bluuebunny/crossref_metadata_2025_split huggingface dataset:
The costs of aggressivity and the benefits of cooperation
Authors: Fox Trevor , Klok Jaco , Harrison Jon , Fewell Jennifer 
Published: November 2023

Queens of the harvester ant Pogonomrymex californicus have been documented as having two distinct behavioral phenotypes controlling both aggression and the tendency to form foundress associations. Pleometrotic queens found colonies cooperatively with nest‐mates while haplometrotic queens found solitary nests. Haplometrotic queens are larger and more aggressive to other queens, and produce eggs at a higher rate during colony founding. We tested for possible metabolic differences between these types, predicting that the non‐aggressive pleometrotic queens would have lower metabolic rates, and that pairs of pleometrotic queens would have even lower rates (per ant) as prior studies have shown reduced work and per capita egg production in pairs relative to solitary founders. CO2 emission and O2 consumption was measured using a stop‐flow respirometry system. We tested individual haplo‐ and pleometrotic individuals and pairs of pleometrotic queens. Respiratory quotients averaged. 68 and did not differ among treatments, suggesting that these queens were primarily metabolizing lipids. Indeed, our results showed that the paired pleometrotic queen had a significantly lower metabolic rate (.0066 mlCO2/hour·animal) than the individual pleometrotic queens (.0077 mlCO2/hour·animal), while haplometrotic queens had the highest metabolic rate of the three groups (.009 mlCO2/hour×animal), suggesting that the aggressivity and high egg‐laying rates of the haplometrotic queens has a measurable and significant cost, and that cooperative founding reduces per capita energy use. These differences in energy use may partially explain differences in survival of queens, as queens do not forage during the prolonged period of colony founding.Support or Funding InformationThis research was partially supported by NSF IOS 1122157 and NSF DMS 1313312.
Hatchling Phenotype Of Lake Whitefish Incubated At Increased Temperature During Critical Windows Of Development
Authors: Mueller Casey , Eme John , Manzon Richard , Somers Christopher , Boreham Douglas , Wilson Joanna 
Published: November 2023

Phenotypic plasticity is the ability of an animal to modify its phenotype in response to the environment. Embryos may have critical windows during development when they are particularly plastic or susceptible to the environment. We examined whether there are critical windows during Lake whitefish (Coregonus clupeaformis) embryonic development when temperature has an especially strong effect on phenotype. Lake whitefish are a cold‐water fish species that inhabits the North American Great Lakes. This species lays eggs that develop over winter when lake temperatures are near freezing. With 2°C as the overall control temperature, embryos were incubated at either 5°C, 8°C or 11°C for all of embryonic development or only during one of four distinct windows of development: gastrulation, organogenesis, fin development, and late growth. Survival was monitored throughout development. Hatching characteristics, including time to hatch, mass at hatch, and hatchling oxygen consumption rate, were measured to examine if warmer temperatures during the four windows of development altered hatchling phenotype. No embryos survived to hatch when incubated constantly at 11°C, and survival was reduced at constant 8°C. Survival was also reduced when embryos were incubated at 11°C during the windows of gastrulation, organogenesis and fin development, but not during the late growth window. Time to 50% hatch decreased with an increase in constant incubation temperature, and only during the late growth window did an increase in temperature decrease time to hatch. Increased incubation temperature during the late growth window resulted in smaller hatchlings and reduced yolk conversion efficiency compared to embryos incubated constantly at 2°C or embryos incubated in warmer temperatures during earlier windows of development. Incubation at 11°C during organogenesis, fin development and the late growth window also reduced yolk conversion efficiency. Mass‐specific oxygen consumption rate increased with an increase in constant incubation temperature, but incubation at either 5°C, 8°C or 11°C during gastrulation, organogenesis, fin development or the growth window did not have substantial effects on metabolism at hatch. Overall, critical windows for survival in response to increased temperature were present during gastrulation, organogenesis and fin development. However, hatchling size was most influenced by incubation at warm temperatures during the late growth window prior to hatch, due to increased temperature inducing early hatching.Support or Funding InformationC.A.M. and J.E. were supported by a MITACS Accelerate grant to D.R.B. and J.Y.W. Funding was provided by Bruce Power® and a Collaborative Research and Development Grant from the Natural Sciences and Engineering Research Council of Canada to J.Y.W., R.G.M., and C.M.S.
Age Associated Downregulation of Glutamate/GABA Transporters Expression in Rostral Ventral Lateral Medulla (RVLM)
Authors: Balivada Sivasai , Pawar Hitesh J , Montgomery Shawnee , Ganta Chanran K , Kenney Michael J 
Published: November 2023

