bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decrease in afferent evoked glutamate release in the rat NTS in chronic heart failure
Authors: Mastitskaya Svetlana , Gourine Alexander , Ramage Andrew G 
Published: November 2023

Homeostatic mechanisms maintain arterial blood pressure, blood volume and arterial blood gases within a narrow physiological range. One of the important sites in the brain involved in this regulation is the nucleus tractus solitarii (NTS) which receives afferent information from baroreceptors, cardiopulmonary and chemoreceptors. The major transmitter involved is considered to be glutamate (Baude et al 2009, J Chem Neuroanat 38, 145–153), which is released into the NTS when these cardiovascular/visceral afferents are activated. The present study was carried to determine if this release of glutamate from cardiovascular afferents can be detected using glutamate biosensors (Sarissaprobes®) and whether it is altered in heart failure. Heart failure was induced under anaesthesia by ligation of the coronary artery (Pfeffer et al., 1979, Circ Res. 44:503–512). Rats with chronic heart failure (5–6 weeks post‐infarction; infarct size between 30–40 %) or sham‐operated were then anaesthetized with α‐chloralose (100 mg/kg; i.v), neuromuscular blocked and artificially ventilated and the biosensor placed in the NTS. Cardiopulmonary afferents were activated by phenylbiguanide (PBG; 20μg per animal i.a.) and the depressor reflex (baroreceptor activation) by i.v. injection of norepinephrine (0.5 μg/kg). Cardiopulmonary and depressor reflex activation in sham‐operated rats caused a detected release of glutamate in the NTS of 2.6 ± 0.8 μM (n=10) and 1.1 ± 0.2 μM (n=10) respectively. In the case of cardiopulmonary reflex, this was associated with a decrease in MAP of 42 ± 7 mmHg and HR of 99 ± 20 bpm, while for the depressor reflex there was an increase in MAP of 37 ± 5 mmHg and a decrease in HR of 21 ± 8 bpm. In rats with heart failure, although there was no significant difference in the cardiovascular effects caused by activation of these reflexes, the amount of glutamate detected was significantly (P<0.001) reduced to 0.5 ± 0.3 μM (n=6) and 0.2 ± 0.1 μM (n=6) respectively. Resting MAP and HR were similar in both groups. Thus in heart failure there is an approximate reduction of 80% in the glutamate being released by these afferents. This large decrease in the amount of detected glutamate overflow within the NTS in chronic heart failure could indicate a reduction in “spare capacity” in such transmission, although there is still enough to enable a “normal” reflex responses. It is possible that other transmitters may have also come into play to help maintain these reflexes in heart failure.Support or Funding InformationBritish Heart Foundation project grant No PG/13/79/30429
Does trait anxiety influence muscle sympathetic nerve activity responsiveness in humans?
Authors: Carter Jason R , Fonkoue Ida T 
Published: November 2023

The relationship between anxiety and muscle sympathetic nerve activity (MSNA) remains equivocal. The purpose of this study was to examine associations between trait anxiety and MSNA in young, healthy adults. We hypothesized that trait anxiety would be positively correlated to resting MSNA and MSNA reactivity to mental stress. Twenty adults (11 men, 9 women; 22±1 years; 24±1 kg/m2) were examined during a 10 min supine baseline and 5 min of mental stress (via mental arithmetic). Psychological measurement included trait anxiety determined using the State‐Trait Anxiety Inventory (STAI), and autonomic measurements included blood pressure (sphygmomanometer and finger plethysomography), heart rate (HR; electrocardiogram), and MSNA (micro neurography). Standardized trait anxiety was 43±2 arbitrary units (range 30 – 57; n=20), while mean baseline values of mean arterial pressure (MAP; n=20), HR (n=20), and MSNA (n=13) were 77±2 mmHg, 68±3 beats/min, and 11±1 bursts/min, respectively. Mental stress significantly (p<0.05) increased MAP (Δ7±1 mmHg; n=20), HR (Δ15±2 beats/min n=20), and MSNA (Δ2±1 burst/min; n=10). Trait anxiety was not correlated with resting MAP (r=−0.053, p=0.824), HR (r=0.193; p=0.415), MSNA burst frequency (r=−0.158; p=0.605), or MSNA burst incidence (r=−0.147; p=0.632). MAP (r=0.311; p=0.182) and HR (r=0.047; p=0.876) reactivity to mental stress were not correlated with trait anxiety. In contrast, trait anxiety was strongly correlated with MSNA reactivity to mental stress quantified as changes (Δ) in MSNA burst frequency (r=−0.742; p=0.014), Δ MSNA burst incidence (r=−0.750; p=0.013), and % change in total MSNA (r=−0.700; p=0.024). Contrary to our initial hypothesis, the associations between trait anxiety and MSNA reactivity to mental stress were negative. In conclusion, this pilot study suggests a negative association between trait anxiety and MSNA reactivity to mental stress. Our findings advocate for the inclusion of basic psychological surveys such as STAI prior to micro neurographic sessions, and we posit that future studies might pool data across various laboratories to more definitively determine the role of psychological states and traits on sympathetic neural activity and reactivity in humans.Support or Funding InformationSupport from NIH (HL‐122919).
