bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of intracerebroventricular injection of nesfatin‐1 on autonomic nerve activities in rats and mice
Authors: Tanida Mamoru , Shibamoto Toshishige 
Published: November 2023

Nesfatin‐1, one of neuropeptides, reduces appetite and enhances energy expenditure in animals. Previous our experiment showed that intracerebroventricular (ICV) administration of nesfatin‐1 suppressed food intake and stimulated sympathetic nerve outflows to the kidney and the white adipose tissue through the hypothalamic ERK signals (Tanida M., et al., Diabetes 2015). However, it has not been examined whether central nesfatin‐1 affects efferent sympathetic nerve activities to the adrenal gland or the brown adipose tissue regulating cardiovascular function or thermogenesis, respectively, and efferent vagal nerve outflow. Here, we investigated effects of ICV injection of nesfatin‐1 on efferent adrenal sympathetic nerve activity (ASNA) and brown adipose tissue sympathetic nerve activity (BAT‐SNA), and efferent gastric vagal nerve activity (GVNA) in anesthetized rats. In addition, to check species difference in nesfatin‐1 action on autonomic nerves, sympathetic response to ICV injection of nesfatin‐1 was determined in anesthetized mice.Electrophysiological recordings of autonomic nerve activities in anesthetized rats and mice were performed within the scope of our previous studies (Tanida M., et al., Diabetes 2015, Tanida M., Neuroscience 2013). All animal care and handling procedures were approved by the Animal Research Committees of Kanazawa Medical University. 7–10days after ICV surgery, rats and mice were anesthetized with intraperitoneal injections of a urethane (750 mg/kg) and a‐chloralose (75 mg/kg) mixture. ASNA, BAT‐SNA and GVNA in rats, and sympathetic nerve to the kidney in mice were measured by electrophysiological system.In the present study, we found that ICV injection of nesfatin‐1 (20, 200 pmol) activated ASNA and BAT‐SNA in dose‐dependent manner while the GVNA was suppressed by nesfatin‐1. In addition, pretreatment with the melanocortin‐3/4 receptor antagonist, SHU9119, attenuated the increase in ASNA induced by nesfatin‐1. These data suggest that hypothalamic nesfatin‐1 stimulates not only renal sympathetic nerve but also sympathetic nerve activities to the adrenal gland and the brown adipose tissue via the hypothalamic melanocortin system to regulate cardiovascular and thermogenic actions. Similar with sympathetic responses of rats to nesfatin‐1, nesfatin‐1 injection to the mice also activated renal sympathetic outflow, indicating that sympathoexcitation of the kidney was also induced in mice.
The Role of Angiotensin Converting Enzyme 1 (ACE1) within the Median Preoptic Nucleus (MnPO) in Chronic Intermittent Hypoxia (CIH) Hypertension
Authors: Faulk Katelynn , Shell Brent , Nedungandi T. Prashant , Cunningham J. Thomas 
Published: November 2023

Sleep apnea is associated with a sustained increase in diurnal blood pressure and increased sympathetic tone. CIH simulates the arterial hypoxemia of sleep apnea and produces a sustained increase in blood pressure during the diurnal cycle as well as increased sympathetic activation. Many CNS regions have been shown to contribute to CIH hypertension through increased neuronal activation. FosB, an AP‐1 transcription factor, is associated with increased neuronal activation. Following CIH, FosB positive neurons increase within the MnPO and dominant negative inhibition of MnPO FosB blocks the sustained, diurnal component of CIH hypertension. PCR array analysis following a dominant negative inhibition of FosB within the MnPO during CIH identified several candidate AP‐1 regulated genes that may contribute to the sustained hypertension seen in CIH. ACE1, which converts angiotensin I to angiotensin II, was increased within the MnPO following CIH and this effect was blocked by inhibition of FosB. Increased expression of ACE1 through FosB activation within the MnPO may provide a possible mechanism by which downstream regions, such as the Paraventricular Nucleus (PVN), are activated to sustain diurnal hypertension. Our hypothesis is that CIH increases the expression of ACE1 in MnPO neurons that project to the PVN and that this increase in expression is due to a direct interaction between FosB and the ACE1 gene. We first tested this hypothesis by microinjecting isoflurane anesthetized adult male rats with 200nl of a retrograde tracer, flourogold, unilaterally into PVN. Rats were then exposed to CIH for 7 days through 3 minute