Physiological function is altered with advancing age, including changes in sympathetic nervous system regulation. Studies focused on Glutamate/GABA ionotropic receptors using pharmacological agonists and antagonists in the rostral ventral lateral medulla (RVLM) indicates changes in medullary mechanisms regulating sympathetic nerve discharge (SND) in aged Fisher 344 rats. Identifying molecular mechanisms involved in this alteration is necessary to understand the regulation of central sympathetic neural circuits. Based on this rationale, we hypothesized that aging alters the basal regulation of RVLM Glutamate/GABA system‐associated genes. To test this hypothesis, the RVLM containing area was micro‐punched from young, middle‐aged and aged Fisher 344 rats. RNA level expression changes in RVLM GABA/Glutamate system‐associated genes were analyzed using RT2 profiler array and Taqman® real‐time PCR. Genes that showed >2fold differences in expression were analyzed at protein level by using immunoblot analysis. Downregulation of RVLM glutamate (Slc1a6) and GABA (Slc6a13) transporter genes was observed in aged compared with young rats at the RNA level, with a similar trend at the protein level. Slc1a6 and Slc6a13 transporters are known to modulate the amount of Glutamate/GABA in synaptic cleft and extra synaptic space. Down regulation of these transporters suggests there may be an altered Glutamergic/GABAergic balance in the aged RVLM.Support or Funding InformationSupported by NIH AG‐041948.
Neuronal Nitric Oxide Synthase Colocalizes with N‐methyl‐D‐aspartate (NMDA) and Alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic Acid (AMPA) Receptors in the Dorsolateral Periaqueductal Gray of Rats
Authors: Lin Li‐Hsien , Jones Susan , Dampney Roger A. , Talman William T. 
Published: November 2023

The midbrain periaqueductal gray (PAG) plays an important role in cardiovascular regulation, respiratory control, pain modulation, and autonomic responses to stressful stimuli. Among the four columns of the PAG, the dorsolateral PAG (dlPAG) contains the highest density of neurons that express neuronal nitric oxide synthase (nNOS), the enzyme for synthesis of nitric oxide (NO) in neurons. Because inhibition of NO synthesis in the dlPAG produces pressor responses, attenuates fear responses and attenuates stress responses, it has been suggested that NO may modulate cardiovascular regulation and responses to fear and stress. NMDA type and AMPA type glutamate receptors are also expressed in the dlPAG and have been implicated in cardiovascular control and defensive behavior. Physiological studies have suggested that NO and glutamate receptors may interact in the dlPAG in cardiovascular regulation and stress responses. An NO donor injected into the dlPAG has been shown to decrease cardiovascular responses induced by NMDA, while an nNOS inhibitor increased them. NO‐induced flight behavior was prevented by antagonists to NMDA or AMPA receptors in the dlPAG. However, anatomical data to support interactions between NO and glutamate receptors in the dlPAG have been missing. We performed fluorescent immunohistochemistry for nNOS, NMDAR1 (subunit of NMDA receptor) and GluR2 (subunit of AMPA receptor) and examined labeled sections with confocal microscopy to test the hypothesis that nNOS and glutamate receptors colocalize in the rat dlPAG. We found that nNOS and NMDAR1 immunoreactivity (IR) colocalize in dlPAG neurons in rat. We noted 94.9 ± 1.1% nNOS‐IR containing neurons in the dlPAG also contained NMDR1‐IR, while 26.9 ± 4.2% NMDAR1‐IR containing cells also contained nNOS‐IR. Colocalization of nNOS‐IR and GluR2‐IR was also observed in the dlPAG with 91.9 ± 2.3% of nNOS‐IR containing neurons also containing GluR2‐IR and 28.2 ± 5.5% of GluR2‐IR containing cells also containing nNOS‐IR. NMDAR1‐IR and GluR2‐IR also colocalized in the dlPAG. Of the NMDAR1‐IR containing dlPAG cells 78.6 ± 9.1% were positive for GluR2‐IR while 65.7 ± 1.7% of GluR2‐IR containing dlPAG cells were positive for NMDAR1‐IR. Our data support our hypothesis that nNOS colocalizes with NMDA and AMPA receptors in the dlPAG and provide an anatomical basis for interaction between NO and glutamate receptors in regulating cardiovascular function and responses to fear and stress by the dlPAG.Support or Funding InformationNIH R01HL088090 and VA Merit Review
Hypoxia‐Inducible Factor (HIF)‐1 Alpha Expression Induced by Proinflammatory Cytokines in NG108‐15 Neuronal Cells
Authors: Haibara Andrea S , Sharma Neeru M , Patel Kaushik P 
Published: November 2023

