bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impairment of Neurovascular Coupling by Chronic Stress
Authors: Longden Thomas , Dabertrand Fabrice , Hammack Sayamwong E , Nelson Mark T 
Published: June 2021

Chronic stress (CS) is a contributory factor in a wide range of diseases. To date, no studies have focused on the effects of chronic stress on neurovascular coupling (NVC). NVC matches neuronal activity with an increase in local blood flow, ensuring that the metabolic demands of the active tissue are satisfied.We studied NVC in a rat model of CS. Rats were exposed to one of 5 stressors each day for 7 days; we have previously shown that this produces an anxious behavioral phenotype. NVC was impaired by CS: vasodilation of parenchymal arterioles evoked by electrical field stimulation in brain slices was greatly reduced, whereas evoked astrocyte endfoot [Ca2+] was enhanced. In isolated amygdalar arterioles of CS rats, dilation evoked by increasing [K+]o was diminished, suggesting an impairment of inward‐rectifier K+ (Kir) channels. In myocytes from CS rats we observed a decrease in Kir current density. Corticosterone delivery produced a similar NVC phenotype to CS, suggesting that this molecule might mediate NVC impairment. These data suggest that CS causes a decrease in Kir channel number in myocytes of amygdalar parenchymal arterioles, possibly through the actions of corticosterone, rendering the vessel less able to respond to small increases in [K+]o released from astrocyte endfeet and resulting in impaired vasodilation after neuronal activity. This impairment may contribute to CNS disorders with a stress component.
Ultrasonic actuation (UA) reduces the brain inflammatory response to neural microelectrode insertion
Authors: Clark Catharine Grace , Chen Po‐Cheng , Gilmour Robert F. , Lal Amit , Schaffer Chris B. 
Published: June 2021

Neural electrodes are increasingly being used for the treatment of disease conditions (e.g. control of prosthetic limbs, brain disorders, hypertension). Over time neural electrodes fail, likely due to inflammatory responses, limiting the utility of this treatment approach. We tested the hypothesis that ultrasonic actuation (UA) would reduce the insertion force and brain inflammatory response of neurally implanted electrodes. A custom electrode was fabricated which allows for measurement of force, recording of neural signals and UA (V) of the electrode. Acute insertion in the mouse cortex demonstrated that UA reduced the implantation force in a voltage dependent manner (9.6 ± 0.7 vs 3.8 ± 0.5 mN, 0 vs 30V, p<0.05). UA also resulted in a significant decrease in the area of damaged brain tissue (56246 ± 6889 vs 34141 ± 5613 pixels, 0V vs 30V, p<0.05). Using transgenic mice to selectively examine microglia revealed a reduction in the inflammatory response surrounding the electrode (e.g. 56 ± 6 vs 34 ± 7 # microglia, 0 vs. 30V, p<0.05), such that UA was not different from control mice (56 ± 6 # microglia). These findings demonstrate that UA decreases the insertion force and brain inflammatory response of implanted neural electrodes and represents a novel means to increase the functionality of brain electrodes.DARPA MTO under the auspices of Dr. J. Judy through the Space and Naval Warfare Systems Center Grant N66001–11‐1–4011.
Central Sympathoinhibition Ameliorates the Reduction of Splenic Regulatory T Cells with Decreased IL‐17 Production in Hypertensive Rats
Authors: Katsuki Masato , Hirooka Yoshitaka , Kishi Takuya , Sunagawa Kenji 
Published: June 2021

BackgroundRegulatory T cells (Tregs) have been reported to prevent organ damages in hypertension. This effect might be caused by anti‐inflammatory process. We examined Treg expression and number focusing on spleen where T cells are abundant. The aim of the present study was to determine whether Tregs is altered in the spleen, and blockade of brain Ang II type 1 receptors (AT1R) for central sympathoinhibition affects splenic Tregs in hypertensive rats.Methods and ResultsStroke‐prone spontaneously hypertensive rats (SHRSP) with sympathetic hyperactivity were treated with intracerebroventricular infusion of an AT1R blocker (losartan, 1mg/kg/day for 14 days, ARB) or vehicle (VEH). Wister Kyoto rats (WKY) served as control. Splenic Foxp3 (an essential transcription factor of Tregs) mRNA and CD4+CD25+Foxp3+ cells were lower in SHRSP‐VHE than in WKY (Foxp3 mRNA: 0.47±0.03 vs. 1.02±0.03, P<0.05). Splenic Foxp3 mRNA expression levels were upregulated in ARB‐SHRSP (ARB: 0.44±0.04 vs. VEH: 0.31±0.02, P<0.05), while systolic blood pressure and 24‐hour urinary norepinephrine excretion were decreased. IL‐17 mRNA in the spleen was significantly lower in SHRSP‐ARB than in SHRSP‐VEH (ARB: 0.27±0.04 vs. VEH: 0.47±0.03, P<0.01).ConclusionCentral sympathoinhibition induced by blockade of brain AT1R ameliorates the reduction of splenic Tregs possibly via decreased IL‐17 production in SHRSP.
Electrical stimulation of the aortic depressor nerve in conscious state elicits similar hemodynamic responses in heart failure and control rats
Authors: Teixeira‐Pinto Tomás , de Toledo Durand Marina , Lataro Renata Maria , Castania Jaci Airton , Silva Carlos Alberto Aguiar , Fazan Rubens , Salgado Helio Cesar 
Published: June 2021

