bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Arginine-vasopressin in the Brain on Social Behavior and Communication in a Psychosocial Stress Animal Model
Authors: Gil Mario , Dominguez Fernando , Hinojosa Ariana , Alaniz Esperanza 
Published: May 2024

Psychosocial stressors (e.g., anxiety, personality traits, social isolation) are risk factors for negative health outcomes, including cardiovascular disease and neuropsychiatric disorders. However, there is a knowledge gap regarding the biological mechanisms that underlie these risk-outcome relationships. To address this gap, our team uses the Syrian hamster ( Mesocricetus auratus) as an animal model for investigating psychosocial behaviors and stress responses. Our previous findings and work reported by others indicate that the neuropeptide arginine-vasopressin (AVP) acts in the brain to regulate the expression of social behavior and communication. In the present study, stereotaxic surgeries were used to cannulate six adult hamsters (1 female, 5 males) with cannulae aimed at different forebrain regions, mostly focusing on hypothalamic areas. Cannulated animals were microinjected with 200 nl of a 9 μM AVP solution and saline in counterbalanced order with a 4-day inter-test interval. Three of the six animals displayed a type of social communication behavior called flank marking in response to AVP, whereas none of the animals flank marked in response to saline; these group differences were statistically significant (χ2 (1, N=6)= 4.0, p< 0.05). Previous research groups confirmed the anterior hypothalamic area (AHA) as a site of action for the effects of AVP on social behaviors. Our results suggest that, in addition to the AHA, the dorsomedial hypothalamic nucleus (DM) and posterior hypothalamic area (PH) may also be sites of action for AVP. We are currently testing the behavioral effects of AVP when microinjected into the midbrain. The preliminary findings reported here will help us identify areas of the brain that are part of a larger neural network that is involved in the regulation of social behavior and stress responses by AVP. Our long-term goal is to develop a psychosocial stress model to test the hypothesis that AVP may have therapeutic potential for psychosocial stress-associated conditions, including cardiovascular disease and neuropsychiatric disorders. This research is supported by NIH grant #5K01HL145339-03 (PI: M. Gil). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Mitochondrial-targeted Antioxidant Enhancing Effects on Vascular Endothelial Function in Middle-aged and Older Adults Is Influenced by Cardiorespiratory Fitness
Authors: Carlini Nicholas A. , Holder Kia J. , Brown Mikaela K. , Hughes Ryan P. , Harber Matthew P. , Fleenor Bradley S. 
Published: May 2024

Vascular endothelial dysfunction in middle-aged and older (MA/O, ≥ 45 y) adults is partly attributable to excess mitochondrial reactive oxygen species (mtROS) production. Aerobic exercise preserves endothelial function in preclinical models via lower mtROS and mitigates the deleterious effects of aging on cardiorespiratory fitness (CRF). However, the acute effects of a mitochondrial-targeted antioxidant on age-related vascular endothelial function in the context of CRF are currently unknown. We hypothesized lower CRF resulting from a physically inactive lifestyle contributing to age-related endothelial dysfunction is mediated via greater mtROS in humans. In a double-blind, randomized, placebo-controlled crossover study design MA/O adults were divided into two groups: exercisers (EX, n=11, age 60.0 ± 4.0 y, BMI 25.0 ± 0.9 kg/m2) and non-exercisers (NEX, n=12, age 64.0 ± 2.8 y, BMI 28.2 ± 1.0 kg/m2). CRF, assessed via VO2max, was measured on a cycle ergometer from an incremental ramp protocol (10 or 20 watts/min). Vascular endothelial function from brachial artery flow mediated dilation (FMDBA) was acquired before (pre-ingestion) and ~1 h after MitoQ (single dose, 80 mg) or placebo supplementation. A two-way repeated measures ANOVA with a Bonferroni post-hoc analysis was used to determine the effects of MitoQ and placebo on FMDBA. Compared to placebo, MitoQ increased