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Sample records for serotonin phenotype chlorpyrifos

  1. Functional Coding Variation in Recombinant Inbred Mouse Lines Reveals Novel Serotonin Transporter-Associated Phenotypes

    Energy Technology Data Exchange (ETDEWEB)

    Carneiro, Ana [Vanderbilt University; Airey, David [University of Tennessee Health Science Center, Memphis; Thompson, Brent [Vanderbilt University; Zhu, C [Vanderbilt University; Rinchik, Eugene M [ORNL; Lu, Lu [University of Tennessee Health Science Center, Memphis; Chesler, Elissa J [ORNL; Erikson, Keith [University of North Carolina; Blakely, Randy [Vanderbilt University

    2009-01-01

    The human serotonin (5-hydroxytryptamine, 5-HT) transporter (hSERT, SLC6A4) figures prominently in the etiology or treatment of many prevalent neurobehavioral disorders including anxiety, alcoholism, depression, autism and obsessive-compulsive disorder (OCD). Here we utilize naturally occurring polymorphisms in recombinant inbred (RI) lines to identify novel phenotypes associated with altered SERT function. The widely used mouse strain C57BL/6J, harbors a SERT haplotype defined by two nonsynonymous coding variants (Gly39 and Lys152 (GK)). At these positions, many other mouse lines, including DBA/2J, encode Glu39 and Arg152 (ER haplotype), assignments found also in hSERT. Synaptosomal 5-HT transport studies revealed reduced uptake associated with the GK variant. Heterologous expression studies confirmed a reduced SERT turnover rate for the GK variant. Experimental and in silico approaches using RI lines (C57Bl/6J X DBA/2J=BXD) identifies multiple anatomical, biochemical and behavioral phenotypes specifically impacted by GK/ER variation. Among our findings are multiple traits associated with anxiety and alcohol consumption, as well as of the control of dopamine (DA) signaling. Further bioinformatic analysis of BXD phenotypes, combined with biochemical evaluation of SERT knockout mice, nominates SERT-dependent 5-HT signaling as a major determinant of midbrain iron homeostasis that, in turn, dictates ironregulated DA phenotypes. Our studies provide a novel example of the power of coordinated in vitro, in vivo and in silico approaches using murine RI lines to elucidate and quantify the system-level impact of gene variation.

  2. Identification of genetic modifiers of behavioral phenotypes in serotonin transporter knockout rats

    Directory of Open Access Journals (Sweden)

    Nijman Isaäc J

    2010-05-01

    Full Text Available Abstract Background Genetic variation in the regulatory region of the human serotonin transporter gene (SLC6A4 has been shown to affect brain functionality and personality. However, large heterogeneity in its biological effects is observed, which is at least partially due to genetic modifiers. To gain insight into serotonin transporter (SERT-specific genetic modifiers, we studied an intercross between the Wistar SERT-/- rat and the behaviorally and genetically divergent Brown Norway rat, and performed a QTL analysis. Results In a cohort of >150 intercross SERT-/- and control (SERT+/+ rats we characterized 12 traits that were previously associated with SERT deficiency, including activity, exploratory pattern, cocaine-induced locomotor activity, and abdominal and subcutaneous fat. Using 325 genetic markers, 10 SERT-/--specific quantitative trait loci (QTLs for parameters related to activity and exploratory pattern (Chr.1,9,11,14, and cocaine-induced anxiety and locomotor activity (Chr.5,8 were identified. No significant QTLs were found for fat parameters. Using in silico approaches we explored potential causal genes within modifier QTL regions and found interesting candidates, amongst others, the 5-HT1D receptor (Chr. 5, dopamine D2 receptor (Chr. 8, cannabinoid receptor 2 (Chr. 5, and genes involved in fetal development and plasticity (across chromosomes. Conclusions We anticipate that the SERT-/--specific QTLs may lead to the identification of new modulators of serotonergic signaling, which may be targets for pharmacogenetic and therapeutic approaches.

  3. Patients with high-bone-mass phenotype owing to Lrp5-T253I mutation have low plasma levels of serotonin

    DEFF Research Database (Denmark)

    Frost, Morten; Andersen, Tom E.; Yadav, Vijay

    2010-01-01

    The Lrp5 gene is a major determinant of bone mass accrual. It has been demonstrated recently to achieve this function by hampering the synthesis of gut-derived serotonin, which is a powerful inhibitor of bone formation. In this study we analyzed plasma serotonin levels in patients with a high......-bone-mass (HBM) phenotype owing to gain-of-function mutation of Lrp5 (T253I). A total of 9 HBM patients were compared with 18 sex- and age-matched controls. In HBM patients, the serotonin concentrations in platelet-poor plasma were significantly lower than in the controls (mean +/- SEM: 2.16 +/- 0.28 ng....../mL versus 3.51 +/- 0.49 ng/mL, respectively, p Lrp5 in humans. (c) 2010 American Society for Bone and Mineral Research....

  4. Serotonin syndrome

    Science.gov (United States)

    Hyperserotonemia; Serotonergic syndrome; Serotonin toxicity; SSRI - serotonin syndrome; MAO - serotonin syndrome ... brain area. For example, you can develop this syndrome if you take migraine medicines called triptans together ...

  5. Levels of serotonin, sclerostin, bone turnover markers as well as bone density and microarchitecture in patients with high bone mass phenotype due to a mutation in Lrp5

    DEFF Research Database (Denmark)

    Nielsen, Morten Frost; Andersen, Tom E.; Gossiel, F

    2011-01-01

    CONTEXT: Patients with an activation mutation of the Lrp5 gene exhibit high bone mass (HBM). Limited information is available regarding compartment specific changes in bone. The relationship between the phenotype and serum serotonin is not well documented. Objective: to evaluate bone, serotonin...... and bone turnover markers (BTM) in Lrp5-HBM patients. DESIGN: We studied 19 Lrp5-HBM patients (T253I) and 19 age- and sex-matched controls. DXA and HR-pQCT were used to assess BMD and bone structure. Serum serotonin, sclerostin, DKK1 and BTM were evaluated. RESULTS: Z-scores for the forearm, total hip......, lumbar spine, forearm and whole body were significantly increased (mean ± SD) between 4.94 ± 1.45 and 7.52 ± 1.99 in cases as compared to -0.19 ± 1.19 to 0.58 ± 0.84 in controls. Tibial and radial cortical areas, thicknesses and BMD were significantly higher in cases. In cases, BMD at the lumbar spine...

  6. Revised Human Health Risk Assessment on Chlorpyrifos

    Science.gov (United States)

    We have revised our human health risk assessment and drinking water exposure assessment for chlorpyrifos that supported our October 2015 proposal to revoke all food residue tolerances for chlorpyrifos. Learn about the revised analysis.

  7. Individual differences in scanpaths correspond with serotonin transporter genotype and behavioral phenotype in rhesus monkeys (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Robert R Gibboni

    2009-11-01

    Full Text Available Scanpaths (the succession of fixations and saccades during spontaneous viewing contain information about the image but also about the viewer. To determine the viewer-dependent factors in the scanpaths of monkeys, we trained three adult males (Macaca mulatta to look for 3 s at images of conspecific facial expressions with either direct or averted gaze. The subjects showed significant differences on four basic scanpath parameters (number of fixations, fixation duration, saccade length, and total scanpath length when viewing the same facial expression/gaze direction combinations. Furthermore, we found differences between monkeys in feature preference and in the temporal order in which features were visited on different facial expressions. Overall, the between-subject variability was larger than the within- subject variability, suggesting that scanpaths reflect individual preferences in allocating visual attention to various features in aggressive, neutral, and appeasing facial expressions. Individual scanpath characteristics were brought into register with the genotype for the serotonin transporter regulatory gene (5-HTTLPR and with behavioral characteristics such as expression of anticipatory anxiety and impulsiveness/hesitation in approaching food in the presence of a potentially dangerous object.

  8. Serotonin & Depression

    OpenAIRE

    Axholm, Ida; Haxgart, Nina; Ranum, Kasper; Svendsen, Astrid Helmer

    2014-01-01

    350.000.000 people worldwide have a depression and 150.000 Danes are affected every year. Depresion is defined by WHO from it’s syptoms. The diagnose is given from a point system for the patient’s symptoms, for instance HAM-D scale and MADRS scale Serotonin in the brain is synthesized from L-tryptophan in the presynaptic parts of the neuron and is released into the synapse as a transmitter drug. According to the serotonin theory, the concentration of serotonin in the brain is low in depressio...

  9. Serotonin Test

    Science.gov (United States)

    ... acute myocardial infarction ( heart attack ), cystic fibrosis , and dumping syndrome . The serotonin test is not usually ordered ... Thank you. Contact a Scientist Find Us On Social Media: Facebook Twitter Google Plus Footer Menu Home ...

  10. Serotonin Test

    Science.gov (United States)

    ... High-sensitivity C-reactive Protein (hs-CRP) Histamine Histone Antibody HIV Antibody and HIV Antigen (p24) HIV ... 282515-overview. Accessed December 2010. (© 1995-2010). Unit Code 84395: Serotonin, Serum. Mayo Clinic, Mayo Medical Laboratories [ ...

  11. Epigenetic Mechanisms of Serotonin Signaling.

    Science.gov (United States)

    Holloway, Terrell; González-Maeso, Javier

    2015-07-15

    Histone modifications and DNA methylation represent central dynamic and reversible processes that regulate gene expression and contribute to cellular phenotypes. These epigenetic marks have been shown to play fundamental roles in a diverse set of signaling and behavioral outcomes. Serotonin is a monoamine that regulates numerous physiological responses including those in the central nervous system. The cardinal signal transduction mechanisms via serotonin and its receptors are well established, but fundamental questions regarding complex interactions between the serotonin system and heritable epigenetic modifications that exert control on gene function remain a topic of intense research and debate. This review focuses on recent advances and contributions to our understanding of epigenetic mechanisms of serotonin receptor-dependent signaling, with focus on psychiatric disorders such as schizophrenia and depression.

  12. Fast microencapsulation of chlorpyrifos and bioassay

    National Research Council Canada - National Science Library

    Zhu, Ling; Wang, Zhenghui; Zhang, Shuting; Long, Xiaoyan

    2010-01-01

    ...%, were prepared by fast interfacial polymerization at room temperature. Formulations based on the prepared microcapsules are stable in neutral medium and release chlorpyrifos in both acidic and alkaline media...

  13. Degradation of chlorpyrifos in humid tropical soils.

    Science.gov (United States)

    Chai, Lian-Kuet; Wong, Mee-Hua; Bruun Hansen, Hans Christian

    2013-08-15

    The insecticide chlorpyrifos is extensively used in the humid tropics for insect control on crops and soils. Chlorpyrifos degradation and mineralization was studied under laboratory conditions to characterize the critical factors controlling the degradation and mineralization in three humid tropical soils from Malaysia. The degradation was fastest in moist soils (t1/2 53.3-77.0 days), compared to dry (t1/2 49.5-120 days) and wet soils (t1/2 63.0-124 days). Degradation increased markedly with temperature with activation energies of 29.0-76.5 kJ mol(-1). Abiotic degradation which is important for chlorpyrifos degradation in sub-soils containing less soil microbial populations resulted in t½ of 173-257 days. Higher chlorpyrifos dosages (5-fold) which are often applied in the tropics due to severe insects infestations caused degradation and mineralization rates to decrease by 2-fold. The mineralization rates were more sensitive to the chlorpyrifos application rates reflecting that degradation of metabolites is rate limiting and the toxic effects of some of the metabolites produced. Despite that chlorpyrifos is frequently used and often in larger amounts on tropical soils compared with temperate soils, higher temperature, moderate moisture and high activity of soil microorganisms will stimulate degradation and mineralization. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Chlorpyrifos

    African Journals Online (AJOL)

    Bheema

    these techniques require technically skilled labor for their operational usage besides being time- consuming, expensive and cannot be used for continuous monitoring. Though, to some extent the biological techniques such as immunoassays and biosensors have also been tried for the determination of organo-phosphorous ...

  15. Degradation of chlorpyrifos in tropical rice soils.

    Science.gov (United States)

    Das, Subhasis; Adhya, Tapan K

    2015-04-01

    Chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridinol) phosphorothioate] is used worldwide as an agricultural insecticide against a broad spectrum of insect pests of economically important crops including rice, and soil application to control termites. The insecticide mostly undergoes hydrolysis to diethyl thiophosphoric acid (DETP) and 3,5,6-trichloro-2-pyridinol (TCP), and negligible amounts of other intermediate products. In a laboratory-cum-greenhouse study, chlorpyrifos, applied at a rate of 10 mg kg(-1) soil to five tropical rice soils of wide physico-chemical variability, degraded with a half-life ranging from 27.07 to 3.82 days. TCP was the major metabolite under both non-flooded and flooded conditions. Chlorpyrifos degradation had significant negative relationship with electrical conductivity (EC), cation exchange capacity (CEC), clay and sand contents of the soils under non-flooded conditions. Results indicate that degradation of chlorpyrifos was accelerated with increase in its application frequency, across the representative rice soils. Management regimes including moisture content and presence or absence of rice plants also influenced the process. Biotic factors also play an important role in the degradation of chlorpyrifos as demonstrated by its convincing degradation in mineral salts medium inoculated with non-sterile soil suspension. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Variation characteristics of chlorpyrifos in nonsterile wetland plant hydroponic system.

    Science.gov (United States)

    Wang, Chuan; Zhou, Qiaohong; Zhang, Liping; Zhang, Yan; Xiao, Enrong; Wu, Zhenbin

    2013-01-01

    Six wetland plants were investigated for their effect on the degradation characteristics of chlorpyrifos in nonsterile hydroponic system at constant temperature of 28 degrees C. The results showed that the removal rates of chlorpyrifos in the water of plant systems were 1.26-5.56% higher than that in the control without plants. Scirpus validus and Typha angustifolia were better than other hygrophytes in elimination of chlorpyrifos. The removal rates of the two systems were up to 88%. Plants of acaulescent group had an advantage over caulescent group in removing chlorpyrifos. Phytoaccumulation of chlorpyrifos was observed, and the order of chlorpyrifos concentration in different plant tissues was root > stem > leaf. It was also found that chlorpyrifos and its metabolite TCP decreased rapidly at the initial step of the experiment.

  17. Dermal absorption of chlorpyrifos in human volunteers

    NARCIS (Netherlands)

    Meuling, W.J.; Ravensberg, L.C.; Roza, L.; Hemmen, J.J. van

    2005-01-01

    Objective: The methods and results are described of a study on the dermal absorption of chlorpyrifos (CPF) in humans established via urinary excretion of the metabolite 3,5,6-trichloro-2-pyridinol (TCP). Methods: Two dermal, single, doses of CPF were applied in two study groups (A and B) each

  18. 76 FR 39399 - Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Notice of Availability

    Science.gov (United States)

    2011-07-06

    ... AGENCY Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Notice of Availability... availability of EPA's preliminary human health risk assessment for the registration review of chlorpyrifos and... comprehensive preliminary human health risk assessment for all chlorpyrifos uses. After reviewing comments...

  19. 76 FR 52945 - Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Extension of Comment...

    Science.gov (United States)

    2011-08-24

    ... AGENCY Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Extension of Comment... availability of the chlorpyrifos registration review; preliminary human health risk assessment. This document... for the chlorpyrifos reregistration review, preliminary human health risk assessment, established in...

  20. Metal ion promoted degradation mechanism of chlorpyrifos and phoxim

    Directory of Open Access Journals (Sweden)

    Masoumeh Sarkouhi

    2016-01-01

    Full Text Available This study evaluate the degradation of the two organophosphorus pesticides: chlorpyrifos and phoxim in the presence of Ag+ at fixed initial concentration and temperature. Chlorpyrifos and phoxim were used as model compounds to develop experimental methods for the investigation of kinetic and degradation pathways. In order to determine what metabolites will be formed after degradation we used 31P NMR. Chlorpyrifos and phoxim were found to degrade in the presence of Ag+ and the result shown in lower chlorpyrifos to Ag+ ratio (<8, only one product formed and its concentration increased versus time. Degradation of chlorpyrifos and phoxim in methanolic solution in the presence of Ag+ followed first-order exponential decay kinetics, and the half-life (t1/2 of chlorpyrifos and phoxim are 693 and 1155, respectively.

  1. Scanning electron microscopic study of the effect of chlorpyrifos on ...

    African Journals Online (AJOL)

    Miriam R.R.F. Abdelmalek

    2016-01-21

    Jan 21, 2016 ... maturation of sea urchin embryos during the specific period during which development is regulated by neurotrophic factors.23 Recent evidence suggests that chlorpyrifos itself may directly influence brain cell replication and differentia- tion.11–13 Chlorpyrifos has immediate direct inhibitory actions on DNA ...

  2. The termicidal effects of Chlorpyrifos 48 EC, Endosulfan 35 EC ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-01-05

    Jan 5, 2009 ... four insecticides (Chlorpyrifos 48 EC, Endosulfan 35 EC, Dichlorvos 1000 EC and Diazinon 600 EC) on termites (workers and soldier castes). The results showed that for both topical and residual action tests, worker caste mortality rates ranging from 70 to 100% were recorded for Chlorpyrifos, Endosulfan,.

  3. Photodegradation and Hydrolysis of Chlorpyrifos in Aqueous Systems

    African Journals Online (AJOL)

    Hydrolysis and photodegradation of chlorpyrifos a widely used organophosphorus pesticide was studied. Hydrolysis is a dominant ... in aqueous systems. Implication for this study is relevant in understanding the fate of chlorpyrifos once released into the environment with possible application in water/wastewater treatment.

  4. The Effect of Chlorpyrifos on Isolated Thoracic Aorta in Rats

    Directory of Open Access Journals (Sweden)

    Ebru Yıldırım

    2013-01-01

    Full Text Available This study investigated the effect of chlorpyrifos on thoracic aorta and on the level of NO in plasma and aorta. The effect of chlorpyrifos on thoracic aorta in organ bath was determined in 10 rats. Another 45 rats were assigned to 3 groups with 15 rats each: control group 1 received distilled water, control group 2 was given corn oil, and the last group was given 13.5 mg/kg chlorpyrifos dissolved in corn oil every other day for 8 weeks orally. Chlorpyrifos (10−10 M–10−5 M showed no effect on isolated thoracic aorta. Plasma AChE activity was decreased, while LDH, ALT, GGT, and AST activities were increased in chlorpyrifos group compared to control groups. Plasma NO level was increased in chlorpyrifos group compared to control groups. iNOS expression was present in all groups in the cytoplasm of the endothelia and in the smooth muscle cells of aorta. According to semiquantitative histomorphological analysis, iNOS immunopositive reactions were seen in the decreasing order in chlorpyrifos, control 2, and control 1 groups. eNOS immunopositive reactions were observed in the endothelial cell cytoplasm, rarely in the subintimal layer, and the smooth muscle cells of aorta. There were no differences among the groups in terms of eNOS immunostaining. In conclusion, chlorpyrifos induced NO production in aorta following an increase in NOS expression.

  5. Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

    Energy Technology Data Exchange (ETDEWEB)

    Li, Bin, E-mail: binli@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Eyer, Peter, E-mail: peter.eyer@lrz.uni-muenchen.de [Walther-Straub-Institut Für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, 80336 München (Germany); Eddleston, Michael, E-mail: M.Eddleston@ed.ac.uk [Clinical Pharmacology Unit, University of Edinburgh, Edinburgh (United Kingdom); Jiang, Wei, E-mail: wjiang@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Schopfer, Lawrence M., E-mail: lmschopf@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Lockridge, Oksana, E-mail: olockrid@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States)

    2013-06-15

    Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5 days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos. - Highlights: • Chlorpyrifos-poisoned patients have adducts on protein tyrosine. • Diethoxyphosphate-tyrosine does not lose an alkyl group. • Proteins in addition to AChE and BChE are modified by organophosphates.

  6. Isolation and characterization of five chlorpyrifos degrading bacteria ...

    African Journals Online (AJOL)

    trichloropyridinol (TCP) produced were assessed in IRLM.1 by using high performance liquid chromatography (HPLC) techniques. Additionally, the location of the chlorpyrifos-degrading enzyme was determined by comparing the activity of intact bacteria to ...

  7. Chlorpyrifos chronic toxicity in broilers and effect of vitamin C

    Directory of Open Access Journals (Sweden)

    A.M. Kammon

    2011-02-01

    Full Text Available An experiment was conducted to study chlorpyrifos chronic toxicity in broilers and the protective effect of vitamin C. Oral administration of 0.8 mg/kg body weight (bw (1/50 LD50 chlorpyrifos (Radar®, produced mild diarrhea and gross lesions comprised of paleness, flaccid consistency and slightly enlargement of liver. Histopathologically, chlorpyrifos produced degenerative changes in various organs. Oral administration of 100 mg/kg bw vitamin C partially ameliorated the degenerative changes in kidney and heart. There was insignificant alteration in biochemical and haematological profiles. It is concluded that supplementation of vitamin C reduced the severity of lesions induced by chronic chlorpyrifos toxicity in broilers.

  8. Serotonin Receptors in Hippocampus

    Science.gov (United States)

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

  9. Toxicity of chlorpyrifos, carbofuran, mancozeb and their formulations to the tropical earthworm Perionyx excavatus.

    NARCIS (Netherlands)

    De Silva, P.M.C.S.; Pathiratne, A.; van Gestel, C.A.M.

    2010-01-01

    Effects of chlorpyrifos, carbofuran, mancozeb and their formulated products on survival, growth and reproduction of the tropical earthworm Perionyx excavatus were investigated in standard artificial soil. The toxicity of the three chemicals decreased in the order carbofuran > chlorpyrifos >

  10. Mobility Studies of (14)C-Chlorpyrifos in Malaysian Oil Palm Soils.

    Science.gov (United States)

    Halimah, Muhamad; Ismail, B Sahid; Nashriyah, Mat; Maznah, Zainol

    2016-01-01

    The mobility of (14)C-chlorpyrifos using soil TLC was investigated in this study. It was found that chlorpyrifos was not mobile in clay, clay loam and peat soil. The mobility of (14)C-chlorpyrifos and non-labelled chlorpyrifos was also tested with silica gel TLC using three types of developing solvent hexane (100%), hexane:ethyl acetate (95:5, v/v); and hexane:ethyl acetate (98:2, v/v). The study showed that both the (14)C-labelled and non-labelled chlorpyrifos have the same Retardation Factor (Rf) for different developing solvent systems. From the soil column study on mobility of chlorpyrifos, it was observed that no chlorpyrifos residue was found below 5 cm depth in three types of soil at simulation rainfall of 20, 50 and 100 mm. Therefore, the soil column and TLC studies have shown similar findings in the mobility of chlorpyrifos.

  11. Adsorption and desorption of chlorpyrifos to soils and sediments.

    Science.gov (United States)

    Gebremariam, Seyoum Yami; Beutel, Marc W; Yonge, David R; Flury, Markus; Harsh, James B

    2012-01-01

    Chlorpyrifos, one of the most widely used insecticides, has been detected in air, rain, marine sediments, surface waters, drinking water wells, and solid and liquid dietary samples collected from urban and rural areas. Its metabolite, TCP, has also been widely detected in urinary samples collected from people of various age groups. With a goal of elucidating the factors that control the environmental contamination, impact, persistence, and ecotoxicity of chlorpyrifos, we examine, in this review, the peer-reviewed literature relating to chlorpyrifos adsorption and desorption behavior in various solid-phase matrices. Adsorption tends to reduce chlorpyrifos mobility, but adsorption to erodible particulates, dissolved organic matter, or mobile inorganic colloids enhances its mobility. Adsorption to suspended sediments and particulates constitutes a major off-site migration route for chlorpyrifos to surface waters, wherein it poses a potential danger to aquatic organisms. Adsorption increases the persistence of chlorpyrifos in the environment by reducing its avail- ability to a wide range of dissipative and degradative forces, whereas the effect of adsorption on its ecotoxicity is dependent upon the route of exposure. Chlorpyrifos adsorbs to soils, aquatic sediments, organic matter, and clay minerals to differing degrees. Its adsorption strongly correlates with organic carbon con- tent of the soils and sediments. A comprehensive review of studies that relied on the batch equilibrium technique yields mean and median Kd values for chlorpyrifos of 271 and 116 L/kg for soils, and 385 and 403 L/kg for aquatic sediments. Chlorpyrifos adsorption coefficients spanned two orders of magnitude in soils. Normalizing the partition coefficient to organic content failed to substantially reduce variability to commonly acceptable level of variation. Mean and median values for chlorpyrifos partition coefficients normalized to organic carbon, K, were 8,163 and 7,227 L/kg for soils and 13

  12. Studies on the atmospheric degradation of chlorpyrifos-methyl.

    Science.gov (United States)

    Muñoz, Amalia; Vera, Teresa; Sidebottom, Howard; Mellouki, Abdelwahid; Borrás, Esther; Ródenas, Milagros; Clemente, Eva; Vázquez, Mónica

    2011-03-01

    The gas-phase atmospheric degradation of chlorpyrifos-methyl (a widely used organophosphate insecticide in Southern European regions) has been investigated at the large outdoor European Photoreactor (EUPHORE) in Valencia, Spain. Photolysis under sunlight conditions and reaction with ozone were shown to be unimportant. The rate constant for reaction of chlorpyrifos-methyl with OH radicals was measured using a conventional relative rate method with cyclohexane and n-octane employed as reference compounds with k = (4.1 ± 0.4) × 10(-11) cm(3) molecule(-1) s(-1) at 300 ± 5 K and atmospheric pressure. The available evidence indicates that tropospheric degradation of chlorpyrifos-methyl is mainly controlled by reaction with OH radicals and that the tropospheric lifetime is estimated to be around 3.5 h. Significant aerosol formation was observed following the reaction of chlorpyrifos-methyl with OH radicals, and the main carbon-containing products detected in the gas phase were chlorpyrifos-methyl oxone and 3,5,6-trichloro-2-pyridinol.

