bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial decrease in muscle activation induced by acute passive static stretching: a possible neuromuscular compartmentalization of the gastrocnemius muscle
Authors: Esposito Fabio , Toninelli Nicholas , Longo Stefano , Coratella Giuseppe , Rampichini Susanna , Limonta Eloisa , Borrelli Marta , Doria Christian , Padulo Johnny , Cè Emiliano 
Published: May 2023

Recently, spatial adaptation of muscle excitability during sustained muscle voluntary contractions (MVC) up to fatigue has been reported, suggesting a functional muscle compartmentalization. Acute passive stretching (PS) can induce a reduction in surface electromyography (sEMG) amplitude; however, it is not clear whether PS may decrease motor-unit activity heterogeneously, similar to what occurs with fatigue. Therefore, the aim of the study was to evaluate possible heterogeneity in muscle activation following PS intervention in the gastrocnemius muscle. Thirty healthy men (age: 24±2 yrs., stature: 1.78±0.07 m, body mass: 77±6 kg) underwent a 5-min PS intervention (5 x 45s-on/15s-off cycles). Before (PRE), immediately after (POST) and after 5 (POST5) and 10 min (POST10), participants performed MVCs of the plantar-flexor muscles. Spatial muscle activation was recorded by means of high-density sEMG (HD-sEMG) in the gastrocnemius medialis and lateralis of the stretched and of the contralateral, non-stretched limb. The HD-sEMG root mean square (RMS) and its centroid were calculated. During stretching, the fascicle length and pennation angle (ultrasound approach) were measured for the proximal and distal portion of both muscles, together with the perceived level of discomfort (0-10 visual analogue scale). HD-sEMG RMS was reduced in POST, POST5 and POST10 in both gastrocnemius medialis (p<0.05 in all) and lateralis (p<0.05 in all) of the stretched limb, while the centroid shifted toward a more caudal direction (p<0.05). Interestingly, the same behaviour was found in the contralateral limb in POST for both muscles (both p<0.05). No differences were found in control. During stretching, no differences were found in fascicle length and pennation angle between the proximal and distal portion, whereas a higher discomfort was perceived in the distal portion of both muscles (p<0.05 in all). The uneven spatial decrease in muscle activation following acute PS suggests differences in neuromuscular organization of the gastrocnemius muscle. Possibly, a different discomfort perception between the proximal and distal portion could have induced a different inhibitory effect. The study was funded by a grant of the Universitnà degli Studi di Milano This is the full abstract presented at the American Physiology Summit 2023 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.
A novel therapeutic Ang(1-7) analogue improves neurovascular function in mice with vascular contributions to cognitive impairment and dementia
Authors: Hoyer-Kimura Christina , Hoyer-Kimura Christina , Konhilas John , Pires Paulo , Banek Christopher , Dennis Melissa , Salcedo Victoria , Hay Meredith 
Published: May 2023

Dynamic cerebral blood flow (CBF) regulation via neurovascular coupling (NVC) is essential to meet localized brain oxygen and nutrient demands. Cerebral microvascular dysfunction contributes to the pathogenesis of many types of dementias. Previous studies suggest that oxidative stress play a critical role in endothelial disfunction, cerebral microvascular impairments, and blunted NVC responses. Increased reactive oxidative species (ROS), inflammatory cytokines, and decreased brain blood flow contribute to the progression of both vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer's disease related dementia (ADRD).Our novel synthetic glycosylated Angiotensin-(1-7) derivative, PNA5, reverses cognitive deficits, inhibits brain ROS and inflammatory cytokine production, and limits microglial activation in our preclinical model of heart failure (HF)-induced VCID. We hypothesize that heart failure (HF) impairs cerebral vascular dilation and NVC, and that treatment with extended release PNA5 (PNA5ER) will improved cerebral vascular dilation and NVC. Adult male C57BL/6J mice (6-10/group) were subjected to HF via left anterior artery ligation or sham surgery 5 weeks prior to treatment with either 1) Vehicle (DMSO) or 2) 1.5mg PNA5ER (30uL of 50 mg/mL). Treatments were delivered subcutaneously at time= 3 weeks and again at t= 1 week prior to vascular evaluation and sacrifice. NVC was assessed using laser speckle imaging. Basal cerebral perfusion and NVC after somatosensory stimulation were assessed by laser speckle contrast imaging. NVC was calculated as a percent change in perfusion from baseline induced by stimulation. Basilar arteries were mounted on a wire myograph to assess cerebral vascular function. HF mice receiving vehicle treatment (n=2, mean= 4.41, Std Deviation=2.32) trend to have decreased NVC response compared to Sham (n=5, mean= 13.63, Std Deviation= 10.35), which may be rescued by PNA5ER (n=3, mean= 10.32, Std Deviation= 4.499). Endothelium-dependent dilation of basilar arteries, induced by cumulative concentrations of NS309 and 2-Methylthio-ADP, was impaired in HF compared to Sham mice; PNA5ER improved vasodilatory responses in the basilar artery.Our preliminary data suggest that PNA5ER protects against NVC impairments and improves basilar artery vasodilation in mice with HF-induced VCID, thereby potentially increasing the ability of the vasculature to meet the localized metabolic demands of the brain. Supported by NIA This is the full abstract presented at the American Physiology Summit 2023 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.
