bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistence of Exercise Training Effect on Amyloid Pathology
Authors: Lawson Justin E , Dobbs Kaylin C. , Jensen Jordan L. , Phelps Eva A. , Timson Benjamin F. , Zimmerman Scott D.
Published: June 2021

Background

Early life aerobic exercise training (ET) reduces amyloid beta (Aβ) plaque load and improves cognition in transgenic mouse models of Alzheimer's Disease (Yuede, et al. Neurobiology of Disease, 35, 2009). Many people are physically active into early adulthood, but it is less likely that they continue lifelong ET. In addition, it is unclear if the benefits of early ET persist into later life. We examined the persistence of ET effects by measuring cognition and plaque load at 12 months of age in transgenic mice that had participated in ET during various periods of life.

Methods

Three groups of male APP/PS1 mice ran on a motorized treadmill at 20 m/min five days a week for 12 weeks at different times during their first year of life; EARLY (from 3–6 months), MIDLIFE (from 6–9 months), and LATE (from 9–12 months of age). A fourth group did not exercise train and served as sedentary controls (SED). At 12 months of age, all groups underwent Novel Object Recognition (NOR) and Morris Water Maze (MWM) testing to assess recognition memory and spatial learning. Brain hemispheres were collected for Thioflavin S staining to assay plaque load and for protein quantification. Soleus muscles were assayed for citrate synthase activity to verify the effectiveness of the ET regimen.

Results

One‐way ANOVA revealed a significant main effect of ET on citrate synthase activity with the LATE group having 25.8% greater activity. There was also a significant effect of ET on cognition though the effect was limited to the most recently trained groups and absent in the EARLY animals. There was a main effect of ET group on the latency to platform during the MWM Place Trials with significantly lower latencies in the MIDLIFE and LATE groups compared to SED and EARLY. Similarly, there was an increased time in target region in the LATE group compared to others in the MWM Probe trials. Recognition memory was also improved in the LATE group as demonstrated by a greater novel investigation time relative to the other groups. Finally, there was significantly lower plaque load in MIDLIFE and LATE animals (59.6% and 45.8% lower than SED, respectively).

Conclusion

There are significant cognitive benefit of ET, but little persistence once ET is discontinued in APP/PS1 mice. Interestingly, LATE group data provide evidence that beginning ET later in the amyloidogenic process is still effective at preserving cognitive function and reducing plaque load. Protein analysis is on‐going and will assess the impact of ET on brain signaling and clearance proteins in these 4 groups.

Support or Funding Information

Supported by Missouri State Research Funds

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 Phase Response to Exertional Heat Stroke in Mice
Authors: Iwaniec John D , Robinson Gerard D , Garcia Christian D , Murray Kevin D , Laitano Orlando D , Clanton Thomas D
Published: June 2021

Exertional heat stroke (EHS) is a serious illness and a common occurrence for military personnel, athletes, and occupational workers. Innate immunity is vital for cell survival and tissue repair needed for recovery following EHS. Previously, our group revealed a unique cytokine response to EHS where circulating interleukin‐6 (IL‐6) peaked at 0.5 h post EHS; however, little is known about the acute phase response, a subsequent response to IL‐6 signaling. Therefore, we hypothesized that EHS would induce an acute phase response that would be observed in skeletal muscles, hepatocytes, and in the circulation.

Purpose

To determine if acute phase proteins (APPs), fibrinogen, lipocalin, and serum amyloid A1 (SAA1) are expressed in liver and skeletal muscle following EHS and whether these result in their accumulation in the circulation.

Methods

Mice were subject to a standardized EHS protocol using a forced running wheel. While running, the mice experienced environmental temps of 37.5 (EHS) or 22.5 (exercise control) until they experienced loss of consciousness (at a core temperature of ~42.2). The tibialis anterior, soleus, liver, and plasma were collected from the mice (n = 8/group) at 0.5, 3, 24, 96, 216, or 336 h post‐EHS. Tissue samples from exercise controls were retrieved at 3 and 96 h post exercise.

Results

Using protein immunoblots, a significant increase of SAA1 was observed in liver at 3 h of recovery and peaked at 24 h when compared to the exercise control (2.4 ± 1.2*, 2.5 ± 1.4* vs. 0.1 ± 0.1 AU/total protein; respectively). Moreover, circulating SAA1 was observed at the 3 h time point (5.0 ± 3.8 AU/TP). No difference for SAA1 was observed for any other time points when compared to the control. In the liver, fibrinogen, and lipocalin were undetectable for any of the recovery timepoints. No acute phase proteins were detected in skeletal muscle; although, preliminary data revealed that SAA1 expression is elevated in skeletal muscle during sepsis.

Conclusion

A single episode of EHS alters the expression of SAA1 in mouse liver and plasma. This observation is consistent with an acute phase response to thermal damage, in response to IL‐6 signaling, initiating cell survival and tissue repair pathways needed for recovery.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Perception of Weight Status and BMI Based on Self‐Reported Weight and Height Among Undergraduate Students
Authors: Khanna Deepesh
Published: June 2021

Introduction

University students, especially women perceive themselves as overweight. This is of major concern because inappropriate weight perceptions can lead to inappropriate dietary behaviors or a sedentary lifestyle. Perception of overweight at the normal or underweight range of BMI leads to conditions like anorexia nervosa or bulimia.