  13. Extreme variability in the formation of chlorpyrifos oxon (CPO) in patients poisoned by chlorpyrifos (CPF).

    Science.gov (United States)

    Eyer, Florian; Roberts, Darren M; Buckley, Nicholas A; Eddleston, Michael; Thiermann, Horst; Worek, Franz; Eyer, Peter

    2009-09-01

    Chlorpyrifos (CPF) is a pesticide that causes tens of thousands of deaths per year worldwide. Chlorpyrifos oxon (CPO) is the active metabolite of CPF that inhibits acetylcholinesterase. However, this presumed metabolite has escaped detection in human samples by conventional methods (HPLC, GC-MS, LC-MS) until now. A recently developed enzyme-based assay allowed the determination of CPO in the nanomolar range and was successfully employed to detect this metabolite. CPO and CPF were analysed in consecutive plasma samples of 74 patients with intentional CPF poisoning. A wide concentration range of CPO and CPF was observed and the ratio of CPO/CPF varied considerably between individuals and over time. The ratio increased during the course of poisoning from a mean of 0.005 in the first few hours after ingestion up to an apparent steady-state mean of 0.03 between 30 and 72h. There was a hundred-fold variation in the ratio between samples and the interquartile range (between individuals) indicated over half the samples had a 5-fold or greater variation from the mean. The ratio was independent of the CPF concentration and the pralidoxime regimen. CPO was present in sufficient quantities to explain any observed acetylcholinesterase inhibitory activity. The effectiveness of pralidoxime in reactivating the inhibited acetylcholinesterase is strongly dependent on the CPO concentration. Differences in clinical outcomes and the response to antidotes in patients with acute poisoning may occur due to inter-individual variability in metabolism.

  14. Mifepristone modulates serotonin transporter function

    OpenAIRE

    Li, Chaokun; Shan, Linlin; Li, Xinjuan; Wei, Linyu; Li, Dongliang

    2014-01-01

    Regulating serotonin expression can be used to treat psychotic depression. Mifepristone, a glucocorticoid receptor antagonist, is an effective candidate for psychotic depression treatment. However, the underlying mechanism related to serotonin transporter expression is poorly understood. In this study, we cloned the human brain serotonin transporter into Xenopus oocytes, to establish an in vitro expression system. Two-electrode voltage clamp recordings were used to detect serotonin transporte...

  15. Examining the joint toxicity of chlorpyrifos and atrazine in the aquatic species: Lepomis macrochirus, Pimephales promelas and Chironomus tentans

    Energy Technology Data Exchange (ETDEWEB)

    Tyler Mehler, W.; Schuler, Lance J. [Fisheries and Illinois Aquaculture Center and Department of Zoology, Southern Illinois University at Carbondale, Carbondale, IL 62901-6511 (United States); Lydy, Michael J. [Fisheries and Illinois Aquaculture Center and Department of Zoology, Southern Illinois University at Carbondale, Carbondale, IL 62901-6511 (United States)], E-mail: mlydy@siu.edu

    2008-03-15

    The joint toxicity of chlorpyrifos and atrazine was compared to that of chlorpyrifos alone to discern any greater than additive response using both acute toxicity testing and whole-body residue analysis. In addition, acetylcholinesterase (AChE) inhibition and biotransformation were investigated to evaluate the toxic mode of action of chlorpyrifos in the presence of atrazine. The joint toxicity of atrazine and chlorpyrifos exhibited no significant difference in Lepomis macrochirus compared to chlorpyrifos alone; while studies performed with Pimephales promelas and Chironomus tentans, did show significant differences. AChE activity and biotransformation showed no significant differences between the joint toxicity of atrazine and chlorpyrifos and that of chlorpyrifos alone. From the data collected, the combination of atrazine and chlorpyrifos pose little additional risk than that of chlorpyrifos alone to the tested fish species. - The joint toxicity between atrazine and chlorpyrifos caused greater than additive responses in invertebrates, but the interactions in vertebrates was less pronounced.

  16. Chlorpyrifos degradation in soils with different treatment regimes within Nzoia River Drainage Basin, Kenya.

    Science.gov (United States)

    Mutua, Gershom Kyalo; Ngigi, Anastasiah Njoki; Getenga, Zachary Moranga

    2015-03-01

    Two organic amendments, filter mud compost and Tithonia diversifolia leaves generated within a sugarcane growing area were used to enhance the degradation of chlorpyrifos in soil. Filter mud compost and T. diversifolia leaves significantly enhanced degradation of chlorpyrifos in soils (p degradation of chlorpyrifos in soil with prior exposure to chlorpyrifos was significantly enhanced (p = 0.034) with DT50 of 21 days compared to 30 days in soil with no previous exposure. Degradation of chlorpyrifos in sterile and non-sterile soils were significantly different (p = 0.023) with DT50 values of 161 and 27 days, respectively. Results show enhanced degradation of chlorpyrifos in organically amended soils and soils with prior exposure to the pesticide. These amendments show promise in a continuing effort to reduce chlorpyrifos concentrations in soils.

  17. Genotoxicity of Chlorpyrifos, Alpha-thrin, Efekto virikop and ...

    African Journals Online (AJOL)

    Genotoxicity was measured by comparing the number of cells/1000 in aberrant division stages at each dose with the negative control using the Mann- Whitney test. Chlorpyrifos was genotoxic (P < 0.05), inducing chromosome lagging and bridges, pulverized and stick chromosomes, multipolar anaphase and telophase.

  18. Genotoxicity of Chlorpyrifos, Alpha-thrin, Efekto virikop and ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-03

    Dec 3, 2008 ... The pesticides, chlorpyrifos, Alpha-thrin, Efekto virikop and springbok were assessed for cytotoxicity and genotoxicity in the ... alcohol, washed in ice cold water, hydrolyzed in warm 1 N HCl, stained with aceto-carmine and squashed on glass slide ... The acute systemic toxicity of organo- phosphates reflects ...

  19. The beneficial role of resveratrol on chlorpyrifos-induced cognitive ...

    African Journals Online (AJOL)

    Chlorpyrifos (CPF) has been associated with cognitive and psychomotor impairments in both humans and animals. This cognitive impairment has been linked to its enhanced reactive oxygen species (ROS) generating capacity. Therefore, antioxidant treatment may provide a novel therapeutic window for the management of ...

  20. Biodegradation of chlorpyrifos by bacterial consortium isolated from agriculture soil.

    Science.gov (United States)

    Sasikala, Chitrambalam; Jiwal, Sonia; Rout, Pallabi; Ramya, Mohandass

    2012-03-01

    Organophosphorous pesticides are widely used in agriculture to control major insect pests. Chlorpyrifos is one of the major organophosphorous pesticides which is used to control insects including termites, beetles. The widespread use of these pesticides is hazardous to the environment and also toxic to mammals, thus it is essential to remove the same from the environment. From the chlorpyrifos contaminated soil nine morphologically different bacterial strains, one actinomycete and two fungal strains were isolated. Among those isolates four bacterial strains which were more efficient were developed as consortium. The four bacterial isolates namely Pseudomonas putida (NII 1117), Klebsiella sp., (NII 1118), Pseudomonas stutzeri (NII 1119), Pseudomonas aeruginosa (NII 1120) present in the consortia were identified on the basis of 16S rDNA analysis. The intracellular fractions of the consortium exhibited more organophosphorus hydrolase activity (0.171 ± 0.003 U/mL/min). The degradation studies were carried out at neutral pH and temperature 37°C with chlorpyrifos concentration 500 mg L(-1). LC-mass spectral analysis showed the presence of metabolites chlopyrifos-oxon and Diethylphosphorothioate. These results highlight an important potential use of this consortium for the cleanup of chlorpyrifos contaminated pesticide waste in the environment.

  1. Scanning electron microscopic study of the effect of chlorpyrifos on ...

    African Journals Online (AJOL)

    Background: Arsenic is an important environmental toxicant which is usually found in drinking water in inorganic form. Arsenic exposure in pregnant mice causes neural tube defects (NTDs). Chlorpyrifos, an organophosphorus insecticide, recommended universally and in Egypt to control various pests, was evaluated for its ...

  2. Effects of pesticide (Chlorpyrifos Ethyl) on the fingerlings of catfish ...

    African Journals Online (AJOL)

    Acute toxicity bioassay of the organophosphate pesticide chlorpyrifos ethyl on the fingerlings of Clarias gariepinus was evaluated to determine its effect on the survival, body morphology and the lethal concentration (LC50). Following a preliminary bioassay in mg/l concentration which showed 100% mortality, fish were ...

  3. Comparison of the fate and toxicity of chlorpyrifos--laboratory versus a coastal mesocosm system.

    Science.gov (United States)

    Pablo, F; Krassoi, F R; Jones, P R F; Colville, A E; Hose, G C; Lim, R P

    2008-09-01

    The widespread use of chlorpyrifos for pest control in urban and rural environments poses a risk of contamination to aquatic environments via runoff, spray drift or spillage. The aim of this study was to assess the fate of chlorpyrifos and its toxicity to common freshwater invertebrates in the laboratory and in stream mesocosms. Chlorpyrifos was rapidly lost from the test systems but the rates of loss varied considerably, such that losses in the mesocosms could not be reliably predicted from the static laboratory studies. This was likely due to the mass transport of chlorpyrifos from the mesocosm via stream flow. Chlorpyrifos was acutely toxic to all invertebrates tested with the cladoceran species (laboratory 48h LC(50) values 0.07-0.10 microg L(-1)) being most sensitive. Despite the differences in the dynamics of chlorpyrifos in the laboratory and mesocosm systems, the sensitivities of the mayfly Atalophlebia australis and the cladoceran Simocephalus vetulus were similar in the 2 systems.

  4. Effects of storage and processing on residue levels of chlorpyrifos in soybeans.

    Science.gov (United States)

    Zhao, Liuwei; Ge, Jing; Liu, Fengmao; Jiang, Naiwen

    2014-05-01

    The residue levels of chlorpyrifos in soybeans during storage and processing were investigated. Soybeans were treated with chlorpyrifos aqueous solution and placed in a sealed plastic container. The residue of chlorpyrifos was determined in soybeans at six time points within 0 and 112days during storage and oil processing of the soybeans was conducted. The analysis of the residues of chlorpyrifos was carried out by gas chromatography-mass spectrometry (GC-MS). Results show that the dissipation of chlorpyrifos in soybeans is about 62% during the storage period. Moreover, the carryover of the residues from soybeans into oil is found to be related to the processing methods. Processing factor, which is defined as the ratio of chlorpyrifos residue concentration in oil sample to that in the soybean samples, was 11 and 0.25 after cold and hot pressing, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. The Effects of Serotonin in Immune Cells

    OpenAIRE

    Nadine Herr; Christoph Bode; Daniel Duerschmied

    2017-01-01

    Serotonin [5-hydroxytryptamine (5-HT)] plays an important role in many organs as a peripheral hormone. Most of the body’s serotonin is circulating in the bloodstream, transported by blood platelets and is released upon activation. The functions of serotonin are mediated by members of the 7 known mammalian serotonin receptor subtype classes (15 known subtypes), the serotonin transporter (SERT), and by covalent binding of serotonin to different effector proteins. Almost all immune cells express...

  6. Concentrations of diazinon, chlorpyrifos, and bendiocarb after application in offices.

    Science.gov (United States)

    Currie, K L; McDonald, E C; Chung, L T; Higgs, A R

    1990-01-01

    Airborne and surface concentrations of diazinon, chlorpyrifos (Dursban), and bendiocarb (Ficam) were measured at intervals up to 10 days after broadcast spray application onto the floors of seven offices. Results from this work can provide information to evaluate health hazards for workers and others entering treated buildings and can assist public agencies in setting guidelines or regulations. Diazinon and chlorpyrifos airborne concentrations peaked 4 hr after application at 163 and 27 micrograms/m3 of air sampled, respectively. The highest level of bendiocarb (2.7 micrograms/m3) was measured during treatment. Airborne concentrations measured for diazinon indicate that building occupants should not enter unventilated rooms for at least 2 days after spraying. Reentry into unventilated rooms 1 day after treatment with chlorpyrifos or bendiocarb would appear to be safe, however. Residues on aluminum plates and furniture were examined at intervals of up to 48 hr after spraying. In many cases, surface concentrations were higher at 24 or 48 hr than at 1 hr. Concentrations of residues removed from wood and painted metal furniture generally were higher than those on the aluminum plates. Peak residue concentrations were diazinon, 38 ng/cm2 of surface area sampled at 48 hr; chlorpyrifos, 5.9 ng/cm2 at 48 hr; and bendiocarb, 25 ng/cm2 at 1 and 24 hr. Workers who must enter buildings after insecticide application often are unaware of treatment plans and, therefore, are unable to take precautions to minimize their exposure. Inhalation and skin contact with insecticides can be reduced by providing office workers and building occupants with information on treatment times, health effects of insecticide overexposure, steps to take to reduce contact, and the perceived health risk. It is essential that treated areas be ventilated adequately before workers return to their offices.

  7. Development of a Freeze-Dried Fungal Wettable Powder Preparation Able to Biodegrade Chlorpyrifos on Vegetables: e103558

    National Research Council Canada - National Science Library

    Jie Liu; Yue He; Shaohua Chen; Ying Xiao; Meiying Hu; Guohua Zhong

    2014-01-01

    .... Based on a chlorpyrifos-degrading fungus Cladosporium cladosporioides strain Hu-01 (collection number: CCTCC M 20711), a fungal wettable powder preparation was developed aiming to efficiently remove chlorpyrifos residues from vegetables...

  8. Chlorpyrifos and chlorpyrifos oxon impair the transport of membrane bound organelles in rat cortical axons.

    Science.gov (United States)

    Gao, Jie; Naughton, Sean X; Beck, Wayne D; Hernandez, Caterina M; Wu, Guangyu; Wei, Zhe; Yang, Xiangkun; Bartlett, Michael G; Terry, Alvin V

    2017-09-01

    Chlorpyrifos (CPF) is an extensively used organophosphorus pesticide that has recently come under increasing scrutiny due to environmental health concerns particularly its association with neurodevelopmental defects. While the insecticidal actions and acute toxicity of CPF are attributed to its oxon metabolite (CPO) which potently inhibits the cholinergic enzyme acetylcholinesterase (AChE), there is significant evidence that CPF, CPO, and other organophosphates may affect a variety of neuronal targets and processes that are not directly related to AChE. Previously, in adult rat sciatic nerves ex vivo and postnatal neurons from rats in vitro we observed that CPF and CPO impaired the movements of vesicles and mitochondria in axons. Here, in embryonic neurons from rats in culture, we evaluated 24h exposures to CPF and CPO across picomolar to micromolar concentrations for effects on fast axonal transport of membrane bound organelles (MBOs) that contained the amyloid precursor protein (APP) tagged with the fluorescent marker, Dendra2 (APPDendra2). The most notable observations of this study were concentration-dependent decreases in the velocity and percentage of MBOs moving in the anterograde direction, an increase in the number of stationary MBOs, and an increased frequency of pauses associated with both CPF and CPO. These effects occurred at concentrations that did not significantly inhibit AChE activity, they were not blocked by cholinergic receptor antagonists, and they were not associated with compromised cell viability. These effects of CPF and CPO may be significant given the importance of axonal transport to neuronal development as well the function of fully developed neurons. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Phytoremediation of chlorpyrifos in aqueous system by riverine macrophyte, Acorus calamus: toxicity and removal rate.

    Science.gov (United States)

    Wang, Qinghai; Li, Cui; Zheng, Ruilun; Que, Xiaoe

    2016-08-01

    The potential of Acorus calamus to remove chlorpyrifos from water was assessed under laboratory conditions. Toxic effects of the insecticide in A. calamus were evaluated using pulse-amplitude modulated chlorophyll fluorescence techniques as well. At exposure concentrations above 8 mg L(-1), A. calamus showed obvious phytotoxic symptom with significant reduction in quantum efficiency of PSII (ΦPSII) and photochemical quenching coefficient (qP) in 20-day test; the inhibition of maximal quantum efficiency of PSII (Fv/Fm) was accompanied by a significant rise in initial chlorophyll fluorescence (Fo) within 15-day exposures. Fv/Fm and Fo recover to the normal level after 20-day exposure. The reduced removal rate to chlorpyrifos was observed with increase of initial chlorpyrifos concentrations. At application levels of 1, 2, and 4 mg L(-1), the disappearance rate of chlorpyrifos in the hydroponic system with plants was significantly greater than that without plants during the 20-day test periods. Chlorpyrifos was taken up from medium and transferred to above ground tissues by the plant and significant amounts of chlorpyrifos accumulated in plant tissues. The result indicated that A. calamus can promote the disappearance of chlorpyrifos from water and may be used for phytoremediation of water contaminated with a relatively low concentration of chlorpyrifos insecticide (<4 mg L(-1)).

  10. Acute toxicity of chlorpyrifos to embryo and larvae of banded gourami Trichogaster fasciata

    NARCIS (Netherlands)

    Sumon, Kizar Ahmed; Saha, Sampa; Brink, van den Paul J.; Peeters, Edwin T.H.M.; Bosma, Roel H.; Rashid, Harunur

    2017-01-01

    This study elucidated the acute toxicity of chlorpyrifos on the early life stages of banded gourami (Trichogaster fasciata). To determine the acute effects of chlorpyrifos on their survival and development, we exposedthe embryos and two-day-old larvae to six concentrations (0, 0.01, 0.10, 1.0, 10

  11. Binding and detoxification of chlorpyrifos by lactic acid bacteria on rice straw silage fermentation.

    Science.gov (United States)

    Wang, Yan-Su; Wu, Tian-Hao; Yang, Yao; Zhu, Cen-Ling; Ding, Cheng-Long; Dai, Chuan-Chao

    2016-01-01

    This investigation examined the reduction of pesticide residues on straw inoculated with lactic acid bacteria (LAB) during ensiling. Lactobacillus casei WYS3 was isolated from rice straw that contained pesticide residues. Non-sterilized rice straw, which was inoculated with L. casei WYS3, showed increased removal of chlorpyrifos after ensiling, compared with rice straw that was not inoculated with L. casei WYS3 or sterilized rice straw. In pure culture, these strains can bind chlorpyrifos as indicated by high-performance liquid chromatography analysis. Viable L. casei WYS3 was shown to bind 33.3-42% of exogenously added chlorpyrifos. These results are similar to those of acid-treated cells but less than those of heat-treated cells, which were found to bind 32.0% and 77.2% of the added chlorpyrifos respectively. Furthermore, gas chromatography-mass spectrometry analysis determined that L. casei WYS3 detoxified chlorpyrifos via P-O-C cleavage. Real-time polymerized chain reaction analysis determined that organophosphorus hydrolase gene expression tripled after the addition of chlorpyrifos to LAB cultures, compared with the control group (without chlorpyrifos). This paper highlights the potential use of LAB starter cultures for the detoxification and removal of chlorpyrifos residues in the environment.

  12. Fate and effects of the insecticide chlorpyrifos in outdoor plankton-dominated microcosms in Thailand.

    NARCIS (Netherlands)

    Daam, M.A.; Crum, S.J.H.; Brink, van den P.J.; Nogueira, A.J.A.

    2008-01-01

    The fate and effects of the insecticide chlorpyrifos were studied in plankton-dominated, freshwater microcosms in Thailand. Disappearance rates of chlorpyrifos from the water column in the present study were similar to those in temperate regions. Insecticide accumulation in the sediment was

  13. Problems induced by the use of acetone as a solvent to dose chlorpyrifos in a microecosystem

    NARCIS (Netherlands)

    Kersting, K.

    1995-01-01

    Recycling aquatic microecosystems consisting of three subsystems with a total volume of 7.5 L were used to study the effects of the insecticide chlorpyrifos. The poorly soluble chlorpyrifos was dosed dissolved in 0.5 ml of acetone. Acetone was found to be responsible for some of the observed

  14. Determination of Chlorpyrifos in Human Blood by Gas Chromatography-Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Xinhua Dai

    2017-01-01

    Full Text Available Gas chromatography-mass spectrometry method was developed for the qualitative and quantitative analyses of chlorpyrifos in human blood samples. The chlorpyrifos and parathion (internal standard in human blood were extracted with a mixed solvent of hexane and acetonitrile. Chlorpyrifos was well separated from the internal standard. The linear range of chlorpyrifos was 0.01–2 μg/ml in blood. The limit of detection and limit of quantification were estimated at 0.002 and 0.01 μg/ml, respectively. The inter- and intra-day precisions, accuracy, and recovery were assessed to verify this method. The results showed that the developed method is rapid, sensitive, and reliable. It is suitable for the determination of chlorpyrifos in forensic toxicological analysis and clinical diagnosis.

  15. Serotonin, inhibition, and negative mood

    National Research Council Canada - National Science Library

    Dayan, Peter; Huys, Quentin J M

    2008-01-01

    .... There is considerable evidence for the involvement of serotonin in both the learning of these predictions and the inhibitory consequences that ensue, although less for a causal relationship between the two...

  16. Selective Serotonin Reuptake Inhibitors (SSRIs)

    Science.gov (United States)

    ... Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects. http://www.uptodate.com/home. Accessed June 2, 2016. Mental health medications. National Institute of Mental Health. http://www. ...

  17. Peripheral serotonin regulates maternal calcium trafficking in mammary epithelial cells during lactation in mice.

    Directory of Open Access Journals (Sweden)

    Jimena Laporta

    Full Text Available Lactation is characterized by massive transcellular flux of calcium, from the basolateral side of the mammary alveolar epithelium (blood into the ductal lumen (milk. Regulation of calcium transport during lactation is critical for maternal and neonatal health. The monoamine serotonin (5-HT is synthesized by the mammary gland and functions as a homeostatic regulation of lactation. Genetic ablation of tryptophan hydroxylase 1 (Tph1, which encodes the rate-limiting enzyme in non-neuronal serotonin synthesis, causes a deficiency in circulating serotonin. As a consequence maternal calcium concentrations decrease, mammary epithelial cell morphology is altered, and cell proliferation is decreased during lactation. Here we demonstrate that serotonin deficiency decreases the expression and disrupts the normal localization of calcium transporters located in the apical (PMCA2 and basolateral (CaSR, ORAI-1 membranes of the lactating mammary gland. In addition, serotonin deficiency decreases the mRNA expression of calcium transporters located in intracellular compartments (SERCA2, SPCA1 and 2. Mammary expression of serotonin receptor isoform 2b and its downstream pathways (PLCβ3, PKC and MAP-ERK1/2 are also decreased by serotonin deficiency, which might explain the numerous phenotypic alterations described above. In most cases, addition of exogenous 5-hydroxy-L-tryptophan to the Tph1 deficient mice rescued the phenotype. Our data supports the hypothesis that serotonin is necessary for proper mammary gland structure and function, to regulate blood and mammary epithelial cell transport of calcium during lactation. These findings can be applicable to the treatment of lactation-induced hypocalcemia in dairy cows and can have profound implications in humans, given the wide-spread use of selective serotonin reuptake inhibitors as antidepressants during pregnancy and lactation.