Optogenetic activation of enkephalinergic neurons reveals excitatory effects in the respiratory rhythm generating network
Authors: Loginov Grigory , Baertsch Nathan 
Published: May 2023

The primary cause of death during opioid overdose is respiratory depression. Opioid-induced respiratory depression (OIRD) is characterized by a pronounced decrease in the frequency and regularity of inspiratory efforts. This rhythm suppression is caused, in part, by activation of mu-opioid receptors (MORs) in the preBötzinger Compex (preBötC), a region in the ventral medulla that generates respiratory rhythm. In response to exogenous opioids, MOR-expressing preBötC neurons undergo modest hyperpolarization and glutamatergic synaptic transmission is suppressed via effects on presynaptic release. While MOR activation often leads to [LG1] destabilization and cessation of the inspiratory rhythm, under conditions of elevated network excitability it can also stabilize rhythm generation. In addition to MOR-expressing neurons, the preBötC also contains neurons that express enkephalin, an endogenous ligand for the MOR encoded by the Penk gene. Yet, little is known about how enkephalinergic neurons and endogenous MOR signaling affect respiratory rhythm generation. We hypothesized that activation of Penk neurons in the preBötC would suppress rhythm generation which under conditions of high excitability stabilizes network activity. To test this hypothesis, we optogenetically stimulated enkephalinergic preBötC neurons while recording respiratory activityin brainstem slices from PenkCre; Rosa26Chr2:YFP neonatal mice. To our surprise, optogenetic activation of Penk neurons strongly excited, rather than suppressed, the preBötC network. Specifically, brief 200-ms light pulses evoked inspiratory bursts with a high probability and low latency, consistent with the effects of activating glutamatergic preBötC neurons. Further, prolonged 30-Hz or continuous stimulations of Penk neurons increased the frequency of the inspiratory rhythm and these effects persisted following blockade of MORs with Naloxone. Based on the initial results, we predict that Penk neurons predominantly affect preBötC activity through glutamatergic signaling. The co-release of enkephalin may serve as a negative feedback mechanism that regulates the presynaptic release of glutamate to protect against network over-excitation. Understanding the role of endogenous MOR signaling in this vital respiratory network may inspire strategies to prevent respiratory depression during administration of exogenous opioids. R00 HL145004 (Baertsch) This is the full abstract presented at the American Physiology Summit 2023 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.