Effects of angiotensin II receptor type 2 (AT2R) modulation on fear memory in a mouse model of Posttraumatic Stress Disorder (PTSD)
Authors: Swiercz Adam P , Wiaderkiewicz Jan P , Moshfegh Cassandra , Hopkins Lauren , Marvar Paul J 
Published: November 2023

While the most widely known function of renin angiotensin system (RAS) is related to cardiovascular regulation, evidence also suggests an important role of RAS in the response to emotional stress. Our previous studies in a mouse model of PTSD have shown that peripheral AT1R inhibition with losartan increases the extinction (learned inhibition) of a traumatic fear memory and this affects brain AT1R mRNA expression. Therefore the purpose of this study was to further investigate brain RAS in the consolidation of fear memory. We performed classical Pavlovian fear conditioning in mice pairing auditory cues with foot shocks and examined mRNA expression of components of brain RAS and examined fear extinction behavior (% freezing to conditioned stimulus). Following the acquisition of fear, there was a 5 fold and 3 fold increase (*p <0.05, n=6) in mRNA expression of AT2R and angiotensin converting enzyme 2 (ACE2) in the central amygdala (CeA) and bed nucleus stria terminalis (BNST), regions involved in the consolidation of fear memory. However, mRNA expressions of the classical RAS pathway (AT1R and ACE) were unaltered in these brain regions. Thus we examined the effect of AT2R on long‐term fear memory. Mice received intraparietal (IP) or intracerebral (ICV) injections of either the novel non‐peptide AT2R‐agonist, Compound 21 (C21), or AT2R antagonist PD123,319 (PD) during classical Pavlovian fear conditioning. Twenty‐four hours following fear conditioning both C21 (10 mg/kg IP or 2μg/kg ICV) and PD (15 mg/kg IP or 200 μg/kg ICV) had no effect on extinction of fear memory compared to the vehicle. However, when fear memory retention was tested, the ICV C21 treated mice exhibited a trend for decreased freezing (C21 – 38%) (t(15) = 1.7; p = 0.1) versus saline (55%) and PD (64%) injected animals. These data suggest that brain AT2Rs and ACE2 may play a role in fear memory formation and / or retrieval.Support or Funding InformationNIH R00 HL107675‐03
Chronic Endurance Exercise Training Preserves Contraction‐Induced Rapid Vasodilation in Older Adults
Authors: Hughes William E. , Ganger Charles T. , Ueda Kenichi , Casey Darren P. 