  18. Larval exposure to chlorpyrifos affects nutritional physiology and induces genotoxicity in silkworm Philosamia ricini (Lepidoptera: Saturnidae

    Directory of Open Access Journals (Sweden)

    Moni Kankana Kalita

    2016-11-01

    Full Text Available Chlorpyrifos is a most widely used organophosphate insecticide because of its cost effectiveness and degradable nature. However, this pesticide enters and contaminates the environment either by direct application, spray drifts or crop run off and shows adverse effect on the non-targeted organisms. Philosamia ricini (eri silkworm, one of the most exploited, domesticated and commercialized non mulberry silkworm is known for mass production of eri silk. The silkworm larvae get exposed to pesticide residues on the leaves of food plants. The present study investigates the effect of commercial formulation of chlorpyrifos (Pyrifos-20 EC on eri silkworm. Initially the LC50 value of chlorpyrifos was determined at 24 - 96 h and further experiments were carried out with sub lethal concentrations of the chlorpyrifos after 24 h of exposure period. The potential toxicity of chlorpyrifos was evaluated as a fuction of metabolism and nutritional physiology in 3rd, 4th and 5th instar larvae. Alteration in histoarchitecture of 5th instar eri silkworm gut exposed to sub lethal concentration of chlorpyrifos formulation was also studied. Chlorpyrifos induced genotoxicity in silkworm hemocytes was also investigated by single cell gel electrophoresis, micronuclei assay and apoptosis assay. Herein, LC50 values of chlorpyrifos were calculated as 3.83, 3.35, 2.68 and 2.35 mg/L at 24 h, 48 h, 72 h and 96 h respectively. A significant decrease in trehalose activity along with digestive enzyme activity was observed in chlorpyrifos affected groups (P < 0.05. Further, genotoxicity study revealed higher tail percentage, tail length and tail moment of the damage DNA in chlorpyrifos exposed groups (P < 0.001. Moreover, at 2.0 mg/L concentration, ~ 10 fold increases in tail length was observed as compared to the control. Results showed activation of caspase activity following 24 hr chlorpyrifos exposure (1.5 mg/L and 2.0 mg/L in a dose-dependent manner. Moreover, in control group

  19. Degradation of chlorpyrifos residues in apple under temperate conditions of Kashmir Valley.

    Science.gov (United States)

    Mukhtar, Malik; Sherwani, Asma; Wani, Ashraf Alam; Ahmed, Sheikh Bilal; Sofi, Javid Ahmad; Bano, Parveena

    2015-08-01

    The present studies were carried out to observe the dissipation pattern of chlorpyrifos on apple in Kashmir Valley. Persistence of chlorpyrifos in apple was studied following two applications rates of chlorpyrifos (Dursban 20 EC) at 200 g a.i. ha(-1) (single dose T 1) and 400 g a.i. ha(-1) (double dose T 2). The average initial deposit of chlorpyrifos was found to be 1.61 and 1.98 μg g(-1) for T 1 and T 2 application rates respectively on apple. The residues dissipated to 0.09 and 0.06 μg g(-1) after 15- and 30-day post treatment with half-life periods of 3.34 and 5.47 days in T 1 and T 2 application rates, respectively. The residues of chlorpyrifos dissipated to below limit of quantification (LOQ) of 0.04 μg g(-1) after 30 day at T 1 application rate. A waiting period of 6 days must be observed for chlorpyrifos on apple at recommended application rate for the safety of consumers. Theoretical maximum residue contribution (TMRC) values were found to be far less than maximum permissible intake (MPI) at 0 day in both the dosages suggesting chlorpyrifos on apple in Kashmir is unlikely to cause health risks.

  20. Degradation of chlorpyrifos contaminated soil by bioslurry reactor operated in sequencing batch mode: bioprocess monitoring.

    Science.gov (United States)

    Mohan, S Venkata; Sirisha, K; Rao, N Chandrasekhara; Sarma, P N; Reddy, S Jayarama

    2004-12-10

    Bioslurry reactor (SS-SBR) was studied for the degradation of chlorpyrifos contaminated soil using native mixed microflora, by adopting sequencing batch mode (anoxic-aerobic-anoxic) operation. Reactor operation was monitored for a total cycle period of 72 h consisting of 3 h of FILL, 64 h REACT, 2 h of SETTLE, and 3 h of DECANT with chlorpyrifos concentrations of 3000 micrpg/g, 6000 microg/g and 12000 microg/g. At 3000 microg/g of chlorpyrifos concentration, 91% was degraded after 72 h of the cycle period, whereas in the case of 6000 microg/g of chlorpyrifos, 82.5% was degraded. However, for 12000 microg/g of chlorpyrifos, only 14.5% degradation was observed. The degradation rate was rapid at lower substrate concentration and 12000 microg/g of substrate concentration was found to be inhibitory. Chlorpyrifos removal rate was slow during the initial phase of the sequence operation. Half-life of chlorpyrifos degradation (t0.5) was estimated to be 6.3 h for 3000 microg/g of substrate, 17.5 h for 6000 microg/g and 732.2 h for 12000 microg/g. Process performance was assessed by monitoring chlorpyrifos concentration and biochemical process parameters viz., pH, oxidation and reduction potential (ORP), dissolved oxygen (DO), oxygen consumption rate (OCR) and microbial count (CFU) during sequence operation. From the experimental data obtained it can be concluded that the rate-limiting step with the bioslurry phase reactor in the process of chlorpyrifos degradation may be attributed to the concentration of substrate present in either soil or liquid phase. Periodic operations (SBR) by varying individual components of substrate with time in each process step place micro-organisms under nutritional changes from feast to famine and maintains a wide distribution in the population of micro-organisms resulting in high uptake of the substrate in the bioslurry reactor.

  1. An integrated vegetated ditch system reduces chlorpyrifos loading in agricultural runoff.

    Science.gov (United States)

    Phillips, Bryn M; Anderson, Brian S; Cahn, Michael; Rego, Jessa L; Voorhees, Jennifer P; Siegler, Katie; Zhang, Xuyang; Budd, Robert; Goh, Kean; Tjeerdema, Ron S

    2017-03-01

    Agricultural runoff containing toxic concentrations of the organophosphate pesticide chlorpyrifos has led to impaired water body listings and total maximum daily load restrictions in California's central coast watersheds. Chlorpyrifos use is now tightly regulated by the Central Coast Regional Water Quality Control Board. This study evaluated treatments designed to reduce chlorpyrifos in agricultural runoff. Initial trials evaluated the efficacy of 3 different drainage ditch installations individually: compost filters, granulated activated carbon (GAC) filters, and native grasses in a vegetated ditch. Treatments were compared to bare ditch controls, and experiments were conducted with simulated runoff spiked with chlorpyrifos at a 1.9 L/s flow rate. Chlorpyrifos concentrations and toxicity to Ceriodaphnia dubia were measured at the input and output of the system. Input concentrations of chlorpyrifos ranged from 858 ng/L to 2840 ng/L. Carbon filters and vegetation provided the greatest load reduction of chlorpyrifos (99% and 90%, respectively). Toxicity was completely removed in only one of the carbon filter trials. A second set of trials evaluated an integrated approach combining all 3 treatments. Three trials were conducted each at 3.2 L/s and 6.3 L/s flow rates at input concentrations ranging from 282 ng/L to 973 ng/L. Chlorpyrifos loadings were reduced by an average of 98% at the low flow rate and 94% at the high flow rate. Final chlorpyrifos concentrations ranged from nondetect (Environ Assess Manag 2017;13:423-430. © 2016 SETAC. © 2016 SETAC.

  2. Energetic Cost of Subacute Chlorpyrifos Intoxication in the German Cockroach (Dictyoptera: Blattellidae)

    DEFF Research Database (Denmark)

    Nielsen, Søren Achim; Jensen, Karl-Martin Vagn; Kristensen, Michael

    2006-01-01

    The energetic cost of a sublethal treatment with chlorpyrifos was estimated by use of direct microcalorimetry to measure metabolic heat in susceptible and resistant strains of the German cockroach Blattella germanica L. Moreover, one of the detoxifcation enzyme systems known to be involved...... in detoxifcation of chlorpyrifos, glutathione-S-transferase, was measured. Individual cockroaches were exposed for 20 min on a glass-surfaces treated with 1.14 ...  g/cm2 of chlorpyrifos. There was no difference in glutathione-S-transferase activity of susceptible or resistant strains after the treatment. The heat...

  3. Serotonin Activates Bacterial Quorum Sensing and Enhances the Virulence of Pseudomonas aeruginosa in the Host

    Directory of Open Access Journals (Sweden)

    Leslie D. Knecht

    2016-07-01

    Full Text Available Bacteria in humans play an important role in health and disease. Considerable emphasis has been placed in understanding the role of bacteria in host-microbiome interkingdom communication. Here we show that serotonin, responsible for mood in the brain and motility in the gut, can also act as a bacterial signaling molecule for pathogenic bacteria. Specifically, we found that serotonin acts as an interkingdom signaling molecule via quorum sensing and that it stimulates the production of bacterial virulence factors and increases biofilm formation in vitro and in vivo in a novel mouse infection model. This discovery points out at roles of serotonin both in bacteria and humans, and at phenotypic implications not only manifested in mood behavior but also in infection processes in the host. Thus, regulating serotonin concentrations in the gut may provide with paradigm shifting therapeutic approaches.

  4. Serotonin Activates Bacterial Quorum Sensing and Enhances the Virulence of Pseudomonas aeruginosa in the Host.

    Science.gov (United States)

    Knecht, Leslie D; O'Connor, Gregory; Mittal, Rahul; Liu, Xue Z; Daftarian, Pirouz; Deo, Sapna K; Daunert, Sylvia

    2016-07-01

    Bacteria in humans play an important role in health and disease. Considerable emphasis has been placed in understanding the role of bacteria in host-microbiome interkingdom communication. Here we show that serotonin, responsible for mood in the brain and motility in the gut, can also act as a bacterial signaling molecule for pathogenic bacteria. Specifically, we found that serotonin acts as an interkingdom signaling molecule via quorum sensing and that it stimulates the production of bacterial virulence factors and increases biofilm formation in vitro and in vivo in a novel mouse infection model. This discovery points out at roles of serotonin both in bacteria and humans, and at phenotypic implications not only manifested in mood behavior but also in infection processes in the host. Thus, regulating serotonin concentrations in the gut may provide with paradigm shifting therapeutic approaches. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Serotonin mediated immunoregulation and neural functions: Complicity in the aetiology of autism spectrum disorders.

    Science.gov (United States)

    Jaiswal, Preeti; Mohanakumar, Kochupurackal P; Rajamma, Usha

    2015-08-01

    Serotonergic system has long been implicated in the aetiology of autism spectrum disorders (ASD), since platelet hyperserotonemia is consistently observed in a subset of autistic patients, who respond well to selective serotonin reuptake inhibitors. Apart from being a neurotransmitter, serotonin functions as a neurotrophic factor directing brain development and as an immunoregulator modulating immune responses. Serotonin transporter (SERT) regulates serotonin level in lymphoid tissues to ensure its proper functioning in innate and adaptive responses. Immunological molecules such as cytokines in turn regulate the transcription and activity of SERT. Dysregulation of serotonergic system could trigger signalling cascades that affect normal neural-immune interactions culminating in neurodevelopmental and neural connectivity defects precipitating behavioural abnormalities, or the disease phenotypes. Therefore, we suggest that a better understanding of the cross talk between serotonergic genes, immune systems and serotonergic neurotransmission will open wider avenues to develop pharmacological leads for addressing the core ASD behavioural deficits. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Deletion of the serotonin transporter in rats disturbs serotonin homeostasis without impairing liver regeneration

    NARCIS (Netherlands)

    Matondo, R.B.; Punt, C.; Homberg, J.R.; Toussaint, M.J.; Kisjes, R.; Korporaal, S.J.; Akkerman, J.W.; Cuppen, E.; de Bruin, A.

    2009-01-01

    The serotonin transporter is implicated in the uptake of the vasoconstrictor serotonin from the circulation into the platelets, where 95% of all blood serotonin is stored and released in response to vascular injury. In vivo studies indicated that platelet-derived serotonin mediates liver

  7. Deletion of the serotonin transporter in rats disturbs serotonin homeostasis without impairing liver regeneration.

    NARCIS (Netherlands)

    Matondo, R.B.; Punt, C.; Homberg, J.R.; Toussaint, M.J.; Kisjes, R.; Korporaal, S.J.; Akkerman, J.W.; Cuppen, E.; Bruin, A. de

    2009-01-01

    The serotonin transporter is implicated in the uptake of the vasoconstrictor serotonin from the circulation into the platelets, where 95% of all blood serotonin is stored and released in response to vascular injury. In vivo studies indicated that platelet-derived serotonin mediates liver

  8. Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

    Science.gov (United States)

    ... Effexor XR) ― also approved to treat anxiety and panic disorder All SNRIs work in a similar way ... such as aspirin or warfarin (Coumadin, Jantoven). Serotonin syndrome. Rarely, serotonin syndrome can occur when you take ...

  9. A tachykinin-like neuroendocrine signalling axis couples central serotonin action and nutrient sensing with peripheral lipid metabolism

    Science.gov (United States)

    Palamiuc, Lavinia; Noble, Tallie; Witham, Emily; Ratanpal, Harkaranveer; Vaughan, Megan; Srinivasan, Supriya

    2017-01-01

    Serotonin, a central neuromodulator with ancient ties to feeding and metabolism, is a major driver of body fat loss. However, mechanisms by which central serotonin action leads to fat loss remain unknown. Here, we report that the FLP-7 neuropeptide and its cognate receptor, NPR-22, function as the ligand-receptor pair that defines the neuroendocrine axis of serotonergic body fat loss in Caenorhabditis elegans. FLP-7 is secreted as a neuroendocrine peptide in proportion to fluctuations in neural serotonin circuit functions, and its release is regulated from secretory neurons via the nutrient sensor AMPK. FLP-7 acts via the NPR-22/Tachykinin2 receptor in the intestine and drives fat loss via the adipocyte triglyceride lipase ATGL-1. Importantly, this ligand-receptor pair does not alter other serotonin-dependent behaviours including food intake. For global modulators such as serotonin, the use of distinct neuroendocrine peptides for each output may be one means to achieve phenotypic selectivity. PMID:28128367

  10. Blood platelet serotonin following enterectomy in rats.

    Science.gov (United States)

    Osim, E E; Wyllie, J H

    1991-01-01

    The role of the intestine as a source of platelet serotonin was investigated. Radioactive serotonin precursor. 5-Hydroxytryptophan was injected into enterectomised and sham-operated rats. Blood samples were taken at time intervals and serotonin uptake was estimated by radioactive counting. Soon (1-2 hrs) after surgery and under sodium pentobarbital anaesthesia, platelet 5HT activity was higher in enterectomised rats than in controls. The intestine may not be the major source of platelet serotonin.

  11. Feasibility of constructed wetlands for removing chlorothalonil and chlorpyrifos from aqueous mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Sherrard, R.M.; Bearr, J.S.; Murray-Gulde, C.L.; Rodgers, J.H.; Shah, Y.T

    2004-02-01

    Chlorpyrifos (an insecticide) and chlorothalonil (a fungicide) are transported in stormwater runoff and can be lethal to receiving aquatic system biota. This study determined removal rates of chlorpyrifos and chlorothalonil in simulated stormwater runoff treated in constructed wetland mesocosms. Using sentinel species, Ceriodaphnia dubia and Pimephales promelas, observed declines in toxicity of the simulated runoff after treatment were 98 and 100%, respectively. First order removal rates were 0.039/h for chlorpyrifos and 0.295/h for chlorothalonil in these experiments. Constructed wetland mesocosms were effective for decreasing concentrations of chlorpyrifos and chlorothalonil in simulated stormwater runoff, and decreasing P. promelas and C. dubia mortality resulting from these exposures. The results from this study indicate that constructed wetlands could be part of an efficient mitigation strategy for stormwater runoff containing these pesticides. - Constructed wetlands have potential for treatment of pesticide mixtures in stormwater runoff.

  12. Soil bacteria showing a potential of chlorpyrifos degradation and plant growth enhancement

    Directory of Open Access Journals (Sweden)

    Shamsa Akbar

    Full Text Available ABSTRACT Background: Since 1960s, the organophosphate pesticide chlorpyrifos has been widely used for the purpose of pest control. However, given its persistence and toxicity towards life forms, the elimination of chlorpyrifos from contaminated sites has become an urgent issue. For this process bioremediation is the method of choice. Results: Two bacterial strains, JCp4 and FCp1, exhibiting chlorpyrifos-degradation potential were isolated from pesticide contaminated agricultural fields. These isolates were able to degrade 84.4% and 78.6% of the initial concentration of chlorpyrifos (100 mg L-1 within a period of only 10 days. Based on 16S rRNA sequence analysis, these strains were identified as Achromobacter xylosoxidans (JCp4 and Ochrobactrum sp. (FCp1. These strains exhibited the ability to degrade chlorpyrifos in sterilized as well as non-sterilized soils, and were able to degrade 93-100% of the input concentration (200 mg kg-1 within 42 days. The rate of degradation in inoculated soils ranged from 4.40 to 4.76 mg-1 kg-1 d-1 with rate constants varying between 0.047 and 0.069 d-1. These strains also displayed substantial plant growth promoting traits such as phosphate solubilization, indole acetic acid production and ammonia production both in absence as well as in the presence of chlorpyrifos. However, presence of chlorpyrifos (100 and 200 mg L-1 was found to have a negative effect on indole acetic acid production and phosphate solubilization with percentage reduction values ranging between 2.65-10.6% and 4.5-17.6%, respectively. Plant growth experiment demonstrated that chlorpyrifos has a negative effect on plant growth and causes a decrease in parameters such as percentage germination, plant height and biomass. Inoculation of soil with chlorpyrifos-degrading strains was found to enhance plant growth significantly in terms of plant length and weight. Moreover, it was noted that these strains degraded chlorpyrifos at an increased rate (5

  13. The enzyme toxicity and genotoxicity of chlorpyrifos and its toxic metabolite TCP to zebrafish Danio rerio.

    Science.gov (United States)

    Wang, Jun; Wang, Jinhua; Zhu, Lusheng; Xie, Hui; Shao, Bo; Hou, Xinxin

    2014-12-01

    Chlorpyrifos is a broad-spectrum organophosphorus insecticide (O,O-diethyl -O-3,5,6-trichloro-2-pyridyl phosphorothioate) that is used in numerous agricultural and urban pest controls. The primary metabolite of chlorpyrifos is 3,5,6-trichloro pyridine-2-phenol (TCP). Because of its strong water solubility and mobility, this harmful metabolite exists in the environment in a large amount. Although TCP has potentially harmful effects on organisms in the environment, few studies have addressed TCP pollution. Therefore, this study was undertaken to investigate the effect of chlorpyrifos and TCP on the microsomal cytochrome P450 content in the liver, on the activity of NADPH-P450 reductase and antioxidative enzymes [catalase (CAT) and superoxide dismutase (SOD)], and on reactive oxygen species (ROS) generation and DNA damage in zebrafish. Male and female zebrafish were separated and exposed to a control solution and three concentrations of chlorpyrifos (0.01, 0.1, 1 mg L(-1)) and TCP (0.01, 0.1, 0.5 mg L(-1)), respectively, sampled after 5, 10, 15, 20 and 25 days. The results indicated that the P450 content and the NADPH-P450 reductase and antioxidative enzyme (CAT and SOD) activities could be induced by chlorpyrifos and TCP. DNA damage of zebrafish was enhanced with increasing chlorpyrifos and TCP concentrations. Meanwhile, chlorpyrifos and TCP induced a significant increase of ROS generation in the zebrafish hepatopancreas. In conclusion, this study proved that chlorpyrifos (0.01-1 mg L(-1)) and TCP (0.01-0.5 mg L(-1)) are both highly toxic to zebrafish.

  14. Development of a freeze-dried fungal wettable powder preparation able to biodegrade chlorpyrifos on vegetables.

    Directory of Open Access Journals (Sweden)

    Jie Liu

    Full Text Available Continuous use of the pesticide chlorpyrifos has resulted in harmful contaminations in environment and species. Based on a chlorpyrifos-degrading fungus Cladosporium cladosporioides strain Hu-01 (collection number: CCTCC M 20711, a fungal wettable powder preparation was developed aiming to efficiently remove chlorpyrifos residues from vegetables. The formula was determined to be 11.0% of carboxymethyl cellulose-Na, 9.0% of polyethylene glycol 6000, 5.0% of primary alcohol ethoxylate, 2.5% of glycine, 5.0% of fucose, 27.5% of kaolin and 40% of freeze dried fungi by response surface methodology (RSM. The results of quality inspection indicated that the fungal preparation could reach manufacturing standards. Finally, the degradation of chlorpyrifos by this fungal preparation was determined on pre-harvest cabbage. Compared to the controls without fungal preparation, the degradation of chlorpyrifos on cabbages, which was sprayed with the fungal preparation, was up to 91% after 7 d. These results suggested this freeze-dried fungal wettable powder may possess potential for biodegradation of chlorpyrifos residues on vegetables and provide a potential strategy for food and environment safety against pesticide residues.

  15. Exogenous salicylic acid alleviates the toxicity of chlorpyrifos in wheat plants (Triticum aestivum).

    Science.gov (United States)

    Wang, Caixia; Zhang, Qingming

    2017-03-01

    The role of exogenous salicylic acid (SA) in protecting wheat plants (Triticum aestivum) from contamination by the insecticide chlorpyrifos was investigated in this study. The wheat plants were grown in soils with different concentrations (5, 10, 20, and 40mgkg-1) of chlorpyrifos. When the third leaf emerged, the wheat leaves were sprayed with 1, 2, 4, 8, and 16mgL-1 of SA once a day for 6 days. The results showed that wheat exposed to higher concentrations of chlorpyrifos (≥20mgkg-1) caused declines in growth and chlorophyll content and altered the activities of a series of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX). Interestingly, treatments with different concentrations of SA mitigated the stress generated by chlorpyrifos and improved the measured parameters to varying degrees. Furthermore, a reverse transcription and quantitative PCR experiment revealed that the activities of SOD and CAT can be regulated by their target gene in wheat when treated with SA. We also found that SA is able to block the accumulation of chlorpyrifos in wheat. However, the effect of SA was related to its concentration. In this study, the application of 2mgL-1 of SA had the greatest ameliorating effect on chlorpyrifos toxicity in wheat plants. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Toxicological effects of chlorpyrifos on growth, enzyme activity and chlorophyll a synthesis of freshwater microalgae.

    Science.gov (United States)

    Chen, Shangchao; Chen, Mindong; Wang, Zhuang; Qiu, Weijian; Wang, Junfeng; Shen, Yafei; Wang, Yajun; Ge, Shun

    2016-07-01

    This paper aims to acquire the experimental data on the eco-toxicological effects of agricultural pollutants on the aquatic plants and the data can support the assessment of toxicity on the phytoplankton. The pesticide of Chlorpyrifos used as a good model to investigate its eco-toxicological effect on the different microalgae in freshwater. In order to address the pollutants derived from forestry and agricultural applications, freshwater microalgae were considered as a good sample to investigate the impact of pesticides such as Chlorpyrifos on aquatic life species. Two microalgae of Chlorella pyrenoidosa and Merismopedia sp. were employed to evaluate toxicity of Chlorpyrifos in short time and long time by means of measuring the growth inhibition rate, the redox system and the content of chlorophyll a, respectively. In this study, the results showed that EC50 values ranging from 7.63 to 19.64mg/L, indicating the Chlorpyrifos had a relatively limited to the growth of algae during the period of the acute toxicity experiment. Moreover, when two kinds of algae were exposed to a medium level of Chlorpyrifos, SOD and CAT activities were importantly advanced. Therefore, the growth rate and SOD and CAT activities can be highly recommended for the eco-toxicological assessment. In addition, chlorophyll a also could be used as a targeted parameter for assessing the eco-toxicity of Chlorpyrifos on both Chlorella pyrenoidosa and Merismopedia sp. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Acute Toxicity and Neurotoxicity of Chlorpyrifos in Black Tiger Shrimp, Penaeus monodon

    Directory of Open Access Journals (Sweden)

    Tassanee Eamkamon

    2012-01-01

    Full Text Available Acute toxicity and neurotoxicity of chlorpyrifos were determined in black tiger shrimp, P. monodon. LC50 values after 24 to 96 h of exposure were between 149.55 and 59.16 nmol/L. To determine the neurotoxicity of chlorpyrifos, the inhibition of acetylcholinesterase was monitored in the gill of the shrimps exposed to lethal (0.019, 0.194, and 1.942 µmol/L and sub-lethal (0.019, 0.194, and 1.942 nmol/L concentrations of chlorpyrifos. In lethal dose exposure, the AChE activities observed in shrimp exposed to 0.194, and 1.942 µmol/L of chlorpyrifos were significantly lower (1.7 and 3.3 times than that of control shrimp after 30 min of exposure (p<0.05. In sub-lethal exposure tests, the AChE activity of shrimp was significantly lower (1.9 times than that of control shrimp after exposure to 1.942 nmol/L of chlorpyrifos for 72 h (p<0.05. The sensitive reduction of AChE activity at the sub-lethal concentration, which was 30 times lower than 96 h LC50 value found in this study, indicates the potential use as a biomarker of chlorpyrifos exposure.