Previous studies have shown that upregulation of proinflammatory cytokines, such as interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α, in the paraventricular nucleus (PVN) has been related to the increased sympathetic outflow seen in heart failure. Recently, we have observed that HIF‐1α, a transcription factor responsible for inducing various genes, is also increased in the PVN of rats with heart failure. In addition, HIF‐1α siRNA administered to the PVN normalizes the increased renal sympathetic nerve activity in rats with HF. However, the specific relationship between proinflammatory cytokines and HIF‐1α expression remains unclear. Therefore, we hypothesized that the increased proinflammatory cytokines would cause augmentation of the HIF‐1α expression. To test this hypothesis, we stimulated NG108‐15 neuronal cell culture with IL‐1β and TNF‐α (10 ng/ml) and evaluated the HIF‐1α protein expression using the Western Blot technique at different time points (4, 8, 16 and 24h). Our results showed a significant increase (1.7 fold) in the expression of HIF‐1α 24h after the treatment of the cells with IL‐1β in comparison with untreated cells. Concomitantly, IL‐1β treatment also induced significant increase in nNOS expression (2.2 fold). In contrast, the treatment of the cells with TNF‐α failed to induce any significant changes in HIF‐1α over this time frame, but induced a significant increase (1.5 fold) in the nNOS expression 16h after treatment. Taken together, these results show that cytokines, particularly IL‐1β, induces enhanced expression of HIF‐1α in NG108‐15 cultured neurons and also suggest that perhaps increased expression of HIF‐1α due to the proinflammatory cytokines is may not be directly involved in the up‐regulation of nNOS in cultured NG108‐15 cells.Support or Funding InformationCNPq‐Brazil 234520/2014‐0 and NIH grants HL124104 & HL62222
Microinjection of Brain‐Derived Neurotrophic Factor (BDNF) into the Subfornical Organ Decreases Blood Pressure
Authors: Smith Pauline M , Ferguson Alastair V 
Published: November 2023

Brain‐derived neurotrophic factor (BDNF) is a peptide known to be involved in several mammalian physiological processes including cardiovascular homeostasis. Intracerebroventricular (icv) BDNF administration and microinjection of BDNF into discrete brainstem nuclei have been shown to increase blood pressure. Expression of BDNF transcripts have been identified in the subfornical organ (SFO), a forebrain circumventricular organ with well‐documented roles in cardiovascular regulation. Whole‐cell patch clamp electrophysiological studies from our laboratory have shown that BDNF influences the activity of the majority of SFO neurons tested. Given the involvement of the SFO in cardiovascular regulation and electrophysiological evidence from our laboratory that BDNF influences the activity of SFO neurons, the present study was undertaken to determine the effects of direct administration of the BDNF into the SFO of urethane anesthetized male Sprague Dawley rats. Microinjection of BDNF (0.5μl, 2nM) into the SFO resulted in rapid, short duration decreases in BP (mean AUC = −134.8 ± 22.2 mmHg*sec, n=4) without effect on HR (mean AUC = 2.4 ± 0.3, n=4). These hypotensive effects were site specific as microinjection into non‐SFO sites were without effect on BP (mean AUC = −13.5 ± 8.4 mmHg*sec, n=5) or HR (mean AUC = 0.8 ± 1.4 beats, n=5). These observations identify the SFO as a possible CNS location at which BDNF may act to influence cardiovascular regulation.Support or Funding InformationSupported by the Canadian Institutes of Health Research
The Effects of Chronic Treatment with Ivabradine on the Cardiovascular Reflexes Sensitivity in Rats
Authors: Chianca Deoclecio Alves , Paiva Franciny A. , Silva Fernanda C. , Caldeira Henrique M. A. , de Menezes Rodrigo C. , Dias da Silva Valdo J. 
Published: November 2023