Published: November 2023

Aging is associated with attenuated exercise hyperemia and vasodilation after a single skeletal muscle contraction, as well as during steady state exercise. Chronic exercise training preserves exercise hyperemia and vasodilation in older adults during steady‐state exercise; however, whether chronic exercise training ameliorates the attenuated rapid vasodilator response to a single skeletal muscle contraction in older adults is currently unknown. Therefore, the purpose of this study was to examine the impact of chronic exercise training on rapid vasodilator responses in older adults, as well as investigate the relationship between exercise capacity (VO2peak) and peak vasodilator responses (ΔVCpeak). Young (n = 14; 23±1yr; 9M/5F), older untrained (n = 16; 66±1yr; 10M/6F) and trained older adults (n = 16; 66±2yr; 9M/7F) performed single muscle contractions in the forearm (10%, 20%, and 40% MVC) and leg (20%, 40%, 60% WRmax). Blood flow (ml·min−1) was measured using Doppler ultrasound and vascular conductance was calculated from blood flow and mean arterial pressure (mmHg) and normalized for muscle mass (kg). The peak and total hyperemic and vasodilator responses were greater in trained older adults across leg exercise intensities compared to untrained older adults (P < 0.05), while there were no differences in responses between trained older and young adults (P > 0.05). Within arm intensities, trained older adults exhibited higher ΔVCtotal at 10%, and ΔVCpeak at 40% compared to untrained older adults (P < 0.05).There were no differences for rapid hyperemic and vasodilator responses between trained older adults and young adults at any arm exercise intensity (P > 0.05). VO2peak was moderately associated with ΔVCpeak at moderate and higher leg exercise intensities in older adults (r = 0.46 and 0.55 respectively; P < 0.01) but only at higher exercise intensities in young adults (r = 0.60; P < 0.05). Within the arm, VO2peak was moderately associated with ΔVCpeak across exercise intensities in older adults (10% r = 0.37, 20% r = 0.36, 40% r = 0.36; P < 0.05 for all), but not in young adults (r = −0.062–0.10; P > 0.05). When separated by training status, there were no associations between VO2peak and ΔVCpeak in the arm or leg (P > 0.05). Our data demonstrate that 1) chronic endurance exercise training preserves rapid hyperemic and vasodilator responses within both the arm and leg of trained older adults, such that age related differences in the rapid vasodilator response are abolished; and 2) VO2peak is moderately associated with peak vasodilator responses in the arm and leg of older, but not young adults.Support or Funding InformationFunded by NIH HL‐105467 (DPC) and NIH CTSA U54TR001356
Cold fluid ingestion extends exercise capacity of heat‐sensitive individuals with Multiple Sclerosis in a warm environment
Authors: Chaseling Georgia K , Filingeri Davide , Hoang Phu , Barnett Michael , Davis Scott L , Jay Ollie 
Published: November 2023

Exposure to a hot environment or heat gained during exercise can elicit a transient worsening of clinical symptoms in person with multiple sclerosis (MS), a demyelinating disease of the central nervous system). Heat‐related fatigue has been reported in 60–80% of individuals with MS, potentially limiting physical activity. Therefore, simple interventions that mitigate heat‐related reductions in exercise capacity in persons with MS are needed. Our aim was to test the hypothesis that cold fluid ingestion prolongs exercise duration of individuals with relapsing‐remitting MS cycling in a warm (30°C, 35% RH) environment. On two randomized occasions, 7 participants (54 ± 7 y; 76.1 ± 10.9 kg; 1.71 ± 0.09 m) diagnosed with relapsing‐remitting MS exercised at a low intensity (heat production: 3.2 ± 0.5 W·kg−1) for a maximum of 60 min (or until exhaustion), while ingesting a 3.2 mL·kg−1 aliquot every 15 min of either cold (1.5°C: CLD) or thermoneutral (37°C: NEU) water. Rectal (Tre) and mean skin (Tsk) temperature