  18. Pharmacogenetic workup of perioperative serotonin syndrome.

    Science.gov (United States)

    Beatty, Nicole C; Nicholson, Wayne T; Langman, Loralie J; Curry, Timothy B; Eisenach, John H

    2013-12-01

    Serotonin syndrome is gaining attention in perioperative and chronic pain settings due to the growing prevalence of multimodal therapies that increase serotonin levels and thereby heighten patient risk. A patient's genetic make-up may further increase the risk of serotonin syndrome. A case of serotonin syndrome on emergence after general anesthesia is presented. A subsequent cytochrome P4502D6 genetic test result suggested a potential alteration in metabolism. For this patient, who was taking combination antidepressant medications and receiving common perioperative medicines, additive pharmacodynamic effects converged with a pharmacogenetic predisposition, resulting in serotonin syndrome. © 2013 Elsevier Inc. All rights reserved.

  19. Serotonin and Blood Pressure Regulation

    Science.gov (United States)

    Morrison, Shaun F.; Davis, Robert Patrick; Barman, Susan M.

    2012-01-01

    5-Hydroxytryptamine (5-HT; serotonin) was discovered more than 60 years ago as a substance isolated from blood. The neural effects of 5-HT have been well investigated and understood, thanks in part to the pharmacological tools available to dissect the serotonergic system and the development of the frequently prescribed selective serotonin-reuptake inhibitors. By contrast, our understanding of the role of 5-HT in the control and modification of blood pressure pales in comparison. Here we focus on the role of 5-HT in systemic blood pressure control. This review provides an in-depth study of the function and pharmacology of 5-HT in those tissues that can modify blood pressure (blood, vasculature, heart, adrenal gland, kidney, brain), with a focus on the autonomic nervous system that includes mechanisms of action and pharmacology of 5-HT within each system. We compare the change in blood pressure produced in different species by short- and long-term administration of 5-HT or selective serotonin receptor agonists. To further our understanding of the mechanisms through which 5-HT modifies blood pressure, we also describe the blood pressure effects of commonly used drugs that modify the actions of 5-HT. The pharmacology and physiological actions of 5-HT in modifying blood pressure are important, given its involvement in circulatory shock, orthostatic hypotension, serotonin syndrome and hypertension. PMID:22407614

  20. ROLE OF SEROTONIN IN FISH REPRODUCTION

    Directory of Open Access Journals (Sweden)

    Parvathy ePrasad

    2015-06-01

    Full Text Available The neuroendocrine mechanism regulates reproduction through the hypothalamo-pituitary-gonadal (HPG axis which is evolutionarily conserved in vertebrates. The HPG axis is regulated by a variety of internal as well as external factors. Serotonin, a monoamine neurotransmitter, is involved in a wide range of reproductive functions. In mammals, serotonin regulates sexual behaviours, gonadotropin release and gonadotropin-release hormone (GnRH secretion. However, the serotonin system in teleost may play unique role in the control of reproduction as the mechanism of reproductive control in teleosts is not always the same as in the mammalian models. In fish, the serotonin system is also regulated by natural environmental factors as well as chemical substances. In particular, selective serotonin reuptake inhibitors (SSRIs are commonly detected as pharmaceutical contaminants in the natural environment. Those factors may influence fish reproductive functions via the serotonin system. This review summarizes the functional significance of serotonin in the teleosts reproduction.

  1. Effects of chlorpyrifos on soil carboxylesterase activity at an aggregate-size scale.

    Science.gov (United States)

    Sanchez-Hernandez, Juan C; Sandoval, Marco

    2017-08-01

    The impact of pesticides on extracellular enzyme activity has been mostly studied on the bulk soil scale, and our understanding of the impact on an aggregate-size scale remains limited. Because microbial processes, and their extracellular enzyme production, are dependent on the size of soil aggregates, we hypothesized that the effect of pesticides on enzyme activities is aggregate-size specific. We performed three experiments using an Andisol to test the interaction between carboxylesterase (CbE) activity and the organophosphorus (OP) chlorpyrifos. First, we compared esterase activity among aggregates of different size spiked with chlorpyrifos (10mgkg-1 wet soil). Next, we examined the inhibition of CbE activity by chlorpyrifos and its metabolite chlorpyrifos-oxon in vitro to explore the aggregate size-dependent affinity of the pesticides for the active site of the enzyme. Lastly, we assessed the capability of CbEs to alleviate chlorpyrifos toxicity upon soil microorganisms. Our principal findings were: 1) CbE activity was significantly inhibited (30-67% of controls) in the microaggregates (1.0mm) compared with the corresponding controls (i.e., pesticide-free aggregates), 2) chlorpyrifos-oxon was a more potent CbE inhibitor than chlorpyrifos; however, no significant differences in the CbE inhibition were found between micro- and macroaggregates, and 3) dose-response relationships between CbE activity and chlorpyrifos concentrations revealed the capability of the enzyme to bind chlorpyrifos-oxon, which was dependent on the time of exposure. This chemical interaction resulted in a safeguarding mechanism against chlorpyrifos-oxon toxicity on soil microbial activity, as evidenced by the unchanged activity of dehydrogenase and related extracellular enzymes in the pesticide-treated aggregates. Taken together, these results suggest that environmental risk assessments of OP-polluted soils should consider the fractionation of soil in aggregates of different size to measure

  2. A Human Life-Stage Physiologically Based Pharmacokinetic and Pharmacodynamic Model for Chlorpyrifos: Development and Validation

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Jordan N.; Hinderliter, Paul M.; Timchalk, Charles; Bartels, M. J.; Poet, Torka S.

    2014-08-01

    Sensitivity to chemicals in animals and humans are known to vary with age. Age-related changes in sensitivity to chlorpyrifos have been reported in animal models. A life-stage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed to computationally predict disposition of CPF and its metabolites, chlorpyrifos-oxon (the ultimate toxicant) and 3,5,6-trichloro-2-pyridinol (TCPy), as well as B-esterase inhibition by chlorpyrifos-oxon in humans. In this model, age-dependent body weight was calculated from a generalized Gompertz function, and compartments (liver, brain, fat, blood, diaphragm, rapid, and slow) were scaled based on body weight from polynomial functions on a fractional body weight basis. Blood flows among compartments were calculated as a constant flow per compartment volume. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Model simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ≥ 0.55 mg/kg of chlorpyrifos (significantly higher than environmental exposure levels), 6 mo old children are predicted to have higher levels of chlorpyrifos-oxon in blood and higher levels of red blood cell cholinesterase inhibition compared to adults from equivalent oral doses of chlorpyrifos. At lower doses that are more relevant to environmental exposures, the model predicts that adults will have slightly higher levels of chlorpyrifos-oxon in blood and greater cholinesterase inhibition. This model provides a computational framework for age-comparative simulations that can be utilized to predict CPF disposition and biological response over various postnatal life-stages.

  3. Increased Expression of P-Glycoprotein Is Associated With Chlorpyrifos Resistance in the German Cockroach (Blattodea: Blattellidae).

    Science.gov (United States)

    Hou, Weiyuan; Jiang, Chu; Zhou, Xiaojie; Qian, Kun; Wang, Lei; Shen, Yanhui; Zhao, Yan

    2016-12-01

    A principal method for control of the German cockroach, Blattella germanica (L.), is the broad-spectrum organophosphorus insecticide, chlorpyrifos (O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate); however, extensive and repeated application has resulted in the development of resistance to chlorpyrifos in this insect. Evidence suggests that ATP-binding cassette protein transporters, including P-glycoprotein, are involved in insecticide resistance. However, little is known of the role of P-glycoprotein in insecticide resistance in the German cockroach. Here, we developed a chlorpyrifos-resistant strain of German cockroach and investigated the relationship between P-glycoprotein and chlorpyrifos resistance using toxicity assays; inhibition studies with two P-glycoprotein inhibitors, verapamil and quinine; P-glycoprotein-ATPase activity assays; and western blotting analysis. After 23 generations of selection from susceptible strain cockroaches, we obtained animals with high resistance to chlorpyrifos. When P-glycoprotein-ATPase activity was inhibited by verapamil and quinine, we observed enhanced susceptibility to chlorpyrifos in both control and chlorpyrifos-resistant cockroaches. No significant alterations of P-glycoprotein expression or ATPase activity were observed in cockroaches acutely exposed to LD50 doses of chlorpyrifos for 24 h, while P-glycoprotein expression and ATPase activity were clearly elevated in the chlorpyrifos-resistant cockroach strain. Thus, we conclude that P-glycoprotein is associated with chlorpyrifos resistance in the German cockroach and that elevated levels of P-glycoprotein expression and ATPase activity may be an important mechanism of chlorpyrifos resistance in the German cockroach. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Serotonin in fear conditioning processes.

    Science.gov (United States)

    Bauer, Elizabeth P

    2015-01-15

    This review describes the latest developments in our understanding of how the serotonergic system modulates Pavlovian fear conditioning, fear expression and fear extinction. These different phases of classical fear conditioning involve coordinated interactions between the extended amygdala, hippocampus and prefrontal cortices. Here, I first define the different stages of learning involved in cued and context fear conditioning and describe the neural circuits underlying these processes. The serotonergic system can be manipulated by administering serotonin receptor agonists and antagonists, as well as selective serotonin reuptake inhibitors (SSRIs), and these can have significant effects on emotional learning and memory. Moreover, variations in serotonergic genes can influence fear conditioning and extinction processes, and can underlie differential responses to pharmacological manipulations. This research has considerable translational significance as imbalances in the serotonergic system have been linked to anxiety and depression, while abnormalities in the mechanisms of conditioned fear contribute to anxiety disorders. Copyright © 2014. Published by Elsevier B.V.

  5. Degradation of chlorpyrifos contaminated soil by bioslurry reactor operated in sequencing batch mode: bioprocess monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Mohan, S. Venkata [Biochemical and Environmental Engineering Centre, Indian Institute of Chemical Technology, Hyderabad 500007 (India); Sirisha, K. [Electrochemical Research Laboratories, Department of Chemistry, Sri Venkateswara University, Tirupati 517502 (India); Rao, N. Chandrasekhara [Biochemical and Environmental Engineering Centre, Indian Institute of Chemical Technology, Hyderabad 500007 (India); Sarma, P.N. [Biochemical and Environmental Engineering Centre, Indian Institute of Chemical Technology, Hyderabad 500007 (India); Reddy, S. Jayarama [Electrochemical Research Laboratories, Department of Chemistry, Sri Venkateswara University, Tirupati 517502 (India)]. E-mail: profjreddy_s@yahoo.co.in

    2004-12-10

    Bioslurry reactor (SS-SBR) was studied for the degradation of chlorpyrifos contaminated soil using native mixed microflora, by adopting sequencing batch mode (anoxic-aerobic-anoxic) operation. Reactor operation was monitored for a total cycle period of 72 h consisting of 3 h of FILL, 64 h REACT, 2 h of SETTLE, and 3 h of DECANT with chlorpyrifos concentrations of 3000 {mu}g/g, 6000 {mu}g/g and 12000 {mu}g/g. At 3000 {mu}g/g of chlorpyrifos concentration, 91% was degraded after 72 h of the cycle period, whereas in the case of 6000 {mu}g/g of chlorpyrifos, 82.5% was degraded. However, for 12000 {mu}g/g of chlorpyrifos, only 14.5% degradation was observed. The degradation rate was rapid at lower substrate concentration and 12000 {mu}g/g of substrate concentration was found to be inhibitory. Chlorpyrifos removal rate was slow during the initial phase of the sequence operation. Half-life of chlorpyrifos degradation (t{sub 0.5}) was estimated to be 6.3 h for 3000 {mu}g/g of substrate, 17.5 h for 6000 {mu}g/g and 732.2 h for 12000 {mu}g/g. Process performance was assessed by monitoring chlorpyrifos concentration and biochemical process parameters viz., pH, oxidation and reduction potential (ORP), dissolved oxygen (DO), oxygen consumption rate (OCR) and microbial count (CFU) during sequence operation. From the experimental data obtained it can be concluded that the rate-limiting step with the bioslurry phase reactor in the process of chlorpyrifos degradation may be attributed to the concentration of substrate present in either soil or liquid phase. Periodic operations (SBR) by varying individual components of substrate with time in each process step place micro-organisms under nutritional changes from feast to famine and maintains a wide distribution in the population of micro-organisms resulting in high uptake of the substrate in the bioslurry reactor.

  6. Sub-lethal toxicity of chlorpyrifos on Common carp, Cyprinus carpio (Linnaeus, 1758: Biochemical response

    Directory of Open Access Journals (Sweden)

    Mahdi Banaee

    2014-01-01

    Full Text Available Chlorpyrifos, an organophosphate pesticide, is widely used to control pests in agriculture farms and orchards of fruit trees. In this study, the fish were exposed to sub-lethal concentrations of chlorpyrifos which were determined based on numerical value of 96 h LC50. Blood was sampled after 10, 20 and 30 days and biochemical parameters including glucose, total protein, albumin, globulin, triglyceride and cholesterol levels, and aspartate aminotransferase (AST, alanine aminotransferase (ALT, lactate dehydrogenase (LDH, creatine kinase (CK, alkaline phosphatase (ALP and acetylcholinsetrase (AChE activities were measured. Behavioral changes in the fish were also recorded during the experiment. Unbalanced swimming, swimming in the surface water and hyperglycemia, increased blood triglyceride, and increased levels of AST, LDH and CK activities as well as decreased levels of AChE activity were important changes that were observed in the specimens exposed to chlorpyrifos during experimental periods. The most important alterations in the blood biochemical parameters were measured in the specimens exposed to 40 µg/L chlorpyrifos on the 20th and 30th day of the trial. In conclusion, results of the present study indicated that exposure to sub-lethal concentrations of chlorpyrifos as low as 40 µg/L may cause biochemical and behavioral changes in Cyprinus carpio.

  7. Chlorpyrifos Exposure and Respiratory Health among Adolescent Agricultural Workers

    Directory of Open Access Journals (Sweden)

    Catherine L. Callahan

    2014-12-01

    Full Text Available Chlorpyrifos (CPF is a commonly used organophosphate insecticide (OP. In adults, exposure to OPs has been inconsistently associated with reduced lung function. OP exposure and lung function has not been assessed in adolescents. The objective of this study was to assess CPF exposure and lung function among Egyptian adolescents. We conducted a 10-month study of male adolescent pesticide applicators (n = 38 and non-applicators of similar age (n = 24. Urinary 3,5,6-trichloro-2-pyridinol (TPCy, a CPF-specific metabolite, was analyzed in specimens collected throughout the study. Spirometry was performed twice after pesticide application: day 146, when TCPy levels were elevated and day 269, when TCPy levels were near baseline. Applicators had higher levels of TCPy (mean cumulative TCPy day 146 = 33,217.6; standard deviation (SD = 49,179.3 than non-applicators (mean cumulative TCPy day 146 = 3290.8; SD = 3994.9. Compared with non-applicators, applicators had higher odds of reporting wheeze, odds ratio = 3.41 (95% CI: 0.70; 17.41. Cumulative urinary TCPy was inversely associated with spirometric measurements at day 146, but not at day 269. Although generally non-significant, results were consistent with an inverse association between exposure to CPF and lung function.

  8. Chlorpyrifos induces endoplasmic reticulum stress in JEG-3 cells.

    Science.gov (United States)

    Reyna, Luciana; Flores-Martín, Jésica; Ridano, Magali E; Panzetta-Dutari, Graciela M; Genti-Raimondi, Susana

    2017-04-01

    Chlorpyrifos (CPF) is an organophosphorous pesticide widely used in agricultural, industrial, and household applications. We have previously shown that JEG-3 cells are able to attenuate the oxidative stress induced by CPF through the adaptive activation of the Nrf2/ARE pathway. Considering that there is a relationship between oxidative stress and endoplasmic reticulum stress (ER), herein we investigated whether CPF also induces ER stress in JEG-3 cells. Cells were exposed to 50μM or 100μM CPF during 24h in conditions where cell viability was not altered. Western blot and PCR assays were used to explore the protein and mRNA levels of ER stress biomarkers, respectively. CPF induced an increase of the typical ER stress-related proteins, such as GRP78/BiP and IRE1α, a sensor for the unfolded protein response, as well as in phospho-eIF2α and XBP1 mRNA splicing. Additionally, CPF led to a decrease in p53 protein expression. The downregulation of p53 levels induced by CPF was partially blocked when cells were exposed to CPF in the presence of the proteasome inhibitor MG132. Altogether, these findings point out that CPF induces ER stress in JEG-3 cells; however these cells are able to attenuate it downregulating the levels of the pro-apoptotic protein p53. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. A regenerative and selective electrochemical aptasensor based on copper oxide nanoflowers-single walled carbon nanotubes nanocomposite for chlorpyrifos detection.

    Science.gov (United States)

    Xu, Guoli; Huo, Danqun; Hou, Changjun; Zhao, Yanan; Bao, Jing; Yang, Mei; Fa, Huanbao

    2018-02-01

    Chlorpyrifos is a commonly used organophosphorus pesticide in agriculture. However, its neurotoxicity poses a huge threat to human health. To detect trace amounts of chlorpyrifos, we herein developed a regenerative electrochemical aptasensor for the sensitive detection of chlorpyrifos. The nanocomposite consisting of copper oxide nanoflowers (CuO NFs) and carboxyl-functionalized single walled carbon nanotubes (c-SWCNTs) was prepared to improve the sensing performance for chlorpyrifos detection. Various characterization methods such as scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FT-IR) and cyclic voltammetry (CV) were used to demonstrate the successful fabrication of biosensor. Differential pulse voltammetry (DPV) was utilized to optimize test conditions and quantify chlorpyrifos. Under optimal conditions, the biosensor obtained a good linearity for chlorpyrifos ranging from 0.1 to 150ng/mL, with a lower detection limit of 70pg/mL. This aptasensor also exhibited high selectivity and outstanding repeatability, and was successfully applied to the determination of chlorpyrifos in spiked apple and celery cabbage with satisfactory recoveries. Furthermore, the sensor can be easily regenerated by urea for continuous application. With all the features, the proposed strategy provides an excellent platform for regenerative and selective detection of chlorpyrifos. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. SEROTONIN METABOLISM FOLLOWING PLATINUM-BASED CHEMOTHERAPY COMBINED WITH THE SEROTONIN TYPE-3 ANTAGONIST TROPISETRON

    NARCIS (Netherlands)

    SCHRODER, CP; VANDERGRAAF, WTA; KEMA, IP; GROENEWEGEN, A; SLEIJFER, DT; DEVRIES, EGE

    1995-01-01

    The administration of platinum-based chemotherapy induces serotonin release from the enterochromaffin cells, causing nausea and vomiting. This study was conducted to evaluate parameters of serotonin metabolism following platinum-based chemotherapy given in combination with the serotonin type-3

  11. Reactive oxygen species regulated mitochondria-mediated apoptosis in PC12 cells exposed to chlorpyrifos

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Eun [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Park, Jae Hyeon [Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); Shin, In Chul [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Koh, Hyun Chul, E-mail: hckoh@hanyang.ac.kr [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of)

    2012-09-01

    Reactive oxidative species (ROS) generated by environmental toxicants including pesticides could be one of the factors underlying the neuronal cell damage in neurodegenerative diseases. In this study we found that chlorpyrifos (CPF) induced apoptosis in dopaminergic neuronal components of PC12 cells as demonstrated by the activation of caspases and nuclear condensation. Furthermore, CPF also reduced the tyrosine hydroxylase-positive immunoreactivity in substantia nigra of the rat. In addition, CPF induced inhibition of mitochondrial complex I activity. Importantly, N-acetyl cysteine (NAC) treatment effectively blocked apoptosis via the caspase-9 and caspase-3 pathways while NAC attenuated the inhibition of mitochondrial complex I activity as well as the oxidative metabolism of dopamine (DA). These results demonstrated that CPF-induced apoptosis was involved in mitochondrial dysfunction through the production of ROS. In the response of cellular antioxidant systems to CPF, we found that CPF treatment increased HO-1 expression while the expression of CuZnSOD and MnSOD was reduced. In addition, we found that CPF treatment activated MAPK pathways, including ERK 1/2, the JNK, and the p38 MAP kinase in a time-dependent manner. NAC treatment abolished MAPK phosphorylation caused by CPF, indicating that ROS are upstream signals of MAPK. Interestingly, MAPK inhibitors abolished cytotoxicity and reduced ROS generation by CPF treatment. Our results demonstrate that CPF induced neuronal cell death in part through MAPK activation via ROS generation, suggesting its potential to generate oxidative stress via mitochondrial damage and its involvement in oxidative stress-related neurodegenerative disease. -- Highlights: ► Chlorpyrifos induces apoptosis. ► Chlorpyrifos inhibits mitochondrial complex I activity. ► ROS is involved in chlorpyrifos-induced apoptosis. ► Chlorpyrifos affects cellular antioxidant systems. ► Chlorpyrifos-induced apoptosis mediates activation of MAPK.

  12. Developmental sub-chronic exposure to chlorpyrifos reduces anxiety-related behavior in zebrafish larvae.

    Science.gov (United States)

    Richendrfer, Holly; Pelkowski, Sean D; Colwill, Ruth M; Créton, Robbert

    2012-07-01

    Neurobehavioral disorders such as anxiety, autism, and attention deficit hyperactivity disorders are typically influenced by genetic and environmental factors. Although several genetic risk factors have been identified in recent years, little is known about the environmental factors that either cause neurobehavioral disorders or contribute to their progression in genetically predisposed individuals. One environmental factor that has raised concerns is chlorpyrifos, an organophosphate pesticide that is widely used in agriculture and is found ubiquitously in the environment. In the present study, we examined the effects of sub-chronic chlorpyrifos exposure on anxiety-related behavior during development using zebrafish larvae. We found that sub-chronic exposure to 0.01 or 0.1 μM chlorpyrifos during development induces specific behavioral defects in 7-day-old zebrafish larvae. The larvae displayed decreases in swim speed and thigmotaxis, yet no changes in avoidance behavior were seen. Exposure to 0.001 μM chlorpyrifos did not affect swimming, thigmotaxis, or avoidance behavior and exposure to 1 μM chlorpyrifos induced behavioral defects, but also induced defects in larval morphology. Since thigmotaxis, a preference for the edge, is an anxiety-related behavior in zebrafish larvae, we propose that sub-chronic chlorpyrifos exposure interferes with the development of anxiety-related behaviors. The results of this study provide a good starting point for examination of the molecular, cellular, developmental, and neural mechanisms that are affected by environmentally relevant concentrations of organophosphate pesticides. A more detailed understanding of these mechanisms is important for the development of predictive models and refined health policies to prevent toxicant-induced neurobehavioral disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Effets de la toxicité des pesticides Maneb et Chlorpyrifos-Ethyl sur ...

    African Journals Online (AJOL)

    Dr Gatsing

    0,15 et 0,19 mg/l de Chlorpyrifos-Ethyl. Des corrélations (r = + 0,96 pour le Chlorpyrifos-Ethyl et r = + 0,98 pour le Maneb) ont été positives et fortes entre les taux de mortalité et les concentrations. La concentration létale 50% pendant 24 heures d'exposition (CL50-24h) a été relativement élevée avec le Maneb (1,93 mg/l) et.

  14. Data on the phosphorylation of p38MAPK and JNK induced by chlorpyrifos in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    J.E.S. Batista

    2016-12-01

    Full Text Available Exposure to organophosphate compounds, such as chlorpyrifos, has been linked to disturbances on cell signaling pathways. Mitogen activated protein kinases (MAPK are a family of protein kinases involved in a range of cellular processes, including stress response, apoptosis and survival. Therefore, changes in the activation state of these kinases may characterize key mechanisms of toxicity elicited by xenobiotics. Here we report data on the phosphorylation of p38MAPK and JNK, members of the MAPK family, in Drosophila melanogaster exposed to chlorpyrifos, as characterized by western blotting assays.

  15. Serotonin modulates insect hemocyte phagocytosis via two different serotonin receptors.

    Science.gov (United States)

    Qi, Yi-Xiang; Huang, Jia; Li, Meng-Qi; Wu, Ya-Su; Xia, Ren-Ying; Ye, Gong-Yin

    2016-03-14

    Serotonin (5-HT) modulates both neural and immune responses in vertebrates, but its role in insect immunity remains uncertain. We report that hemocytes in the caterpillar, Pieris rapae are able to synthesize 5-HT following activation by lipopolysaccharide. The inhibition of a serotonin-generating enzyme with either pharmacological blockade or RNAi knock-down impaired hemocyte phagocytosis. Biochemical and functional experiments showed that naive hemocytes primarily express 5-HT1B and 5-HT2B receptors. The blockade of 5-HT1B significantly reduced phagocytic ability; however, the blockade of 5-HT2B increased hemocyte phagocytosis. The 5-HT1B-null Drosophila melanogaster mutants showed higher mortality than controls when infected with bacteria, due to their decreased phagocytotic ability. Flies expressing 5-HT1B or 5-HT2B RNAi in hemocytes also showed similar sensitivity to infection. Combined, these data demonstrate that 5-HT mediates hemocyte phagocytosis through 5-HT1B and 5-HT2B receptors and serotonergic signaling performs critical modulatory functions in immune systems of animals separated by 500 million years of evolution.