A low resting heart rate would be of great benefit for patients with cardiovascular disease. In this sense, ivabradine which selectively inhibits the pacemaker If channel with no negative inotropic or proarrhythmic effects, has emerged as promising bradycardic agent. However, little is known about the ivabradine effects on the heart rate (HR) autonomic control. Since the cardiovascular reflexes are components of the autonomic control, in this study we examined the effects of chronic treatment with ivabradine on the Baroreflex and Bezold‐Jarish reflex sensitivity. Rats were divided into 2 groups: receiving intraperitoneal injection of PBS 1mL/Kg (n=4) or ivabradine 2mg/kg (n=4) for 7 consecutive days. The rats were submitted to vessels femoral cannulation and cardiovascular recordings (blood pressure and heart rate) on the fifth and seventh‐day of treatment, respectively. We performed Phenylephrine (PHE; 2μg/kg i.v.) and Sodium Nitroprusside injections (SNP; 8μg/kg i.v.) and ΔHR/ΔMAP index was calculated to assess the Baroreflex sensitivity. We also performed different Phenylbiguanide doses (PBG; 1.25; 2.5 and 5μg/kg i.v.) to evaluate the Bezold‐Jarish reflex sensitivity. The animals treated with ivabradine presented baseline HR 240±19bpm vs. 369±15bpm (p<0.05) in the controls rats. In relation to Baroreflex sensitivity, our results demonstrated an increase in tachycardia gain in the ivabradine‐treated rats (ΔHR/ΔMAP index; PBS: −2.2±0.5 bpm/mmHg vs. ivabradine: −10.7±2.9 bpm/mmHg; p<0.05). About the Bezold‐Jarish reflex, we observed that ivabradine treatment decreases the bradycardic responses evoked by PBG doses (PBG 2.5μg/kg; PBS: −215±38bpm vs. ivabradine: −70±52bpm; p<0.05), (PBG 5μg/kg; PBS: −194±51bpm vs. Ivabradine: −79±28 bpm; p<0.05). Our results suggest an increase in the Baroreflex gain and a decrease in the Cardiopulmonary reflex in ivabradine treated animals.Support or Funding InformationCAPES, CNPq, FAPEMIG and UFOP.
Defect Mitochondrial Biogenesis at Rostral Ventrolateral Medulla in Neurogenic Hypertension under Peripheral Inflammation
Authors: Chan Julie YH , Wu Kay LH 
Published: November 2023

Neuroinflammation‐associated oxidative stress in rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons reside, is involved in neurogenic hypertension developed under peripheral inflammation. In this study, we investigated whether this neurogenic hypertension is attributable to defect mitochondrial biogenesis. In normotensive Sprague‐Dawley rats, intraperitoneal infusion of a low dose of E. coli lipopolysaccharide (LPS) for 7 days promoted a pressor response, alongside a decrease in mitochondrial DNA (mtDNA) copy number, reductions in protein expression of nuclear DNA‐encoded transcription factors for mitochondrial biogenesis, including mitochondrial transcription factor A (TFAM) and nuclear factor erythroid‐derived 2‐like 2 (Nrf2), and suppression of nuclear translocation of the phosphorylated Nrf2 (p‐Nrf2) in RVLM neurons; all of which were abrogated by treatment with intracisternal infusion of an interleukin‐1β (IL‐1β) blocker, IL‐1Rα, or a mitochondrial electron carrier, coenzyme Q. Microinjection into RVLM of IL‐1β suppressed the expressions of p‐Nrf2 and TFAM, and evoked a pressor response; conversely, the Nrf2 inducer, tert‐butylhydroquinone, lessened the LPS‐induced suppression TFAM expression and pressor response. At cellular level, exposure of N2a cells to IL‐1β decreased mtDNA copy number, increased protein interaction of Nrf2 to its negative regulator, kelch‐like ECH‐associated protein 1 (Keap1), and reduced DNA binding activity of p‐Nrf2 to Tfam gene. Together these results indicate that defect mitochondrial biogenesis in RVLM neurons entailing a redox‐sensitive and IL‐1β‐dependent suppression of TFAM because of the increase in the formation of Keap1/Nrf2 complex, reductions in nuclear translocation of the activated Nrf2 and its binding to the Tfam gene promoter may underlie neurogenic hypertension developed under the peripheral inflammation.Support or Funding InformationThis study was supported by grant (CMRPG8C0051) from Kaohsiung Chang Gung Memorial Hospital.
Methionine Sulfoxide Reductase‐A Deficient Mice Exhibit Sympathetic Activity‐Dependent Oxidative Stress: Implications for End‐Organ Damage
Authors: Sabharwal Rasna , Abboud Francois M. , Chapleau Mark W. 
Published: November 2023