periods of hypoxia (10% oxygen) and 3 minute periods of normoxia (21% oxygen) for 8 hours per day (0800–1600 h). Controls were only exposed to room air. Mean arterial blood pressure (MAP) was recorded using radio telemetry. Forebrains were fixed through 4% paraformaldehyde perfusion and later processed for ACE1 and FosB immunohistochemistry. In separate groups, we performed a Chromatin Immunoprecipitation (ChIP) assay from the MnPOs of rats following 7 days of CIH treatment. The MnPOs were combined from 2 rats within the same treatment group (CIH or normoxic) in order to get sufficient amount of DNA. ChIP assays were performed with ChIP grade antibodies against FosB and a nonimmune IgG to control for nonspecific antibody binding. MnPO neurons expressing ACE1 and the fluorogold tract tracer significantly increased colocalization with FosB expression following CIH as compared to normoxic controls (P<0.05). FosB also significantly increased association with the ACE1 gene within the MnPO following 7 days of CIH as compared to the normoxic controls (P<0.05). These results demonstrate that FosB and ACE1 are co‐expressed in PVN‐projecting MnPO neurons following CIH and increased ACE1 expression associated with CIH is mediated by FosB.Support or Funding InformationP01 HL088052
Increased Sympathetic Nerve Activity Due to Relaxin in the Subfornical Organ Is Mediated by RXFP1 Receptors on Astrocytes and Ultimate Activation of Projection Neurons to the Paraventricular Nucleus of the Hypothalamus in Both Female and Male Rats
Authors: Coldren K. Max , Hasser Eileen M. , Heesch Cheryl M. 
Published: November 2023

Endogenous relaxin (RLX), an ovarian hormone which is elevated in pregnancy, contributes to peripheral vasodilation in pregnant women and rats. Recent clinical trials in both male and female hospitalized acute heart failure patients (the majority of whom were also receiving blockers of the renin‐angiotensin system) indicate that exogenous administration of human recombinant RLX‐2 (i.v., 48 hrs) relieved dyspnea (due to reductions in pulmonary edema) within hours and reduced post‐discharge mortality at 180 days. In both males and females, RLX receptors are present in the vasculature, heart, and brain. Vascular actions of RLX are inhibitory and mediated through nitric oxide mechanisms, while central nervous system actions of circulating RLX are generally excitatory, mediated by angiotensin II mechanisms, and dependent on RLX receptors (RXFP1) in brain regions devoid of a blood brain barrier. Previously we demonstrated in anesthetized arterial baroreceptor denervated female rats that microinjection of synthetic human RLX‐2 into the subfornical organ (SFO, 0.77 pmol in 50 nl) produced sustained increases in lumbar sympathetic nerve activity (8 ± 3%) and mean arterial pressure (MAP, 26 ± 4 mmHg). Intra‐carotid artery (ica) infusion of a sub‐pressor concentration of RLX (155 pmol/ml/hr; 1.5 hr) increased heart rate (+50 ± 5 bpm) and activated neurons (increased Fos‐IR) in the SFO and in spinally‐projecting (19 ± 2%) neurons in the PVN. We now demonstrate that RLX receptors in the SFO are distributed in an annular pattern dorsal and lateral to activated (Fos‐IR) neurons. In both male and female rats, RLX receptors in the SFO were not located on PVN‐projecting neurons nor on microglia (Iba1‐IR). Astrocytes in the SFO are the major source of angiotensinogen and RLX receptors were associated with astrocytic cell bodies (S100B‐IR) and processes (GFAP‐IR) which were in close apposition to PVN projecting neurons. These data provide an anatomical substrate for a role of circulating RLX to modulate SNA through a mechanism possibly dependent on local formation of angiotensin II in the SFO. We speculate that RLX administration to decompensated heart failure patients could produce central sympathoexcitatory effects, but that continued treatment with angiotensin converting enzyme inhibitors or AT1 receptor antagonists in clinical trials may have blunted these untoward effects and contributed to positive outcomes.Support or Funding InformationNIH R01‐HL091164
Quantification of Cardiac Baroreflex Sensitivity during Autonomic Stimulation
Authors: Sharma Purnima , Mavai Manisha , bhagat Om lata , Murugesh Meghna , Sircar Sabyasachi 
Published: November 2023