Methods

The cross‐sectional study was conducted among undergraduate students at a university in Arkansas during August‐December 2018. Face‐to‐face interviews using a validated questionnaire were employed to collect the data. BMI was calculated based on the self‐reported height and weight. Perceptions regarding weight were elicited using two questions: “Do you consider yourself to be underweight, overweight, or about right”? And, “if overweight, do you consider yourself to be obese or not?” The association between self‐reported BMI and weight perception was assessed with Chi‐Square tests for males and females. Level of significance was set at 0.05.

Results

Data are presented as mean ± SD. Total 126 undergraduate students participated in the study, 86 males and 36 females. Descriptive statistics showed BMI of 27.07 ± 5.61 kg/m2 in males and 25.69 ± 4.52 kg/m2 in females. Majority of students reported a BMI range of normal weight which is 18.5–24.9 kg/m2 (88.9% of males, 72.2% of females). Out of the total males who self‐reported normal BMI, 3.7% considered themselves underweight and 7.4% considered overweight (χ2 = 33.6, p = 0.000). On the other hand, females who reported normal BMI, 16.7% considered themselves underweight and 11.1% considered overweight (χ2 = 13.250, p = 0.01). Among males who considered themselves overweight, 74.1% did not perceive themselves as obese (χ2 = 51.7, p = 0.000). On the other hand, among females who considered themselves overweight, 78.6% did not perceive themselves as obese (χ2 = 5.7, p = 0.677).

Conclusion

Results show that the average BMI is higher for males as compared to females. Weight standards are rather uniform between males and females, with female students more likely to perceive themselves as overweight and underweight at a normal BMI range. Furthermore, among males and females who perceived themselves as overweight, most of them do not consider themselves as obese. These findings are important for future primary and secondary prevention efforts. The gender differences advocate the need for gender‐tailored intervention programs.

Support or Funding Information

Department of Health & Physical Education, Arkansas Tech University, Russellville, AR

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Tumor microenvironment regulates endothelial cell transformation via modulation of TRPV4 channels
Authors: Guarino Brianna D , Adapala Ravi K , Kanugula Anantha K , Lenkey Nina M , Paruchuri Sailaja , Thodeti Charles K
Published: June 2021

Abnormal angiogenesis and hyper‐permeable vessels characterize the tumor vasculature. Together, these attributes contribute to atypical growth rate and metastasis of tumor cells. We have recently shown that the mechanosensitive ion channel, transient receptor vanilloid 4 (TRPV4) expression and activity is significantly reduced in tumor endothelial cells (TEC), and that activation of TRPV4 normalized tumor vasculature and improved cancer therapy. However, whether and how the tumor microenvironment downregulates TRPV4 and transforms normal endothelial cell phenotype remains unknown. To explore this, we repeatedly exposed normal human endothelial cells (NhEC) to human lung adenocarcinoma (tumor) cell conditioned media and measured phenotypic changes, angiogenesis, and functional expression of TRPV4. We found that treatment with cancer cell conditioned media changed NhEC to a tumor endothelial‐like phenotype (ThEC) as evidenced by; increased expression of tumor endothelial cell marker 8 (TEM8) and exhibition of abnormal angiogenesis on 2D‐Matrigels compared to normal NhEC. Mechanistically, we observed that expression and activity of TRPV4 was reduced in ThEC. Finally, we found that treatment with a Rho kinase inhibitor, Y‐27632 normalized abnormal tube formation exhibited by ThEC. Taken together, our results suggest that the tumor microenvironment transforms normal endothelial cells into tumor endothelial cell‐like phenotype through the downregulation of TRPV4.

Support or Funding Information

NIH (1RO1HL119705), NIH (1R15CA202847‐01), and start‐up funds from NEOMED (CKT).

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The effect of a high fat diet in the regulation of MAP kinase in left ventricle fibrosis
Authors: Cudnoch‐Jedrzejewska Agnieszka , Czarzasta Katarzyna , Koperski Lukasz , Segiet Agnieszka , Fus Lukasz , Gornicka Barbara
Published: June 2021

Introduction

It is well known that obesity contributes to the development of systemic inflammatory responses, which in turn may be involved in the process of interstitial fibrosis and left ventricular (LV) remodeling. Activation of proinflammatory factors such as transforming growth factor β (TGF‐β) can directly stimulate mitogen‐activated protein kinase (MAPK) p38 and JNK.

Purpose

The aim of this study was to evaluate the level of TGF‐β, MAPK p38 and JNK in the LV in Sprague Dawley (SPRD) rats maintained on a high fat diet (HFD).

Methods

The SPRD rats were maintained on a normal fat diet (NFD) or on a HFD from 4 weeks of age for 12 weeks (NFD 16‐week‐old rats, NFD 16‐wk; or HFD 16‐week‐old rats, HFD 16‐wk) or for 16 weeks (NFD 20‐week‐old rats, NFD 20‐wk; or HFD 20‐week‐old rats, HFD 20‐wk). At the end of the experiment, blood and LV were collected from all rats for further analysis (Real‐Time PCR, histopathological and immunohistochemical analysis). Consent was obtained from The Local Animal Research Ethics Committee (33/2011).