FMDBA in NEX (pre: 4.9 ± 0.4 vs post: 7.0 ± 0.4 %, p<0.05) by +37% and brachial artery diameter (pre: 0.18 ± 0.02 vs post: 0.24 ± 0.02 mm, p<0.05) by +34% whereas no changes were observed for FMDBA (pre: 6.8 ± 0.5 vs post: 7.0 ± 0.3 %, p>0.05) or brachial artery diameter (pre: 0.25 ± 0.02 vs post: 0.26 ± 0.02 mm, p>0.05) in EX. CRF was positively correlated with baseline FMDBA (n=17, r=0.56, p=0.01) whereas the change in FMDBA with MitoQ was inversely correlated with CRF (r=-0.54, p=0.02). These data demonstrate the acute MitoQ-enhancing effects on vascular endothelial function in MA/O adults is attributable, in part, to greater mtROS in physically inactive adults with lower CRF. Funding for this study was provided, in part, by Ball State University ASPiRE internal research grant (N.A. Carlini). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Stromal Vascular Fraction Derived Vasculogenesis Is Associated with the Formation of Malformed Lymphatic Vessel Structure
Authors: Hu Nien-Wen , Shang Hulan , Katz Adam J , Murfee Walter L 
Published: May 2024

Tissue engineering and the development of therapies aimed at manipulating microvascular function require the ability to generate both blood and lymphatic vessels. Adipose-derived stromal vascular fraction (SVF), consisting of endothelial cells, stem cells, pericytes, smooth muscle cells, fibroblasts and immune cells, has emerged as a potential heterogeneous stem cell population for de novo vessel growth. SVF derived vasculogenesis has been reported to result in the dramatic formation of blood vessel segments that can connect with host vasculatures. Understanding how SVF can be used to therapeutically form vessels requires 1) exploration of the cell dynamics involved in the vasculogenesis process and 2) cauterization of the vessel structures. The objective of this study was to characterize SVF de novo vessel formation in an intact adult murine tissue environments. SVF was isolated from subcutaneous adipose in the inguinal region from adult C57BL/6 mice, labeled with DiI and seeded onto avascular mesentery tissues and then cultured in MEM + 10% fetal bovine serum (FBS) for up to 5 days (35 μl SVF cells/tissue; isolated from 1.8 g inguinal fats and resuspended in 200 μl MEM+FBS). Tissues were then labeled for PECAM (endothelial marker) + Lyve-1 (lymphatic marker) or NG2 (pericyte marker). By day 1, individual SVF cells started to form multi-cellular PECAM positive chord structures. Day 3 tissues displayed apparent vessel structures characterized by asterisk shaped clusters displaying a central PECAM positive “hub” and radial “spoke-like” extensions. At later time points and in regions of increased vascular coverage, the vessel structures were connected in a network pattern. In additional studies for which angiogenesis was pre-stimulated in the normally avascular mouse mesenteries, the SVF derived vessels connected to the host networks. A subset of structures during the vasculogenesis process displayed blunt ended lymphatic-like vessel structures termed “blebs.” The endothelial cell “blebs” were characterized by large, irregular diameters and a mosaic of Lyve-1 positive and negative cells. The “blebs” were also observed to connect with nearby SVF derived PECAM positive vessel segments. Our evidence of PECAM positive hub and lymphatic-like blebs provoke questions about SVF derived vessel function and suggest a previously undiscovered potential for SVF to form lymphatic vessel structures. NIH grant R21HL159501. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Arterial stiffness and wave reflection responses to acute and chronic high intensity interval training in healthy older adults
Authors: Kim Jin-Su , Lapierre-Nguyen Stephanie , Soonhuae Chatchamarn , Sakarya Yasemin , Riesco Eléonor , Robinson Katherine , Handberg Eileen 
Published: May 2024

