bluuebunny/crossref_metadata_2025_split huggingface dataset:
Annexin a1 and formyl peptide receptor 2/3 like: Interaction between hypothalamic–pituitary–adrenal axis and hippocampal memory in a model of corticosterone‐induced depressive like behavior
Authors: Crupi Rosalia , Peritore Alessio Filippo , Gugliandolo Enrico , Siracusa Rosalba , Impellizzeri Daniela , Fusco Roberta , Cordaro Marika , D'Amico Ramona , Di Paola Rosanna , Cuzzocrea Salvatore 
Published: June 2021

The activity of the hypothalamic‐pituitary‐adrenal axis is commonly disregulated in stress‐related psychiatric disorders. Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe‐associated molecules. It was demonstrated that Fpr2/3 deficient mice show a distinct profile of behaviour characterised by reduced anxiety. Annexin 1 (ANXA1), an endogenous ligand of Formyl Peptide receptor 2/3 like (FPRL 2/3) is a member of the family of phospholipids and calcium annexes proteins with a well‐defined role in the delayed early inhibitory feedback of glucocorticoids in the pituitary gland. The aim of study was first, to evaluate the potential role of ANXA1 and FPRL 2/3 as mediator cell‐mediator of the inhibitory effects of glucocrticoids on corticotrophin secretion (ACTH), subsequently the possible correlation between depression like behaviour and memory impairment in the hippocampus studying Ras/ERK pathway. C57BL/6 (CORT +), Anx a1 −/− and Fpr 2/3 −/− mice were exposed to corticosterone (35 μ/ml/day) to induce depression like state via drinking water for 28 days and then behavioural test was performed to measure immobility time in the forced swimming test, locomotor activity in the open field test, sucrose consumption in the sucrose preference test, anxiety in the novelty suppressed feeding and short‐term memory, intermediate‐term memory and long‐term memory in the novel object recognition test. Anx a1−/− mice showed an improvement in depression‐like behavior compared to Fpr 2/3 like −/− and CORT + mice. Histological analyses were performed to evaluate the number of neurons in the dentate gyrus, as well as the degree of neurogenesis through the neurotrophic factors of BDNF and GDNF. In conclusion, we can state that the absence of the anx a1 protein, even more than the absence of FPR 2/3, improves the depressive behavior induced by chronic administration of glucocorticoids, as it appears to have a neuroprotective role in the hippocampus following a damage caused from a chronic condition of depressionSupport or Funding Informationno fundingThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Non‐coding RNAs as Markers of Neuropathic Pain
Authors: Wilkerson Jenny , Jiang Jinmai , Felix Jasmine , Bray Julie , da Silva Lais , McMahon Lance , Schmittgen Thomas 
Published: June 2021

Pain is one of the most common reasons to seek medical attention and chronic pain is a worldwide epidemic. Under some circumstances, incoming protective nociceptive signaling is prolonged leading to clinical manifestations of pathological neuronal signaling. The chronic constriction injury (CCI) of the sciatic nerve is a widely used preclinical model of pathological neuropathic pain. Over the past decade, investigators have come to appreciate the extracellular actions of RNA located within cells such as mRNA, micro (mi) RNA, and other long and short noncoding (nc) RNAs. The development and/or maintenance of chronic pain could be controlled epigenetically through ncRNAs. Here we seek to characterize ncRNAs in blood, sciatic nerve, and spinal cord in a mouse model of neuropathic pain as this may serve to elucidate potential biomarkers relevant to pathological pain in humans. Male C57BL6/J mice (6 CCI and 6 sham procedure) underwent surgery for sciatic nerve ligation with chromic gut sutures. Following 7 days, mechanical allodynia was quantified using the von Frey assay. Mice were then euthanized for collection of spinal cord, sciatic nerve, and blood. cDNA was synthesized to 322 unique mature miRNAs from the total RNA. Of the 627 miRNAs examined, 414 and 376 were detectable (CT ≤ 35) in the spinal column and sciatic nerve, respectively. In the CCI mice that displayed mechanical allodynia, 11 and 126 miRNAs were differentially expressed (i.e., greater than 1.5‐fold increase or decrease; P < 0.05) in the spinal column and sciatic nerve, respectively, as compared to sham controls. Three members of the miR‐183 cluster (miR‐183, miR‐182 and miR‐96) were reduced in both the spinal column and sciatic nerve. Our data support the use of miRNAs as biomarkers to identify subpopulations of patients with neuropathic pain. Further, targeting miRNAs may hold promise for the treatment of pathological pain.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Anxiolytic Effects of Overexpressing Angiotensin Converting Enzyme 2 (ACE2) in Female Mice
Authors: Cahill Karlena Maria , Alleyne Amy , Johnson Dominique , Scott Karen , Raizada Mohan , De Kloet Annette , Krause Eric 
Published: June 2021