was continuously measured. Exercise duration was significantly longer (P=0.05) in the CLD trial (54.3 ± 11.0 min) compared to the NEU trial (46.4 ± 14.1 min). Indeed, after 45‐min of exercise, 3 of 7 participants remained in NEU, whereas 6 of 7 participants remained in CLD. All subjects were able to complete a minimum of 31 minutes of exercise. At this time point, absolute Tre (CLD: 37.08 ± 0.34°C, NEU: 36.99 ± 0.26°C; P = 0.59), the change in Tre (CLD: 0.25 ± 0.30°C, NEU: 0.25 ± 0.15°C; P =0.99), absolute Tsk (CLD: 34.41 ± 0.45°C, NEU: 34.31 ± 0.30°C; P = 0.57), and the change in Tsk (CLD: 1.35 ± 0.54°C, NEU: 1.41 ± 0.53°C; P = 0.63) were all similar between CLD and NEU. Additionally, at the termination end‐point of exercise, absolute Tre (CLD: 37.23 ± 0.30°C, NEU: 37.20 ± 0.26°C; P = 0.82), the change in Tre (CLD: 0.32 ± 0.30°C, NEU: 0.45 ± 0.18°C; P =0.70), absolute Tsk (CLD: 34.81 ± 0.27°C, NEU: 34.61 ± 0.35°C; P = 0.15), and the change in Tsk (CLD: 1.75 ± 0.85°C, NEU: 1.68 ± 0.88°C; P = 0.72) were all similar between CLD and NEU. In conclusion, during physical activity in a warm environment, heat‐sensitive individuals with MS exercised for longer before exhaustion with the ingestion of a cold compared to a thermoneutral fluid.Support or Funding InformationThis study was supported by a MS Research Australia Incubator Grant (Holders: Jay, Barnett, Hoang and Davis) and a University of Sydney International Collaboration Research Award (IRCA) (Holders: Davis and Jay). Dr Filingeri was supported by a Government of Australia Endeavour Fellowship
Isolating the independent effect of decreasing mean skin temperature on local thermal sensitivity of human hands and feet during cold stress
Authors: Filingeri Davide , Morris Nathan B , Jay Ollie 
Published: November 2023

Whether reductions in whole‐body mean skin temperature (Tsk), with no concurrent changes in core temperature (Tc), alter local thermal sensitivity (TS) of human skin is currently unknown. On 4 separate occasions, 8 males (27±5y) underwent a 30‐min whole‐body cooling protocol (water‐perfused suit: ~5°C), during which a quantitative thermo‐sensory test, consisting of reporting (visual analogue scale) perceived magnitude of local warm (38°C) and cold (22°C) thermal stimuli (25‐cm2 thermal probe) applied to hand (palm/dorsum) and foot (sole/dorsum), was performed before cooling and every 10min thereafter. The cooling protocol resulted in large progressive reductions in Tsk (10min: −3.36±0.67°C; 20min: −5.21±1.00°C; 30min: −6.32±1.14°C; p<0.001), with minimal changes in Tc (10min: −0.08±0.04°C; 20min: −0.07±0.07°C; 30min: −0.07±0.09°C; p<0.001). While no differences in TS to the local cold stimulus were observed for any skin region at any stage of the cooling protocol (ΔTS from baseline; 10min: −2.05±5.9%; 20min: −0.3±7.8%; 30min: −1.1±8.5%; p=0.790), a significant and progressive increase in warm TS occurred at each level of Tsk for all skin regions (10min: +4.9±7.5; 20 min: +6.1±4.5; 30 min: +7.9±6.1%; p=0.004). A significant association between decreasing levels of Tsk and increases in warm TS was observed (y= −1.217x+0.2139; R2=0.98; p=0.003), indicating a 1.4% increase in warm TS per 1°C drop in whole‐body Tsk. Overall, the same local warm stimulus (hence same increase in skin temperature) was perceived to be warmer with progressive reductions in whole‐body Tsk, indicating that, independently of Tc, decreases in whole‐body Tsk significantly alter local warmth, but not cold, TS of human hands and feet.Support or Funding InformationMr Morris was supported by a University of Sydney International Postgraduate Research Scholarship (IPRS). Dr Filingeri was supported by a Government of Australia Endeavour Fellowship
Effects of Modest Weight Gain on Estrogens in Healthy Men
Authors: Singh Prachi , Covassin Naima , Sert‐Kuniyoshi Fatima H , Romero‐Corral Abel , Davison Diane , Singh Ravinder J. , Jensen Michael D. , Somers Virend K 
Published: November 2023