Aging leads to large elastic artery stiffness which is associated with early return of wave reflection. These age-related alterations increase left ventricular afterload, predisposing older adults to cardiovascular disease. Endurance training is an effective strategy to reduce cardiovascular disease risk. We have developed a supervised home-based exercise intervention using high intensity interval training on an all-extremity non-weight-bearing ergometer (HIIT-ANE). This study aimed to test the following hypotheses in healthy older adults: 1) arterial stiffness and wave reflection would decrease in response to chronic HIIT-ANE, 2) arterial stiffness and wave reflection responses to acute HIIT-ANE would differ in the untrained compared to the trained states, and 3) arterial stiffness and aortic wave reflection responses to acute and chronic HIIT-ANE would be related. Twenty older adults (66±1 years, mean ± SE; 11 postmenopausal women and 9 men) participated in this study. Carotid-femoral pulse wave velocity (cfPWV) and augmentation index at heart rate 75 bpm (AIx@75)—indices of arterial stiffness and wave reflection, respectively—were assessed by SphygmoCor XCEL at baseline (T0), following 8 weeks of normal lifestyle (T1; control condition), and following 8 weeks of supervised home-based HIIT-ANE (T2). Acute cfPWV and AIx@75 responses to HIIT-ANE were assessed at pre-, end-of-, 1-hr post- and 24-hrs post-exercise, in the untrained and trained states. cfPWV increased after 8 weeks of normal lifestyle (T0 vs. T1: 7.9±0.3 vs. 8.2±0.3 m/s, P=0.03), but it decreased following 8 weeks of HIIT-ANE (T1 vs. T2: 8.2±0.3 vs. 7.7±0.3 m/s, P<0.001). AIx@75 decreased after 8 weeks of HIIT-ANE compared to baseline and following 8 weeks of normal lifestyle (T0 vs. T2: 23.7±1.8 vs. 17.8±1.9 %, P<0.001; T1 vs. T2: 24.9±2.2 vs. 17.8±1.9 %, P<0.001). Acute cfPWV and AIx@75 responses to HIIT-ANE were similar in the untrained and trained states ( P for condition×time interaction; cfPWV: P=0.8; AIx@75: P=0.9). cfPWV and AIx@75 responses to chronic HIIT-ANE were not significantly related with acute responses to HIIT-ANE in the untrained (cfPWV: r=0.07, P=0.8; AIx@75: r=-0.32, P=0.2) and trained states (cfPWV: r=0.10, P=0.7; AIx@75: r=-0.32, P=0.2). In conclusion, we have demonstrated that supervised home-based HIIT-ANE has beneficial vascular effects in healthy older adults. We also showed that acute vascular responses to HIIT-ANE do not change from the untrained to trained state and are not predictive of chronic vascular responses to HIIT-ANE. This work was supported by the National Institute of Aging grant AG063143. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Consumption of probiotic SLAB51 enhances ventilatory acclimatization to high altitude
Authors: Moya Esteban A. , Yu James J , Kaya Kiana , Ochoa Tim , Cheng Hunter , Simonson Tatum 
Published: May 2024

Ventilatory acclimatization to hypoxia (VAH) is crucial for adjusting to physiologically stressful high-altitude environments. Increased ventilatory and cardiac responses to low-oxygen (O2) may partially mitigate deleterious effects at high altitude. Previous studies show that administration of the probiotic SLAB51 (O2booster; Hecto, Seoul, South Korea) improves O2 saturation in patients suffering from COVID-19 and O2-treated prematurely born babies. Since changes in ventilation may contribute to increase O2 saturation, we hypothesize that acute administration of SLAB51 to sojourners traveling to high altitude will increase respiratory responses to hypoxia. We measured minute ventilation (VI) and heart rate (HR) during normoxia and acute isocapnic hypoxia in 17 healthy participants (9 males, 8 females) of Latino ancestry with residence at sea level in San Diego and surrounding areas. We performed control experiments at sea level and then the participants were taken to White Mountain Barcroft Station (12,470ft / 3,800m) to repeat the measurements. At high altitude, the participants underwent a double-blind, placebo-controlled study with administration of placebo (n=8) or SLAB51 probiotic (n=9) up to three times per day for up to four days. Recordings of physiological parameters were obtained during steady-state at different gas mixtures with continuous monitoring of O2 saturation to target 10% desaturation during the acute hypoxia stimulus. We measured hypoxic ventilatory and heart rate responses (HVR and HHRR, respectively) and compared results between