Results

The LV fibrosis area in relation to the entire LV area was significantly higher in the HFD 16‐wk rats and the HFD 20‐wk rats compared with the NFD 16‐wk rats and the NFD 20‐wk rats, respectively. TGF‐β mRNA expression did not differ between the study groups of rats. However, p38 MAPK mRNA expression and c‐jun mRNA expression were significantly lower in the HFD 20‐wk rats than in the HFD 16‐wk rats. TGF‐β type II receptor (TβRII) protein demonstrated only cytoplasmic reactivity, while p38 MAPK protein and c‐jun protein showed both nuclear and cytoplasmic reactivity. The p38 MAPK nuclear reaction did not differ significantly between the study groups of rats. In contrast, the cytoplasmic response of the p38 MAPK was dependent on the administration of both HFD in two time intervals to the groups of rats. Significant differences in the nuclear reaction for c‐jun were observed between the exanimated groups of rats. The c‐jun nuclear expression was significantly lower in the HFD 20‐wk rats than in the HFD 16‐wk rats.

Conclusion

A high fat diet caused an increase in LV fibrosis in SPRD rats. Additionally, extension by the next 4 weeks the duration of HFD intake did not increase the LV fibrosis area. Moreover, high fat diet in both intervals significantly influences the expression of p38 MAPK and JNK in the LV. However, demonstrating their potential involvement in the processes of interstitial myocardial fibrosis and left ventricular remodeling requires further research.

Support or Funding Information

This study was financially supported by statutory funds from the Medical University of Warsaw (1MA/N/2018).

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Vascular Action of Insulin in Pregnancy
Authors: Reyes Betzabel Rodríguez , Pérez Muñoz Eduardo I , López Mayorga Ruth M , Lugo Rosa Amalia Bobadilla
Published: June 2021

Physiological insulin resistance associated with pregnancy is attributed to the increase of anti‐insulin hormones such as placental lactogen and p85 (potent negative regulator of PI3K), human growth hormone, TNFα, as well as adipokines. Besides, AT1 receptor for angiotensin II has a clear role in insulin resistance while the role of AT2 receptors is not well understood. On the other hand, it has been described an increased vascular expression of AT2 receptor during pregnancy. On the other hand, insulin has shown a PI3K‐AKT NO mediated vasodilator effect that may contribute to its metabolic actions. Therefore, the aim of this study was to evaluate if pregnancy decrease in the vasodilatory action of insulin and AT2 receptors participation in this change. Using a conventional isolated organ preparation, the vasodilator effect of cumulative concentrations of insulin was evaluated in rat aortic rings pre‐contracted with phenylephrine. Vasorelaxation of aorta rings was compared at day 14 and day 20 (term) of pregnancy in the presence and absence of the AT2 receptor antagonist PD123319. Pregnancy produced resistance to insulin induced vasodilatation in the thoracic aorta while the vasodilator effect increased in the abdominal aorta only in rings with intact endothelium. AT2 receptors participation on the insulin induced vasodilation was more evident on day 14 (half) gestation. These results suggest that the vascular action of insulin is enhanced by the participation of AT2 receptors for angiotensin II. Also, that both insulin action and AT2 receptor participation during pregnancy depend on the vascular territory studied.

Support or Funding Information

SIP Instituto Politécnico Nacional, COFFAA

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Angiotensin Converting Enzyme Polymorphism in Acute Myocardial Infarction
Authors: de Moraes Oscar Albuquerque , Scapini Katia , Jensen Leonado , de Souza Leandro Eziquiel , Irigoyen Maria Claudia
Published: June 2021

It has been established that renin angiotensin system gene polymorphism, such as angiotensin converting enzyme (ACE), could contribute to a higher occurrence of acute myocardial infarction (AMI). Thus, the objective of this study was to evaluate the effects of the variation of the number of copies of the ACE gene in the AMI. Adult mice, genetically modified to express different concentrations of the ACE were used (one, two and three copies – ACE 1, ACE 2 and ACE 3). The animals were divided into 9 groups (n = 10): 3 without AMI ‐ ACE 1, ACE 2 and ACE 3; 3 infarcted groups assessed 7 days after AMI ‐ ACE 1‐MI7, ACE 2‐MI7 and ACE 3‐MI7; 3 infarcted groups assessed 28 days after AMI ‐ ACE 1‐MI28, ACE 2‐MI28 and ACE 3‐MI28. Infarcted animals were submitted to AMI by ligature of the left coronary artery. Cardiac function by echocardiography, heart rate variability (HRV) and baroreflex sensitivity were evaluated. Regarding the echocardiographic data, the E/A ratio was higher in the ACE group 3‐MI7 than in the non‐infarcted groups with one and two copies of ACE and higher than in the infarcted group with two copies of the ACE gene (ACE 3‐MI7: 3.47 ± 0.50 vs. ACE 1: 1.08 ± 0.14, ACE 2: 1.24 ± 0.16 and ACE 2‐MI7: 1.74 ± 0.25); the fractional area change was lower in the infarcted groups ACE 1‐MI7, ACE 2‐MI7 and ACE 3‐MI7 compared to non‐infarcted and was lower in the ACE group 3‐MI7 than in the ACE groups 2‐MI7 and ACE 1‐MI7 (ACE 3‐MI7: 21,30 ± 1,47 vs. ACE 1‐MI7: 30,10 ± 1,80 and ACE 2‐MI7: 31,12 ± 1,47%). Regarding the autonomic parameters sympathetic modulation was higher in the ACE group 3‐MI7 than in the ACE 1, ACE 2 and ACE 1‐MI7 groups (ACE 3‐MI7: 14.85 ± 2.36 vs. ACE 1: 4.76 ± 2.00, ACE 2: 4.34 ± 1.40 and ACE 1‐MI7: 5.13 ± 1.88 ms2); and the sympatovagal balance was higher in the ACE group 3‐MI7 than in the ACE group 1‐MI7 (ACE 3‐MI7: 2.22 ± 0.17 vs. ACE 1‐MI7: 0.81 ± 0.25). When comparing infarcted groups 7 and 28 days after AMI, it was observed that the baroreflex efficiency index was higher in the ACE group 1‐MI28 than in the infarcted groups assessed 7 days after the infarction (ACE 1‐MI28: 0.28 ± 0.03 vs. ACE 1‐MI7: 0.15 ± 0.02, ACE 2‐MI7: 0.17 ± 0.01 and ACE 3‐MI7: 0.17 ± 0.01). Infarcted animals with 3 copies of the ACE gene had lower survival (41%) and animals with 1 copy of the ACE gene had greater survival (71%) at the end of the study.