  16. Sleep and Rhythm Consequences of a Genetically Induced Loss of Serotonin

    Science.gov (United States)

    Leu-Semenescu, Smaranda; Arnulf, Isabelle; Decaix, Caroline; Moussa, Fathi; Clot, Fabienne; Boniol, Camille; Touitou, Yvan; Levy, Richard; Vidailhet, Marie; Roze, Emmanuel

    2010-01-01

    Background: A genetic deficiency in sepiapterin reductase leads to a combined deficit of serotonin and dopamine. The motor phenotype is characterized by a dopa–responsive fluctuating generalized dystonia–parkinsonism. The non–motor symptoms are poorly recognized. In particular, the effects of brain serotonin deficiency on sleep have not been thoroughly studied. Objective: We examine the sleep, sleep–wake rhythms, CSF neurotransmitters, and melatonin profile in a patient with sepiapterin reductase deficiency. Patient: The patient was a 28–year–old man with fluctuating generalized dystonia–parkinsonism caused by sepiapterin reductase deficiency. Methods: A sleep interview, wrist actigraphy, sleep log over 14 days, 48–h continuous sleep and core temperature monitoring, and measurement of CSF neurotransmitters and circadian serum melatonin and cortisol levels before and after treatment with 5–hydroxytryptophan (the precursor of serotonin) and levodopa were performed. Results: Before treatment, the patient had mild hypersomnia with long sleep time (704 min), ultradian sleep–wake rhythm (sleep occurred every 11.8 ± 5.3 h), organic hyperphagia, attention/executive dysfunction, and no depression. The serotonin metabolism in the CSF was reduced, and the serum melatonin profile was flat, while cortisol and core temperature profiles were normal. Supplementation with 5–hydroxytryptophan, but not with levodopa, normalized serotonin metabolism in the CSF, reduced sleep time to 540 min, normalized the eating disorder and the melatonin profile, restored a circadian sleep–wake rhythm (sleep occurred every 24±1.7 h, P melatonin deficiency (caused by a lack of its substrate, serotonin) may cause the ultradian sleep–wake rhythm. Citation: Leu–Semenescu S; Arnulf I; Dicaix C; Moussa F; Clot F; Boniol C; Touitou Y; Levy R; Vidailhet M; Roze E. Sleep and rhythm consequences of a genetically induced loss of serotonin. SLEEP 2010;33(3):307–314. PMID:20337188

  17. BLOOD CHEMISTRY AND PLATELET SEROTONIN UPTAKE As ...

    African Journals Online (AJOL)

    'AFRICAN JOURNAL OF CLINICAL AND EXPERIMENTAL MICROBIOLOGY MAY 2004 ISSN 1595-689X VOL.5 No.2 ... investigations by means of a questionnaire. .... platelet otomeh'ically. Protein concentration in platelet—rich plasma and in the discharged serotonin was determined serotonin, were determined by the ...

  18. Genetic polymorphism of serotonin transporter 5-HTTLPR ...

    Indian Academy of Sciences (India)

    genetic polymorphism of serotonin transporter in smoking behaviour is reviewed considering the interactive effect of genetic factors. ..... depression. Lancet 347, 731–733. Olausson P., Engel J. A. and Söderpalm B. 2002 Involvement of serotonin in nicotine dependence: processes relevant to positive and negative regulation ...

  19. The serotonin transporter knockout rat : A review

    NARCIS (Netherlands)

    Olivier, Jocelien; Cools, Alexander; Ellenbroek, Bart A.; Cuppen, E.; Homberg, Judith; Kalueff, Allan V.; LaPorte, Justin L.

    2010-01-01

    This chapter dicusses the most recent data on the serotonin transporter knock-out rat, a unique rat model that has been generated by target-selected N-ethyl-N-nitrosourea (ENU) driven mutagenesis. The knock-out rat is the result of a premature stopcodon in the serotonin transporter gene, and the

  20. Serotonin: Modulator of a Drive to Withdraw

    Science.gov (United States)

    Tops, Mattie; Russo, Sascha; Boksem, Maarten A. S.; Tucker, Don M.

    2009-01-01

    Serotonin is a fundamental neuromodulator in both vertebrate and invertebrate nervous systems, with a suspected role in many human mental disorders. Yet, because of the complexity of serotonergic function, researchers have been unable to agree on a general theory. One function suggested for serotonin systems is the avoidance of threat. We propose…

  1. Molecular fMRI of Serotonin Transport.

    Science.gov (United States)

    Hai, Aviad; Cai, Lili X; Lee, Taekwan; Lelyveld, Victor S; Jasanoff, Alan

    2016-11-23

    Reuptake of neurotransmitters from the brain interstitium shapes chemical signaling processes and is disrupted in several pathologies. Serotonin reuptake in particular is important for mood regulation and is inhibited by first-line drugs for treatment of depression. Here we introduce a molecular-level fMRI technique for micron-scale mapping of serotonin transport in live animals. Intracranial injection of an MRI-detectable serotonin sensor complexed with serotonin, together with serial imaging and compartmental analysis, permits neurotransmitter transport to be quantified as serotonin dissociates from the probe. Application of this strategy to much of the striatum and surrounding areas reveals widespread nonsaturating serotonin removal with maximal rates in the lateral septum. The serotonin reuptake inhibitor fluoxetine selectively suppresses serotonin removal in septal subregions, whereas both fluoxetine and a dopamine transporter blocker depress reuptake in striatum. These results highlight promiscuous pharmacological influences on the serotonergic system and demonstrate the utility of molecular fMRI for characterization of neurochemical dynamics. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Serotonin-related pathways and developmental plasticity: relevance for psychiatric disorders

    Science.gov (United States)

    Dayer, Alexandre

    2014-01-01

    Risk for adult psychiatric disorders is partially determined by early-life alterations occurring during neural circuit formation and maturation. In this perspective, recent data show that the serotonin system regulates key cellular processes involved in the construction of cortical circuits. Translational data for rodents indicate that early-life serotonin dysregulation leads to a wide range of behavioral alterations, ranging from stress-related phenotypes to social deficits. Studies in humans have revealed that serotonin-related genetic variants interact with early-life stress to regulate stress-induced cortisol responsiveness and activate the neural circuits involved in mood and anxiety disorders. Emerging data demonstrate that early-life adversity induces epigenetic modifications in serotonin-related genes. Finally, recent findings reveal that selective serotonin reuptake inhibitors can reinstate juvenile-like forms of neural plasticity, thus allowing the erasure of long-lasting fear memories. These approaches are providing new insights on the biological mechanisms and clinical application of antidepressants. PMID:24733969

  3. How serotonin shapes moral judgment and behavior

    Science.gov (United States)

    Siegel, Jenifer Z; Crockett, Molly J

    2013-01-01

    Neuroscientists are now discovering how hormones and brain chemicals shape social behavior, opening potential avenues for pharmacological manipulation of ethical values. Here, we review recent studies showing how altering brain chemistry can alter moral judgment and behavior, focusing in particular on the neuromodulator serotonin and its role in shaping values related to harm and fairness. We synthesize previous findings and consider the potential mechanisms through which serotonin could increase the aversion to harming others. We present a process model whereby serotonin influences social behavior by shifting social preferences in the positive direction, enhancing the value people place on others’ outcomes. This model may explain previous findings relating serotonin function to prosocial behavior, and makes new predictions regarding how serotonin may influence the neural computation of value in social contexts. PMID:25627116

  4. Development and application of assays for serotonin

    Energy Technology Data Exchange (ETDEWEB)

    Gow, I.F.

    1987-01-01

    In this thesis, two assays for serotonin were developed, validated, and used to investigate the relationship between platelet aggregation, serotonin levels and sodium status and serotonin levels and platelet function in patients with cardiovascular disease. A radioimmunoassay (RIA) using an (/sup 125/I)-labelled tracer was developed and validated for the measurement of serotonin in human platelet-rich plasma (PRP) and rat serum. Antisera were raised against N-succinamylserotonin conjugated to bovine albumin and, to improve assay sensitivity, the analyte was made chemically similar to the immunogen by conversion to N-acetylserotonin prior to assay, using the specific amino reagent N-acetoxysuccinimide. An assay for serotonin using high-pressure liquid chromatography with electrochemical detection (HPLC-ECD) was developed, and used to validate the RIA. The RIA can be used to assay up to 100 samples/day compared with 10-20/day by the HPLC-ECD assay.

  5. Toxicity of chlorpyrifos and chlorpyrifos oxon in a transgenic mouse model of the human paraoxonase (PON1) Q192R polymorphism

    Energy Technology Data Exchange (ETDEWEB)

    Cole, Toby B.; Walter, Betsy J.; Shih, Diana M.; Tward, Aaron D.; Lusis, Aldons J.; Timchalk, Chuck; Richter, Rebecca J.; Costa, Lucio G.; Furlong, Clement E.

    2005-08-01

    The Q192R polymorphism of paraoxonase (PON1) has been shown to affect hydrolysis of organophosphorus compounds. The Q192 and R192 alloforms exhibit equivalent catalytic efficiencies of hydrolysis for diazoxon, the oxon form of the pesticide (DZ). However, the R192 alloform has a higher catalytic efficiency of hydrolysis than does the Q192 alloform for chlorpyrifos oxon (CPO), the oxon form of the pesticide chlorpyrifos (CPS). The current study examined the relevance of these observations for in-vivo exposures to chlorpyrifos and chlorpyrifos oxon. Methods Using a transgenic mouse model we examined the relevance of the Q192R polymorphism for exposure to CPS and CPO in vivo. Transgenic mice were generated that expressed either human PON1Q192 or PON1R192 at equivalent levels, in the absence of endogenous mouse PON1. Dose-response and time course experiments were performed on adult mice exposed dermally to CPS or CPO. Morbidity and acetylcholinesterase (AChE) activity in the brain and diaphragm were determined in the first 24 h following exposure. Results Mice expressing PON1Q192 were significantly more sensitive to CPO, and to a lesser extent CPS, than were mice expressing PON1R192. The time course of inhibition following exposure to 1.2 mg/kg CPO revealed maximum inhibition of brain AChE at 6?12 h, with PON1R192, PON1Q192, and PON1? /? mice exhibiting 40, 70 and 85% inhibition, respectively, relative to control mice. The effect of PON1 removal on the dose?response curve for CPS exposure was remarkably consistent with a PBPK/PD model of CPS exposure. Conclusion These results indicate that individuals expressing only the PON1Q192 allele would be more sensitive to the adverse effects of CPO or CPS exposure, especially if they are expressing a low level of plasma PON1Q192.

  6. Serotonin, neural markers and memory

    Directory of Open Access Journals (Sweden)

    Alfredo eMeneses

    2015-07-01

    Full Text Available Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly understood. Hence, neural markers and cerebral functions and dysfunctions are revised. To our knowledge no previous systematic works have been published addressing these issues. The interactions among behavioral tasks, control groups and molecular changes and/or pharmacological effects are mentioned. Neurotransmitter receptors and signaling pathways, during normal and abnormally functioning memory with an emphasis on the behavioral aspects of memory are revised. With focus on serotonin, since as it is a well characterized neurotransmitter, with multiple pharmacological tools, and well characterized downstream signaling in mammals’ species. 5-HT1A, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 receptors as well as SERT (serotonin transporter seem to be useful neural markers and/or therapeutic targets. Certainly, if the mentioned evidence is replicated, then the translatability from preclinical and clinical studies to neural changes might be confirmed. Hypothesis and theories might provide appropriate limits and perspectives of evidence

  7. Chlorpyrifos exposure reduces reproductive capacity owing to a damaging effect on gametogenesis in the nematode Caenorhabditis elegans.

    Science.gov (United States)

    Ruan, Qin-Li; Ju, Jing-Juan; Li, Yun-Hui; Li, Xiao-Bo; Liu, Ran; Liang, Ge-Yu; Zhang, Juan; Pu, Yue-Pu; Wang, Da-Yong; Yin, Li-Hong

    2012-07-01

    Previous studies have revealed that chlorpyrifos exposure adversely affects the reproductive capacity of male rodents. The present study investigated the reproductive toxicity of chlorpyrifos exposure and possible related mechanisms using the nematode Caenorhabditis elegans. L4 nematode larvae were exposed to chlorpyrifos at concentrations of 0.003, 0.03, 0.3 and 3.0 mg l(-1) for different durations. In addition to decreased brood size, reduced spermatid size, increased percentage of abnormal spermatids, suppressed spermatid activation and motility of sperm, damaged oocyte morphology, increased numbers of apoptotic cells and unfertilized oocytes were observed in nematodes exposed to various concentrations of chlorpyrifos. Moreover, expression patterns of the genes spe-10, spe-15, fer-1, prg-1, glp-1, mlh-1, cyb-3, ced-3, ced-4 and ced-9 (which are associated with spermatid size, spermatid activation and morphology, oocyte morphology, oocyte function, and apoptosis) were altered after chlorpyrifos exposure. Therefore, chlorpyrifos exposure may adversely affect fertility in nematodes by influencing both spermatogenesis and oogenesis. Alterations in the expression patterns of genes involved in gametogenesis may explain the corresponding changes in gametogenesis in nematodes exposed to chlorpyrifos. Hence, the model organism Caenorhabditis elegans is recommended for assessment of reproductive toxicity relating to gametogenesis. Copyright © 2011 John Wiley & Sons, Ltd.

  8. The effects of chlorpyrifos on cholinesterase activity and foraging behavior in the dragonfly, Anax junius (Odonata)

    Science.gov (United States)

    Brewer, S.K.; Atchison, G.J.

    1999-01-01

    We examined head capsule cholinesterase (ChE) and foraging behavior in nymphs of the dragonfly, Anax junius, exposed for 24 h to 0.2, 0.6 and 1.0 ??g l-1 of the organophosphorus (OP) insecticide, chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridyl) phosphorothioate]. The invertebrate community is an important component of the structure and function of wetland ecosystems, yet the potential effects of insecticides on wetland ecosystems are largely unknown. Our objectives were to determine if exposure to environmentally realistic concentrations of chlorpyrifos affected foraging behavior and ChE activity in head capsules of dragonfly nymphs. Nymphs were exposed to different concentrations of chlorpyrifos and different prey densities in a factorial design. ChE activities and foraging behaviors of treated nymphs were not statistically different (p ??? 0.05) from control groups. Prey density effects exerted a greater effect on dragonfly foraging than toxicant exposures. Nymphs offered higher prey densities exhibited more foraging behaviors but also missed their prey more often. High variability in ChE activities within the control group and across treated groups precluded determination of relationships between ChE and foraging behaviors. It appears that A. junius is relatively tolerant of chlorpyrifos, although the concentrations we tested have been shown in other work to adversely affect the prey base; therefore the introduction of this insecticide may have indirect adverse affects on top invertebrate predators such as Odonata.

  9. CHANGES IN THE RAT EEG SPECTRA AND CORE TEMPERATURE AFTER EXPOSURE TO DIFFERENT DOSES OF CHLORPYRIFOS.

    Science.gov (United States)

    Our previous study showed that single exposure to 25 mg/kg (p.o.) of organophsphate pesticide chlorpyrifos (CHP) led to significant alterations in all EEG frequency bands within 0.1-50 Hz range, reduction in core temperature (Tc) and motor activity (MA). The alterations in EEG pe...

  10. Serum glucose concentration in subacute intoxication with chlorpyrifos – Organophosphate insecticide

    Directory of Open Access Journals (Sweden)

    Anna Łukaszewicz-Hussain

    2013-08-01

    Full Text Available Background: Epidemiological studies suggest that exposure to organophosphate insecticides enhances the risk of various diseases, including neurological disorders, e.g. Parkinson's or Alzheimer's disease, arteriosclerosis and diabetes mellitus. For this reason the aim of the presented study was to estimate serum concentration of glucose in subchronic intoxication with low doses of chlorpyrifos, an organophosphate insecticide. Materials and Methods: The rats received chlorpyrifos at a daily dose of 0.2, 2 or 5 mg/kg b.w./day for 14 or 28 days. For biochemical determinations of serum glucose in the rats ready-to-use kit was applied. Results: In subacute intoxication with chlorpyrifos the increased serum concentration of glucose was observed after 14 days of intoxication with the highest dose (5 mg/kg b.w. and after 28 days of intoxication with all dose levels used. Conclusions: The results of this study showing the increased concentration of serum glucose in subacute intoxication with low doses of chlorpyrifos, as well as the literature data suggest that exposure to organophosphate insecticides can increase the risk of diabetes mellitus. It may thus be concluded that people occupationally exposed to these compounds should be subjected to diagnostic tests for early detection of diabetes. Med Pr 2013;64(4:527–531

  11. Effects of chlorpyrifos and trichloropyridinol on HEK 293 human embryonic kidney cells

    Science.gov (United States)

    Chlorpyrifos (CPF) [O, O-diethyl -O-3, 5, 6-trichloro-2-pyridyl phosphorothioate] is an organophosphate insecticide widely used for agricultural and urban pest control. Trichloropyridinol (TCP; 3,5,6-trichloro-2-pyridinol), the primary metabolite of CPF, is often used as a generi...

  12. Toxicity of the chlorpyrifos-based pesticide Termifos ® : effects on ...

    African Journals Online (AJOL)

    ... abnormalities including erratic swimming movements, hyperactivity, faster opercular movement, surfacing to gulp air, secretion of copious mucus and loss of balance. Chlorpyrifos should be applied with caution in the environment, especially near water bodies, to avoid the possible ecotoxicological risks associated with its ...

  13. Effects of dissolved organic matter from animal waste effluent on chlorpyrifos sorption by soils.

    Science.gov (United States)

    Huang, X; Lee, L S

    2001-01-01

    The increased use of animal waste-derived effluents for irrigation could result in the enhanced movement of pesticides through complexation with dissolved organic materials. Batch equilibrium studies were conducted to measure the interaction among soil, chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridyl) phosphorothioate], and dissolved organic matter (DOM) from poultry, swine, and cow waste-derived lagoon effluents. All DOM was found to have a strong affinity for chlorpyrifos, resulting in reduced sorption of chlorpyrifos by soil, thus the potential for DOM-enhanced mobility. Effluent DOM was observed to sorb to soils. Thus, for increasingly higher soil mass to solution volume ratios, the effect of chlorpyrifos association with water-borne DOM on sorption decreases significantly. For high soil mass to solution volume ratios typical of soil profiles in the landscape, the potential for DOM-enhanced transport will be greatly attenuated. Dissolved organic matter concentration and the nonpolar nature of DOM in the lagoon effluent decreased with increasing residence time in the cells of the lagoon system, thus reducing the potential for DOM-enhanced transport.

  14. Impact of single and repeated applications of the insecticide chlorpyrifos on tropical freshwater plankton communities

    NARCIS (Netherlands)

    Daam, M.A.; Brink, van den P.J.; Nogueira, A.J.A.

    2008-01-01

    This paper describes the effects of a single and a repeated application of the organophosphorus insecticide chlorpyrifos on zooplankton and phytoplankton communities in outdoor microcosms in Thailand. Treatment levels of 1 mu g L-1 were applied once or twice with a 2-week interval. Both treatments

  15. Specific surface area effect on adsorption of chlorpyrifos and TCP by soils and modeling

    Science.gov (United States)

    The adsorption of chlorpyrifos and TCP (3,5,6, trichloro-2-pyridinol) was determined in four soils (Mollisol, Inceptisol, Entisol, Alfisol) having different specific surface areas (19–84 m2/g) but rather similar organic matter content (2.4–3.5%). Adsorption isotherms were derived from batch equilibr...

  16. Inhibition of acetylcholinesterase in guppies (Poecilia reticulata) by chlorpyrifos at sublethal concentrations: Methodological aspects

    Energy Technology Data Exchange (ETDEWEB)

    van der Wel, H.; Welling, W.

    1989-04-01

    Acetylcholinesterase activity is a potential biochemical indicator of toxic stress in fish and a sensitive parameter for testing water for the presence of organophosphates. A number of methodological aspects regarding the determination of the in vivo effect of chlorpyrifos on acetylcholinesterase in guppies have been investigated. It was found that with acetylthiocholine as a substrate, the contribution of pseudocholinesterase to the total cholinesterase activity can be neglected. Protection of acetylcholinesterase of guppies exposed to chlorpyrifos from additional, artifactual in vitro enzyme inhibition during homogenization is necessary. Very low concentrations of acetone in the exposure medium, resulting from dilution of the stock solution of chlorpyrifos in acetone, can result in large decreases in the oxygen content of this medium. This may affect the uptake rate of the toxic compound and, thereby, cholinesterase inhibition. Very low, sublethal concentrations of chlorpyrifos result in high inhibition levels of acetylcholinesterase (80-90%) in guppies within 2 weeks of continuous exposure. Recovery of the enzyme activity occurs after the exposed animals are kept in clean medium for 4 days, but the rate of recovery is considerably lower than the rate of inhibition.

  17. Removal of chlorpyrifos insecticide in constructed wetlands with different plant species

    Directory of Open Access Journals (Sweden)

    Tamara D. de Souza

    Full Text Available ABSTRACT The objective of this study was to evaluate the remediation of water containing the insecticide chlorpyrifos by using constructed wetlands (CW cultivated with Polygonum punctatum, Cynodon spp. and Mentha aquatica, operated under different hydraulic retention times: 24, 48, 96, 144 and 192 h. The system efficiency was based on reduction of the initial concentration of chlorpyrifos and toxicity of the contaminated water. The results showed that constructed wetlands are an excellent alternative for remediation of the insecticide chlorpyrifos in aqueous medium. It was observed that the average overall removal efficiency of the insecticide was 98.6%, and in the first hydraulic retention time, 24 h, chlorpyrifos was removed to levels below the detection limit in all CW. This result is mainly attributed to adsorption and microbial degradation. For the qualitative standard acute toxicity tests with Daphnia similis, for most samples there was a reduction in toxicity greater than 80%. It was reported that the ecotoxicological tests with the effluents of the constructed wetland are a good option as an indicator of the effectiveness of treatments and a promising alternative to complement the physical and chemical analyses.

  18. Hepatotoxicity of Chlorpyrifos in Zebrafish Liver Cells by NMR-based Metabolomics

    Science.gov (United States)

    For decades chlorpyrifos (CPS) has been one of the most widely used organophosphate insecticides for a variety of agricultural and public health applications. The extensive use of CPS inevitably results in exposure to a small number of the human population. It is believed that ...

  19. Effects of chlorpyrifos, carbendazim and linuron on the ecology of a small indoor aquatic microcosm

    NARCIS (Netherlands)

    Daam, M.A.; Brink, van den P.J.

    2007-01-01

    To validate the use of small indoor microcosms for the risk assessment of pesticides, the fate and effects of chlorpyrifos, carbendazim, and linuron were studied in 8.5¿liter indoor freshwater microcosms. Functional and structural responses to selected concentrations were evaluated and compared with

  20. Effects of chlorpyrifos on individuals and populations of Daphnia pulex in the laboratory and field

    NARCIS (Netherlands)

    Hoeven, N. van der; Gerritsen, A.A.M.

    1997-01-01

    Effects of the insecticide chlorpyrifos (cpf) on young (

  1. Effects of chlorpyrifos in freshwater model ecosystems: the influence of experimental conditions on ecotoxicological thresholds

    NARCIS (Netherlands)

    Wijngaarden, van R.P.A.; Brock, T.C.M.; Douglas, M.T.

    2005-01-01

    Three experiments were conducted to determine the impact of the insecticide chlorpyrifos (single applications of 0.01 to 10 µg AI litre-1) in plankton-dominated nutrient-rich microcosms. The microcosms (water volume approximately 14 litres) were established in the laboratory under temperature, light

  2. Volatilization of the pesticides chlorpyrifos and fenpropimorph from a potato crop

    NARCIS (Netherlands)

    Leistra, M.; Smelt, J.H.; Hilbrand Weststrate, J.; Berg, F. van den; Aalderink, R.

