated through changes to the neural architecture of the ventilatory control system. Our results suggest chronically altered ventilatory control in BPD.Support or Funding InformationChildren's Research Hospital of Wisconsin Research Institute, NIH R01 HL 122358, & Parker B. Francis FoundationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Changes in keyboard typing accuracy and spatial perception after cardiovascular fitness exercise
Authors: Moon Myeonggon , Hong Yonggeun 
Published: June 2021

This study aimed to identify the association between cardiopulmonary exercise and neurological activation through measuring dictation accuracy and the extent of spatial perception. First of all, body composition of subjects were analyzed to verify their physical intactness. Then the subjects were given treadmill exercise using modified Bruce protocol. Before and after the treadmill exercise, spatial perception test and dictation task with auditory and visual stimulation were carried out to identify the changes in neurological activation. The Scores of spatial perception after treadmill exercise were higher than those before treadmill exercise (p <0.05). The accuracy of post‐treadmill dictation task with auditory stimulation was decreased compared to that of pre‐treadmill dictation task. Likewise, accuracy of post‐treadmill dictation task with visual stimulation was significantly decreased compared to that of pre‐treadmill dictation task (p <0.05). However, speed of post‐treadmill dictation task with visual stimulation was significantly increased compared to that of pre‐treadmill dictation task (p <0.05). In this study, typing accuracy and spatial perception were assessed to identify alteration of neurological activation following treadmill exercise. Unlike improved spatial perception, typing accuracy was reduced due interference of upper body motions with arm stability during treadmill exercise. In this study, spatial perception and speed of visual dictation was increased. Therefore, cardiovascular fitness exercise was proved to increase neurological activation by accelerating typing speed and spatial perception.Support or Funding InformationNRF‐2017R1A2A2A01067169, KGM4611821, 2016 Creative Research Program of Inje University, Republic of KoreaThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Positive Reinforcement as a Method to Encourage Behavioral Modification
Authors: Landry Elizabeth 
Published: June 2021

This research was conducted at a mental health institute in Chattanooga, TN to determine the efficacy of positive reinforcement through a hospital‐wide, weekly television broadcast on behavioral outbursts, communication, and patient confidence. A weekly broadcast written, filmed, and hosted by patients is the means of positive reinforcement. This broadcast includes segments such as patient spotlights for exceptional behaviors or acts of kindness, staff spotlights, patient talent segments, and a congratulations for the patients successfully discharging. The hypothesis is when given more responsibility and more praise for good behaviors the behavioral outburst of the patients will decrease, and their ability to effectively communicate and work as a team will increase. According to patient feedback, there is an increase in morale, confidence, and a constant encouragement for good behavior. Additionally, patients from outside of the broadcast team have noted that seeing their peers is encouraging and inspiring for them, and the patient spotlight section is an encouragement for them to strive to go to the extra mile in their daily activities. This research is based on a model from the AIMS Center in Chattanooga, TN, and seeks to better understand how to actively involve patients in their treatment process in an effective and constructive way.Support or Funding InformationNoneThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Neural activity and network during cognitive tasks in heat‐stressed individuals
Authors: Kobayashi Fumino , Nakata Hiroki , Shibasaki Manabu 
Published: June 2021

Reductions in cerebral blood flow accompanying heat stress‐induced hypocapnia via hyperventilation are likely to decrease the cognitive function, but the mechanism remains unknown. Using electroencephalographic event‐related potentials (EEG‐ERP) and functional magnetic resonance imaging (fMRI), we evaluated temporal (EEG) and spatial (fMRI) characteristics during cognitive tasks in heat‐stressed humans. Healthy young volunteers performed a visual cognitive task (Go/No‐go task) before (i.e., normothermia) and during heat stress on separate days. The external canal temperature during heat stress was increased by ~ 1.1°C from the normothermic condition. Decreased cerebral blood flow during heat stress was confirmed by reductions in middle cerebral artery blood velocity (MCAV) and internal carotid blood flow in the EEG‐ERP trial. The amplitudes of the Go‐P300 (i.e., execution) and No‐go‐P300 (i.e., inhibition) components were decreased during heat stress. In the fMRI trial, we observed broadly activated brain regions, including the dorsolateral and ventrolateral prefrontal cortices, and motor‐related areas such as the supplementary motor area and premotor area during heat stress rather than during normothermia. These results suggest that heat stress increases the load of neural activity while performing cognitive tasks, relative to normothermia, while heat stress reduced cerebral blood flow and neural activity.Support or Funding InformationJSPS KAKENHI 18H03166This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cross‐Sensitization to Binge Alcohol Intake Following Binge Intake of Palatable Diets
Authors: Coker Caitlin Rae , Aguilar Elizabeth , Silberman Yuval 
Published: June 2021