CONCLUSION

Our results of cardiac function, cardiovascular autonomic function and survival curve indicate that animals with three copies of the ACE gene presented a worse evolution after myocardial infarction in relation to the animals with one copy of the ACE gene.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
IMPAIRMENT ON CARDIOVASCULAR AND AUTONOMIC ADJUSTMENTS TO ISOMETRIC EXERCISE IN OBESE SUBJECTS: CORRELATIONS WITH INDEXES OF OBESITY
Authors: da Silva Reberth Magalhães , Viana Ariane , dos Santos Thiago Lucio , De Angelis Katia
Published: June 2021

Obese individuals are susceptible to developing hypertension due to impaired sympathetic and/or parasympathetic modulation and reduced heart rate variability (HRV), and baroreflex sensitivity at rest. Isometric exercise is a challenge for the cardiovascular system and may contribute to triggering early changes in susceptible individuals. The aim of the presente study was to investigate cardiovascular parameters and HRV in obese subjects at rest and in response to isometric exercise using a handgrip. We performed metabolic, cardiovascular and autonomic evaluations in healthy and sedentary individuals (21.09 ± 2.35 years) distributed into 2 groups: Obese (OG, n = 06) and Eutrophic (EG, n = 06) at rest and in response to 90 seconds of physical stress with HandGrip (HG, 30% of the maximal load). We observed increased body mass (p = 0.001), abdominal circumference (p = 0.006), waist circumference (p = 0.007), hip circumference (p = 0.002) and BMI (p = 0.001) in OG, characterizing the sample. We did not observe differences between the groups for blood pressure or blood glucose, triglycerides (p = 0.06) and cholesterol. At rest, the OG showed an increase in the cardiac LF band of HRV in absolute values (p = 0.04), which represents na impairment on cardiac sympathetic modulation in comparison to the EG. In addition, the OG showed an exacerbated response for both systolic (SBP, p = 0.02) and diastolic blood pressure (DBP, p = 0.006) immediately post HG when compared to EG. In addition, after 15 minutes of recovery of the HG, SBP (p = 0.01) and DBP (p = 0.002) of EG returned to baseline values, which was not observed in OG. We also observed improved total HRV post HG in EG in relation to resting values (p = 0.001), which was not observe in the OG. We observed positive correlations for both, final DBP and abdominal circumference (r = 0.74, p = 0.02), and for final DBP and fat mass percentages by skin folds (r = 0.73, p = 0.01). Considering that increased waist circumference, % fat mass and BMI are proven cardiovascular risk factors, we observed here that these factors associated with sedentary lifestyle are correlated with exacerbated blood pressure responses to isometric physical stress. Therefore, although young obese individuals are apparently healthy, they may present increase on sympathetic modulation to the heart at rest and impaired responses to isometric exercise, demonstrating early markers of cardiovascular risk in this population.

Support or Funding Information

Finacial Support: UNINOVE, CAPES, CNPq.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Study of Quality Characteristics and Functional Evaluation of E. cottonii
Authors: Kang Myunghwa , Jeong Bit‐na , An Su‐mi , Kim Do‐Hee
Published: June 2021

Seaweeds contain potentially good nutrients along with sources of protein, carbohydrates, fibers, minerals and vitamins, and have low lipid content. Among them, E. cottonii is a potential and interesting new It is known to be a source of natural materials.

In this study, the characteristics, physical properties and functional evaluation of E. cottonii were compared and studied. Moisture content was highest in G.E and high in non roasted samples. Crude protein content was the highest in C.S.E and high in non roasted samples. The content of ash was highest in R.G.E and it was generally higher in the samples grown. The crude fat content was the highest in R.C.S.E and it was measured higher in the cultured and treated samples. The total carbohydrate content of R.G.E and R.C.S.E was higher than that of roasted carbohydrate. The yield of carrageenan was the highest in R.C.S.E and it was high in cultured and treated samples. The physical properties of Carrageenan were generally higher in G.E. Leucine was the essential amino acid and glutamic acid and aspartic acid were the most essential amino acids. The content of K was the highest in the mineral contents, Fe and P were significantly lower than the other values, and the content of Se was not found. The electron donating ability was the highest value of water extracted samples. Among them, C.S.E and R.C.S.E were the highest. ABTs radical scavenging activity was the highest value of 80% ethanol extracted and R.C.S.E was the highest. SOD‐liked activit was highest in 80% ethanol and R.C.S.E was the highest. Reducing power activity showed no significant difference between the samples. Total phenolic acid content also showed no significant difference among the samples. Total flavonoid content was highest in water samples and G.E was the highest.