Heart Failure (HF) is characterized by attenuation of the baroreflex. The present study investigated the hypotensive and bradycardic responses produced by electrical stimulation of the aortic depressor nerve (ADN) in HF rats. HF was induced by left coronary artery ligation. Six weeks after ligation (n=11), or sham surgery (control rats; n=12), the animals were anesthetized for femoral artery and vein cannulation and implantation of bipolar electrodes for ADN stimulation. Twenty‐four hours later, electrical stimulation of the ADN was applied during 20s (5, 15, 30, 60 and 90 Hz; 1mA; 2ms duration). Baseline mean arterial pressure (105 ± 3 vs 100 ± 4 mmHg in HF) and heart rate (341±10 vs 324±13 bpm in HF) were similar between HF and control rats. Electrical stimulation of the ADN (5 to 90 Hz) elicited similar hypotensive (14±2 to 49±6 vs 10±3 to 41±3 mmHg in HF rats) and bradycardic (17±6 to 75±15 vs 21±6 to 67±9 bpm in HF rats) responses in both groups. Taken into account that HF is characterized by baroreflex attenuation, these findings indicate a derangement of the baroreceptor endings and/or the electrical stimulation overriding the baroreflex attenuation in HF rats.Financial Support: FAPESP, CNPq.
Apnea Alters the Pattern of Intermittent Hypoxia‐Induced Long Term Facilitation in Anesthetized Mice
Authors: ElMallah Mai Kamal , Sandhu Milap S , Lee Kun‐Ze , Baekey David M , Fuller David D 
Published: June 2021

Intermittent hypoxia (IH) can trigger persistent increases in efferent hypoglossal (XII) motor output (i.e. long‐term facilitation, LTF) in several species, but this response has not been investigated in the mouse. As a prelude to studies in genetic “knockout” mice, our first objective was to determine if the pattern of XII LTF evoked by IH in anesthetized 129SVE mice was similar to that reported in other species. Our second purpose was to test the hypothesis that the expression of XII LTF would be altered if IH was preceded by a period of apnea‐induced XII inactivity. Mice were anesthetized with urethane, tracheotomized and vagotomized, and XII nerve activity was recorded bilaterally. A “time control” group (N=4) showed no changes in efferent XII output over a 90 min recording period with PETCO2 maintained constant at or near 35 mmHg. In another group (N=6), baseline was followed by IH (3 × 1 min hypoxia, 10%O2, separated by 3 min of hyperoxia, 50% O2). These mice showed robust facilitation, but surprisingly this was evident immediately following the final bout of hypoxia. In contrast, mice that experienced a brief (~ 3 min) period of apnea (N=4) before IH showed a gradual increase in XII bursting over the 90 min post‐IH period. These preliminary results indicate that IH triggers robust XII LTF in urethane anesthetized mice, and a brief period of apnea can alter the pattern of LTF expression.Funding: Parker B. Francis Fellowship (MKE), 2R01HD052682–06A1 (DDF), Craig H. Neilsen Foundation #220521 (MSS)
Expressions of epithelial Na+ channel subunits in the supraoptic nucleus of the hypothalamus in the male rat in response to dietary NaCl intake
Authors: Haque Masudul , Wilson Lori L , Teruyama Ryoichi 
Published: June 2021