BackgroundThe cardiac baroreflex system plays a major role in the short‐term regulation of the blood pressure. The baroreflex function as an interface between the central nervous and cardiovascular systems and in consideration of its clinical significance, the quantification of Baroreflex function is of high relevance. Its functional properties are strongly influenced by the parasympathetic system. In this study, we quantified Baroreflex sensitivity (BRS) during slow deep breathing (SDB) and cold pressor test (CPT).Material and MethodsIn 14 healthy volunteers’ (7 males and 7 females; mean age 17–21 yrs) baroreflex sensitivity (BRS) was quantified by applying sequence analysis based on continuous recording of blood pressure and heart rate. The BRS was quantified during slow deep breathing at 6 breaths/minute, cold pressor test at 5°C temperature for maximum 5 minutes.ResultsA significant increase in BRS up sequences was observed during the SDB as compared to the rest (18.57 ± 11.84 vs 31.52 ± 11.69; p = 0.01). Cold pressor test did not show any significant difference in the BRS up sequences compared to the rest (18.57 ± 11.84 vs 18.34 ± 9.89; p > 0.05). A significant lower BRS up sequence was observed during CPT as compared to the rest (18.34 ± 9.89 vs 31.52 ± 11.69; p = 0.01). A significantly higher BRS down sequences were observed during SDB as compared to the CPT (13.64 ± 8.03 vs 25.68 ± 8.44; p = 0.04). A significantly higher BRS all sequence was observed during the SDB as compared to the CPT (17.37 ± 8.57 vs 28.28 ± 7.2; p = 0.02).ConclusionThe present study revealed a substantial increase in baroreflex sensitivity during slow deep breathing, which constitutes a widely accepted measures of parasympathetic tone.Support or Funding InformationIndian Council of Medical Research (ICMR)
Reduced bone marrow adrenergic receptor signaling modulates PVN inflammatory factors
Authors: Ahmari Niousha , Schmidt Jordan T , Martyniuk Christopher T , Zubcevic Jasenka 
Published: November 2023

INTRODUCTIONNeurogenic hypertension is characterized by neuroinflammation and increased sympathetic nerve activity (SNA) to the periphery, including the bone marrow (BM). The BM SNA governs diurnal regulation of the BM hematopoietic cell turnover, with inflammatory cells typically released during the active period. We have previously shown that chronic increase in the BM SNA leads to elevation of inflammatory factors and release of inflammatory cells in angiotensin II (Ang II) hypertension (HTN). Moreover, extravasation of the BM‐derived inflammatory cells to the brain cardioregulatory regions, including the paraventricular nucleus (PVN), contributes to neuroinflammation and thus the pathophysiology of HTN. Therefore, we hypothesize that reduction in the effects of SNA on BM inflammatory cells will result in suppression of the inflammatory profiles in BM and PVN.METHODSA novel chimeric BM mouse was created by reconstituting sub lethally‐ irradiated C57BL/6J mice with whole BM cells from adrenergic beta 1 and beta 2 receptor knock out (AdrB1.B2KO) mice (Jax Labs). Following recovery, relative expression levels of Adrb1 in circulating mononuclear cells were assessed using quantitative RT PCR, in order to confirm the success of irradiation/reconstitution. Total RNA from PVN and BM was isolated and purified, and gene expression profiles were determined using a mouse 60K Agilent array. Differentially expressed gene networks were determined in each tissue using Pathway Studio (Elsevier).RESULTSThere were 8563 and 477 differentially expressed probes in the BM and PVN of AdrB1.B2 KO mice, respectively (FDR <0.05). Upon further investigation into the 53 gene networks differentially expressed in the BM and PVN in the AdrB1.B2 KO mice compared to CNT, it was determined that 13 pathways were related to the immune system. In the BM alone, 41 gene networks associated to immunity were observed in the KO chimera vs CNT (p <0.05). This included a decrease in gene network that included T cell adhesion and leukocyte accumulation gene networks (P<0.05). In terms of specific transcripts associated with these networks, CD4 and CD8a expression was downregulated by 1.3 fold (p<0.007), and 2.6 fold (p<0.01) respectively. In the PVN, there was a 1.3 fold downregulation of IL17 receptor alpha and beta (p<0.015), as well as a decrease in CCL2 expression (p<0.018).CONCLUSIONIn summary, reduction in responsiveness of the BM hematopoietic cells to SNA is associated with a reduction of inflammatory mediators in both the BM and PVN. Therefore, BM cells’ ability to respond to SNA stimulation can affect both central and peripheral inflammatory responses. This is expected to have significant implication in neurogenic HTN, characterized by both increased sympathetic drive and exaggerated immune responses.