placebo and probiotic groups (mean ± SEM). As expected, high altitude increased VI and HR values compared to sea-level measurements in all participants. However, at high altitude, we found a significant increase of VI (p<0.02) in participants consuming SLAB51 (0.275+0.015 L/min per Kg) when compared to those administered with placebo (0.207±0.025 L/min per Kg) during exposure to acute hypoxia. Administration of SLAB51 did not produce differences in HR responses at high altitude, and HVR and HHRR were not significantly different with SLAB51 treatment. Our results show that consumption of the probiotic SLAB51 increases ventilatory responses to hypoxia at high altitude without affecting hypoxia-induced changes in HR, suggesting that SLAB51 probiotic intervention may contribute to ventilatory acclimatization to hypoxia, although future studies are required to determine the mechanisms underlying this potential response. Supported by LEA Altitude Performance Fund. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Juxtaglomerular (JG) cell-specific deletion of the NADPH oxidase accessory protein, NOXA1, decreases pro-renin and proteinuria in vivo in a mouse model of diabetes
Authors: Mendez Mariela , Ortiz-Capisano Maria Cecilia , Liao Tang Dong , Baiden Isaac , Maskey Dipak 
Published: May 2024

A large fraction of patients with diabetes develops diabetic nephropathy. Plasma pro-renin levels are elevated in diabetic patients and thought to contribute to hypertension, renal damage and inflammation. Studying the mechanisms by which diabetes reprograms JG cells to increase pro-renin release could provide new targets for kidney disease. We previously found that JG cells from diabetic mice had higher reactive oxygen species production (superoxide and H2O2), pro-renin expression and pro-renin and renin release. We hypothesized that increased ROS production by specific NADPH oxidases (NOXs) in JG cells is responsible for higher pro-renin release and contributes to glomerular damage in diabetes. Western Blots showed that the NADPH oxidase isoform NOX1 and NOXA1 are upregulated in JG cells from diabetic mice (C57=100%; Akita=147±10%; n=4; p<0.05), whereas NOX2 or NOX4 were not different. Confocal microscopy showed that NOX1 and NOXA1 are present in JG cells and co-localize with renin-containing granules (n=3). Silencing NOX1 in primary cultures of JG cells from diabetic mice decreased renin release to C57 control levels; (n=6; p<0.01) whereas silencing NOX4 had no effect (n=6). To study the role of NOXA1 and NOX1 in JG cells in vivo, we used Cas9 mediated silencing in kidneys of control mice. Adenoviruses expressing Cas9 under control of the Ren1 promoter (AV-Ren1-Cas9) and AAV-gRNA-NOXA1 were loaded into 28-day minipumps and delivered into the renal subcapsular space in C57 mice. After 5 weeks, we obtained control (non-transduced) and Ren-Cas9-NOXA1-edited kidneys and isolated JG cells. NOXA1 expression was reduced by 60±22% in isolated JG cells and pro-renin expression was decreased by 46±19% compared to non-transduced kidneys (n=3). We then specifically deleted NOXA1 from JG cells in diabetic mice by subcapsular delivery of AV-Ren1-Cre in the kidney cortex of transgenic NOXA1 floxed diabetic Akita mice. JG cell-specific deletion of NOXA1 in diabetic mice decreased urinary ROS (8-Isoprostane pg/24hrs: Akita=4091±307; NOXA1 JG/KO=3086 ±137; n=4; p<0.05), and glomerular damage as indicated by decrease proteinuria (24h Ualbumin Akita= 98.6± 9.4; NOXA1 JG/KO= 57.8± 16.4 μg/24h; n=4; p<0.05). We conclude that enhanced NOX1/NOXA1 induced ROS in JG cells drive enhanced pro-renin release from JG cells which contribute to glomerular damage in diabetes. Thus, NOXA1/NOX1 in JG cells are a potential new target for diabetic nephropathy. DK105300-RO3 Henry Ford Hospital Institutional Funds. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Postprandial Increase of Adenosine 2B Receptor in Adipose Tissue Promotes Lipotoxicity
Authors: Lank Daniel 
Published: May 2024