All three epithelial Na+ channel (ENaC) subunits (α, β, and γ) were demonstrated in vasopressin (VP) synthesizing magnocellular neurons (MNCs) in the hypothalamic supraoptic (SON) and paraventricular nuclei. Our recent findings showed that ENaC mediates a Na+ leak current that changes the frequency of action potentials in MNCs. In the present study, we assessed the effect of dietary NaCl intake on ENaC subunits in the SON. Male rats were fed either a 8% NaCl diet, a NaCl deficient, or a control diet for two weeks. Then, relative changes in the subunit mRNAs in the SON and kidney were measured by real‐time RT‐PCR. The 8% NaCl diet caused significant increase in β‐ and γ‐ENaC mRNAs in the SON, while expression of α‐ENaC did not change. In contrast, the 8% NaCl diet did not cause any marked changes in expressions of the subunits in the kidney, while a deficiency in dietary NaCl caused a significant rise in α‐ENaC mRNA. Change in the subcellular distribution of α‐ENaC immunoreactivety in MNCs was also observed using confocal microscopy. The labeling in the MNCs from the 8% NaCl diet group was distinctively concentrated towards the plasma membrane in all 5 rats tested, while those from the NaCl deficient and control groups were mainly dispersed in the cytoplasm with no distinct labeling at the plasma membrane. These findings imply that dietary NaCl affects ENaC activity in VP MNCs, which, in turn, affects VP secretion.NIH grant: R21 HL093728
PI3‐kinase is involved in plasticity of adult myofibers acting as a nodal step that originates divergent pathways for gene expression
Authors: Jorquera Gonzalo , Altamirano Francisco , Buvinic Sonja , Contreras‐Ferrat Ariel , Jaimovich Enrique , Casas Mariana 
Published: June 2021

In skeletal myofibers, transcription of a specific group of genes is regulated by different stimulation frequencies, process known as muscle plasticity. We described IP3‐dependent calcium signals after slow frequency stimulation which were dependent on Cav1.1 and ATP release through pannexin channels. Phosphatidyl inositol 3 kinase (PI3K) is one of the downstream proteins involved in activation of this signaling pathway. Here we present a central role for PI3K in muscle plasticity. We studied expression of sarcomeric (slow and fast troponin I) and metabolic (citrate synthase and enolase) genes, ATP release and IP3 production in adult myofibers from murine FDB muscle. We found a biphasic ATP release and intracellular IP3 increments after 20 Hz stimulation, as well as an increase in TnI‐slow and a decrease in TnI‐fast mRNA levels. In metabolic genes, we observed an increase in citrate synthase and a decrease in enolase mRNA levels. These events were dependent on Cav1.1, pannexin and PI3K. Cav1.1 and Pannexin co‐localize at the T‐tubule membrane. Nevertheless, when fibers were treated with an IP3R blocker (5 μM xestospongin B), we observed an inhibition of TnI gene expression but not of metabolic genes. At 90 Hz, gene expression appears to be independent of IP3‐driven calcium movements. These results show PI3K as a nodal step for plasticity‐related gene expression where signals originated by low frequency stimulation diverge to different routes that control the expression of some sarcomeric genes on one hand and of some metabolic genes on the other.FONDECYT‐1110467/ACT‐1111, AT‐24110054
Mechanical ventilation impairs sarcomeric protein function in rat diaphragm single fibers
Authors: Ahn Bumsoo S. , Sollanek Kurt J. , Smuder Ashley J. , Wiggs Michael P. , Powers Scott K. , Ferreira Leonardo F. 
Published: June 2021

Mechanical ventilation (MV) is a widely used clinical intervention for patients unable to maintain alveolar ventilation. Although a life‐saving measure for patients suffering from respiratory failure, MV promotes diaphragm atrophy and contractile dysfunction. The cellular basis of contractile dysfunction remains unclear. The mechanisms of contractile dysfunction are important to understand because MV‐induced diaphragm weakness can delay the weaning process. We studied triton‐permeabilized diaphragm single fibers from rats after 12 hrs of spontaneous breathing (SB) and MV (n = 4/group). Key parameters of isometric contractile properties were maximal specific tetanic force (sPo), rate constant of tension redevelopment (ktr), and calcium sensitivity (pCa50). In type I diaphragm fibers, sPo did not differ between groups. MV slowed ktr by ~6% and decreased the pCa50 such that calcium concentration eliciting 50% sPo increased by ~20%. In type II diaphragm fibers, MV diminished sPo by ~32% and slowed ktr by ~22%. However, pCa50 did not differ between groups. Together, our data suggest that MV impairs diaphragm sarcomeric protein function as evidenced by diminished specific force and calcium sensitivity, and slowing of cross bridge cycling kinetics in membrane‐permeabilized single fibers.Funding support: NIH R00‐HL098453 (LFF) and HL087839 (SKP)
Muscle disuse atrophy is greater in young compared with elderly individuals
Authors: Dirks Marlou , Wall Benjamin , Snijders Tim , Verdijk Lex , van Loon Luc 
Published: June 2021