Do Standard Laboratory Practices Lead to Obese Zebrafish Populations?
Authors: Watts Stephen Andrew , Dennis Lacey , Fowler Lauren Adele , Williams Michael Britt , Yuan Yuan , Barry Robert Jeff , Farmer Susan , D'Abramo Louis R , Powell Mickie Lynn 
Published: November 2023

The value of the zebrafish model is well established and its widespread utility is without question in the study of early development, environmental science, and translational approaches to human disease onset and progression. Outcome variability due to the absence of nutritional standardization within and among laboratories remains, and can be magnified due to a minimal understanding of the potential role of nutrition. The community continues to use embryos and adults derived from stocks in which the nutritional history is not defined, thus, direct or indirect effects of nutrients on outcomes cannot be evaluated. In this study we compared the growth demographics and body composition associated with feeding common commercial diets (closed formulation) and a purified reference diet to zebrafish.Twenty‐one day old juvenile fish were fed one of six diets (commonly used by the majority of laboratories in the US as determined by the Zebrafish Husbandry Association). Each diet treatment contained nine 2.8 L tanks, each containing 13 zebrafish (n=117 ind/treatment). Fish were fed twice daily (09:00 and 17:00 hr) at a ration of >5% body weight per day (based on the fastest growing treatment). Rations were adjusted biweekly. Weight gain varied among the diets, with 14 week mean weights varying among treatments from 670 to 950 mg fresh weight. Lipid content of males and females (ovary removed) ranged from 22 to 42 and 18 to 45% dry matter, respectively. As compared to fat content estimated in wild fish populations, the levels of body lipid reported here would suggest these lab‐reared zebrafish have excessive body fat that is relative to that observed in human obesity. These data support recent metabolic literature indicating zebrafish are excellent models for the study of obesity and related morbidities. Variations in growth and body composition analysis in response to common laboratory diets and practices highlight the problems associated with the lack of nutritional information and standardization of diets in the zebrafish research community. There is a critical need for the development of standardized diets and feed management strategies. This should be a high‐priority community effort among laboratories with support from ASN and NIH. The long‐term goal of nutrition research in zebrafish will be to identify the daily nutritional requirements and to develop appropriate standardized reference and open formulation diets for the zebrafish community.Support or Funding InformationResearch and animal care supported in part by the American College of Laboratory Medicine and the Aquatic Animals Research Core within the UAB NORC (P30DK056336).
