bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the discriminative stimulus effects of the delta‐opioid receptor agonist, SNC80, in rats
Authors: Matthews Ashleigh L. , Rice Kenner C. , Jutkiewicz Emily M. 
Published: June 2021

Delta opioid receptor (DOR) agonists produce antihyperalgesia and antidepressant‐like effects, but they also induce convulsions limiting their clinical development. Recently, some work has shown that not all DOR agonists produce convulsions in rodents. Therefore, the current study aimed to further evaluate the pharmacological properties of these DOR ligands using a drug discrimination paradigm in male Sprague‐Dawley rats. The drug discrimination assay is useful for identifying compounds with similar interoceptive properties and evaluating the pharmacological activity of ligands in vivo. For this study, rats were trained to discriminate 3.2 mg/kg SNC80 from saline on a fixed ratio (FR) 10 schedule of reinforcement in a food‐reinforced, drug discrimination paradigm. Substitution patterns with purported DOR agonists AZD2327, DPI287, KNT127, and MMP2200 were evaluated as well as profiles of antagonism following pretreatment with naltrindole. Agonists that are structurally similar to SNC80, AZD2327 and DPI287, generalized to SNC80 while structurally unrelated agonists, KNT127 and MMP2200, did not. Morphine, ketamine, desipramine, cocaine, and nicotine failed to generalize to SNC80 up to doses that suppressed responding; however, amphetamine produced partial generalization to the discriminative stimulus effects of SNC80. The DOR antagonist naltrindole produced parallel, rightward shifts in the SNC80 dose effect curve. Overall, these data suggest that interoceptive effects differ among DOR agonists, which may contribute to their distinct profiles of behavioral activity and potentially diverse mechanisms of action. Future studies will further probe the pharmacological and/or signaling mechanisms that differentiate the behavioral effects of DOR agonists.Support or Funding InformationThis work is supported in part by R01 DA042092 (EMJ) and the IRPs of NIDA and NIAAA (KCR).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Leukemia Inhibitory Factor Modulates the Post‐Stroke Immune Response in Rats
Authors: Davis Stephanie M. , Collier Lisa A. , Leonardo Christopher C. , Ajmo Craig T. , Kopper Timothy J. , Gensel John C. , Pennypacker Keith R. 
Published: June 2021

ObjectiveTo determine if leukemia inhibitory factor (LIF) administration after permanent focal stroke decreases post‐stroke neuroinflammation.MethodsFocal ischemia was induced in 3 month old male and 18 month old male/female Sprague‐Dawley using the middle cerebral artery occlusion (MCAO) procedure. Animals were treated with PBS or LIF at 6, 24, and 48 h after MCAO (125 μg/kg). Animals were euthanized at at 72 h post‐MCAO. Protein levels of CD11b, IL‐12 p40, IFNγ, and IP‐10 were measured in splenic tissue using immunoblotting and/or ELISA. Isolectin staining and immunoblotting were used to detect levels of CD11b+ macrophages/microglia in the brain. Murine bone marrow derived macrophages (BMDMs) stimulated with LPS (50 ng/ml) and IFNγ (20 ng/ml) in the presence or absense of LIF and IL‐12 p40/IL‐10 levels were detected in the supernatant.ResultsLIF treatment significantly increased the average spleen weight at 72 h after MCAO compared to PBS‐treated rats (p<0.05) and decreased splenic LIFR expression compared to sham operated (p<0.01) and PBS‐treated (p = 0.0682) rats. LIF‐treated rats showed significantly decreased levels of IL‐12 p40 (p <0.05) and IFNγ (p = 0.0644) in splenic tissue at 72 h after MCAO compared PBS‐treated animals. LIF treatment also counteracted the significant increase in splenic IP‐10 expression observed in the PBS‐treated rats (*p<0.01 compared to sham‐operated rats). CD11b levels were significantly lower in the spleens of LIF‐treated (p<0.001) and PBS‐treated (p<0.01) rats compared to sham rats. However, LIF treated significantly decreased normalized CD11b protein levels (p<0.05) and decreased isolectin reactivity in the brain at 72 h post‐MCAO compared to PBS‐treated animals. BMDMs treated with LIF prior to IFNγ and LPS stimulation released significantly lower levels of IL‐12 p40 and significantly higher levels of IL‐10 (p ≤ 0.05) compared to BMDMs treated with PBS prior to LPS+IFNγ stimulation.ConclusionLIF confers anti‐inflammatory signaling after stroke through modulation of the IL‐12 p40/IFNγ/IP‐10 axis in splenocytes and decreasing the infiltration of CD11b+ monocytes/macrophages into the ischemic brain.Support or Funding InformationProject Number: 5R01NS091146‐03 (NINDS; PI: Pennypacker)Project Number: 55R01NS091582‐03 (NINDS; PI: Gensel)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Schematic diagram of the neural protective role of IMMH004 after TGCI/R Pharmacological Induction of Mitochondrial Biogenesis using the β2‐Adrenoreceptor Agonist Formoterol for the Treatment of Spinal Cord Injury
Authors: Scholpa Natalie E. , Wang Wenxue , Corum Daniel , Narang Aarti , Tomlinson Stephen , Schnellmann Rick G. 
Published: June 2021