Considerable evidence has implicated the renin‐angiotensin system (RAS) as an important target for the therapeutic alleviation of stress‐related mood disorders. Along these lines, the ‘pro‐stress’ actions of Angiotensin‐II are largely thought to be mediated by the angiotensin type‐1 receptor (AT1R). On the other hand, the protective limb of the RAS that depends on the conversion of angiotensin‐II to angiotensin‐(1–7) by angiotensin‐converting enzyme 2 (ACE2) has been postulated to dampen stress and relieve anxiety. We have previously found that augmenting ACE2 activity has potent anxiolytic and hypothalamic‐pituitary‐adrenal (HPA) axis‐dampening effects in male mice. Relative to males, females are more susceptible to stress‐related mood disorders; however, whether increasing ACE2 activity in females also blunts stress responses has not been determined. This study tests the hypothesis that ACE2 overexpression decreases anxiety‐like behavior and attenuates stress‐induced HPA axis activation in female mice. We used the Cre/Lox system to generate female mice that ubiquitously overexpress ACE2. Female ACE2 knock‐in (ACEKI) mice and their wild‐type littermate controls were tested in the elevated‐plus maze (EPM), Light‐Dark Box (LDB), and Graham Cracker Test to evaluate the impact that augmenting ACE2 expression has on anxiety‐like behavior. Female mice were also subjected to an acute 30 min restraint stress challenge and blood samples were collected in order to evaluate HPA (i.e., corticosterone) reactivity. As expected, Cre‐Lox mediated overexpression of ACE2 resulted in elevated ACE2 mRNA and enzymatic activity in all tissues examined (i.e., hypothalamus, pituitary, blood, and brain). Relative to controls, ACE2KI mice spent significantly (p < 0.05) more time in the open arms of the EPM and in the light side of the LDB. When placed in a novel environment, ACEKI mice exhibited a significantly (p<0.05) decreased latency to consume graham crackers relative to controls. Importantly, total distance traveled in the EPM was not different between the groups, indicating that the locomotor activity of the female mice is unchanged by ACE2 overexpression. Interestingly, basal and acute stress‐induced corticosterone levels did not differ between ACE2KI and WT female mice. These results suggest that although neuroendocrine response to acute restraint was unaffected in females, ACE2 overexpression has anxiolytic effects on both male and female ACE2KI mice. Furthermore, our findings support the idea that the RAS may be a worthy target in the search for novel therapeutic interventions for stress‐related disorders.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Development of a Cell‐based Assay for the Discovery of KCa3.1 Inhibitors by Highthroughput Screening
Authors: Jakakul Chanon , Muanprasat Chatchai 
Published: June 2021

Inhibition of KCa3.1 potassium channel has been demonstrated to have beneficial effects in a wide variety of human diseases including inflammation‐associated disorders and cancers. However, there is currently no therapeutic KCa3.1 inhibitor available for human use. This study aimed to establish a high‐throughput screening assay for identifying modulators of KCa3.1 in native cells, and to identify and study KCa3.1 inhibitors from a library of compounds derived from natural resources in Thailand. The screening platform was successfully developed based on thallium flux assay. Control groups treated with NS309 (KCa3.1 activator) or TRAM‐34 (KCa3.1 inhibitor) produced significantly different fluorescent signals. A primary screening of 1,352 compounds using the developed thallium flux assays identified 23 active compounds. A secondary screening using electrophysiological analyses has verified the inhibitory effect of 9 compounds. Dose‐response analysis of these compounds has identified several KCa3.1 inhibitors with low micromolar potency. The most potent compound (N134) had the IC50 of ~ 0.1 μM. These results indicate that the high‐throughput screening assay based on endogenous expression of KCa3.1 is capable of identifying small molecule inhibitors. These novel KCa3.1 inhibitors might be further developed into novel therapy of inflammation‐associated disorders and cancers.Support or Funding InformationThis work was supported by the Thailand Research Fund (DBG5980001), Faculty of Science Mahidol University, Faculty of Graduate Studies Mahidol University and Medical Scholars Program, Mahidol University.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cardiovascular effects of the scorpions Centruroides margaritatus, Centruroides limpidus and Centruroides noxius crude venom
Authors: Santos Cláudia Ferreira , Céron Jessica Dayana Galíndez , Bindá Alexandre Havt , Possani Lourival D , Vidal José Béltran , Fonteles Manassés Claudino , Nascimento Nilberto Robson Falcão 
Published: June 2021