Support or Funding Information

As a result of this study, the samples treated with the culture solution were measured at higher values. The yield of Carrageenan was close to 20% in R.C.S.E and as a result, carrageenan contained in E. cottonii was found to be able to obtain optimal yields in the future through the use of gelling agents, thickeners, stabilizers, surfactants, And the like. In addition, E. Cottonii is expected to be used as a natural antioxidant.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Home‐Based Exercise Training on Post‐Exercise Peripheral Muscle Oxygenation in Children with Congenital Heart Disease
Authors: Lahti Dana S , Blushke Corey R , Pockett Charissa , Bradley Timothy J , Pharis Scott , Butcher Scotty J , Kosokowsky Kylee , Boyes Natasha G , Wright Kristi D , Erlandson Marta C , Tomczak Corey R
Published: June 2021

A hallmark feature of children with congenital heart disease (CHD) is exercise intolerance, along with slow post‐exercise muscle oxygenation recovery. Exercise rehabilitation programs have been shown to improve peak V̇O2 in children with CHD; however, exercise tolerance is still limited compared to healthy matched controls. Whether exercise training improves post‐exercise recovery of muscle oxygenation (as measured by tissue oxygenation index, TOI) in children with CHD compared to healthy children is unknown.

PURPOSE

To determine whether a 12‐week home‐based exercise intervention can improve post‐exercise TOI response after peak exercise in children with CHD compared to controls.

METHODS

Eight children with CHD (f/m = 4/4; mean ± SD age: 12 ± 2 yrs) with simple and complex lesions and seven healthy controls (f/m = 3/4; age: 12 ± 3 yrs) were studied. Children with CHD completed a home‐based exercise program 3 times/week for 12 weeks, in addition to 6 biweekly in‐person sessions. Exercise tolerance was assessed with peak V̇O2 testing to volitional fatigue on a cycle ergometer, followed by 4 minutes of 20‐W recovery. Vastus lateralis TOI was continuously sampled during exercise and recovery via near‐infrared spectroscopy. Post‐exercise TOI recovery data was normalized from 0% (end‐exercise) to 100% (4 min post‐exercise) and data analyzed at set time points to characterize TOI time course changes (0s, 15s, 30s, 60s, 90s, 120s, 180s and 240s). Pre vs. post training changes in TOI were analyzed using paired t‐tests. Significance was accepted when P<0.05.

RESULTS

Post‐exercise TOI was significantly lower in CHD pre‐training compared to controls at 15s (9 ± 9 vs. 27 ± 16 %; P = 0.018) and 30s (32 ± 17 vs. 72 ± 35%; P = 0.012). Similarly, post‐exercise TOI in CHD after exercise training was significantly lower than controls at 15s (9 ± 7 vs. 27 ± 16 %; P = 0.014) and 30s (36 ± 22 vs. 72 ± 35%; P = 0.030)‐‐‐.

CONCLUSION

Excessive post‐exercise impairment in TOI recovery persists after home‐based exercise in children with CHD compared to controls.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Orthopedic Injury‐Induced Hypercoagulability in Rats
Authors: Palei Ana Carolina , Carter Kristen T. , Witcher Brycen M. , Spradley Frank T. , Kutcher Matthew E.
Published: June 2021

Trauma‐associated hypercoagulability is estimated to occur in 28% of injured patients, leading to thromboembolic complications such as deep venous thrombosis and pulmonary embolism. Orthopedic injury accounts for >45% of injuries requiring hospitalization. However, few clinically relevant models exist to examine the specific mechanisms underlying orthopedic injury‐induced hypercoagulability. Therefore, the aim of this study was to establish a novel rodent model of hypercoagulability after bilateral hindlimb injury mimicking the hypercoagulability found in trauma patients. For this purpose, 16‐week‐old male Wistar rats (n=5, mean body weight=381±21 g) were anesthetized; had carotid catheters placed for serial blood sampling; and were subjected to bilateral hindlimb fibula fracture with controlled soft tissue and muscular crush injury followed by injection of bone homogenate, mimicking injuries sustained with bilateral femur fracture. Blood samples were drawn into 4% sodium citrate, incubated for 30 min at room temperature while rocking, and analyzed by native thromboelastography (TEG) at 3, 6, 12, and 24 h post‐injury. TEG is a viscoelastic assay that allows for comprehensive assessment of clot formation and degradation in whole blood which, unlike standard clinical coagulation tests, can detect hypercoagulability. Baseline TEG studies were performed in triplicate immediately after catheter placement. Compared to baseline measurements, mean TEG parameters did not significantly differ at 3 and 6 h time points. However, significant hypercoagulability was noted at 12 h in maximal amplitude of clot firmness (1.2‐fold increase, p=0.002), overall clot strength (TEG ‘G’ value, 2.1‐fold increase, p=0.003), and thrombin generation (1.2‐fold increase, p=0.003); these parameters remained persistently elevated at 24 h (1.3, 2.5, and 1.2‐fold higher than baseline, respectively; all p<0.003). There were no significant differences compared to baseline at any time points in the TEG parameters R (reflecting time to clot initiation), K or angle (reflecting fibrin polymerization kinetics), or lysis index (reflecting fibrinolysis; all p>0.05). In summary, a rodent model of bilateral hindlimb orthopedic injury recapitulates post‐injury hypercoagulability identified in human trauma patients, as identified by TEG. Hypercoagulability is specifically manifested as increased clot strength and thrombin generation, with no changes alterations in time to clot formation, fibrin polymerization kinetics, or fibrinolysis. We propose that this model will allow for investigation of mechanisms mediating injury‐induced hypercoagulability to assist in identifying novel strategies for thromboprophylaxis.