Allelic modulation of mesenteric artery mechanical properties in young and adult APOE3 and APOE4 mice
Authors: Frantz Jana , Wagner Katherine , Dunlap Jazmin , Sharma Nikhil , Pathan Khalil , Gallo Jason , Gusek Brikena , Jones Carleton , Eckman Delrae 
Published: May 2023

Previous studies from our lab have demonstrated age-related changes in vascular structure/function in posterior cerebral arteries (PCA) and left common carotid artery (CA) in male and female mice expressing human-ApoE targeted replacement of APOE3 (B6.129P2-Apoetm2(APOE*3)MaeN8) and APOE4 (B6.129P2-Apoetm3(APOE*4)Mae N8) (Taconic Labs). Therefore, we hypothesized that similar changes may be observed in the peripheral circulation. We isolated 3rd-order mesenteric arteries (MA) from young (Y, 3 to 4 mo) and adult (A, 7 to 10 mo), male and female mice expressing hPOE3 and hAPOE4. Mesenteric artery segments (5-8 mm in length) were isolated and cannulated on an arteriograph to assess vascular mechanical properties (lumen diameter (LD), wall thickness (WT), wall cross-sectional area (CSA), wall:lumen ratio (WL), distensibility (Dist), and stress/strain (SvS) under passive conditions (Ca2+-free Krebs + diltiazem) at intraluminal pressures ranging from 10-140 mmHg. Data were analyzed using two-way ANOVA, Student’s t-test, and analysis of nonlinear fit. Values were considered statistically different at P<0.05. Our data indicate that LD was greater in YE4 compared to YE3 mice (P<0.05), but was smaller in AE4 compared to AE3 mice (P<0.05). WT and WL was greater in YE3 mice compared to YE4 mice (P<0.05), but greater in AE4 compared to AE3 mice (P<0.05). While Dist was similar between YE3 and YE4 mice, AE4 mice exhibited less Dist than AE3 mice (P<0.05). Interestingly, distensibility increased between YE3 and AE3 mice (P<0.05), but was not significantly different between YE4 and AE4 mice. While compliance was similar between YE3 and YE4 mice, and similar between AE3 and AE4 mice, AE4 mice displayed decreased compliance compared to YE4 mice. No difference was seen between YE3 and AE3 mice. Wall stress was greater in YE4 mice compared to YE3 mice, but smaller in AE4 mice compared to AE3 mice (P<0.05), and an analogous pattern was observed in Einc for young and adult mice (P<0.05). These data indicate contrasting patterns of age-related vascular changes between allelotypes. Furthermore, these preliminary findings suggest that MA from A E4 mice exhibit a trend toward a hypertensive phenotype. Support: ABRC/ADHS18-205211 (DME, CBJ), Arizona Alzheimer's Consortium (funded by the Arizona Department of Health Services, Contract No. CTR040636) and matching funds from Midwestern University (DME), Biomedical Sciences Program (JF, KW, JD, DME), Biomedical Sciences Start-up Funds (DME) This is the full abstract presented at the American Physiology Summit 2023 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.
Wheel running intensity effects on mice tendon mechanics
Authors: Valencia Miles , Ibáñez Rincon Apolo , Monroy Jenna , Garland Theodore , Horner Angela 
Published: May 2023

Exercise has numerous effects on the musculoskeletal system, including muscle hypertrophy and tendon remodeling. Although exercise is well documented to affect tendon materials properties, the impacts of exercise intensity are less understood. To study the effects of exercise intensity on adult tendon, we used a line of mice artificially selected for high voluntary wheel running for over 90 generations (High Runner, HR). HR and control line mice were separated into wheel running and sedentary training groups at 9-weeks of age. Wheel activity was quantified using tachometers and collected weekly. After 9 weeks of exercise, mice were sacrificed and stored at -20 °C until the plantarflexor tendons were isolated for processing. Tendon cross-sectional area and length were measured in ImageJ. Tendons were marked with indelible ink for direct strain measurements and then were attached to an ergometer for sinusoidal and ramp-to-failure excursions. Force and lever displacement were recorded directly from the ergometer while actual tissue strain was obtained via high-speed videography. When analyzing our data with body mass as a covariate, our results suggest that exercise or linetype have no significant effect on tendon morphology; however, tendon length is significantly affected by the interaction of linetype and exercise. The interaction of exercise and linetype significantly affected yield and failure strain where wheel training increased strain in control mice and decreased strain in HR mice. Interestingly, wheel exercise and training intensity do not synergistically affect tendon material properties but result in varying changes. Total kilometers ran per day had an inverse relationship with yield and failure strain for control mice whereas HR mice showed no correlation for either; ultimately, no relationships with total kilometers ran per day were significant. Future studies should incorporate histological approaches to understand the tendon compositional changes leading to these variable responses. This is the full abstract presented at the American Physiology Summit 2023 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.