A hallmark of the progressive cascade of damage referred to as secondary spinal cord injury (SCI) is vascular disruption resulting in ischemia and decreased oxygen delivery, which directly reduces the ability of mitochondria to maintain homeostasis. This leads to loss of ATP‐dependent cellular functions, Ca2+ overload, excitotoxicity and oxidative stress, further exacerbating injury. While therapeutics targeting restoration of single facets of mitochondrial function have proven largely ineffective post‐SCI, comprehensively addressing mitochondrial dysfunction via pharmacological stimulation of mitochondrial biogenesis (MB) is an underexplored strategy. The FDA‐approved, highly selective and potent β2‐adrenoreceptor (ADRB2) agonist formoterol is an effective inducer of MB in multiple organ systems in mice, including the spinal cord, as evidenced by increased mitochondrial DNA content and PGC‐1α expression. This study examined the effects of formoterol‐induced MB on recovery from SCI using a force‐controlled pneumatic impactor‐induced contusion model. Female C57bl/6 mice were subjected to moderate SCI (80 Kdyn) followed by daily formoterol administration (0.1 mg/kg, i.p) beginning 1 or 8 h post‐injury and continuing until euthanasia. SCI resulted in decreased mitochondrial protein expression, including PGC‐1α, in the injury and peri‐injury sites as early as 3 d after injury. Formoterol treatment attenuated this early decrease in PGC‐1α and restored downstream mitochondrial proteins to levels similar to that of sham controls by 15 d post‐SCI. Formoterol‐treated mice also exhibited less histological damage than vehicle‐treated mice 3 d after injury, namely reduced loss of white matter and structural preservation of the central canal and anterior median fissure. Importantly, as measured by the Basso‐Mouse Scale, the locomotor ability of formoterol‐treated injured mice reached twice that of vehicle‐treated SCI mice by 15 d (4.5 v 2), depicting nearly 50% recovery. Interestingly, a comparable degree of functional recovery was observed when formoterol treatment initiation was delayed until 8 h post‐SCI. These data provide evidence of ADRB2‐mediated MB as a therapeutic avenue for the treatment of SCI.Support or Funding InformationNational Institutes of Health National Institute of General Medical Sciences, Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs, South Carolina Spinal Cord Injury Research FundThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sodium butyrate exerts neuroprotective effects in spinal cord injury.
Authors: Lanza Marika , Campolo Michela , Casili Giovanna , Filippone Alessia , Cuzzocrea Salvatore , Esposito Emanuela 
Published: June 2021

Sodium butyrate (SB) is a dietary microbial fermentation product of dietary fiber and serves as an important neuromodulator in the central nervous system. Recent experimental evidence has suggested potential therapeutic applications for butyrate, including its utility in treating metabolic and inflammatory diseases. The aim of the present study was to evaluate the potential beneficial effects of SB in a mouse model of spinal cord injury (SCI) and its possible mechanism of action. SCI was produced by extradural compression for 1 min of the spinal cord at the T6–7 level using an aneurysm clip, and SB (10–30–100mg/kg) were administered by oral gavage 1 and 6 h after SCI. For locomotor activity, study mice were treated with SB once daily for 10 days. Morphological examination was performed by light microscopy through hematoxylin‐eosin (H&E) staining. In addition, NF‐kB, IkB‐alfa, COX2 and iNOS expression were assayed by western blot analysis and IL‐1beta and TNF‐alfa levels by immunohistochemistry analysis. The results showed that SB treatment significantly ameliorated histopathology changes and improved recovery of motor function changes in spinal cord injury in dose‐dependet manner. Moreover, from the results obtained, SB modulated NF‐kB pathway showing a reduction in cytokines expression. This study showed that SB exerts neuroprotective effects on spinal cord injury and anti‐inflammatory properties. The observed neuroprotective action suggests that SB may serve as a potential candidate for future treatment of spinal cord injury.Support or Funding InformationNo foundingThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impact of Cannabis use on the Antipsychotic Therapy of Schizophrenia Symptoms
Authors: Thomas‐Brown Peta‐Gaye Latoya , Martin Jacqueline Simone , Sewell Clayton A. , Abel Wendel D. , Gossell‐Williams Maxine D. 
Published: June 2021