Support or Funding Information

NIH HL105324, NIH HL130577, NIH TR001417, and NIH GM115428

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The absence of AMPK beta1 exacerbates the acute olanzapine‐induced hyperglycemia in female mice
Authors: Shamshoum Hesham , Medak Kyle D. , Wojdyla Gabriela , Peppler Willem T. , Townsend Logan K. , Kemp Bruce E. , Wright David C.
Published: June 2021

Olanzapine is a second‐generation antipsychotic drug used widely in the treatment of schizophrenia. Though effective in reducing psychoses, acute olanzapine treatment causes acute increases in blood glucose and chronically leads to weight gain. A primary contributor to acute olanzapine‐induced hyperglycemia is glucagon mediated‐increases in liver glucose production. Prior work by our lab demonstrated that exhaustive exercise or treatment with 5‐Aminoimidazole‐4‐carboxamide ribonucleotide (AICAR), approaches which activates the energy sensing enzyme 5′AMP activated protein kinase (AMPK), protect against olanzapine‐induced hyperglycemia. The purpose of this study was to determine if 1) olanzapine‐induced hyperglycemia would be exacerbated in AMPK b1 deficient (KO) mice and 2) if A769662, a specific allosteric activator of AMPK b1 containing complexes, could mitigate the effects of olanzapine on glucose homeostasis. We hypothesized that the absence of AMPK b1, a subunit which is primarily found in the liver, would worsen the acute metabolic effects of olanzapine and that A769662 would prevent olanzapine‐induced hyperglycemia control mice. Female AMPK b1 KO or wild type (WT) mice were treated with olanzapine (5 mg/kg) and blood glucose was taken at baseline and 30, 60 and 90 minutes post‐injection. As anticipated, the protein content and phosphorylation of AMPKa was significantly reduced in liver from AMPK b1 KO mice and this coincided with a greater olanzapine‐induced increase in blood glucose compared to WT mice. Serum glucagon concentration was not significantly different between genotypes after OLZ treatment nor were there any differences in the protein content of the gluconeogenic enzymes PEPCK and G6Pase. Interestingly, when challenged with glucagon (1.0 mg/kg IP) or epinephrine (0.5 mg/kg IP) the rise in blood glucose was greater in KO compared to WT mice, suggesting that an increase in the responsiveness to hormonal gluconeogenic signals could explain the potentiated effect of olanzapine in AMPK b1 KO. Surprisingly, co‐treatment with A769662 (30 mg/kg) did not attenuate olanzapine‐induced increases in blood glucose in female C57BL6/J mice. Our findings provide evidence that reductions in AMPK activity potentiate the effects of acute olanzapine treatment on blood glucose, whereas specifically targeting AMPK b1 containing complexes is not sufficient to protect against olanzapine‐induced hyperglycemia.

Support or Funding Information

This study was supported by Canadian Institutes of Health Research

Support or Funding Information

This study was supported by Canadian Institutes of Health Research

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The result of histochemical research in the diagnosis of steatosis in cows
Authors: Votinceva Aleksandra , Nikitina Anastasiya , Nikitin Georgiy , Kovalev Sergej , Plemyashov Kirill , Anipchenko Polina , Netschajew Andrej , Herbakov Grigorij SHC
Published: June 2021

Ration disbalancing in highly‐productive cows, as well as the influence of toxic elements often leads to the development of steatosis, which almost always occurs latently. As a rule, the development of the first clinical signs is registered already with irreversible damage of hepatocytes, which causing death of animal. In 2018, 13 samples of liver biomaterial obtained from cows with steatosis of different severity of the disease were examined. Material for histological research were fixed in a 95% solution of ethanol for 24 hours. Further, according to the standard method, paraffin is embedded. Slices were made 5–7 microns thick. The resulting sections were stained with hematoxylin and eosin, Schiffod‐iodic acid by McManus to detect glycogen. Morphological study of histological preparations was carried out using a Carl Zeiss light‐optical microscope with a magnification of 50–400. Microphotos were taken using an Axio Scope A1 digital camera. In the analysis of histological samples, pathological changes in the liver were observed in the form of expressed centrolobular local and diffuse small‐droplet and large‐droplet fatty degeneration of hepatocytes (Fig. 1), as well as a decrease and absence of glycogen cells (Fig. 2, 4). The liver had a regular girder structure, it was full‐blooded. The sinusoids of the liver and Disse spaces were medium dilated (Fig. 3). Portal triad had a typical histological structure, in some cases were expanded, in the stroma of the tracts were found hepatic triad, represented by the interlobular artery, vein and bile duct. Thickening of the portal triad with poorly expressed mononuclear infiltration was also noted, with no significant inflammatory changes in the samples presented (Fig. 5). These changes may be toxic. In addition to the above dystrophic and functional changes, a dilation of Disse sinusoidal spaces was also noted (Fig. 3). Staining of Schiff‐iodic acid by MacManus showed the absence of glycogen in four samples. Using the same staining protocol showed positive staining effect of the reticular fibers of the interstitial tissue of the cow's kidney. The remaining samples, the amount of glycogen in the hepatocytes was significantly reduced. In animals whose liver samples showed a lack of glycogen clinical finding of liver dysfunction were expressed. As a result, in the acute form of cows' steatosis, the amount of glycogen in hepatocytes sharply decreases. This leads to irreversible consequences, and often fatal.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Gut Microbiome is Dispensable for Normal Respiratory Function and Chemoreflexes in Adult Mice
Authors: Morales Fatima Beatriz Saldana , Ray Russell Scott
Published: June 2021