It is currently unclear whether elderly individuals are more or less susceptible to muscle disuse atrophy compared with young. Here, we compared the magnitude of muscle disuse atrophy between young and elderly subjects. Twelve healthy young (age 23±2 y) and 11 healthy elderly (age 69±3 y) men were subjected to a 5 day period of one‐legged knee immobilization by means of a full leg cast.Three days prior to and immediately after the immobilization period, single slice CT scans and DXA scans were performed to determine quadriceps cross sectional area (CSA) and leg lean mass, respectively. In addition, muscle biopsies were collected to assess myocellular characteristics (analyses ongoing) and 1RM tests were performed to determine muscle strength. Quadriceps CSA decreased with immobilization in both groups (P<0.001 over time), but to a greater extent in the young (−3.5±0.5 % in young vs −1.1±0.6 % in old, P<0.05 between groups). Leg lean mass declined by 1.4±0.7 % with immobilization in young subjects (P=0.07) while no change was detected in the elderly. Strength was reduced to the same extent in young and old after 5 days (−9.0±2.2 % and −7.6±3.7 % respectively; both P<0.01). We conclude that 5 days of muscle disuse leads to significant muscle atrophy and a substantial decline in muscle strength in both young and old individuals. However, the disuse‐induced loss of muscle mass is greater in young compared with elderly individuals.
Continuous resistance training alters exercise‐induced MMPs activation and expression of ECM components
Authors: Ogasawara Riki , Nakazato Koichi , Sato Koji , Boppart Marni , Fujita Satoshi 
Published: June 2021

Recent studies indicate that matrix metalloproteinases (MMPs) and skeletal muscle extracellular matrix (ECM), especially basal lamina, components play a role in muscle mass regulation, although the effects of resistance training (RT) on those proteins are unclear. Thus, the purpose of the study was to investigate the effects of RT on activities and protein expression of MMPs and ECM. Ten male SD rats were divided into 1‐exercise bout (1B) or 18‐exercise bouts (18B) group. This study was conducted in conformance with the FASEB Statement of Principles for the use of animals in research and education. The right gastrocnemius muscle was isometrically trained via percutaneous electrical stimulation (maximum contraction for 5 sec × 5, 5 sets) every other day, whereas the left leg served as a control. MMP‐2 and MMP‐9 activities (via gelatin zymography) were increased 10 min after acute exercise with no change in expression of tissue inhibitors of metalloproteinases in 1B group. However, repeated bouts attenuated exercise‐induced MMPs activation in 18B group. MMPs expressions were significantly higher in trained muscles. RT increased β1‐integrin expression but not the other ECM proteins. Our results suggest that resistance exercise activates MMPs during initial phase of RT but this response is attenuated with continuation of RT.This study was supported by grant from Meiji Yasuda Life Foundation of Health and Welfare.
Intestine mucosal IL‐22 is reduced following oral probiotic administration: implications on epithelial barrier repair
Authors: Rigby Rachael Jane , Thagia Imtiyaz , Pattisson Charlotte , Ng Siew , Kamm Michael , Knight Stella C 
Published: June 2021

Interleukin‐22 (IL‐22) is known to play a key regulatory role at mucosal surfaces including the gut. IL‐22 receptor is predominantly expressed on intestinal epithelial cells (IEC) and evidence suggests that IL‐22 can promote intestinal inflammation and mucosal healing. This study demonstrates a role of probiotics in reducing mucosal IL‐22 and investigates the functional role of IL‐22 on IEC in vitro.Rectal biopsies were obtained from active ulcerative colitis patients immediately prior to probiotic (VSL#3) oral administration and approx. 2 months post‐exposure. Biopsies were cultured in complete medium overnight, supernatant collected and spontaneous IL‐22 secretion measured using ELISA. Effects of varying IL‐22 concentration (100ngml−1–1ngml−1) were tested in vitro using both cancer (SW480) and non‐transformed IEC lines. Stimulation was carried out for 48h (proliferation) or 2h (mRNA). A significant reduction in IL‐22 secreted from mucosal biopsies was detected following probiotic treatment (n=9; p<0.03). In our system, addition of IL‐22 to in vitro IEC cultures did not significantly change proliferation rates (n=12, per concentration). IL‐22 induced moderate increases in SOCS3 and TNFα mRNA at the 50ng and 10ng/ml doses.The long‐term effects of IL‐22 on IEC and the predominant source of IL‐22 in the intestinal mucosa will now be investigated.
Hypoxia‐Inducible Factor‐2α Promotes Intestinal Inflammation Through Induction of Epithelial TNF‐α
Authors: Xue Xiang , Shah Yatrik M 
Published: June 2021