ObjectivesTo assess the impact of Cannabis usage on risperidone and haloperidol therapy of schizophrenia symptoms.MethodsMale subjects, ≥18 years, admitted to the University Hospital of the West Indies psychiatric ward between February‐December 2013, and diagnosed with schizophrenia were recruited for the study. Consented subjects were prescribed either risperidone‐ or haloperidol‐monotherapy for 7‐days and oral doses converted to chlorpromazine equivalents (CPZE). Subjects were classified as Cannabis users (CU) or non‐users (non‐CU), with presence/absence of Cannabis metabolite in urine samples. Blood samples were collected on days 1&7 for assessment of cannabinoid and antipsychotic concentrations, respectively, using ultra performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS). Psychotic symptoms were assessed with the Brief Psychiatric Rating Scale (BPRS) on days 1&7 and changes in the scores used as a measure of efficacy of the antipsychotic therapy. Inferential statistical analysis involved non‐parametric tests, expressed as median and IQR, with p<0.05 considered significant.ResultsForty‐Six Afro‐Caribbean males were assessed, with median (IQR) age of 25 (8) years. Majority (n=33; 72%) were CU, with Cannabis‐positive urinalysis, confirmed with the quantification of Δ9‐tetrahydrocannabinol (THC) at 3.0 (8.0) ng/mL and Carboxylated‐THC at 51.0 (53.0) ng/mL in serum samples. CU presented with more severe BPRS scores [61 (33) vs 33 (19); p<0.000] than non‐users. Additionally, more CU displayed depression (60%; r=0.403, p=0.001) and motor retardation (79%; r=0.595, p=0.002) which were positively correlated to serum THC concentration. After seven days of antipsychotic therapy, both CU and non‐CU showed significant clinical improvement of schizophrenia symptoms (≥20% reduction in BPRS scores) with risperidone or haloperidol at CPZE doses ≥300 mg/day. A significantly higher oral CPZE dose of haloperidol was prescribed to CU than non‐CU [1000 (250) vs 500 (500) mg/day; p=0.035]. However, serum concentration of haloperidol was significantly less for CU than non‐CU [3 (2) vs 8 (3) ng/mL; p=0.044]. In contrast, oral doses [300 (75) vs 300 (0); p=0.554] and serum concentration of risperidone [12 (5) vs 13 (4) ng/mL; p=0.739] were equivalent between the groups.ConclusionCannabis users display more severe BPRS‐assessed schizophrenia symptoms compared to non‐users, which can be significantly improved after 7 days of antipsychotic therapy. However, Cannabis use reduces the potency of haloperidol, thus, a significantly higher oral dose is required to adequately treat schizophrenia symptoms. Further studies are recommended.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Glycogen Synthase Kinase‐3β Modulation of Basal Aryl Hydrocarbon Receptor Protein Levels in HeLa Cells
Authors: Yang Yujie , Chan William K. 
Published: June 2021