Increasing evidence indicates that changes in respiratory homeostasis and disordered breathing, such as obstructive sleep apnea, intermittent hypoxia or exercise can modulate or are associated with changes in the gut microbiome. Additionally, alterations to gut microbiome have been hypothesized to play a role in autoimmune diseases, social behavioral deficits, and metabolic diseases such as diabetes and cardiovascular disease. We therefore aimed to determine if a model of gut dysbiosis, the absence of a gut microbiome, would result in alterations to respiratory homeostasis.

In order to determine if the lack of a gut microbiome would alter respiratory homeostasis, we assayed 8‐week‐old C57bl6J germ‐free (GF, n=24) and specific‐pathogen‐free (SPF, n=24) mice under normoxic (21%O2, 79%N2) conditions and challenging them with hypercapnic (5%CO2, 21%O2, 74%N2) and hypoxic (10%O2, 90%N2) environments. Whole‐body flow through plethysmography was used to monitor respiratory function and metabolic demand in conscious and unrestrained animals. The experimental protocol consisted of 5 days of habituation to human handling and chamber acclimation prior to respiratory assessment. GF mice habituation was performed inside the germ‐free isolator prior to exiting them for testing. To determine if gut colonization of GF mice may alter respiratory function, 12 GF mice assayed by plethysmography and then orally inoculated with fecal samples from SPF donor mice, while 12 SPF control mice were assayed for respiratory function and then inoculated with sterile saline. All animals were then placed back into the SPF facility for 3 weeks to allow for gut colonization.

Mice were analyzed for respiratory rate (Vf), tidal volume (VT), minute ventilation (VE), oxygen consumption (VO2), and minute ventilation normalized by oxygen consumption (VE/VO2). For GF vs SPF experiments 2‐way ANOVA was performed with Bonferroni multiple comparison correction and a p<0.05 was used to indicate statistical significance. No difference between GF and SPF mice for any parameter was found. For GF gut recolonization experiments, no significant difference was found within group comparing pre‐ and post‐recolonization and between groups. Pre‐ and post‐recolonization data was compared using a paired t‐test while the comparison between groups was done by a 2‐way ANOVA with Bonferroni multiple comparison correction. A p<0.05 was used to indicate statistical significance.

Overall these results suggest that the gut microbiome is dispensable for normal respiratory function and respiratory chemoreflexes in adult mice and that the lack of a gut microbiome, a model of gut dysbiosis, does not result in significant changes in respiratory homeostasis.

Support or Funding Information

McNair Medical Institute

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
MAPPING NEURAL CIRCUITS CRITICAL TO UPPER AIRWAY FUNCTION AND BREATHING‐SWALLOWING COORDINATION
Authors: Shi Huanan , Ray Russell Scott
Published: June 2021

Upper airway control and the coordination between swallowing and breathing are essential to avoid the introduction of food or liquids into the lungs. The neural networks underlying upper airway control and swallowing coordination is poorly understood. However, perturbations to these networks may play a role in Sudden Infant Death Syndrome, obstructive sleep apnea, and neurodegenerative disorders such as Parkinson's disease where as much as 44% mortality is attributed to aspiration pneumonia. Thus, there is a clear need to better understand the neural mechanisms that underlie upper airway control, swallowing coordination, and cough reflex throughout life.

Though GABAergic signaling is critical to modulate breathing, the functional organization of widespread GABAergic neurons throughout the brainstem remains unclear. We hypothesize that the adult GABAergic system is integrated into distinct functional modules within the brainstem respiratory network aligned along early hindbrain rhombomeric origins. To test this hypothesis, we aim to genetically subdivide the adult brainstem GABAergic system based on their embryonic rhombomere of origin for functional and anatomical mapping studies through the use of intersectional genetic techniques and new chemo‐genetic (DREADD) mouse lines combined with whole body barometric plethysmography and metabolic monitoring.

Preliminary studies indicate that inhibitory DREADD hM4De‐mediated perturbation of systemwide GABAergic neurons (Vgat_FLPo positive neurons) results in increased respiratory output and greater breathing instability while excitatory DREADD hM3D‐mediated systemwide perturbation results in increased sighs and decreased metabolic demand. Examination of the respiratory waveform shows mid‐inspiratory pauses indicative of poor glottal control and increased incidences of cough and expiratory reflex movements. Initial results from rhombomere GABAergic mapping studies suggest that GABAergic involvement in adult chemosensory reflexes may be organized along developmental rhombomeres during embryogenesis.