Background & AimsHypoxia can induce a robust inflammatory process termed “hypoxic inflammation”, which is a notable feature in inflammatory bowel disease (IBD). Hypoxic response is mediated by transcription factors hypoxia‐inducible factor (HIF)‐1α and HIF‐2α, both of which are highly induced in IBD. HIF‐1α is a protective factor that limits intestinal barrier dysfunction during inflammation. However, the role of HIF‐2α has not been assessed in hypoxic inflammation and IBD. We hypothesize that HIF‐2α promotes hypoxic inflammation during the progression of IBD.MethodsThe role of HIF‐2α in colitis was assessed in dextran sulfate sodium and citrobacter‐induced colitis mouse models with intestine‐specific gain‐ and loss‐of‐function of HIF‐2α.ResultsActivation of HIF‐2α potentiated colonic inflammation, whereas disruption of HIF‐2α attenuated inflammation in these mouse models of colitis. Further mechanistic analysis showed that HIF‐2α is a master regulator of epithelial derived pro‐inflammatory meditators and directly regulates epithelial tumor necrosis factor (TNF)‐α. In silico analysis predicted and luciferase reporter assay verified that the transcription factor MAZ could bind to TNF‐α promoter and potentiate HIF‐2α mediated TNF‐α induction.ConclusionsThese data demonstrate that HIF‐2α is a critical transcription factor essential in intestinal inflammatory response.Funding:National Institutes of Health (grant CA148828 to Y.M.S.); The University of Michigan Gastrointestinal Peptide Center; Jeffrey A.Colby Colon Cancer Research and the Tom Liu Memorial Funds of the University of Michigan Comprehensive Cancer Center.
The effect of training on individuals’ interactions with visual data
Authors: Pfaff Lee A , Colliard Kitzia , Zumwalt Ann 
Published: June 2021

Traditionally, students demonstrate their learning via testing and demonstrations but little is known about how learners’ interaction with information changes during and after training. Our lab's goal is to explore this question using gaze tracking and quantitative measures. Subjects in the experimental group are trained to use salient features to identify images of cells, which have been assigned a number 1–6. In a post‐training “quiz,” subjects are then asked to identify the cells by number. We tested the hypotheses that, after training: (1) the experimental group will take less time to first fixate on an educationally salient, and (2) the number of subjects who fixate on educationally salient features will increase compared to baseline in the experimental group but not in the controls. Our preliminary results indicate no difference in time to first fixation on an educationally salient feature between experimental [1502.673 +/− 1485.077 ms] and control groups [3046 +/− 2558.974 ms]. The number of subjects in the experimental group that fixate on salient features remains constant after training (means: 6.4 view baseline; 6.2 view after training), whereas the control group viewed them less (7.4 baseline; 4.8 after training). While our second hypothesis was not upheld, these results do indicate an effect of training on gaze patterns, indicating that gaze tracking may be a useful tool to quantify learning.Grant Funding Source: Boston University (Internally funded)
Top‐Down Influences on Visuospatial Human Anatomy Comprehension
Authors: Glena Katlyn , Johnson Marjorie , Nguyen Ngan 
Published: June 2021

The purpose of this study is to examine how learners’ spatial ability and prior domain knowledge contribute to the comprehension of visuospatial anatomical information from instructional animation. Spatial ability refers to one's capacity to construct, maintain, and manipulate mental representations. Prior domain knowledge refers to one's previously acquired knowledge of human anatomy. Visuospatial anatomy refers to the spatial properties of anatomical structures such as their 3D shape, form, position in the body, and relative location to surrounding structures. In cognitive science there is growing evidence suggesting that the educational value of instructional materials depends on how well their design reflects human cognitive architecture. Educational value depends on whether learners have enough cognitive resources to store and process the information presented. This study will provide objective evidence as to how learner's spatial ability and prior anatomy knowledge influence visuospatial anatomy comprehension. It will also help to determine who will benefit the most from instruction with animation. The results can be used to improve the design and implementation of instructional resources that will augment learning of visuospatial anatomical information for all learners, regardless of their innate spatial ability or prior knowledge of anatomy.Grant Funding Source: University of Western Ontario