Scorpions from the Centruroides genus have high toxicity and it is potentially dangerous to humans. In this study we compare the effect of the crude venom of a colombiam scorpion Centruroides margaritatus (Cm) with two Mexican Scorpions, Centruroides limpidus (Cl) e Centruroides noxius (Cn). The venom was injected intravenously in bolus to pentobarbital anesthetized normotensive rats in the doses of 1, 10, 30, 60, 100 e 300 (μg/kg) (n=6/each group). The hemodynamic parameters were evaluted by using a pressure‐volume cateter implanted into the left ventricle (millar pressure‐volume microcatheter) and the direct effect of the venoms on cardiac output, arterial blood pressure, vascular resitsance, ejection fraction, stroke work, maximal and minimal dP/dt and tau. A lead II electrocardiogram was also evaluated. Cm venom injection did not promote significant alterations. Th venom from Cl decreased all hemodynamic parameters such as dP/dt min (dP/dt minct=−10780±2153; dP/dt min300=−5972±2921 (mmHg/s), p<0,05*) and heart rate (FCct=−403±31; FC300=−250±66 (bpm), p<0,05*). The Cn venom significantle decreased the stroke work (TCct=5957±1509; TC100=2611±1583 (mmHg*μL), p<0,05) and all other hemodynamic parameters evaluated. The structural analysis by optical microscopy showed that Cn venom induced lung hemorragy and pulmonary edema. The venom from Cn and Cl induced severe arrhythmias with ventricular extrasystoles and ventricular tachycardia. The venom of Cm is of low toxicity while the venom from Mexican Scorpions such as Cl and especially Cn have severe cardiovascular toxicity.Support or Funding InformationCAPES, CNPq and FUNCAPThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Prenatal Exposure to Bisphenol A and Diethylhexyl Phthalate Induces Apoptosis in the Thymus of Male and Female Offspring
Authors: Dagher Josephine Bou , Al Mansi Maryam , Jacob Elyssa , Kaimal Amrita , Chuang Yen‐Jun , Mohankumar Puliyur S , MohanKumar Sheba M. J. 
Published: June 2021

Bisphenol A (BPA) and Diethylhexyl Phthalate (DEHP) are common environmental endocrine disrupting chemicals (EDCs) that exert a range of potential adverse health effects. EDC exposure can occur in utero and during early postnatal life, when organ systems are differentiating resulting in a number of disorders in adulthood. The aim of this study was to evaluate the immunotoxic effect of prenatal exposure to individual and combinations of BPA and DEHP on male and female rat thymus. From gestational day 6 till 21, Sprague Dawley dams were orally administered either saline (control; n=7), BPA (5μg/Kg BW; n=7), DEHP (7.5mg/Kg BW; n=7), or a mixture of BPA and DEHP (B+D; n=7). Male and female offspring were sacrificed at 16 weeks of age. Thymus and spleen were dissected, weighed, and stored for further processing. Our data showed that spleen weight to body weight (BW) ratio of EDC treated offspring were comparable to those from age‐matched control rats. However, male offspring (but not females) that were prenatally exposed to BPA alone exhibited a 40% decrease (p<0.01) and those exposed to DEHP alone had a 27% reduction in thymus/BW ratio (p<0.05). To understand if prenatal EDC exposure was promoting early thymus involution through apoptosis, we performed Terminal deoxynucleotidyl transferase‐dUTP nick end labeling (TUNEL) staining of nicked DNA on thymic sections. There was significant apoptosis in the thymic cortex in both male and female offspring that were prenatally exposed to individual EDCs. Apoptosis was hardly detected in the medullary region. Apoptosis in the B+D group was markedly reduced compared to individual EDC exposures. These results suggest that prenatal exposure to even low BPA and moderate DEHP levels can promote apoptosis in the thymus. This could possibly affect immune functions in adulthood. Interestingly, exposure to a mixture of these EDCs did not produce any significant change in apoptosis in the thymus.Support or Funding InformationSupported by UGA Research Foundation and start‐up 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.
Chlorogenic Acid Increases Basal Tone with No Effect on Relaxation of Rat Ileal Smooth Muscles by Mechanisms Independent of PKG Mediated Effects on Myosin Light Chain Phosphorylation
Authors: Berman Sarah E , Huston Jamie L , Lail Austin W , Piquette Nicole B , Injeti Elisha R 
Published: June 2021