    2006-01-01

    Volatilization of pesticides from crops in the field can be an important emission pathway. In a field experiment with characterization of meteorological conditions, the pesticides chlorpyrifos and fenpropimorph were sprayed onto a potato crop, after which concentrations in the air and on/in the

  3. SEM study of ultrastructural changes in branchial architecture of Ctenopharyngodon idella (Cuvier & Valenciennes exposed to chlorpyrifos

    Directory of Open Access Journals (Sweden)

    Kaur Mandeep

    2016-01-01

    Full Text Available We evaluated structural modifications in the branchial architecture of grass carp, Ctenopharyngodon idella, chronically exposed to chlorpyrifos (an organophosphate using scanning electron microscopy (SEM. Static renewal tests were conducted for 96 h to determine the LC50 of chlorpyrifos to the fish. Physicochemical analysis of water was done using standard methods. To assess the effect of chronic toxicity, fish were exposed to two sublethal concentrations (1.44 μg/L and 2.41 μg/L of chlorpyrifos for 15, 30 and 60 days, after which gills were examined by SEM, which revealed changes in gill ultrastructure. Branchial alterations included distorted secondary lamellae in the form of curling and shortening, erosion in a few primary filaments and a wrinkled and denuded epithelial surface. Excessive mucosal openings (mucoid hyperplasia on the surface were observed in the gills of fish exposed to both concentrations of chlorpyrifos. Alteration in the microridge pattern of pavement cells and cracks on the gill rakers were also observed, and the intensity of the damage was found to be directly related to the toxicant concentration and exposure period. The present study revealed that the assessment of surface morphology can serve as a novel bioindicator of pollution, disease and toxicity.

  4. Biochemical responses of earthworm (Eisenia foetida) to the pesticides chlorpyrifos and fenvalerate.

    Science.gov (United States)

    Wang, Jin-hua; Zhu, Lu-sheng; Liu, Wei; Wang, Jun; Xie, Hui

    2012-04-01

    The effects of chlorpyrifos and fenvalerate on the activity of the cellulase, superoxide dismutase (SOD) and catalase (CAT) of the earthworm (Eisenia foetida) were studied. Earthworms were exposed to chlorpyrifos and fenvalerate at a final concentration of 10, 20, and 40 mg/kg dry soil, respectively. Tissues from each treatment were collected on days 1, 3, 5, and 7. Compared to the controls, the cellulase activity of E. foetida was inhibited by treatments with chlorpyrifos and fenvalerate. The SOD activity of earthworms exposed to chlorpyrifos was significantly inhibited compared to the control after 1 day of incubation, whereas SOD activity increased on day 3. As exposure to the pesticide progressed, the SOD activity recovered from the stimulative effect and reached the level of the control. The SOD activity of E. foetida in the presence of fenvalerate stress was significantly inhibited at the initial stage of exposure and increased after day 3, whereas the SOD activity continued to decrease in response to increasing exposure to fenvalerate. The CAT activity of E. foetida during pesticide stress first increased and then decreased, after day 5, compared to the controls. Alterations of the enzyme activity under environmental stresses are suggested as indicators of biotic and abiotic stress.

  5. Developmental sub-chronic exposure to chlorpyrifos reduces anxiety-related behavior in zebrafish larvae

    OpenAIRE

    Richendrfer, Holly; Pelkowski, Sean D.; Colwill, Ruth M.; Créton, Robbert

    2012-01-01

    Neurobehavioral disorders such as anxiety, autism, and attention deficit hyperactivity disorders are typically influenced by genetic and environmental factors. Although several genetic risk factors have been identified in recent years, little is known about the environmental factors that either cause neurobehavioral disorders or contribute to their progression in genetically predisposed individuals. One environmental factor that has raised concerns is chlorpyrifos, an organophosphate pesticid...

  6. Short-term effects of chlorpyrifos and other pesticides on earthworm numbers

    Science.gov (United States)

    Chlorpyrifos is generally used on grasses grown for seed to control billbugs (Sphenophorus venatus confluens) and cutworms (various species), and on other crops for crane fly larvae (Tipula sp.), garden symphyllans (Scutigerella immaculate), and wireworms (Agriotes sp.). The indirect impact of cont...

  7. THERMOREGULATION IN THE RAT DURING CHRONIC, DIETARY EXPOSURE TO CHLORPYRIFOS, AN ORGANOPHOSPHATE INSECTICIDE.

    Science.gov (United States)

    Administration of chlorpyrifos (CHP) at a dose of 25 to 80 mg/kg (p.o.) To rats results in hypothermia followed by a fever lasting for several days. To understand if chronic, low level exposure to CHP affects thermoregulation in a comparable manner to acute administration, male L...

  8. Use of molecular typing to investigate bacterial translocation from the intestinal tract of chlorpyrifos-exposed rats.

    Science.gov (United States)

    Joly Condette, Claire; Elion Dzon, Bertin; Hamdad, Farida; Biendo, Maurice; Bach, Véronique; Khorsi-Cauet, Hafida

    2016-01-01

    Human are confronted on a daily basis with contaminant pesticide residues in food, water and other components of the environment. Although the digestive system is the first organ to come into contact with food contaminants, very few data are available on the impact of low-dose pesticide exposure during the in utero and postnatal periods on intestinal bacterial translocation (BT). Previous studies have revealed that chlorpyrifos (CPF) exposure is associated with intestinal dysbiosis and the contamination of sterile organs. Here, molecular typing was used to investigate intestinal bacterial translocation in rats exposed to chlorpyrifos in utero and during lactation. The translocated bacteria were profiled, and CPF tolerance and antibiotic resistance traits were determined. A total of 72 intestinal segments and extra-intestinal organs were obtained from 14 CPF-exposed rats. The samples were cultured to isolate bacterial strains that had tolerated treatment with 1 or 5 mg CPF/kg bodyweight/day in vivo. Strains were identified using matrix-assisted laser desorption/ionization (MALDI) Biotyper. The disk diffusion method was used to determine the antibiotic susceptibility. The isolates were genotyped with PCR assays for the enterobacterial repetitive intergenic consensus sequence and random amplification polymorphic DNA. Bacterial translocation was confirmed for 7 of the 31 strains (22.6 %) isolated from extra-intestinal sites. Overall, the most prevalent bacteria were Staphylococcus aureus (55.5 % of the 72 intestinal and extra-intestinal isolates), Enterococcus faecalis (27.7 %) and Bacillus cereus (9.8 %). 5 % of the S. aureus isolates displayed methicillin resistance. Seventy two strains were identified phenotypically, and seven translocated strains (mainly S. aureus) were identified by genotyping. Genotypically confirmed translocation was mainly observed found in pesticide-exposed groups (6 out of 7). BT from the intestinal tract colonized normally sterile

  9. Soil enzyme dynamics in chlorpyrifos-treated soils under the influence of earthworms.

    Science.gov (United States)

    Sanchez-Hernandez, Juan C; Notario Del Pino, J; Capowiez, Yvan; Mazzia, Christophe; Rault, Magali

    2018-01-15

    Earthworms contribute, directly and indirectly, to contaminant biodegradation. However, most of bioremediation studies using these annelids focus on pollutant dissipation, thus disregarding the health status of the organism implied in bioremediation as well as the recovery of indicators of soil quality. A microcosm study was performed using Lumbricus terrestris to determine whether earthworm density (2 or 4individuals/kg wet soil) and the time of exposure (1, 2, 6, 12, and 18wk) could affect chlorpyrifos persistence in soil initially treated with 20mg active ingredientkg(-1) wet soil. Additionally, selected earthworm biomarkers and soil enzyme activities were measured as indicators of earthworm health and soil quality, respectively. After an 18-wk incubation period, no earthworm was killed by the pesticide, but clear signs of severe intoxication were detected, i.e., 90% inhibition in muscle acetylcholinesterase and carboxylesterase (CbE) activities. Unexpectedly, the earthworm density had no significant impact on chlorpyrifos dissipation rate, for which the measured half-life ranged between 30.3d (control soils) and 44.5d (low earthworm density) or 36.7d (high earthworm density). The dynamic response of several soil enzymes to chlorpyrifos exposure was examined calculating the geometric mean and the treated-soil quality index, which are common enzyme-based indexes of microbial functional diversity. Both indexes showed a significant and linear increase of the global enzyme response after 6wk of chlorpyrifos treatment in the presence of earthworms. Examination of individual enzymes revealed that soil CbE activity could decrease chlorpyrifos-oxon impact upon the rest of enzyme activities. Although L. terrestris was found not to accelerate chlorpyrifos dissipation, a significant increase in the activity of soil enzyme activities was achieved compared with earthworm-free, chlorpyrifos-treated soils. Therefore, the inoculation of organophosphorus-contaminated soils with

  10. Pharmacological manipulation of serotonin receptors during brain embryogenesis favours stress resiliency in female rats

    Directory of Open Access Journals (Sweden)

    Gianluca Lavanco

    2018-02-01

    Full Text Available Manipulations of the serotonin transmission during early development induce long-lasting changes in the serotonergic circuitry throughout the brain. However, little is known on the developmental consequences in the female progeny. Therefore, this study aimed at exploring the behavioural effects of pre- and postnatal stimulation of the serotonergic system by 5-methoxytryptamine in adolescent female rats on behavioural reactivity and anxiety- like phenotype. Our results show that perinatal 5- methoxythyptamine decreased total distance travelled and rearing frequency in the novel enviroment, and increased the preference for the centre of the arena in the open field test. Moreover, perinatal 5-methoxytryptamine increased the percentages of entries and time spent on the open arms of the elevated plus maze, with respect to perinatally vehicle-exposed rats. Thus, perinatal stimulation of serotonin receptors does not impair the functional response to the emotional challenges in female rats, favouring the occurrence of a stress-resilient phenotype.

  11. Dissipation and distribution of chlorpyrifos in selected vegetables through foliage and root uptake.

    Science.gov (United States)

    Ge, Jing; Lu, Mengxiao; Wang, Donglan; Zhang, Zhiyong; Liu, Xianjin; Yu, Xiangyang

    2016-02-01

    Dissipation, distribution and uptake pathways of chlorpyrifos were investigated in pakchoi (Brassica chinensis L.) and lettuce (Lactuca sativa) with foliage treatments under a greenhouse trial and root treatments under a hydroponic experiment. The dissipation trends were similar for chlorpyrifos in pakchoi and lettuce with different treatments. More than 94% of chlorpyrifos was degraded in the samples for both of the vegetables 21 days after the foliage treatments. For the root treatment, the dissipation rate of chlorpyrifos in pakchoi and lettuce at the low concentration was greater than 93%, however, for the high concentrations, the dissipation rates were all under 90%. Both shoots and roots of the vegetables were able to absorb chlorpyrifos from the environment and distribute it inside the plants. Root concentration factor (RCF) values at different concentrations with the hydroponic experiment ranged from 5 to 39 for pakchoi, and from 14 to 35 for lettuce. The translocation factor (TF) representing the capability of the vegetables to translocate contaminants was significantly different for pakchoi and lettuce with foliage and root treatments. The values of TF with foliage treatments ranged from 0.003 to 0.22 for pakchoi, and from 0.032 to 1.63 for lettuce. The values of TF with root treatments ranged from 0.01 to 0.17 for pakchoi, and from 0.003 to 0.23 for lettuce. Significant difference of TF was found between pakchoi and lettuce with foliage treatments, and at high concentrations (10 and 50 mg L(-1)) with root treatments as well. However, there was no significant difference of TF between pakchoi and lettuce at 1 mg L(-1) with root treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Morpho-toxicology of chlorpyrifos to prolactin cells of a freshwater catfish, Heteropneustes fossilis =Morpho-toxicology of chlorpyrifos to prolactin cells of a freshwater catfish, Heteropneustes fossilis

    Directory of Open Access Journals (Sweden)

    Diwakar Mishra

    2012-10-01

    Full Text Available In the present study, an organophosphorus compound Coroban (active ingredient chlorpyrifos – E.C. 20% was used. In short-term exposure the fish were subjected to 0.8 of 96h LC50 value of chlorpyrifos (1.76 mg L-1 for 96h. In long-term exposure the experiment was performed for 28 days by using 0.2 of 96h LC50 value of chlorpyrifos (0.44 mg L-1. Fish were killed on each time intervals from control and experimental (chlorpyrifos groups after 24, 48, 72, and 96h in short-term exposure and after 7, 14, 21, and 28 days in long-term experiment. Blood samples were collected and sera were analyzed for calcium. Pituitary glands were fixed for histological studies and stained with Herlant tetrachrome and Heidenhain’s azan techniques. Short-term exposure of chlorpyrifos caused decrease in the serum calcium levels. No change was noticed in the prolactin cells of chlorpyrifos treated fish. Long-term treatment with chlorpyrifos provoked hypocalcemia. The prolactin cells of treated fish exhibited slight degranulation after 21 days whereas the nuclear volume remained unchanged. After 28 days, the prolactin cells exhibited further degranulation and the nuclear volume recorded an increase. Cytolysis and vacuolization were also visible. No estudo presente, o composto organofosforo Coroban (ingrediente ativo clorpirifo – E.C. 20% foi usado. Na exposição a curto prazo os peixes foram submetido a 0,8 de valor LC50 de 96h de clorpirifo (1,76 mg L-1 durante 96h. Na exposição a longo prazo o experimento foi executado durante 28 dias usando 0,2 de valor LC50 de 96h de clorpirifos (0,44 mg L-1. Os peixes foram mortos a cada intervalo dos grupos controle e experimental (clorpirifos após 24, 48, 72, e 96h em exposição a curto prazo e após 7, 14, 21, e 28 dias no experimento a longo prazo. As amostras de sangue foram colhidas e o soro foi analisado para cálcio. As glândulas pituitárias foram fixadas para estudos histológicos e colorido por tetracromo de

  13. Disruption of Transient Serotonin Accumulation by Non-Serotonin-Producing Neurons Impairs Cortical Map Development

    Directory of Open Access Journals (Sweden)

    Xiaoning Chen

    2015-01-01

    Full Text Available Polymorphisms that alter serotonin transporter SERT expression and functionality increase the risks for autism and psychiatric traits. Here, we investigate how SERT controls serotonin signaling in developing CNS in mice. SERT is transiently expressed in specific sets of glutamatergic neurons and uptakes extrasynaptic serotonin during perinatal CNS development. We show that SERT expression in glutamatergic thalamocortical axons (TCAs dictates sensory map architecture. Knockout of SERT in TCAs causes lasting alterations in TCA patterning, spatial organizations of cortical neurons, and dendritic arborization in sensory cortex. Pharmacological reduction of serotonin synthesis during the first postnatal week rescues sensory maps in SERTGluΔ mice. Furthermore, knockdown of SERT expression in serotonin-producing neurons does not impair barrel maps. We propose that spatiotemporal SERT expression in non-serotonin-producing neurons represents a determinant in early life genetic programming of cortical circuits. Perturbing this SERT function could be involved in the origin of sensory and cognitive deficits associated with neurodevelopmental disorders.

  14. Lasting syndrome of depression produced by reduction in serotonin uptake during postnatal development: evidence from sleep, stress, and behavior.

    Science.gov (United States)

    Popa, Daniela; Léna, Clément; Alexandre, Chloé; Adrien, Joëlle

    2008-04-02

    Dysfunction of the serotonin system is implicated in sleep and emotional disorders. To test whether these impairments could arise during development, we studied the impact of early-life, transient versus genetic, permanent alterations of serotonin reuptake on sleep-wakefulness patterns, depression-related behavior, and associated physiological features. Here, we show that female mice treated neonatally with a highly selective serotonin reuptake inhibitor, escitalopram, exhibited signs of depression in the form of sleep anomalies, anhedonia, increased helplessness reversed by chronic antidepressant treatment, enhanced response to acute stress, and increased serotoninergic autoinhibitory feedback. This syndrome was not reproduced by treatment in naive adults but resembled the phenotype of mutant mice lacking the serotonin transporter, except that these exhibited decreased serotonin autoreceptor sensitivity and additional anxiety-like behavior. Thus, alteration of serotonin reuptake during development, whether induced by external or genetic factors, causes a depressive syndrome lasting into adulthood. Such early-life impairments might predispose individuals to sleep and/or mood disorders.

  15. Effects of time-variable exposure regimes of the insecticide chlorpyrifos on freshwater invertebrate communities in microcosms

    NARCIS (Netherlands)

    Zafar, M.I.; Wijngaarden, van R.; Roessink, I.; Brink, van den P.J.

    2011-01-01

    The present study compared the effects of different time-variable exposure regimes having the same time-weighted average (TWA) concentration of the organophosphate insecticide chlorpyrifos on freshwater invertebrate communities to enable extrapolation of effects across exposure regimes. The

  16. How serotonin shapes moral judgment and behavior

    National Research Council Canada - National Science Library

    Siegel, Jenifer Z; Crockett, Molly J

    2013-01-01

    .... Here, we review recent studies showing how altering brain chemistry can alter moral judgment and behavior, focusing in particular on the neuromodulator serotonin and its role in shaping values...

  17. Inhibition of recombinant human carboxylesterase 1 and 2 and monoacylglycerol lipase by chlorpyrifos oxon, paraoxon and methyl paraoxon

    Energy Technology Data Exchange (ETDEWEB)

    Crow, J. Allen; Bittles, Victoria; Herring, Katye L.; Borazjani, Abdolsamad [Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762 (United States); Potter, Philip M. [Department of Chemical Biology and Therapeutics, St. Jude Children' s Research Hospital, 332 N. Lauderdale, Memphis, TN 38105 (United States); Ross, Matthew K., E-mail: mross@cvm.msstate.edu [Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762 (United States)

    2012-01-01

    Oxons are the bioactivated metabolites of organophosphorus insecticides formed via cytochrome P450 monooxygenase-catalyzed desulfuration of the parent compound. Oxons react covalently with the active site serine residue of serine hydrolases, thereby inactivating the enzyme. A number of serine hydrolases other than acetylcholinesterase, the canonical target of oxons, have been reported to react with and be inhibited by oxons. These off-target serine hydrolases include carboxylesterase 1 (CES1), CES2, and monoacylglycerol lipase. Carboxylesterases (CES, EC 3.1.1.1) metabolize a number of xenobiotic and endobiotic compounds containing ester, amide, and thioester bonds and are important in the metabolism of many pharmaceuticals. Monoglyceride lipase (MGL, EC 3.1.1.23) hydrolyzes monoglycerides including the endocannabinoid, 2-arachidonoylglycerol (2-AG). The physiological consequences and toxicity related to the inhibition of off-target serine hydrolases by oxons due to chronic, low level environmental exposures are poorly understood. Here, we determined the potency of inhibition (IC{sub 50} values; 15 min preincubation, enzyme and inhibitor) of recombinant CES1, CES2, and MGL by chlorpyrifos oxon, paraoxon and methyl paraoxon. The order of potency for these three oxons with CES1, CES2, and MGL was chlorpyrifos oxon > paraoxon > methyl paraoxon, although the difference in potency for chlorpyrifos oxon with CES1 and CES2 did not reach statistical significance. We also determined the bimolecular rate constants (k{sub inact}/K{sub I}) for the covalent reaction of chlorpyrifos oxon, paraoxon and methyl paraoxon with CES1 and CES2. Consistent with the results for the IC{sub 50} values, the order of reactivity for each of the three oxons with CES1 and CES2 was chlorpyrifos oxon > paraoxon > methyl paraoxon. The bimolecular rate constant for the reaction of chlorpyrifos oxon with MGL was also determined and was less than the values determined for chlorpyrifos oxon with CES1

  18. Sleep and rhythm consequences of a genetically induced loss of serotonin.

    Science.gov (United States)

    Leu-Semenescu, Smaranda; Arnulf, Isabelle; Decaix, Caroline; Moussa, Fathi; Clot, Fabienne; Boniol, Camille; Touitou, Yvan; Levy, Richard; Vidailhet, Marie; Roze, Emmanuel

    2010-03-01

    A genetic deficiency in sepiapterin reductase leads to a combined deficit of serotonin and dopamine. The motor phenotype is characterized by a dopa-responsive fluctuating generalized dystonia-parkinsonism. The non-motor symptoms are poorly recognized. In particular, the effects of brain serotonin deficiency on sleep have not been thoroughly studied. We examine the sleep, sleep-wake rhythms, CSF neurotransmitters, and melatonin profile in a patient with sepiapterin reductase deficiency. The patient was a 28-year-old man with fluctuating generalized dystonia-parkinsonism caused by sepiapterin reductase deficiency. A sleep interview, wrist actigraphy, sleep log over 14 days, 48-h continuous sleep and core temperature monitoring, and measurement of CSF neurotransmitters and circadian serum melatonin and cortisol levels before and after treatment with 5-hydroxytryptophan (the precursor of serotonin) and levodopa were performed. Before treatment, the patient had mild hypersomnia with long sleep time (704 min), ultradian sleep-wake rhythm (sleep occurred every 11.8 +/- 5.3 h), organic hyperphagia, attentionlexecutive dysfunction, and no depression. The serotonin metabolism in the CSF was reduced, and the serum melatonin profile was flat, while cortisol and core temperature profiles were normal. Supplementation with 5-hydroxytryptophan, but not with levodopa, normalized serotonin metabolism in the CSF, reduced sleep time to 540 min, normalized the eating disorder and the melatonin profile, restored a circadian sleep-wake rhythm (sleep occurred every 24 +/- 1.7 h, P melatonin deficiency (caused by a lack of its substrate, serotonin) may cause the ultradian sleep-wake rhythm.

  19. Changes of field incurred chlorpyrifos and its toxic metabolite residues in rice during food processing from-RAC-to-consumption.

    Directory of Open Access Journals (Sweden)

    Zhiyong Zhang

    Full Text Available The objectives of this study were to determine the effects of food processing on field incurred residues levels of chlorpyrifos and its metabolite 3,5,6-Trichloro-2-pyridinol (TCP in rice. The chlorpyrifos and TCP were found to be 1.27 and 0.093 mg kg-1 in straw and 0.41 and 0.073 mg kg-1 in grain, respectively. It is observed that the sunlight for 2 hours does not decrease the chlorpyrifos and TCP residues in grain significantly. Their residues in rice were reduced by up to 50% by hulling. The cooking reduced the chlorpyrifos and TCP in rice to undetectable level (below 0.01 mg kg-1. Processing factors (PFs of chlorpyrifos and TCP residues in rice during food processing were similar. Various factors have impacts on the fates of chlorpyrifos and TCP residues and the important steps to reduce their residues in rice were hulling and cooking. The results can contribute to assure the consumer of a safe wholesome food supply.

  20. Characterization of a fungal strain capable of degrading chlorpyrifos and its use in detoxification of the insecticide on vegetables.

    Science.gov (United States)

    Yu, Yun Long; Fang, Hua; Wang, Xiao; Wu, Xiao Mao; Shan, Min; Yu, Jing Quan

    2006-10-01

    A fungal strain capable of utilizing chlorpyrifos as sole carbon and energy sources was isolated from soil by enrichment cultivation approach. The half-lives of degradation (DT(50)) for chlorpyrifos at concentrations of 1, 10, and 100 mg l(-1) by the fungal strain DSP in mineral salt medium were measured to be 2.03, 2.93, and 3.49 days, respectively. Two cell-free extracts [E (1:10) and E (1:20)] from the fungal strain DSP in bran-glucose medium were prepared and used to enhance chlorpyrifos degradation on vegetables. Compared with the controls, the DT(50) of chlorpyrifos were reduced by 70.3%, 65.6%, 80.6%, 80.6%, and 86.1%, and by 53.8%, 43.2%, 66.0%, 54.3%, and 67.7% on E (1:20) and E (1:10) treated pakchoi, water spinach, Malabar spinach, haricot beans, and pepper, respectively. The 7-day residual values (R (7)) of chlorpyrifos on E (1:10) treated vegetables were all lower than the corresponding maximum residue levels of European Union (EU MRLs), except that the R (7) value on haricot beans was slightly higher than the corresponding EU MRLs. The results indicate that cell-free extracts could rapidly degrade chlorpyrifos residues on vegetables.