Methionine sulfoxide reductase A (MsrA) selectively reverses oxidation of protein methionine and protects against oxidative damage. We recently reported that MsrA deficient (−/−) mice exhibit increased sympathetic tone under basal conditions, and augmented angiotensin II (Ang II) hypertension associated with left ventricular (LV) dysfunction and dilatation of ascending aorta; with the Ang II‐related pathologies abrogated by treatment with the sympathoinhibitory drug rilmenidine (RIL) [FASEB J, 2015; Auton Neurosci, 2015]. The aims of this study were to determine if MsrA−/− mice exhibit oxidative stress in LV and ascending aorta, and if basal and Ang II‐induced oxidative stress are dependent on sympathetic activity. Superoxide (O2•−) was measured in tissue sections from LV and ascending aorta (dihydroethidium staining) from untreated control C57BL6 and MsrA−/− mice (12–16 wks of age), and mice infused with Ang II (1000 ng/kg/min, SC) with or without ICV infusion of RIL over the last two weeks of Ang II infusion. O2•− levels in LV and aorta were significantly higher in MsrA−/− (n=8) vs. C57BL6 (n=7) mice, both under basal conditions (untreated) and after 4 weeks of Ang II infusion (Table). Ang II‐induced increases in O2•− were much greater in MsrA−/− mice (Table). Treatment of Ang II‐infused mice with RIL normalized O2•− levels in both genotypes (Table). Furthermore, O2•− levels in Ang II‐infused mice (n=7) were positively correlated with sympathetic tone measured in the same mice (r2 = 0.76 for LV, r2 = 0.88 for ascending aorta, P<0.05). In summary: (1) oxidative stress is evident in LV and ascending aorta of MsrA−/− mice under basal condition, (2) MsrA−/− and Ang II infusion synergistically increase oxidative stress, and (3) oxidative stress during chronic Ang II infusion is entirely dependent on sympathetic activity. Taken together, our results suggest that sympathetic activity‐dependent oxidative stress contributes to LV dysfunction/remodeling and aortic dilatation in MsrA−/− mice.Support or Funding InformationHL14388, VA
Knockdown of Bradykinin B1 Receptor Reduces Neuro‐inflammation and Prevents the Development of Salt‐Sensitive Hypertension
Authors: Sriramula Srinivas , Lazartigues Eric 
Published: November 2023

We previously reported that DOCA‐salt hypertension is associated with increased bradykinin B1 receptor (B1R) expression in the brain. In the present study, we tested the hypothesis that B1R knockdown prevents the development of hypertension. To test this hypothesis, wild‐type (WT) and B1R knockout (KO) mice were implanted with telemetry probes for conscious blood pressure (BP) monitoring. DOCA (1 mg/g, sc) was implanted following baseline BP recording and drinking water was replaced by 1% NaCl solution. Autonomic function was analyzed using a pharmacological method involving ip injection of propranolol (4 mg/kg) and atropine (1 mg/kg). Changes in heart rate (ΔHR) were used as index of sympathetic and parasympathetic tones. Baseline mean arterial pressure (MAP) was not different between WT and B1R KO mice (102±2 vs. 104±5 mmHg), nor were ΔHR following assessment of sympathetic (−73±6 vs. −75±15 beats/minute) or parasympathetic tone (+166±7 vs. +153±12 beats/minute). Three weeks after DOCA‐salt treatment, MAP was significantly increased in WT mice (138±3 mmHg, P<0.01 vs. baseline). However, this increase was blunted in B1R KO mice (121±2 mmHg, P<0.05 vs. WT+DOCA). In addition, DOCA‐salt mediated enhancement of cardiac sympathetic drive (increased bradycardia to propranolol, −145±21 beats/minutes, P<0.01 vs. baseline) and reduction of parasympathetic tone (reduced tachycardia to atropine, +111±8 beats/minute, P<0.01 vs. baseline) were normalized in B1R KO mice (−72±13 and +165±6 beats/minute, respectively, P<0.05 vs. WT+DOCA). DOCA‐salt treatment resulted in sympathoexcitation in WT mice, as indicated by increased urinary norepinephrine levels (299±23 ng/ml, P<0.05 vs. control), but this increase was blunted in B1R KO mice with DOCA (172±30 ng/ml, P<0.05 vs. WT+DOCA). Moreover, pro‐inflammatory high‐mobility group box 1 (HMGB1) and cyclooxygenase 2 protein levels were significantly upregulated in the hypothalamus following DOCA treatment in WT mice (2.5 and 2 fold, respectively, P<0.05 vs. control) but not in B1R KO mice. WT mice treated with DOCA‐salt showed increased inflammation as indicated by increased gene expression of TNF (3 fold, n=9, p<0.001 vs. WT), IL‐1beta (8 fold, n=9, p<0.001 vs. WT) and IL‐6 (5 fold, n=9, p<0.01 vs. WT) in the hypothalamic paraventricular nucleus (PVN) which was attenuated in B1R KO mice. Taken together, these data suggest that B1R knockdown prevents the development of hypertension, possibly through decreased sympathetic activity, reducing HMGB1 expression, and diminishing its downstream neuroinflammatory cascade.Support or Funding Information15SDG25720021 (SS), NIH/NHLBI (HL093178) (EL), and P30GM106392