Obesity and alcoholism, two of the most common chronic conditions in the United States, may be behaviorally linked as binge intake of palatable diets, such as diets high in fat (HFD), and binge alcohol (EtOH) intake may utilize similar neurocircuitry. We hypothesized that binge intake of one modality (i.e. HFD) may sensitize the shared neurocircuitry to further activation by another modality (i.e. EtOH). Therefore, we combined a binge HFD intake model in mice where HFD access is limited to one 24hr session per week (Limited Access HFD: LAH) with a patterned EtOH access schedule that also promotes binge‐like intake in a two‐bottle choice model (Limited Access EtOH: LAE; 4hrs/day, 4days/wk). Control mice were given the same EtOH access schedule but were given continuous ad libitum access to HFD (60% calories from fat) or control Chow diet (10% calories from fat). Six‐week old male C57Bl/6J mice were weight matched, individually housed, and assigned to HFD+LAE, Chow+LAE, or LAH+LAE groups (n=10 per group). All groups of mice were given increasing EtOH concentrations over the course of the study (10% EtOH for three weeks, 15% EtOH for two weeks, and 20% EtOH for two weeks). Body mass was measured daily while EtOH/water intake and EtOH preference were assessed after every drinking session. Over the course of the study, HFD+LAE mice gained significantly more weight than Chow+LAE or LAH+LAE mice (p=0.001; one‐way ANOVA). While weight gain was predominantly linear in HFD+LAE and Chow+LAE mice, LAH+LAE mice showed weight cycling indicating a binge‐like eating pattern. LAH+LAE mice consumed significantly more EtOH than Chow+LAE or HFD+LAE mice (p=0.001, repeated measures two‐way ANOVA), suggesting that binge intake of HFD led to increased binge EtOH intake patterns in LAH mice. LAH+LAE and Chow+LAE mice showed higher preference towards EtOH than HFD+LAE mice (p=0.001, repeated measures two‐way ANOVA). Together, these results suggest limited access to palatable diets induce binge‐like eating patterns that further cross‐sensitize to binge alcohol intake and mitigates the loss of alcohol preference in mice given continuous HFD.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Central Amygdala Angiotensin Type 2 Receptor (AT2R) Activation Reduces Fear‐Related Behavior
Authors: Yu Zhe , Swiercz Adam P. , Krause Eric G. , Marvar Paul J. 
Published: June 2021

BackgroundPrevious retrospective clinical studies identify the renin‐angiotensin system (RAS) as a potential therapeutic target in post‐traumatic stress disorder (PTSD), however the mechanisms are unknown. We propose that brain RAS modulates inhibitory and excitatory fear circuits critical to the consolidation and extinction of fear memory in PTSD.MethodsUsing the angiotensin type 2‐receptor (AT2R)‐eGFP‐BAC reporter mouse combined with pharmacological and behavioral approaches, the aim of the study was to examine the role of the brain AT2R in fear memory.ResultsAT2R‐eGFP+ immunoreactive cells co‐localized with the neuronal specific marker NeuN and were expressed in major subnuclei of the amygdala. They were predominately observed in the medial amygdala (203.8 ± 39.4 cells/mm2) and the medial division of central amygdala (CeM) (224.7 ± 9.4 cells/mm2), while the basolateral amygdala (11.7 ± 1.8 cells/mm2) and lateral division of central amygdala (CeL) (3.2 ± 0.8 cells/mm2) contained minimal to no AT2R‐eGFP expression (Fig. 1). Within the CeM, 96% of the AT2R‐eGFP+ neurons expressed the GABAergic marker GAD1, while approximately 17% GABAergic AT2R‐eGFP+ cells expressed interneuron markers, suggesting the remaining may be GABAergic projection neurons. Moreover, these AT2R‐eGFP+ neurons were negative for the CeL marker PKC‐β. In C57Bl/6 mice, we used cue‐dependent and context‐dependent fear conditioning to examine the behavioral role of AT2R in fear memory. Twenty‐four hours after fear conditioning, bilateral intra‐CeA injection of the AT2R agonist C21 (0.06ug/ul) was administered and mice were exposed to the conditioned cue (30 second auditory tones) or context. Fear expression was quantified by percentage of freezing during cue stimuli or the context exposure. Compared to vehicle controls, mice receiving C21 into the CeA displayed a decreased freezing response to both the cue (61.7% ± 5.4 vehicle vs 42.1% ± 5.7 C21 group, p<0.05, n=10–12) and the context (64.6% ± 4.4 vehicle vs 48.3% ± 3.7 C21 group, p<0.05, n=16–17), indicating reduced fear expression (Fig. 2). These behavioral effects were also independent of generalized anxiety‐like behavior as determined by open‐field and EPM testing.ConclusionThese findings suggest that CeM AT2R‐expressing neurons can modulate CeA outputs that play a role in fear expression and provide evidence for a novel angiotensinergic circuit in the regulation of fear.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.