The aryl hydrocarbon receptor (AHR) is a transcription factor involved in many cellular processes. It has been well accepted that it plays important roles in development, metabolism, immune response, and carcinogenesis. Presently the only known regulation of AHR protein is mediated through proteasomal degradation after ligand activation. In this study, we investigate the mechanisms that govern the AHR protein levels without ligand treatment. The ligand‐free AHR resides in the cytosol and is accompanied by XAP2, Hsp90, and its co‐chaperone p23. We previously discovered that knockdown of p23 can lower the AHR protein levels as well as its message levels. Close examination of the AHR sequence unveils a putative signal for glycogen synthase kinase‐3β (GSK‐3β) phosphorylation which may lead to protein degradation. Treatment of GSK‐3β inhibitors tideglusib and lithium chloride increases the AHR protein levels up to about 2‐fold in wild type HeLa cells but not in p23 knockdown stable HeLa cells. These results suggest that the AHR protein levels can be regulated by GSK‐3β only in the presence of the wild type content of p23. Downregulation of the AHR protein levels by GSK‐3β and p23 appears to be mediated through distinct mechanisms. We will address whether this GSK‐3β effect is p23‐dependent. Additional mechanistic data will be presented to explain the underlying mechanisms.Support or Funding InformationNIEHS, R15ES023104This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Human Antigen R (HuR) Regulates Structure and Function of Brown Adipose Tissue
Authors: Lanzillotta Lindsey , Anthony Sarah R. , Yamamoto Kaila , Jones Shannon , Taylor Zachary , Yoshida George , Owens A. Phillip , Tranter Michael 
Published: June 2021

Human antigen R (HuR) is an RNA binding protein widely expressed throughout the body, including in both white (WAT) and brown (BAT) adipose tissue. Recent work from our lab has shown that adipocyte‐specific HuR knockout (adipo‐HuR−/−) mice gain less weight following a high fat diet (HFD) compared to wild type (WT) controls. In this study, we focused on the role of HuR deletion on the function of BAT, which mediates non‐shivering thermogenesis.Histological analysis revealed that, while the BAT of the chow fed adipo‐HuR−/− mice appeared normal, the BAT of the HFD fed adipo‐HuR−/− mice appears less dense with a cell size that more closely resembles WAT. Upon further examination of BAT function, our results show that, when subjected to cold stress (4°C), adipo‐HuR−/− mice are less cold tolerant compared to their WT counterparts. We also show that, compared to the WT mice, adipo‐HuR−/− mice have decreased mitochondrial density and expression of uncoupling protein‐1 (UCP‐1) in their BAT. This may be caused by a HuR‐dependent decrease in expression of peroxisome proliferator‐activated receptor gamma coactivator 1 alpha (PGC‐1a), which plays a key role in mitochondrial biogenesis and is upregulated during exposure to cold (4°C).In conclusion, our results indicate that HuR regulates both the structure and function of BAT, at least in part through modulation of PGC‐1a mRNA expression.Support or Funding InformationThis work was supported by a University of Cincinnati Heart, Lung, and Vascular Institute Near Horizons Grant (MT, APO).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Population genomics and molecular surveillance for Plasmodium falciparum genetic diversities in an endemic area
Authors: Dokunmu Titilope Modupe , Oladejo David Oladoke , Adjekukor Cynthia Ufoma 
Published: June 2021

Current malaria control strategies in endemic areas target eradication and elimination of the disease as well as improving artemisinin combination treatments (ACTs) and vector control. In this era of reducing transmission, molecular surveillance and bioinformatics tools offer great insights for understanding transmission dynamics. This study aims to determine prevalence rates and molecular diversities in Plasmodium falciparum in an endemic area. Polymerase chain reaction was used to determine presence of malaria infection, and presence of mutation in 2 select gene markers of drug resistance was determined by sequencing amplified products in few isolates. The sequence data was mapped unto the plasmodium genome to detect mutations in the genes using 3D7 strain (PF3D7_1343700.1 and PF3D7_0523000.1) as reference sequence. A high asymptomatic parasite rate (43%) was detected with a low frequency of SNPs in Kelch 13, which is not associated with drug resistance. There is a high rate of infection in this area with some mutations which may not directly modulate drug responses but the influence on transmission and impact on parasite's survival remains to be determined.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Regulation of UGT2A1 by miR‐196a & miR‐196b and Its Implications for Lung Cancer Risk
Authors: Sutliff Aimee Kristina , Chen Gang , Watson Christy J.W. , Lazarus Philip 
Published: June 2021