  1. Exposure to chlorpyrifos in gaseous and particulate form in greenhouses: a pilot study.

    Science.gov (United States)

    Kim, Seung Won; Lee, Eun Gyung; Lee, Taekhee; Lee, Larry A; Harper, Martin

    2014-01-01

    Phase distribution of airborne chemicals is important because intake and uptake mechanisms of each phase are different. The phase distribution and concentrations are needed to determine strategies of exposure assessment, hazard control, and worker protection. However, procedures for establishing phase distribution and concentration have not been standardized. The objective of this study was to compare measurements of an airborne semivolatile pesticide (chlorpyrifos) by phase using two different procedures. Six pesticide applications in two facilities were studied and at each site, samples were collected for three time slots: T1, the first 1 or 2 hr after the commencement of application; T2, a 6-hr period immediately following T1; and T3, a 6-hr period after the required re-entry interval (24 hr for chlorpyrifos).Two phase-separating devices were co-located at the center of each greenhouse: semivolatile aerosol dichotomous sampler (SADS) using flow rates of 1.8 l x min(-1) and 0.2 l x min(-1), corresponding to a total inlet flow rate of 2.0 l x min(-1) with a vapor phase flow fraction of 0.1; and an electrostatic precipitator (ESP), along with a standard OVS XAD-2 tube. Chlorpyrifos in vapor and particulate form in a SADS sampling train and that in vapor form in an ESP sampling train were collected in OVS tubes. Chlorpyrifos in particulate form in the ESP setting would have been collected on aluminum substrate. However, no chlorpyrifos in particulate form was recovered from the ESP. Overall (vapor plus particle) concentrations measured by OVS ranged 11.7-186.6 μg/m(3) at T1 and decreased on average 77.1% and 98.9% at T2 and T3, respectively. Overall concentrations measured by SADS were 66.6%, 72.7%, and 102% of those measured by OVS on average at T1, T2, and T3, respectively. Particle fractions from the overall concentrations measured by SADS were 60.0%, 49.2%, and 13.8%, respectively, for T1, T2, and T3. SADS gives better guidance on the distribution of

  2. Application of a mathematical model to describe the effects of chlorpyrifos on Caenorhabditis elegans development.

    Directory of Open Access Journals (Sweden)

    Windy A Boyd

    2009-09-01

    Full Text Available The nematode Caenorhabditis elegans is being assessed as an alternative model organism as part of an interagency effort to develop better means to test potentially toxic substances. As part of this effort, assays that use the COPAS Biosort flow sorting technology to record optical measurements (time of flight (TOF and extinction (EXT of individual nematodes under various chemical exposure conditions are being developed. A mathematical model has been created that uses Biosort data to quantitatively and qualitatively describe C. elegans growth, and link changes in growth rates to biological events. Chlorpyrifos, an organophosphate pesticide known to cause developmental delays and malformations in mammals, was used as a model toxicant to test the applicability of the growth model for in vivo toxicological testing.L1 larval nematodes were exposed to a range of sub-lethal chlorpyrifos concentrations (0-75 microM and measured every 12 h. In the absence of toxicant, C. elegans matured from L1s to gravid adults by 60 h. A mathematical model was used to estimate nematode size distributions at various times. Mathematical modeling of the distributions allowed the number of measured nematodes and log(EXT and log(TOF growth rates to be estimated. The model revealed three distinct growth phases. The points at which estimated growth rates changed (change points were constant across the ten chlorpyrifos concentrations. Concentration response curves with respect to several model-estimated quantities (numbers of measured nematodes, mean log(TOF and log(EXT, growth rates, and time to reach change points showed a significant decrease in C. elegans growth with increasing chlorpyrifos concentration.Effects of chlorpyrifos on C. elegans growth and development were mathematically modeled. Statistical tests confirmed a significant concentration effect on several model endpoints. This confirmed that chlorpyrifos affects C. elegans development in a concentration dependent

  3. Application of a Mathematical Model to Describe the Effects of Chlorpyrifos on Caenorhabditis elegans Development

    Science.gov (United States)

    Boyd, Windy A.; Smith, Marjolein V.; Kissling, Grace E.; Rice, Julie R.; Snyder, Daniel W.; Portier, Christopher J.; Freedman, Jonathan H.

    2009-01-01

    Background The nematode Caenorhabditis elegans is being assessed as an alternative model organism as part of an interagency effort to develop better means to test potentially toxic substances. As part of this effort, assays that use the COPAS Biosort flow sorting technology to record optical measurements (time of flight (TOF) and extinction (EXT)) of individual nematodes under various chemical exposure conditions are being developed. A mathematical model has been created that uses Biosort data to quantitatively and qualitatively describe C. elegans growth, and link changes in growth rates to biological events. Chlorpyrifos, an organophosphate pesticide known to cause developmental delays and malformations in mammals, was used as a model toxicant to test the applicability of the growth model for in vivo toxicological testing. Methodology/Principal Findings L1 larval nematodes were exposed to a range of sub-lethal chlorpyrifos concentrations (0–75 µM) and measured every 12 h. In the absence of toxicant, C. elegans matured from L1s to gravid adults by 60 h. A mathematical model was used to estimate nematode size distributions at various times. Mathematical modeling of the distributions allowed the number of measured nematodes and log(EXT) and log(TOF) growth rates to be estimated. The model revealed three distinct growth phases. The points at which estimated growth rates changed (change points) were constant across the ten chlorpyrifos concentrations. Concentration response curves with respect to several model-estimated quantities (numbers of measured nematodes, mean log(TOF) and log(EXT), growth rates, and time to reach change points) showed a significant decrease in C. elegans growth with increasing chlorpyrifos concentration. Conclusions Effects of chlorpyrifos on C. elegans growth and development were mathematically modeled. Statistical tests confirmed a significant concentration effect on several model endpoints. This confirmed that chlorpyrifos affects C

  4. Do selective serotonin reuptake inhibitors acutely increase frontal cortex levels of serotonin?

    NARCIS (Netherlands)

    Beyer, Chad E.; Cremers, Thomas I. F. H.

    2008-01-01

    Selective serotonin uptake inhibitors (SSRIs) exert their effects by inhibiting serotonin (5-HT) re-uptake. Although blockade occurs almost immediately, the neurochemical effects on 5-HT, as measured by in vivo microdialysis, have been a matter of considerable debate. In particular, literature

  5. Immunomodulatory Effects Mediated by Serotonin

    Directory of Open Access Journals (Sweden)

    Rodrigo Arreola

    2015-01-01

    Full Text Available Serotonin (5-HT induces concentration-dependent metabolic effects in diverse cell types, including neurons, entherochromaffin cells, adipocytes, pancreatic beta-cells, fibroblasts, smooth muscle cells, epithelial cells, and leukocytes. Three classes of genes regulating 5-HT function are constitutively expressed or induced in these cells: (a membrane proteins that regulate the response to 5-HT, such as SERT, 5HTR-GPCR, and the 5HT3-ion channels; (b downstream signaling transduction proteins; and (c enzymes controlling 5-HT metabolism, such as IDO and MAO, which can generate biologically active catabolites, including melatonin, kynurenines, and kynurenamines. This review covers the clinical and experimental mechanisms involved in 5-HT-induced immunomodulation. These mechanisms are cell-specific and depend on the expression of serotonergic components in immune cells. Consequently, 5-HT can modulate several immunological events, such as chemotaxis, leukocyte activation, proliferation, cytokine secretion, anergy, and apoptosis. The effects of 5-HT on immune cells may be relevant in the clinical outcome of pathologies with an inflammatory component. Major depression, fibromyalgia, Alzheimer disease, psoriasis, arthritis, allergies, and asthma are all associated with changes in the serotonergic system associated with leukocytes. Thus, pharmacological regulation of the serotonergic system may modulate immune function and provide therapeutic alternatives for these diseases.

  6. Immunomodulatory Effects Mediated by Serotonin

    Science.gov (United States)

    Arreola, Rodrigo; Becerril-Villanueva, Enrique; Cruz-Fuentes, Carlos; Velasco-Velázquez, Marco Antonio; Garcés-Alvarez, María Eugenia; Hurtado-Alvarado, Gabriela; Quintero-Fabian, Saray; Pavón, Lenin

    2015-01-01

    Serotonin (5-HT) induces concentration-dependent metabolic effects in diverse cell types, including neurons, entherochromaffin cells, adipocytes, pancreatic beta-cells, fibroblasts, smooth muscle cells, epithelial cells, and leukocytes. Three classes of genes regulating 5-HT function are constitutively expressed or induced in these cells: (a) membrane proteins that regulate the response to 5-HT, such as SERT, 5HTR-GPCR, and the 5HT3-ion channels; (b) downstream signaling transduction proteins; and (c) enzymes controlling 5-HT metabolism, such as IDO and MAO, which can generate biologically active catabolites, including melatonin, kynurenines, and kynurenamines. This review covers the clinical and experimental mechanisms involved in 5-HT-induced immunomodulation. These mechanisms are cell-specific and depend on the expression of serotonergic components in immune cells. Consequently, 5-HT can modulate several immunological events, such as chemotaxis, leukocyte activation, proliferation, cytokine secretion, anergy, and apoptosis. The effects of 5-HT on immune cells may be relevant in the clinical outcome of pathologies with an inflammatory component. Major depression, fibromyalgia, Alzheimer disease, psoriasis, arthritis, allergies, and asthma are all associated with changes in the serotonergic system associated with leukocytes. Thus, pharmacological regulation of the serotonergic system may modulate immune function and provide therapeutic alternatives for these diseases. PMID:25961058

  7. Dissipation and leaching of acephate, chlorpyrifos, and their main metabolites in field soils of Malaysia.

    Science.gov (United States)

    Chai, L K; Mohd-Tahir, N; Hansen, S; Hansen, H C B

    2009-01-01

    Preventive treatment with insecticides at high dosing rates before planting of a new crop- soil drenching- is a common practice in some tropical intensive cropping systems, which may increase the risk of leaching, soil functioning, and pesticide uptake in the next crop. The degradation rates and migration of acephate and chlorpyrifos and their primary metabolites, methamidophos and 3,5,6-trichloropyridinol (TCP), have been studied in clayey red yellow podzolic (Typic Paleudults), alluvial (Typic Udorthents), and red yellow podzolic soils (Typic Kandiudults) of Malaysia under field conditions. The initial concentrations of acephate and chlorpyrifos in topsoils were found to strongly depend on solar radiation. Both pesticides and their metabolites were detected in subsoils at the deepest sampling depth monitored (50 cm) and with maximum concentrations up to 2.3 mg kg(-1) at soil depths of 10 to 20 cm. Extraordinary high dissipation rates for weakly sorbed acephate was in part attributed to preferential flow which was activated due to the high moisture content of the soils, high precipitation and the presence of conducting macropores running from below the A horizons to at least 1 m, as seen from a dye tracer experiment. Transport of chlorpyrifos and TCP which both sorb strongly to soil organic matter was attributed to macropore transport with soil particles. The half-lives for acephate in topsoils were 0.4 to 2.6 d while substantially longer half-lives of between 12.6 and 19.8 d were observed for chlorpyrifos. The transport through preferential flow of strongly sorbed pesticides is of concern in the tropics.

  8. Effects of nickel, chlorpyrifos and their mixture on the Dictyostelium discoideum proteome.

    Science.gov (United States)

    Boatti, Lara; Robotti, Elisa; Marengo, Emilio; Viarengo, Aldo; Marsano, Francesco

    2012-11-23

    Mixtures of chemicals can have additive, synergistic or antagonistic interactions. We investigated the effects of the exposure to nickel, the organophosphate insecticide chlorpyrifos at effect concentrations (EC) of 25% and 50% and their binary mixture (Ec25 + EC25) on Dictyostelium discoideum amoebae based on lysosomal membrane stability (LMS). We treated D. discoideum with these compounds under controlled laboratory conditions and evaluated the changes in protein levels using a two-dimensional gel electrophoresis (2DE) proteomic approach. Nickel treatment at EC25 induced changes in 14 protein spots, 12 of which were down-regulated. Treatment with nickel at EC50 resulted in changes in 15 spots, 10 of which were down-regulated. Treatment with chlorpyrifos at EC25 induced changes in six spots, all of which were down-regulated; treatment with chlorpyrifos at EC50 induced changes in 13 spots, five of which were down-regulated. The mixture corresponding to EC25 of each compound induced changes in 19 spots, 13 of which were down-regulated. The data together reveal that a different protein expression signature exists for each treatment, and that only a few proteins are modulated in multiple different treatments. For a simple binary mixture, the proteomic response does not allow for the identification of each toxicant. The protein spots that showed significant differences were identified by mass spectrometry, which revealed modulations of proteins involved in metal detoxification, stress adaptation, the oxidative stress response and other cellular processes.

  9. Degradation of Chlorpyrifos by an alkaline phosphatase from the cyanobacterium Spirulina platensis.

    Science.gov (United States)

    Thengodkar, Rutwik Ravindra Mandakini; Sivakami, S

    2010-07-01

    Spirulina is a photosynthetic, filamentous, spiral-shaped, multicellular, blue-green microalga. The two most important species are Spirulina maxima and Spirulina platensis. Spirulina is considered an excellent food, lacking toxicity and having corrective properties against viral attacks, anemia, tumor growth and malnutrition. We have observed that cultures of Spirulina platensis grow in media containing up to 80 ppm of the organophosphorous pesticide, Chlorpyrifos. It was found to be due to an alkaline phosphatase (ALP) activity that was detected in cell free extracts of Spirulina platensis. This activity was purified from the cell free extracts using ammonium sulphate precipitation and gel filtration and shown to belong to the class of EC 3.1.3.1 ALP. The purified enzyme degrades 100 ppm Chlorpyrifos to 20 ppm in 1 h transforming it into its primary metabolite 3, 5, 6-trichloro-2-pyridinol. This is the first report of degradation of Chlorpyrifos by Spirulina platensis whose enzymic mechanism has been clearly identified. These findings have immense potential for harnessing Spirulina platensis in bioremediation of polluted ecosystems.

  10. Efficiency of the intestinal bacteria in the degradation of the toxic pesticide, chlorpyrifos.

    Science.gov (United States)

    Harishankar, M K; Sasikala, C; Ramya, M

    2013-04-01

    Chlorpyrifos (CP) is the most commonly used pesticide throughout the world. Its widespread use in agriculture and its potential toxicity to humans from ingestion of CP contaminated food have raised concerns about its risk to health. Human intestinal microflora has the ability to degrade pesticides, but the exact mechanisms involved and the metabolite end-products formed are not well understood. The primary objective of this work was to analyse the in vitro degradation of CP by five model intestinal bacteria namely Lactobacillus lactis, L. fermentum, L. plantarum, Escherichia coli and Enterococcus faecalis. Plate assay results revealed that L. lactis, E. coli and L. fermentum could grow with high concentrations of CP (>1,400 μg/mL), whereas E. faecalis and L. plantarum could grow with concentrations as low as 400 and 100 μg/mL, respectively. The best three CP degraders were therefore used in further experiments. The degradation of CP-induced organophosphorous phosphatase (OPP) production and that OPP concentration were higher in the supernatant (extracellular) rather than inside the cells by factor of up to 28. L. fermentum degraded 70 % CP with 3,5,6-trichloro-2-pyridinol (TCP) detected as the end product. L.lactis degraded up to 61 % CP with chlorpyrifos oxon detected as the end product, whereas E.coli degraded a lesser concentration (16 %) to chlorpyrifos-oxon and diethylphosphate.

  11. Genotoxic effects of commercial formulations of Chlorpyrifos and Tebuconazole on green algae.

    Science.gov (United States)

    Martinez, Ricardo Santiago; Di Marzio, Walter Darío; Sáenz, María Elena

    2015-01-01

    The alkaline single-cell gel electrophoresis assay (comet assay) was used for the study of the genotoxic effects of insecticide Chlorpyrifos and fungicide Tebuconazole (commercial formulations) on two freshwater green algae species, Pseudokirchneriella subcapitata and Nannocloris oculata, after 24 h of exposure. The percentage of DNA in tail of migrating nucleoids was taken as an endpoint of DNA impairment. Cell viability was measured by fluorometric detection of chlorophyll "a" in vivo and the determination of cell auto-fluorescence. Only the higher concentration of Chlorpyrifos tested resulted to affect significantly the cell viability of P. subcapitata, whereas cells of N. oculata were not affected. Tebuconazole assayed concentrations (3 and 6 mg/l) did not affect cell viability of both species. The results of comet assay on P. subcapitata showed that Chlorpyrifos concentration evaluated (0.8 mg/l) exerted a genotoxic effects; while for the other specie a concentration of 10 mg/l was needed. Tebuconazole was genotoxic at 3 and 6 mg/l for both species. The comet assay evidenced damage at the level of DNA simple strains molecule at pesticide concentrations were cytotoxicity was not evident, demonstrating that algae are models to take into account in ecological risk assessments for aquatic environments.

  12. Polymorphism of rs3813034 in Serotonin Transporter Gene SLC6A4 Is Associated With the Selective Serotonin and Serotonin-Norepinephrine Reuptake Inhibitor Response in Depressive Disorder: Sequencing Analysis of SLC6A4.

    Science.gov (United States)

    Nonen, Shinpei; Kato, Masaki; Takekita, Yoshiteru; Wakeno, Masataka; Sakai, Shiho; Serretti, Alessandro; Kinoshita, Toshihiko

    2016-02-01

    Selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRI/SNRI) are commonly used for treating major depression. Regretfully, significant heterogeneity exists regarding the benefits of SSRI/SNRI in individual cases. We previously reported that a polymorphism located in the serotonin transporter linked promoter region (5-HTT LPR) is associated with an interindividual difference in SSRI treatment efficacy. However, this explains only a small part of the variation of this complex phenotype. Other 5-HTT variants in the coding regions, 3' untranslated region (3' UTR), and introns adjacent to each exon could also contribute to treatment response. Therefore, we performed a sequencing analysis of the SLC6A4 gene (coding for 5-HTT) and investigated the association between variants detected in this study and the antidepressant response to SSRI/SNRI in 201 Japanese depressive patients. Seventeen novel mutations were identified by sequencing analysis. We found that the polymorphism G2563T (rs3813034) as a tag single-nucleotide polymorphism of IVS9 A-90G (rs140701), G2356T (rs1042173), and A3641C (rs7224199) is associated with interindividual variability of SSRI/SNRI efficacy at week 6, independent from clinical variables and effect of 5-HTT LPR (P depressive patients in combination with 5-HTT LPR.

  13. Feasibility study of the detection of chlorpyrifos residuals on apple skin based on infrared micro-imaging

    Science.gov (United States)

    Li, Xiaoting; Zhu, Dazhou; Ma, Zhihong; Pan, Ligang; Wang, Dong; Wang, Jihua

    2012-10-01

    Infrared (IR) micro-imaging technology, also named chemical imaging, has potential applications in analytical technology. The IR micro-image provides not only the full spectrum information but also the component and structural information for each pixel point. Therefore, various groups of pesticides appear corresponding to the absorption peaks in the specific area of IR spectrum. In this study, the feasibility of using IR micro-imaging to detect chlopyrifos residuals on the surface of apple skin was explored. Different concentrations of chlorpyrifos solutions including 10,000, 1000, and 100 mg/L were sprayed on apple skin. Then IR micro-images were collected with a wavelength range of 4000 to 750 cm-1. The IR micro-image of chlorpyrifos pure powders was also collected for the contrasted analysis of characteristic absorption peaks. The results showed that there were seven, five, and four characteristic absorption peaks attributed to chlorpyrifos in the IR spectra of apple skin that was sprayed 10,000, 1000, and 100 mg/L chlorpyrifos solutions, respectively. With the decrease of chlorpyrifos solution concentration, the number of characteristic absorption peaks decreased. When the chlorpyrifos solution concentration was as low as 100 mg/L, the peak intensity could be still recognized. The second derivative spectra further validated the above conclusions. The detection limit of quantitative analysis was approximately 0.98 mg/L. The present study indicated that rapid detection of chlorpyrifos on the surface of an apple by IR micro-imaging technology was feasible. It provided useful foundation for the detection of fruits' and vegetables' pesticide residues by IR micro-imaging technology.

  14. alpha 1-Adrenoceptors modulate citalopram-induced serotonin release

    NARCIS (Netherlands)

    Rea, Kieran; Folgering, Joost; Westerink, Ben H. C.; Cremers, Thomas I. F. H.

    Previous studies suggest that noradrenaline may regulate serotonergic (5-HT) neurotransmission at the serotonin cell body and noradrenaline nerve terminal. Using microdialysis coupled to HPLC, we investigated the effects of alpha 1-adrenoceptor manipulation on extracellular serotonin levels in the

  15. Temperament, character and serotonin activity in the human brain

    DEFF Research Database (Denmark)

    Tuominen, L; Salo, J; Hirvonen, J

    2013-01-01

    The psychobiological model of personality by Cloninger and colleagues originally hypothesized that interindividual variability in the temperament dimension 'harm avoidance' (HA) is explained by differences in the activity of the brain serotonin system. We assessed brain serotonin transporter (5-HTT...

  16. TSPAN5, ERICH3 and selective serotonin reuptake inhibitors in major depressive disorder: pharmacometabolomics-informed pharmacogenomics.

    Science.gov (United States)

    Gupta, M; Neavin, D; Liu, D; Biernacka, J; Hall-Flavin, D; Bobo, W V; Frye, M A; Skime, M; Jenkins, G D; Batzler, A; Kalari, K; Matson, W; Bhasin, S S; Zhu, H; Mushiroda, T; Nakamura, Y; Kubo, M; Wang, L; Kaddurah-Daouk, R; Weinshilboum, R M

    2016-12-01

    Millions of patients suffer from major depressive disorder (MDD), but many do not respond to selective serotonin reuptake inhibitor (SSRI) therapy. We used a pharmacometabolomics-informed pharmacogenomics research strategy to identify genes associated with metabolites that were related to SSRI response. Specifically, 306 MDD patients were treated with citalopram or escitalopram and blood was drawn at baseline, 4 and 8 weeks for blood drug levels, genome-wide single nucleotide polymorphism (SNP) genotyping and metabolomic analyses. SSRI treatment decreased plasma serotonin concentrations (Pserotonin concentration changes were associated with clinical outcomes (Pserotonin concentration changes were used as phenotypes for genome-wide association studies (GWAS). GWAS for baseline plasma serotonin concentrations revealed a genome-wide significant (P=7.84E-09) SNP cluster on chromosome four 5' of TSPAN5 and a cluster across ERICH3 on chromosome one (P=9.28E-08) that were also observed during GWAS for change in serotonin at 4 (P=5.6E-08 and P=7.54E-07, respectively) and 8 weeks (P=1.25E-06 and P=3.99E-07, respectively). The SNPs on chromosome four were expression quantitative trait loci for TSPAN5. Knockdown (KD) and overexpression (OE) of TSPAN5 in a neuroblastoma cell line significantly altered the expression of serotonin pathway genes (TPH1, TPH2, DDC and MAOA). Chromosome one SNPs included two ERICH3 nonsynonymous SNPs that resulted in accelerated proteasome-mediated degradation. In addition, ERICH3 and TSPAN5 KD and OE altered media serotonin concentrations. Application of a pharmacometabolomics-informed pharmacogenomic research strategy, followed by functional validation, indicated that TSPAN5 and ERICH3 are associated with plasma serotonin concentrations and may have a role in SSRI treatment outcomes.

  17. The serotonin transporter in psychiatric disorders

    DEFF Research Database (Denmark)

    Spies, Marie; Knudsen, Karen Birgitte Moos; Lanzenberger, Rupert

    2015-01-01

    of various psychiatric disorders and their treatment. We review studies that use PET to measure cerebral serotonin transporter activity in psychiatric disorders, focusing on major depressive disorder and antidepressant treatment. We also discuss opportunities and limitations in the application...... of this neuroimaging method in clinical practice. Although results from individual studies diverge, meta-analysis indicates a trend towards reduced serotonin transporter availability in patients with major depressive disorder. Inconsistencies in results might suggest symptom heterogeneity in major depressive disorder...... and might therefore be relevant for stratification of patients into clinical subsets. PET has enabled the elucidation of mechanisms of response to selective serotonin reuptake inhibitors (SSRIs) and hence provides a basis for rational pharmacological treatment of major depressive disorder. Such imaging...

  18. Mouse phenotyping.

    Science.gov (United States)

    Fuchs, Helmut; Gailus-Durner, Valérie; Adler, Thure; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Calzada-Wack, Julia; Da Silva-Buttkus, Patricia; Neff, Frauke; Götz, Alexander; Hans, Wolfgang; Hölter, Sabine M; Horsch, Marion; Kastenmüller, Gabi; Kemter, Elisabeth; Lengger, Christoph; Maier, Holger; Matloka, Mikolaj; Möller, Gabriele; Naton, Beatrix; Prehn, Cornelia; Puk, Oliver; Rácz, Ildikó; Rathkolb, Birgit; Römisch-Margl, Werner; Rozman, Jan; Wang-Sattler, Rui; Schrewe, Anja; Stöger, Claudia; Tost, Monica; Adamski, Jerzy; Aigner, Bernhard; Beckers, Johannes; Behrendt, Heidrun; Busch, Dirk H; Esposito, Irene; Graw, Jochen; Illig, Thomas; Ivandic, Boris; Klingenspor, Martin; Klopstock, Thomas; Kremmer, Elisabeth; Mempel, Martin; Neschen, Susanne; Ollert, Markus; Schulz, Holger; Suhre, Karsten; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Hrabě de Angelis, Martin

    2011-02-01

    Model organisms like the mouse are important tools to learn more about gene function in man. Within the last 20 years many mutant mouse lines have been generated by different methods such as ENU mutagenesis, constitutive and conditional knock-out approaches, knock-down, introduction of human genes, and knock-in techniques, thus creating models which mimic human conditions. Due to pleiotropic effects, one gene may have different functions in different organ systems or time points during development. Therefore mutant mouse lines have to be phenotyped comprehensively in a highly standardized manner to enable the detection of phenotypes which might otherwise remain hidden. The German Mouse Clinic (GMC) has been established at the Helmholtz Zentrum München as a phenotyping platform with open access to the scientific community (www.mousclinic.de; [1]). The GMC is a member of the EUMODIC consortium which created the European standard workflow EMPReSSslim for the systemic phenotyping of mouse models (http://www.eumodic.org/[2]). Copyright © 2010 Elsevier Inc. All rights reserved.