Chlorogenic acid (CGA) is a dietary polyphenolic compound commonly present in coffee, fruits and vegetables. The pharmacological properties of CGA include antioxidant, antibacterial, anti‐inflammatory, and antithrombotic effects. Previous experimental studies have shown that CGA induces nitric oxide‐sGC‐PKG pathway to cause relaxation of the vascular smooth muscles. But the effects of CGA on ileal smooth muscles are still unknown. The present study is designed to test the effect of CGA on PKG mediated relaxation of rat ileal smooth muscle.Effects of CGA on basal tension and maximum contractile tension induced by physiological salt solution (PSS) containing 140 mM potassium in isolated rat ileal rings (3mm) were determined using tissue bath apparatus. CGA effects on myosin light chain phosphorylation at maximum contractile tension were also measured by freezing the ileal rings and extracting the protein and running Western blots. The role of PKG in regulating smooth muscle relaxation is tested by incubating ileal rings with specific PKG inhibitor Rp‐8‐Br‐cGMPS and measuring the basal tension, maximum contractile tension and myosin light chain phosphorylation as described above.The results show that basal tension increases from 0.27±0.1 (control group) to 0.91±0.3 and 0.87±0.2 (mV) when treated with CGA (10μM) and PKG inhibitor (4μM) respectively. The peak contractile tension in response depolarization by 140 mM K+ PSS changes from 100% (control group) to 101±12.2 % and 117±17.2 % when treated with CGA and PKG inhibitor respectively. The results from Western blots show that myosin light chain phosphorylation didn't change significantly between CGA (36.3±0.8 %) and PKG inhibitor (35.8±0.5 %) treatments.These results suggest that CGA is involved in increasing the basal tone of ileal smooth muscles when compared with the control group. In addition, CGA did not have any effect on the peak contractile tension and myosin light chain phosphorylation, suggesting that it may not be involved in ileal smooth muscle relaxation. However, PKG inhibitor in presence of CGA did increase basal and maximum contractile tension without any corresponding changes in myosin light chain phosphorylation indicating that other mechanisms that doesn't include PKG mediated effects on myosin light chain phosphorylation may be important in regulating basal tone of ileal smooth muscle by CGA.Support or Funding InformationSupported by internal grant of Cedarville University School of PharmacyThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Taurine Protects Against the Neurotoxic Effects of Manganese on the Dopaminergic Control of Lateral Cell Membrane Potential and Ciliary Response in Gill of Crassostrea virginica
Authors: Johnson Alexcia J. , Howard Aliyah , Carroll Margaret A. , Catapane Edward J. 
Published: June 2021