Epicatechin effect in an experimental pre-eclampsia model
Authors: Tufiño Cecilia , Soto Luis , Rodríguez Betzabel , Madrigal Damián , Bobadilla Rosa 
Published: May 2023

Epicatechin effect in an experimental pre-eclampsia model Cecilia del Carmen Tufiño Martínez, Luis Jonathan Soto Ramírez, Betzabel Reyes Rodríguez, Damián Arturo Madrigal Aguilar, Rosa Amalia Bobadilla Lugo.Escuela Superior de Medicina del Instituto Politécnico Nacional (Salvador Díaz Mirón esq. Plan de San Luis S/N, Miguel Hidalgo, Casco de Santo Tomas, 11340 Ciudad de México, CDMX)Preclampsia (PE) is a pregnancy specific disorder characterized by de novo development of hypertension and proteinuria. Both the pathophysiology and the treatment of this disease are not clearly established. Epicatechin is a natural product that has shown beneficial effects in several conditions including hypertensive as well as having recognized antioxidant capacity. The objective of this work was to evaluate if the Epicatechin can reduce blood pressure and vascular contractility in an experimental model of preclampsia. For this purpose, 250g ± 50 pregnant female Wistar rats at term were divided into control and with subrenal aortic coarctation or PE, and treated: a) Vehicle, b) epicatechin (10 mg/Kg/day) p.o. during the first two weeks or c) epicatechin (10 mg/Kg/day) p.o. during the last two weeks of gestation. Blood pressure and weight were recorded, and a glucose tolerance curve was performed. The animals were sacrificed at term (day 20) to assess vascular contractility in aortic rings using a conventional isolated organ device. The results showed that rats with PE have an increase in systolic blood pressure, blood glucose and vascular contractility (abdominal aorta) compared to rats with normal pregnancy. Epicatechin administration during the 1st and 2nd week decrease systolic blood pressure, and the contractile response to phenylephrine and angiotensin II in the abdominal segment but not in the thoracic segment of the aorta of preclamptic rats. We conclude that preventive epicatechin treatment improves systolic blood pressure increase observed in the preclampsia model. However, results suggest epicatechin effect is more relevant on resistance than conductance vessels. Funding: Consejo Nacional de Ciencia y Tecnología (CONACyT) This is the full abstract presented at the American Physiology Summit 2023 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.
Chemosensory deficits and increased apneas in the 5XFAD mouse model of Alzheimer's disease
Authors: Sprenger Ryan , Romero Phinea , Ewald Andrea , Marino Kaitlyn , Gumnit Maia , McCann Erin , Ulland Tyler , Watters Jyoti , Baker Tracy 
Published: May 2023

Alzheimer’s disease (AD) is a neurodegenerative disease commonly associated with aging. Along with a decline in cognition and memory, individuals with AD often have respiratory disturbances such as sleep apnea, insufficient ventilation during sleep, and shortness of breath. Mechanisms underlying respiratory dysfunction in AD are unknown but may involve chemosensory deficits since at least one chemosensitive region, the locus coeruleus, undergoes significant neurodegeneration during AD progression in humans. To test the hypothesis that chemoreflexes are impaired in a mouse model of AD, we measured the hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses using whole body plethysmography in 5XFAD mice as amyloid pathology progressed. We evaluated 2 timepoints of amyloid beta (Aß) pathology: early (4 months of age) and late (8 months of age). Compared to WT mice, 8-month-old male and female 5XFAD mice had a significantly reduced capacity to increase ventilation following challenge with 5% inspired CO2 (males: 5XFAD 99 ± 11% vs WT 168 ± 18%; females: 5XFAD 126 ± 12% vs. WT 212 ± 12%) or 5% inspired O2 (males: 5XFAD 141 ± 20% vs. WT 201 ± 20%; females: 5XFAD 75 ± 7.6% vs. WT 134 ± 12%). In addition, both male and female 5XFAD mice experienced significantly more apneic events (~120 apneas per/h) than their WT counterparts (~50 apneas/h) during presumptive sleep. Consistent with impaired