Polycyclic aromatic hydrocarbons (PAH) are a class of highly lipophilic and mutagenic carcinogenic compounds found in tobacco smoke and incomplete combustion reactions. Once inside the cell, PAHs are oxidized by cytochrome P450s 1C1 and 1B1 to form reactive species that can form DNA adducts. PAHs are primarily detoxified by the UDP‐glucuronosyltransferase (UGT) family of enzymes, which comprise a major family of phase II metabolism responsible for the detoxification of a variety of endogenous and exogenous compounds including steroids, many drugs and chemotherapeutic agents, and carcinogens. UGT2A1 is an aero‐digestive tract‐expressing enzyme shown to be highly selective toward a broad range PAHs and is expressed in tobacco target tissues, including lung. microRNA (miRNA) are short, noncoding RNA sequences that play a role in translational regulation of gene expression by binding primarily to the 3′ untranslated regions (UTR) of mRNA. Significant (P<0.05 and P<0.001) decreases in luciferase activity were observed in cells over‐expressing heterologous vectors containing the 3′‐untranslated region (UTRs) of UGT2A1 with the miR‐196a and miR‐196b mimics, respectively. Pull‐down assays revealed miR‐196a and miR‐196b bound to the 3′ UTR of UGT2A1 at 3.4‐and 5.3‐fold higher levels, respectively, compared to the coding region control sequence. In the lung cancer cell lines, H1944 and H146, a significant trend is observed when cells were transfected with increasing levels of miR‐196a and miR‐196b (Ptrend=0.0065 and Ptrend=0.0114 for H1944, and Ptrend=0.0219 and Ptrend=0.0091 for H146, respectively). These data indicate that miR‐196a and miR‐196b may be important in regulating UGT2A1 expression in human tissues and may be potential biomarkers for cancer risk in smokers.Support or Funding InformationNational Institute of Environmental Health Sciences (NIEHS) of the National Institute of Health (NIH) to Dr. Philip Lazarus (Grant R01‐ES025460) and the Health Sciences and Services Authority of Spokane, WA (Grant WSU002292).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A Role for Protein Kinase C in Gill Lateral Cell Activity of Crassostrea virginica
Authors: Ernest Krystle , Johnson Alexcia , Carroll Margaret A. , Catapane Edward J. 
Published: June 2021

Gill lateral cell cilia of Crassostrea virginica are controlled by serotonergic‐dopaminergic innervations from their ganglia. Dopamine is the neurotransmitter causing cilio‐inhibition and serotonin causing cilio‐excitation. Gill lateral cell dopamine postsynaptic receptors involved in cilio‐inhibitory actions are D2‐like (D2DR). The D2DR signaling pathway involves steps that include inhibition of adenylyl cyclase, which has been well studied, and activation of phospholipase C (PLC). PLC activation generates second messengers diacylglycerol (DAG) and inositol trisphosphate (IP3). IP3 binds to an IP3 receptor which causes the release of intracellular calcium stores. Collectively, DAG and calcium ions are required to activate protein kinase C (PKC). While high cytoplasmic calcium levels have been shown to slow beating rates of gill lateral cell cilia, the role of PKC activation on gill lateral cell cilia has not been studied. We hypothesize PKC activation, which is downstream in the D2DR signaling pathway, is involved in the cilio‐inhibitory response of gill lateral cell cilia caused by dopamine in C. virginica. To study this we conducted acute experiments testing the PKC activator SC9 [N‐(6‐Phenylhexyl)‐5‐chloro‐1‐naphthalenesulfonamide], and the PKC inhibitor rottlerin. Ciliary activity of gill lateral cells was measured by stroboscopic microscopy and expressed as beats/sec ± sem. Statistical analysis was performed by ANOVA. Neither SC9 (10−6 – 10−3M) or rottlerin (10−6 – 10−4M) when applied directly to excise gill altered the gill lateral cell cilia beating rates, nor did they alter the cilio‐excitatory actions of applying serotonin (10−5M) to the gill. However, rottlerin (10−5M) treated gill did not respond normally to dopamine (10−6 – 10−3M) application to the gill, the cilia did not slow down their beating rates. Applying SC9 did not alter the cilio‐inhibitory effects of dopamine. These finding indicate that PKC is involved in the dopamine induced slowing of gill lateral cell cilia in C. virginica. Inhibiting PKC prevents the action of dopamine, while activating PKC by itself did not significantly alter the cilia beating rates. The study suggests that PKC plays a role in cilio‐inhibitory response caused by dopamine, but alone PKC activation is insufficient in generating the cilio‐inhibitory response and therefore other aspects of the D2DR signaling transduction pathway also must be involved. These findings are helpful in furthering the understanding of the D2DR mechanism of gill lateral cells and provides a foundation for further research.Support or Funding InformationSupported by 2R25GM06003 of the Bridge Program of NIGMS.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.