Manganese is a neurotoxin causing manganism, a Parkinson's‐like disease involving disruption of dopaminergic neurotransmission. The mechanism by which manganese produces this dysfunction is not fully resolved. Unlike Parkinson's disease, reports postulate that manganese neurotoxicity is more likely related to downstream neuronal pathways rather than deficits in nigrostriatal function. Lack of effective treatment for manganism has been a major obstacle in its clinical management. The cilia of lateral cell in gill of Crassostrea virginica are controlled by serotonergic‐dopaminergic innervations from their ganglia. Dopamine (DA) hyperpolarizes the cell and causes cilio‐inhibition, while serotonin depolarizes and causes cilio‐excitation. Previous work of our lab showed acute and short‐term manganese treatments blocked the cilio‐inhibitory effect of DA. This neurotoxic action of manganese could be prevented by the drug p‐aminosalicylic acid or by taurine, an amino acid with efficacy in other neurodegenerative disorders. In this study we hypothesize that taurine would effectively prevent the toxic actions of manganese on both dopaminergic membrane hyperpolarization and lateral cilia inhibition. To test this we conducted acute experiments on DA dose responses (10−6 – 10−3 M) of manganese treated excised gill in the presence or absence of taurine. Ciliary activity of gill lateral cells was measured by stroboscopic microscopy and expressed as beats/min ± sem. Cell membrane potentials were simultaneously measured using the fluorescent dye DiBAC4(3). In control gill, the lateral cells responded normally to the DA dose response showing the appropriate decrease in cilia beating rates and membrane hyperpolarization. Gills treated with manganese (2 × 10−4M) had a disrupted DA response, cilio‐inhibition was impaired and the membrane did not hyperpolarize. Taurine treatment (2 × 10−4M) effectively prevented these neurotoxic effects in manganese treated gill. This physiological study in C. virginica shows that manganese disrupts the dopaminergic post‐synaptic response of lateral cells preventing membrane hyperpolarization as well disrupting cilio‐inhibition, and that taurine effectively blocked these neurotoxic actions. These findings are helpful in furthering the understanding of the mechanism of manganese neurotoxicity and provides evidence suggesting taurine be further investigated as a potential therapeutic agent for manganism.Support or Funding InformationThis work was supported in part by grant 2R25GM06003 of the Bridge Program of NIGMS, NIH grant K12GM093854‐07A1 IRACDA Program of Rutgers University and 604060048 of PSC‐CUNY.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Nitrite Disruption in Olfaction and Internal Physiology in Goldfish (Carassius auratus)
Authors: Martinez Melody , Huertas Mar 
Published: June 2021

Freshwater ecosystems have experienced a dramatic increase of nitrogenous compounds as a result of farming and industrial activity. Nitrite accumulates by bacterial denitrification/nitrification in freshwater and saltwater ecosystems, reaching concentrations of 1 mM and 0.5 μM respectively. Exposure to high nitrite concentrations can disrupt the endocrine system and physiological processes such as ion homeostasis, respiratory, and cardiovascular activity. However, the accumulation of nitrite in different internal tissues and its effect on external sensitive organs, such as the olfactory epithelium, is unknown. This study aimed to determine the physiological effects of nitrite and its accumulation in several organs in goldfish (Carassius auratus). Goldfish were exposed to different nitrite treatments (0 mM, 0.3 mM, 1.0 mM, and 10 mM) for five days. Upon completion of experiment, brain, nose, liver, kidney, and gill samples were obtained for biological and histological analysis. Goldfish in two treatments (1.0 mM and 10 mM) experienced irreversible oxidation of hemoglobin known as metahemoglobemia, marked by browning of the blood and darker tissues. Biochemical analysis showed an increase of nitrite in brain, nose, liver, and gill tissues. Brain and nose tissues (240 ±0.004 μM and 260 ±0.002 μM, respectively) accumulated more nitrite than gill tissue (190 ±0.002 μM) in the lowest treatment (0.3 mM), and this trend continued as treatment concentrations increased. Preliminary statistical analysis demonstrated that both the brain and nose tissue accumulated >30% more nitrite than gill tissue in the 0.3 mM treatment. Histological analysis of the olfactory epithelium showed hyperplasia, an increase in cell size and number; furthermore, we observed an increase in the number of mucus cells and mucus production, collapse of columnar cells, and lamella constriction in both the 1.0 mM and 10 mM treatments. Histological analysis of gills showed lamella fusion and vascular congestion. Histological liver samples exhibited melanomacrophage aggregate, nucleus degeneration, and cytoplasmic vacuolation in 10 mM. Preliminary findings from electro‐olfactograms show that nitrite reduced the ability of a goldfish to detect odors at nitrite exposure as low as 0.1 mM. These results suggest that nitrite is accumulating faster in external sensory tissues than internal organs, affecting essential physiological processes such as olfactory food detection and possibly acting as a neurotoxin.Support or Funding InformationResearch support: Texas State University start‐up funding to Dr. Mar Huertas.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.