BackgroundDecreases in estrogen are shown to increase body fat in men. However, obese men have high levels of estrogen and the effects of weight gain on estrogen have not been previously investigated. The objective of this study was to investigate the relationship between regional fat depots and estrogen during modest weight in healthy men.MethodsWe investigated the effects of overfeeding in 25 healthy men (30 ± 7 years, 24.7 ± 3.1 kg/m2). Changes in regional fat depot during weight gain were assessed using dual‐energy X‐ray absorptiometry and abdominal computed tomography scans. Participants gained approximately 5% body weight in 8 weeks. Estrone (E1), 17β‐estradiol (E2) and sex hormone binding globulin (SHBG) were measured at baseline and after weight gain.ResultsOverfeeding was accompanied by 3.9 ± 1.3 kg weight gain. These increases in weight resulted from increases in total body fat mass (18.3 ± 8.5 vs. 21.7 ± 8.8 kg, p<0.001) while the fat free mass did not change (58.4 ± 8.6 vs. 58.9 ± 8.7 kg, p=0.15). E1 (32.28 ± 14.25 vs. 33.44 ± 12.29 pg/mL, p=0.56) and E2 (25.04 ± 8.3 vs. 26.52 ± 7.8 pg/mL, p=0.28) did not change after weight gain. However, weight gain resulted in decreased SHBG (22.8 ± 10.5 vs. 20.8 ± 11.1 nmol/l, p=0.036) and increased E2/SHBG ratio (1.4 ± 1.0 vs 1.63 ± 1.0, p=0.027). The changes in E2/SHBG ratio, a surrogate marker of bioavailable E2, was positively associated with increases in abdominal fat mass (p=0.048, rho=0.39) and increases in visceral fat mass (p=0.049, rho=0.39).ConclusionModest weight gain in healthy men does not alter circulating E1 and E2 levels. However weight gain results in decreased SHBG and increased free E2 (E2/SHBG ratio). The increased E2/SHBG ratio suggesting a pro‐estrogen effect is associated with increases in visceral fat mass during weight gain. Our study therefore suggests a complex relationship between abdominal fat gain and free E2 in men which may conceivably predispose to feminizing characteristics in obese men.Support or Funding InformationPS is supported by AHA Grant 11SDG7260046 and NIH grant DK81014. NC is supported by AHA grant AHA 13POST16420009. MDJ is supported by NIH grants DK45343 and DK40484. VKS is supported by NIH Grants HL73211, and DK81014. This study was made possible by a grant from NCRR (1UL1 RR024150).
The viability and differentiation of fetal spinal cord tissue after transplantation in injured mid‐cervical spinal cord
Authors: Lin Chia‐Ching , Lee Kun‐Ze 
Published: November 2023

Mid‐cervical spinal cord injury interrupts the bulbospinal respiratory pathway and causes a secondary degenerative cascade, including loss of neurons and demyelination. To date, there is no effective treatment for spinal cord injury. Fetal spinal cord (FSC) tissue is composed of neural progenitors, which may have the capability to replace the lost cell and form a neural relay between separated spinal segments. Thus, the present study was design to investigate the viability and differentiation of progenitors derived from FSC after delayed transplantation into the injured spinal cord. Embryonic day 14 FSC expressing green fluorescence protein (GFP) was transplanted into the lesion cavity in rats received unilateral C4 hemisection at 1 week post‐injury. At 8 week post‐transplantation, the viability of FSC was examined by quantifying GFP‐positive area in spinal cord sections. The histological results demonstrated that GFP‐positive area was ~70 % of contralateral (i.e., uninjured side) spinal cord tissue. Immunofluorescence staining revealed that neural cell markers [e.g., neuronal nuclei (NeuN) for neuron; glial fibrillary acidic protein (GFAP) for astrocyte; ionized calcium‐binding adapter molecule 1 (Iba1) for microglia; receptor interacting protein (RIP) for oligodendrocyte] were detected in GFP‐positive tissue. In addition, there are some serotonin and choline acetyltransferase positive cells in the graft region. These results demonstrated that transplants of FSC can survive at least for 8 week post‐transplantation and differentiate into different neural cells, suggesting FSC transplants may have the potential to repair the injured spinal cord.Support or Funding InformationNational Health Research Institutes (NHRI‐EX104‐10223NC); Ministry of Science and Technology (MOST 100‐2320‐B‐110‐004‐MY3)