Obese adipose tissue is known to have higher basal rates of lipolysis than lean adipose tissue. This chronic outflow of lipids leads to the ectopic deposition of lipids into non-adipose, insulin-sensitive tissues such as the heart, liver, and skeletal muscle. This process, known as lipotoxicty, promotes the development of insulin resistance in these tissues. Therefor developing ways to control lipolysis in obese individuals is a useful intervention that would help curtail the development of type II diabetes. Adenosine, a nucleoside released from cells during metabolic stress or inflammation, may play an important role in this process. Our lab has discovered that adipocytes tightly regulate Adenosine receptor 2B (A2BR) expression during the transition from the postabsorptive (fasting) to postprandial (fed) state. QPCR data has confirmed that A2BR levels increase postprandially and decrease postabsorptively in adipose tissue, but not other insulin-sensitive organs. Administration of an A2BR agonist in mice yields a large lipolytic response in the postprandial, but not postabsorptive state. Genetic deletion of A2BR from adipose tissue confirms that this lipolytic response depends on A2BR signaling in the individual adipocytes. Importantly we have also shown that A2BR levels in obese mouse adipose tissue are constitutively high regardless of nutritional state, suggesting these cells are primed for lipolytic stimulation. Therefore, pharmacological antagonists of A2BR could reduce basal lipolysis in obese individuals and in turn improve whole body insulin sensitivity. 5T32GM139787-03 5R01GM136900-04. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Effects of high dose Fentanyl in combination with hypoxia or ketamine in adult female goats
Authors: Hodges Matthew , Neumueller Suzanne , Taylor Reiauna , Hilbert Grace , DeSalvo John , Forster Hubert 
Published: May 2024

The worsening opioid epidemic in the United States continues to claim >80,000 lives each year. Synthetic opioids such as fentanyl are highly useful in the clinical management of pain but at high doses are thought to cause death through opioid-induced respiratory depression (OIRD), impairment of the alveolar to arterial oxygen (A-a O2) gradient and though upper airway and respiratory pump muscles activation causing airway dysfunction and/or Wooden Chest Syndrome (WCS). These negative effects of high dose opioids may be exacerbated when individuals use additional drugs such as ketamine or by an existing hypoxia. We have shown previously that low (sub-lethal) doses of fentanyl (25-125 μg/kg; IV) cause transient apnea (<30 sec), a brief suppression of breathing frequency (FB; <5 min), increased tidal volume (VT), upper airway and pump muscle activity, and an increased A-a O2 gradient with an overall stimulatory effect on ventilation for up to 90 min post-injection (PMID: 37885800). Here we tested the hypothesis that the physiological effects of high doses of fentanyl will be exacerbated when combined with pre-treatment of either mild hypoxia (FIO2=0.12) or IV ketamine (10 mg/kg). Adult female goats (n=3) were surgically instrumented with electromyographic (EMG) wires in airway (genioglossus and thyropharyngeal) and respiratory pump (diaphragm, transverse abdominus and intercostal) muscles and the carotid arteries relocated subcutaneously and allowed 2 weeks for recovery. Arterial blood samples were obtained through a carotid catheter and all injections were via a catheter in the jugular. Following a 30-minute control period, goats were given IV saline (vehicle) or fentanyl (50–500 μg/kg). In most goats, fentanyl doses of 200-250 μg/kg cause immediate apnea up to 60 sec in duration and decreased FB (~40%) and PaO2 (~35 mmHg) while increasing PaCO2 (~70mmHg) along with an EMG activation and increased A-a O2 gradient. These effects tended to be less severe at a given dose when injections were performed during mild hypoxia (15 min; n=2) but were exacerbated by pretreatment with ketamine (n=1). These data suggest high doses of fentanyl in goats cause similar life-threatening features as in humans, and that these effects seem to be mitigated by hypoxic ventilatory stimulation but exacerbated by polypharmacy with ketamine. NIH DA050571. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.