Support or Funding Information

McNair Medical Institute

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 hyperglycemia does not alter central respiratory CO2 chemoreflex responsiveness
Authors: Bird Jordan , Skalk Alexandra , Thrall Scott , Strzalkowski Nicholas , Day Trevor A
Published: June 2021

The control of breathing is modulated by two distinct but interacting respiratory chemoreceptor compartments: peripheral chemoreceptors (PCRs; carotid bodies) and central chemoreceptors (CCRs; brainstem). The PCRs respond to variety of chemostimuli, including arterial oxygen, arterial carbon dioxide, glucose, insulin and temperature, and are now thought to act as metabolic sensors. However, CCRs have only been characterized as carbon dioxide/acid sensors (PCO2/[H+]). PCRs respond to chemostimulation faster than CCRs, which may mask CCR responses to stimuli like acute hyperglycemia. The aim of this study was to characterize the relationship between alterations in blood glucose concentration and central respiratory chemoreflex responsiveness via hyperoxic rebreathing in healthy humans. We hypothesized that experimentally‐induced relative hyperglycemia following an oral glucose tolerance test (OGTT; 75g, 300 ml) would (a) increase the rate of CO2 accumulation during rebreathing and (b) augment central respiratory chemoreflex responsiveness due to a synergistic effect of hyperglycemia on the CO2 sensitivity of CCR neurons. In 10 healthy participants, we measured minute ventilation (VI; L/min; pneumotachometer) and end‐tidal carbon dioxide (PETCO2; Torr; gas analyzer). We used the modified hyperoxic rebreathing test to isolate CCRs and quantify the central chemoreflex responsiveness to increases in metabolically‐derived CO2. Blood glucose levels were higher 30‐min following the OGTT beverage (i.e., glucose‐loaded) compared to fasted (7.8±1.1 vs. 4.7±0.4 mmol/L; P<0.0001). During rebreathing, the rate of end‐tidal (PET)CO2 accumulation was greater in the glucose loaded trial compared to the fasted trial (0.086±0.007 vs. 0.07±0.008 vs. Torr/sec; P=0.0002). These findings confirm the hyperglycemic stimulation between trials. However, the central respiratory chemoreflex responsiveness during rebreathing was not different between glucose loaded and fasted trials (2.3±1.4 vs. 2.5±1.8 vs. L/min/Torr CO2; P=0.59). These preliminary findings suggest that relative hyperglycemia does not affect the central respiratory chemoreflex responsive to hyperoxic rebreathing. The CCRs may be a more specialized respiratory chemoreceptor, with a phenotype to detect only metabolically‐derived accumulations in CO2.

Support or Funding Information

NSERC Discovery and MRU Faculty of Science and Technology

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Evidence for a Role for Sestrin1 in Mediating Leucine‐Induced Activation of mTORC1 in Skeletal Muscle
Authors: Xu Dandan , Shimkus Kevin L. , Lacko Holly A. , Kutzler Lydia , Jefferson Leonard S. , Kimball Scot R.
Published: June 2021

Previous studies established that leucine stimulates protein synthesis in skeletal muscle to the same extent as a complete mixture of amino acids, and the effect occurs through activation of the mechanistic target of rapamycin in complex 1 (mTORC1). Recent studies using cells in culture identified a family of three proteins, Sestrins 1, 2, and 3, that bind leucine and are required for leucine‐dependent activation of mTORC1. However, the role they play in mediating leucine‐dependent activation of the kinase in vivo has been questioned because the dissociation constant of Sestrin2 for leucine is well below circulating and intramuscular levels of the amino acid. The goal of the present study was to compare expression of the Sestrins in skeletal muscle to other tissues, and to assess their relative role in mediating activation of mTORC1 by leucine. The results show that the relative expression of the Sestrin proteins varies widely among tissues, and that in skeletal muscle Sestin1 expression is higher than Sestrin3 while Sestrin2 expression is markedly lower. Analysis of the dissociation constants of the Sestrins for leucine as assessed by leucine‐induced dissociation of the Sestrin•GATOR2 complex revealed that Sestrin1 has the highest affinity for leucine and that Sestrin3 has the lowest affinity. In agreement with the dissociation constants calculated using cells in culture, oral leucine administration promotes disassembly of the Sestrin1•GATOR2 complex, but not the Sestrin3•GATOR2 complex in skeletal muscle. Overall, the results presented herein are consistent with a model in which leucine‐induced activation of mTORC1 in skeletal muscle in vivo occurs primarily through release of Sestrin1 from GATOR2.

Support or Funding Information

Supported by NIH grants DK13499 and DK15658.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Interaction Between Fibrinogen and the Microglial CD11b Receptor Mediates Several Neuropathological Alterations in a Mouse Model of Alzheimer's Disease
Authors: Muthukumar Gayathri , Merlini Mario , Rafalski Victoria A. , Ryu Jae Kyu , Mucke Lennart , Akassoglou Katerina
Published: June 2021

Alzheimer's disease (AD) is characterized by amyloid β (Aβ) deposition, tau pathology, cerebrovascular damage, and microglia‐mediated neuroinflammation. Cerebrovascular damage includes breakdown of the blood‐brain barrier leading to fibrinogen deposition in the AD brain. Fibrinogen is a blood coagulation factor that upon conversion to fibrin binds to the CD11b/CD18 receptor and induces microglial activation. Here, we show that genetic disruption of fibrinogen interaction with the CD11b/CD18 receptor in 10‐month‐old 5XFAD mice crossed with Fggγ390–396A knock‐in mice, which lack the CD11b binding site, have less neuropathology and microglial activation than 5XFAD littermates. Comparative histological analyses revealed reductions in neuronal and presynaptic terminal loss, Iba‐1+ microglia, immunostaining for the lysosomal marker LAMP‐1, and Aβ plaque burden in the hippocampus of 5XFAD:Fggγ390–396A mice. Thus, genetic inhibition of fibrinogen interaction with CD11b/CD18 receptor reduces multiple AD‐relevant neuropathological alterations in 5XFAD mice.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.