Exercise responses in aged rats selected for High versus Low training response
Authors: Sepe Joe , Koch Lauren G. , Britton Steven L. , Diffee Gary 
Published: November 2023

Exercise training improves aerobic capacity, but there are a number of gaps in our understanding of the exercise training response: 1) There is a wide variability in the response to training among individuals (both human subjects and rodents), but little is known about the mechanisms underlying this variability in training response. 2) It is unclear to what extent aging affects the ability to adapt to endurance training. To address these questions, we used a contrasting animal model system in which rats were artificially selected for 19 generations into High Response Trainers (HRT) versus Low Response Trainers (LRT), based on their response to aerobic treadmill training. Exercise capacity (as measured by time to exhaustion, EX‐TIME) and VO2max were measured in 22 month old rats and then animals were divided into Sedentary (SED) vs. Exercise (EX) groups. EX animals were trained 5 days a week for 3 months, with speed and duration gradually increased to the point that animals were running at 14 m/min for 45 min. At the end of the 3‐month training period, exercise capacity and VO2max were again measured in all animals. Mean EX‐TIME and VO2max values significantly (p <0.05) declined in SED animals from Pre‐training (PRE) to Post‐training (POST). EX‐ TIME declined by 35% in POST compared to PRE, while VO2max declined by 26% in POST vs. PRE. In the EX animals there was no significant difference in PRE vs. POST EX‐TIME or VO2max mean values in the LRT group, while in the HRT group, there were significant (p <0.05) increases in EX‐TIME (POST values 147%) of PRE) and VO2max (POST values 131% of PRE). To determine the mechanism of this variability in exercise training response in old animals, we correlated individual animal's improvement in EX‐TIME to measures of their cardiac function using echocardiography and measures of expression of genes related to mitochondrial biogenesis in skeletal muscle. Improvements in EX‐TIME were well correlated with improvements in VO2max. While EX training significantly (p <0.05) improved mean Fractional Shortening (FS%) and Ejection Fraction (EF%) in HRT compared to SED, ( EF% increased by 19% compared to SED; FS% increased by 31%), in individual animals these values did not correlate with improvements in EX‐TIME. However, increases in expression of a number of genes related to mitochondrial biogenesis and PGC‐1alpha signaling were well correlated with improvements in EX‐TIME. These results show that 1) aging animals retain the ability to respond to endurance training with improvements in VO2max and exercise capacity, but a differential to respond between HRT and LRT animals remain, and 2) changes in expression of genes related to mitochondrial biogenesis appear to underlie individual variation in the response to exercise training.Support or Funding InformationSupported by NIH AG 030423
Arginine and Aerobic Training Prevent Impairment in Endothelial Function in Rats Under High Risk to Develop Metabolic Syndrome
Authors: Medeiros Renata Frauches , Gaique Thaiane Gadioli , Bento‐Bernardes Thais , Britto Fernanda Carla Ferreira , Motta Nadia Alice Vieira , de Jesus Oliveira Karen , Nóbrega Antonio Claudio Lucas 
Published: November 2023

It is not elucidated if aerobic training and arginine supplementation can have similar protective effects in individuals with constant exposure to the triggering agent of the metabolic syndrome, with the presence of subclinical alterations, but without the presence of cardiovascular disease. So the purpose of this study was to investigate the effect of arginine supplementation and aerobic training on vascular reactivity of rats under high risk of metabolic syndrome development. Wistar rats, males, adults were, initially, divided in two groups Control group (C; drinking water) and Fructose group (F; water with 10% fructose), after two weeks the F group was divided into four others groups: Fructose group (F), that continued with the same treatment, Fructose Arginine group (FA), Fructose Training group (FT) and Fructose Training Arginine group (FTA) same as F group, adding aerobic training on a treadmill and/or arginine supplementation by gavage (800mg/kg BM/day), in the last 8 weeks. There were no differences in body mass gain and caloric intake between groups (P>0.05). It was observed higher serum insulin in F group compared to control group after two (P=0.046) and ten weeks (P=0.014), while it was not observed any difference between the other groups compared to C group. In relation to serum triacylglycerol levels, after two weeks, there was no difference (P=0.154) between C and F groups. After ten weeks the F group presented higher triacylglycerol concentration (P<0.01) compared to C group and the training normalized this increased, however arginine supplementation had no effect on this parameter. The malondialdehyde serum concentration, an oxidative stress marked, had the same pattern as the triacylglycerol. Concerning vascular reactivity, there was no difference after two weeks of treatment. While at the end of protocol, the F group exhibited increased vasoconstrictory reactivity (P<0.01) to phenylephrine when compared to C and to trained groups (FT and FTA). The F group also presented an impaired endothelial vasodilator response to acetylcholine compared to other groups and the arginine supplementation and the aerobic training were able to prevent this impaired response. Thus aerobic training prevents the metabolic alterations, the hypereactivity to phenylephrine and the endothelial damage of rats with high risk to develop metabolic syndrome, while arginine supplementation was capable only to prevent the endothelial damage in this experimental model, with no potentiating effect.Support or Funding InformationCAPES, CNPq, FAPERJ e FINEP.