ventilation, Aß plaques were abundant in medullary regions of the brainstem where both central chemosensors and rhythm generating neurons reside. Preliminary data suggest that chemoreflex dysfunction may emerge early in disease progression since a trend toward a reduced HCVR (5XFAD 133 ± 23% vs WT 206 ± 39%, combined sexes) was apparent in 4-month-old 5XFAD mice. Surprisingly, and contrary to findings at 8 months, preliminary data in 4-month-old 5XFAD mice indicate that the HVR may be slightly higher indicating that 5XFAD mice may be hypersensitive to hypoxia early in disease progression. Together, these data suggest that responses to ventilatory challenges become significantly disrupted by Aß pathology late in disease progression, deficits which may manifest early in disease and could promote disease progression. Results from our studies will identify the contributions of Aß deposition to respiratory dysfunction in 5XFAD mice, and may have implications for therapeutic interventions in individuals with AD. NIH R01 HL142752, HL142752S1, and T32 AG000213 This is the full abstract presented at the American Physiology Summit 2023 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.
Multi-omics Analyses Identify Galectin-1 as a Potential Novel Mediator of Heart Failure with Preserved Ejection Fraction in Mice and Humans
Authors: Wassenaar Jean , Smart Duncan , Fehrenbach Daniel , Dungan Matthew , Doran Amanda , Shuey Megan , Madhur Meena 
Published: May 2023

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome where patients present with symptoms of volume overload despite having a normal systolic function. HFpEF is associated with elevation of inflammatory biomarkers, but the precise pathways leading to cardiac dysfunction is not known. In a deoxycorticosterone acetate (DOCA)-salt model of hypertension and HFpEF, we performed CITE-Seq analysis on total leukocytes isolated from the heart, which revealed significant differential gene expression primarily in the myeloid population. We then took the top 20 genes that were differentially expressed between myeloid cells from DOCA-salt vs sham treated mice and performed a genetic analysis called PrediXcan in Vanderbilt’s DNA databank, BioVU. Genetically predicted expression of two genes were associated with a HFpEF phenotype in humans. Of these, the gene encoding galectin 1, Lgals1, had the lowest p-value (0.02) and highest beta coefficient (0.32) corresponding to an odds ratio for HFpEF of 1.38. The role of galectin-1 in heart failure is unknown, we hypothesized that overexpression of Lgals1 exacerbates HFpEF. We found that siRNA knockdown of Lgals1 in bone marrow derived macrophages stimulated with lipoprotein saccharide and IFNγ, they expressed significantly more inflammatory genes such as IL-1α (p<0.0001), IL-6 (p=0.0219), iNOS (p=0.043), and TNFα (p=0.0031) using a 2-way ANOVA followed by Sidak’s multiple comparison test. Next, we explored the role of Lgals1 in the pathophysiology of HFpEF using Lgals1-/- mice. Surprisingly, despite both in vitro and in vivo data supporting a role of galectin-1 in HFpEF, Lgals1-/- mice did not show a significant difference in HFpEF phenotype (blood pressure, exercise tolerance, echocardiography, heart weight, or pulmonary congestion) after DOCA-salt treatment compared to littermate Lgals1+/+ controls in either males or females (p > 0.05 using Student’s t-test for all parameters measured, n=10-12). One hypothesis for this negative result is that Lgals1 is ubiquitously expressed, and a total body knockout may have compensatory mechanisms. We therefore created Lgals1 floxed mice and future studies will determine the effect of macrophage specific deletion of galectin-1 on HFpEF. In conclusion, while multi-omics approaches in mice and humans identify galectin-1 as a novel mediator of HFpEF, further studies in mice are needed to confirm its roles as a potential therapeutic target. 1R01HL161212-01A1, 19EIA34480023,,19IPLOI34760558, and 1T32HL144446-01 This is the full abstract presented at the American Physiology Summit 2023 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.