Time Course of Brainstem Glial Activation Following Exposure to Chronic Sustained Hypoxia
Authors: Arbogast Tara Elizabeth , Stokes Jennifer Ann , Powell Frank L 
Published: November 2023

Neuron‐glia communication in the central nervous system (CNS) is proving to be an important component of neuronal signaling and recently we showed that glial activation in the brainstem plays a role in neural plasticity that increases ventilation following chronic sustained hypoxia (CSH) in rats (Stokes JA et al., 2015). In this study we measured the time course of activation of microglia and astrocytes following different lengths of exposure to CSH (10% O2). Rats were exposed to CSH followed by immediate tissue perfusion and brainstem collection at the following time points: 15‐, 30‐ and 60‐minutes, 4‐, 12‐ and 24‐hours, 2‐, 4‐ and 7‐days. We measured activation of glial cells using immunohistochemistry, focusing on respiratory control centers: the nucleus tractus solitarius (NTS) and the retrotrapezoidal nucleus (RTN). Initial results show that microglia (Iba1‐positive cells) display an active morphology at 60 minutes, but are less active in appearance at 24 hours and return to the resting state (as determined by morphology) at 7 days. In contrast, astrocytes progressively increased in GFAP expression over the same time points of 1 hour, 24 hours, and 7 days. The results show that there is an order to glial activation, which we previously showed was necessary for ventilatory acclimatization to hypoxia: microglia are activated first, followed by astrocytes during CSH exposure.Support or Funding InformationNIH RO1 HL‐081823
Intranasal Neuropeptide Y to Prevent Development of Traumatic Stress Elicited Impairments in Rodent PTSD Model
Authors: Sabban Esther , Serova Lidia , Hansson Evelyn 
Published: November 2023

Traumatic stress is a major contributor to the development of PTSD, as well as co‐morbid depression and substance abuse. Treatment of PTSD is extremely challenging and there are few effective options. The NPYergic system is associated with resilience or improved recovery from harmful effects of traumatic stress. Using the single prolonged stress (SPS) model of PTSD, a single infusion of 150 μg NPY immediately after the stressors (SPS/NPY), prevented or greatly reduced development of many of the behavioral, neuroendocrine and molecular impairments (Serova et al, 2013, Neuroscience, 236:298–312; Laukova et al., 2014, Endocrinolgy 155: 3920–33; Sabban et al, J. Neurochem, in press). A week or more after exposure to SPS stressors animals given vehicle (SPS/V) had elevated anxiety, depressive‐like behavior and hyperarousal, especially to high decibels, while the NPY treated rats were similar to unstressed controls. Intranasal NPY also prevented changes in hypothalamus, hippocampus and locus coeruleus. However, all the stressed animals (SPS/V and SPS/NPY) had reduced body weight. Therefor we examined feeding behavior and gene expression in arcuate nucleus, which plays an important role in regulation of food intake and energy homeostasis. With unrestricted access to food, SPS treated animals (SPS/V and SPS/NPY) had reduced food intake in the active (dark) phase as much as two days after SPS stressors. SPS led to reduced mRNA levels of NPY, tyrosine hydroxylase and elevated AGRP mRNA in the arcuate nucleus of SPS/V animals a week after SPS stressors, at time of the behavioral impairments. However these changes in gene expression in the arcuate were not observed in NPY treated animals, which had levels similar to controls. These findings further support likely benefits of early pharmacological intervention with intranasal NPY following exposure to traumatic stress.Support or Funding InformationUS army grant DM102281