  19. The serotonin transporter plays an important role in male sexual behavior: a study in serotonin transporter knockout rats

    NARCIS (Netherlands)

    Chan, J.Y.; Snoeren, E.; Cuppen, E.; Waldinger, M.; Olivier, B.; Oosting, R.

    2011-01-01

    INTRODUCTION: Serotonin (5-HT) is an important neurotransmitter for sexual behaviors. Heterozygous (+/-) serotonin transporter (SERT) rats and SERT knockout rats (-/-) have serotonergic disturbances with significant elevations of basal extracellular 5-HT levels. AIM: To investigate the putative role

  20. Review article: intestinal serotonin signalling in irritable bowel syndrome.

    Science.gov (United States)

    Mawe, G M; Coates, M D; Moses, P L

    2006-04-15

    Alterations in motility, secretion and visceral sensation are hallmarks of irritable bowel syndrome. As all of these aspects of gastrointestinal function involve serotonin signalling between enterochromaffin cells and sensory nerve fibres in the mucosal layer of the gut, potential alterations in mucosal serotonin signalling have been explored as a possible mechanism of altered function and sensation in irritable bowel syndrome. Literature related to intestinal serotonin signalling in normal and pathophysiological conditions has been searched and summarized. Elements of serotonin signalling that are altered in irritable bowel syndrome include: enterochromaffin cell numbers, serotonin content, tryptophan hydroxylase message levels, 5-hydroxyindoleacedic acid levels, serum serotonin levels and expression of the serotonin-selective reuptake transporter. Both genetic and epigenetic factors could contribute to decreased serotonin-selective reuptake transporter in irritable bowel syndrome. A serotonin-selective reuptake transporter gene promoter polymorphism may cause a genetic predisposition, and inflammatory mediators can induce serotonin-selective reuptake transporter downregulation. While a psychiatric co-morbidity exists with IBS, changes in mucosal serotonin handling support the concept that there is a gastrointestinal component to the aetiology of irritable bowel syndrome. Additional studies will be required to gain a more complete understanding of changes in serotonin signalling that are occurring, their cause and effect relationship, and which of these changes have pathophysiological consequences.

  1. [Serotonin and its receptors in the cardiovascular system].

    Science.gov (United States)

    Nadeev, A D; Zharkikh, I L; Avdonin, P V; Goncharov, N V

    2014-01-01

    Serotonin in cardiovascular system plays an important role in blood coagulation, allergy, and inflammation, as well as in blood vessel tone regulation. In this review, the mechanisms of serotonin effects upon the cells of blood vessels are considered and the list of main agonists and antagonists is presented. The signaling pathways activated by serotonin and their interaction in normal and pathological states are described.

  2. Serotonin-Labeled CdSe Nanocrystals: Applications for Neuroscience

    Science.gov (United States)

    Kippeny, Tadd; Adkins, Erika; Adams, Scott; Thomlinson, Ian; Schroeter, Sally; Defelice, Louis; Blakely, Randy; Rosenthal, Sandra

    2000-03-01

    Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter which has been linked to the regulation of critical behaviors including sleep, appetite, and mood. The serotonin transporter (SERT) is a 12-transmembrane domain protein responsible for clearance of serotonin from extracellular spaces following release. In order to assess the potential for use of ligand-conjugated nanocrystals to target cell surface receptors, ion channels, and transporters we have measured the ability of serotonin-labeled CdSe nanocrystals (SNACs) to block the uptake of tritiated serotonin by the human and Drosophila serotonin transporters (hSERT and dSERT). Estimated Ki values, the SNAC concentration at which half of the serotonin transport activity is blocked, were determined by nonlinear regression to be Ki (hSERT ) = 74uM and Ki (dSERT ) = 29uM. These values and our inability to detect free serotonin indicate that SNACs selectively interact with the serotonin recognition site of the transporter. We have also exposed the SNACs to cells containing ionotropic serotonin receptors and have measured the electrical response of the cell using a two microelectrode voltage clamp. We find that serotonin receptors do respond to the SNACs and we measure currents similar to the free serotonin response. These results indicate that ligand-conjugated nanocrystals can be used to label both receptor and transporter proteins. Initial fluorescence labeling experiments will be discussed.

  3. Role of serotonin in seasonal affective disorder.

    Science.gov (United States)

    Gupta, A; Sharma, P K; Garg, V K; Singh, A K; Mondal, S C

    2013-01-01

    This review was prepared with an aim to show role of serotonin in seasonal affective disorder. Seasonal affective disorder, which is also called as winter depression or winter blues, is mood disorder in which persons with normal mental health throughout most of the year will show depressive symptoms in the winter or, less commonly, in the summer. Serotonin is an important endogenous neurotransmitter which also acts as neuromodulator. The least invasive, natural, and researched treatment of seasonal affective disorder is natural or otherwise is light therapy. Negative air ionization, which acts by liberating charged particles on the sleep environment, has also become effective in treatment of seasonal affective disorder.  

  4. Removal of Chlorpyrifos by Water Hyacinth (Eichhornia crassipes) and the Role of a Plant-Associated Bacterium.

    Science.gov (United States)

    Anudechakul, Choochai; Vangnai, Alisa S; Ariyakanon, Naiyanan

    2015-01-01

    The objective of this research was to study the efficiency of water hyacinth (Eichhornia crassipes) and the role of any plant-associated bacteria in removing chlorpyrifos from water. The relative growth rate (RGR) of E. crassipes in the presence of 0.1 mg/L chlorpyrifos was not significantly different from that in its absence and only slightly decreased at concentrations of 0.5 and 1.0 mg/L by ∼1.1- and ∼1.2-fold, respectively, with an observed dry weight based RGRDW for E. crassipes of 0.036-0.041 mg/g/d. The removal rate constants of chlorpyrifos in the absence of plants were low at 3.52, 2.29 and 1.84 h(-1) for concentrations of 0.1, 0.5 and 1.0 mg/L, respectively, but were some 3.89- to 4.87-fold higher in the presence of E. crassipes. Chlorpyrifos removal was markedly facilitated by the presence of a root-associated bacterium, preliminarily identified as Acinetobacter sp. strain WHA. The interaction of E. crassipes and Acinetobacter sp. strain WHA provide an efficient and ecological alternative to accelerate the removal and degradation of chlorpyrifos pollution from aquatic systems including wastewater.

  5. Prenatal Dexamethasone Augments the Sex-Selective Developmental Neurotoxicity of Chlorpyrifos: Implications for Vulnerability after Pharmacotherapy for Preterm Labor

    Science.gov (United States)

    Slotkin, Theodore A.; Card, Jennifer; Infante, Alice; Seidler, Frederic J.

    2013-01-01

    Glucocorticoids are routinely given in preterm labor and are also elevated by maternal stress; organophosphate exposures are virtually ubiquitous, so coexposures to these two agents are pervasive. We administered dexamethasone to pregnant rats on gestational days 17–19 at a standard therapeutic dose (0.2 mg/kg); offspring were then given chlorpyrifos on postnatal days 1–4, at a dose (1 mg/kg) that produces barely-detectable (dexamethasone and chlorpyrifos given individually. Dexamethasone did not enhance the systemic toxicity of chlorpyrifos, as evidenced by weight gain and measurements of cholinesterase inhibition during chlorpyrifos treatment. Nevertheless, it enhanced the loss of presynaptic ACh function selectively in females, who ordinarily show sparing of organophosphate developmental neurotoxicity relative to males. Females receiving the combined treatment showed decrements in choline transporter binding and choline acetyltransferase activity that were unique (not found with either treatment alone), as well as additive decrements in nicotinic receptor binding. On the other hand, males given dexamethasone showed no augmentation of the effects of chlorpyrifos. Our findings indicate that prior dexamethasone exposure could create a subpopulation that is especially vulnerable to the adverse effects of organophosphates or other developmental neurotoxicants. PMID:23416428

  6. Use of Fe-Impregnated Biochar To Efficiently Sorb Chlorpyrifos, Reduce Uptake by Allium fistulosum L., and Enhance Microbial Community Diversity.

    Science.gov (United States)

    Tang, Xiao-Yan; Huang, Wen-Da; Guo, Jing-Jing; Yang, Yang; Tao, Ran; Feng, Xu

    2017-07-05

    Fe-impregnated biochar was assessed as a method to remove the pesticide pollutant chlorpyrifos, utilizing biochar/FeOx composite synthesized via chemical coprecipitation of Fe(3+)/Fe(2+) onto Cyperus alternifolius biochar. Fe-impregnated biochar exhibited a higher sorption capacity than pristine biochar, resulting in more efficient removal of chlorpyrifos from water. Soil was dosed with pristine or Fe-impregnated biochar at 0.1 or 1.0% w/w, to evaluate chlorpyrifos uptake in Allium fistulosum L. (Welsh onion). The results showed that the average concentration of chlorpyrifos and its degradation product, 3,5,6-trichloro-2-pyridinol (TCP), decreased in A. fistulosum L. with increased levels of pristine biochar and Fe-biochar. Fe-biochar was found to be more effective in reducing the uptake of chlorpyrifos by improving the sorption ability and increasing plant root iron plaque. Bioavailability of chlorpyrifos is reduced with both biochar and Fe-biochar soil dosing; however, the greatest persistence of chlorpyrifos residues was observed with 1.0% pristine biochar. Microbial community analysis showed Fe-biochar to have a positive impact on the efficiency of chlorpyrifos degradation in soils, possibly by altering microbial communities.

  7. Indigenous children nearby plantations with chlorpyrifos-treated bags have elevated 3,5,6-trichloro-2-pyridinol (TCPy) urinary concentrations

    NARCIS (Netherlands)

    Wendel de Joode, van B.; Barraza-Ruiz, D.A.; Ruepert, C.; Mora, A.M.; Córdoba, L.; Öberg, M.; Wesseling, C.; Mergler, D.; Lindh, C.

    2012-01-01

    BACKGROUND: The US Environmental Protection Agency voluntary phased-out residential use of chlorpyrifos in 2001. In contrast, in Costa Rica, chlorpyrifos-treated bags are increasingly used to protect banana and plantain fruits from insects and to fulfill product standards, even in populated areas.

  8. Effects of the insecticide Dursban 4E (active ingredient chlorpyrifos) in outdoor experimental ditches: I. comparison of short-term toxicity between the laboratory and the field

    NARCIS (Netherlands)

    Wijngaarden, van R.P.A.; Brink, van den P.J.; Crum, S.J.H.; Oude Voshaar, J.H.; Brock, T.C.M.; Leeuwangh, P.

    1996-01-01

    By means of the insecticide chlorpyrifos, results of acute single-species toxicity tests were compared with direct effects in outdoor mesocosms. In the mesocosms, chlorpyrifos concentrations between 0.1 and 44 Šg/l were sprayed once. Acute effects were observed on arthropods. Effects could be

  9. Measuring the serotonin uptake site using (/sup 3/H)paroxetine--a new serotonin uptake inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Gleiter, C.H.; Nutt, D.J.

    1988-01-01

    Serotonin is an important neurotransmitter that may be involved in ethanol preference and dependence. It is possible to label the serotonin uptake site in brain using the tricyclic antidepressant imipramine, but this also binds to other sites. We have used the new high-affinity uptake blocker paroxetine to define binding to this site and report it to have advantages over imipramine as a ligand.

  10. Perspectives on genetic animal models of serotonin toxicity.

    Science.gov (United States)

    Kalueff, Allan V; LaPorte, Justin L; Murphy, Dennis L

    2008-01-01

    Serotonin syndrome, or serotonin toxicity, is a serious disorder attributable to exaggerated serotonergic function in the brain, most commonly after antidepressant overdose or after combining several psychotropic medications. Similar condition (serotonin syndrome-like behavior) can be evoked in animals experimentally, following administration of serotonergic drugs. In addition to pharmacological stimulation, some genetic and other factors may contribute to serotonin toxicity, prompting the need for new experimental genetic models relevant to this disorder. Here we discuss current problems and perspectives regarding genetic animal models of serotonin-related syndromes, and outline the potential utility of these models in experimental neurochemistry and clinical research.

  11. Clinical chemistry of serotonin and metabolites

    NARCIS (Netherlands)

    Kema, IP; de Vries, EGE; Muskiet, FAJ

    2000-01-01

    Analyses of serotonin and other 5-hydroxyindoles, such as its precursor 5-hydroxytryptophan and major metabolite 5-hydroxyindoleacetic acid (5-HIAA), are indispensable for the elucidation of their (patho)physiological roles. In clinical chemistry attention is mainly focused on the diagnosis and

  12. Central serotonin metabolism and frequency of depression

    NARCIS (Netherlands)

    Praag, H.M. van; Haan, S. de

    1979-01-01

    Central serotonin (5-hydroxytryptamine; 5-HT) metabolism can be disturbed in a subgroup of patients with vital (endogenous, primary) depression. Presumably these disturbances do not result from the depression and have a predisposing rather than a causative relationship to it. This latter statement

  13. Genetic polymorphism of serotonin transporter 5-HTTLPR ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 90; Issue 1. Genetic polymorphism of serotonin transporter 5-HTTLPR: involvement in smoking behaviour. Maria Angelica Ehara Watanabe Sandra Odebrechet Vargas Nunes Marla Karine Amarante Roberta Losi Guembarovski Julie Massayo Maeda Oda Kalil William Alves De ...

  14. Infrared Spectra of Protonated Neurotransmitters: Serotonin

    NARCIS (Netherlands)

    Lagutschenkov, A.; Langer, J.; G. Berden,; Oomens, J.; Dopfer, O.

    2010-01-01

    The gas-phase IR spectrum of the protonated neurotransmitter serotonin (5-hydroxytryptamine) was measured in the fingerprint range by means of IR multiple photon dissociation (IRMPD) spectroscopy. The IRMPD spectrum was recorded in a Fourier transform ion cyclotron resonance mass spectrometer

  15. Infrared spectra of protonated neurotransmitters: serotonin

    NARCIS (Netherlands)

    Lagutschenkov, A.; Langer, J.; Berden, G.; Oomens, J.; Dopfer, O.

    2010-01-01

    The gas-phase IR spectrum of the protonated neurotransmitter serotonin (5-hydroxytryptamine) was measured in the fingerprint range by means of IR multiple photon dissociation (IRMPD) spectroscopy. The IRMPD spectrum was recorded in a Fourier transform ion cyclotron resonance mass spectrometer

  16. Serotonin syndrome caused by olanzapine and clomipramine.

    Science.gov (United States)

    Verre, M; Bossio, F; Mammone, A; Piccirillo, M; Tancioni, F; Tortorella, V; Varano, M

    2008-01-01

    We describe a case of severe serotonin syndrome. The patient was simultaneously taking the atypical antidepressant olanzapine and a tricyclical antidepressant, clomipramine. Symptoms included altered mental state resulting in coma, myoclonus, hyperreflexia, diaphoresis, diarrhoea, disorientation and fever. After suspension of antidepressant drugs, intensive symptomatic treatment and administration of biperiden and cyproheptadine, the patient's condition improved.

  17. Modulation of defensive reflex conditioning in snails by serotonin

    Science.gov (United States)

    Andrianov, Vyatcheslav V.; Bogodvid, Tatiana K.; Deryabina, Irina B.; Golovchenko, Aleksandra N.; Muranova, Lyudmila N.; Tagirova, Roza R.; Vinarskaya, Aliya K.; Gainutdinov, Khalil L.

    2015-01-01

    Highlights Daily injection of serotonin before a training session accelerated defensive reflex conditioning in snails.Daily injection of 5-hydroxytryptophan before a training session in snails with a deficiency of serotonin induced by the “neurotoxic” analog of serotonin 5,7-dihydroxytryptamine, restored the ability of snails to learn.After injection of the “neurotoxic” analogs of serotonin 5,6- and 5,7-dihydroxytryptamine as well as serotonin, depolarization of the membrane and decrease of the threshold potential of premotor interneurons was observed. We studied the role of serotonin in the mechanisms of learning in terrestrial snails. To produce a serotonin deficit, the “neurotoxic” analogs of serotonin, 5,6- or 5,7-dihydroxytryptamine (5,6/5,7-DHT) were used. Injection of 5,6/5,7-DHT was found to disrupt defensive reflex conditioning. Within 2 weeks of neurotoxin application, the ability to learn had recovered. Daily injection of serotonin before a training session accelerated defensive reflex conditioning and daily injections of 5-HTP in snails with a deficiency of serotonin induced by 5,7-DHT restored the snail's ability to learn. We discovered that injections of the neurotoxins 5,6/5,7-DHT as well as serotonin, caused a decrease in the resting and threshold potentials of the premotor interneurons LPa3 and RPa3. PMID:26557063

  18. Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review.

    Science.gov (United States)

    Beakley, Burton D; Kaye, Adam M; Kaye, Alan D

    2015-01-01

    Serotonin syndrome is a mild to potentially life-threatening syndrome associated with excessive serotonergic activity within the central nervous system. Serotonin syndrome is associated with medication use, drug interactions, and overdose. While serotonin syndrome is often associated with the use of selective serotonin inhibitors (SSRI), an increasing number of reports are being presented involving the use of tramadol. This review article contains an overview of serotonin syndrome while specifically looking at tramadol's pharmacology and risk factors for serotonin syndrome. With tramadol's increasing popularity, the goal of this article is to make physicians more alert and aware of this potential side effect associated with tramadol. In conclusion, with the increasing incidence of serotonin syndrome, prescribing physicians should be aware of and educate their patients on the potential side effects of tramadol. It is important that the prescribing physician reviews patient medications for concurrent serotonergic drugs and monitors for potential abuse.

  19. Perturbation of Serotonin Homeostasis during Adulthood Affects Serotonergic Neuronal Circuitry.

    Science.gov (United States)

    Pratelli, Marta; Migliarini, Sara; Pelosi, Barbara; Napolitano, Francesco; Usiello, Alessandro; Pasqualetti, Massimo

    2017-01-01

    Growing evidence shows that the neurotransmitter serotonin (5-HT) modulates the fine-tuning of neuron development and the establishment of wiring patterns in the brain. However, whether serotonin is involved in the maintenance of neuronal circuitry in the adult brain remains elusive. Here, we use a Tph2(fl)°(x) conditional knockout (cKO) mouse line to assess the impact of serotonin depletion during adulthood on serotonergic system organization. Data show that the density of serotonergic fibers is increased in the hippocampus and decreased in the thalamic paraventricular nucleus (PVN) as a consequence of brain serotonin depletion. Strikingly, these defects are rescued following reestablishment of brain 5-HT signaling via administration of the serotonin precursor 5-hydroxytryptophan (5-HTP). Finally, 3D reconstruction of serotonergic fibers reveals that changes in serotonin homeostasis affect axonal branching complexity. These data demonstrate that maintaining proper serotonin homeostasis in the adult brain is crucial to preserve the correct serotonergic axonal wiring.

  20. Characterization of soil organic matter by FT-IR spectroscopy and its relationship with chlorpyrifos sorption.

    Science.gov (United States)

    Parolo, María Eugenia; Savini, Mónica Claudia; Loewy, Ruth Miriam

    2017-07-01

    Sorption of non-ionic organic compounds to soil is usually expressed as the carbon-normalized partition coefficient (KOC) assuming that the main factor that influences the amount sorbed is the organic carbon content (OC) of the soil. However, KOC can vary across a range of soils. The influence of certain soil characteristics on the chlorpyrifos KOC values variation for 12 representative soils of the Northpatagonian Argentinian region with different physicochemical properties was investigated for this study. The chlorpyrifos sorption coefficients normalized by the OC content were experimentally obtained using the batch equilibrium method; the KOC values ranged between 9000-20,000 L kg-1. The soil characteristics assessed were pH, clay content and spectral data indicative of soil organic matter (SOM) quality measured by FT-IR on the whole soil. The bands considered in the spectroscopic analyses were those corresponding to the aliphatic components, 2947-2858 cm-1 (band A) and the hydrophilic components, 1647-1633 cm-1 (band B). A significant relationship was found (R2 = 0.66) between chlorpyrifos sorption (KOC) and the variables pH and A/B height band ratio. The correlation between the values predicted by the derived model and the experimental data was significant (r = 0.89 p soil properties represents a valuable contribution to the understanding of the attenuation phenomena of the organic contaminants off-site migration in the environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Degradation of pesticides chlorpyrifos, cypermethrin and chlorothalonil in aqueous solution by TiO2 photocatalysis.

    Science.gov (United States)

    Affam, Augustine Chioma; Chaudhuri, Malay

    2013-11-30

    Degradation of pesticides chlorpyrifos, cypermethrin and chlorothalonil in aqueous solution by TiO2 photocatalysis under UVA (365 nm) irradiation was examined. Enhancement of degradation and improvement in biodegradability index (BOD5/COD ratio) by H2O2 addition were also evaluated. UVA irradiation per se produced insignificant degradation of the pesticides. In UV/TiO2 photocatalysis (TiO2 1.5 g L(-1), pH 6 and 300 min irradiation), COD and TOC removal were 25.95 and 8.45%, respectively. In UV/TiO2/H2O2 photocatalysis (TiO2 1.5 g L(-1), H2O2 100 mg L(-1), pH 6 and 300 min irradiation), COD and TOC removal were 53.62 and 21.54%, respectively and biodegradability index improved to 0.26. Ammonia-nitrogen (NH3-N) decreased from 22 to 7.8 mg L(-1) and nitrate-nitrogen (NO3(-)-N) increased from 0.7 to 13.8 mg L(-1) in 300 min, indicating mineralization. Photocatalytic degradation followed pseudo-first order kinetics with rate constant (k) of 0.0025 and 0.0008 min(-1) for COD and TOC removal, respectively. FTIR spectra indicated degradation of the organic bonds of the pesticides. UV/TiO2/H2O2 photocatalysis is effective in degradation of pesticides chlorpyrifos, cypermethrin and chlorothalonil in aqueous solution. UV/TiO2/H2O2 photocatalysis may be applied as pretreatment of a chlorpyrifos, cypermethrin and chlorothalonil pesticide wastewater at pH 6, for biological treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Effect of In Vivo Nicotine Exposure on Chlorpyrifos Pharmacokinetics and Pharmacodynamics in Rats

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sookwang; Poet, Torka S.; Smith, Jordan N.; Busby-Hjerpe, Andrea L.; Timchalk, Charles

    2010-03-30

    Routine use of tobacco products may modify physiological and metabolic functions, including drug metabolizing enzymes, which may impact the pharmacokinetics of environmental contaminants. Chlorpyrifos is an organophosphorus (OP) insecticide that is bioactivated to chlorpyrifos-oxon, and manifests its neurotoxicity by inhibiting acetylcholinesterase (AChE). The objective of this study was to evaluate the impact of repeated nicotine exposure on the pharmacokinetics of chlorpyrifos (CPF) and its major metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urine and also to determine the impact on cholinesterase (ChE) activity in plasma and brain. Animals were exposed to 7-daily doses of either 1 mg nicotine/kg or saline (sc), and to either a single oral dose of 35 mg CPF/kg or a repeated dose of 5 mg CPF/kg/day for 7 days. Groups of rats were then sacrificed at multiple time-points after receiving the last dose of CPF. Repeated nicotine and CPF exposures resulted in enhanced metabolism of CPF to TCPy, as evidenced by increases in the measured TCPy concentration and AUC in blood. However, there was no significant difference in the amount of TCPy (free or total) excreted in the urine. The extent of brain acetylcholinesterase (AChE) inhibition was reduced due to nicotine co-exposure consistent with an increase in CYP450-mediated dearylation (detoxification) versus desulfuration. It was of interest to note that the impact of nicotine co-exposure was experimentally observed only after repeated CPF doses. Physiologically based pharmacokinetic model simulations of CPF-oxon concentrations in blood and brain were predicted to be lower in nicotine treated groups, which were simulated by increasing the dearylation Vmax based upon previously conducted in vitro metabolism studies. These results were consistent with the experimental data. The current study demonstrated that repeated nicotine exposure could alter CPF metabolism in vivo, further modulating brain AChE inhibition.

  3. Recovery of cholinesterase activity in the earthworm Eisenia fetida Savigny following exposure to chlorpyrifos.

    Science.gov (United States)

    Aamodt, Solveig; Konestabo, Heidi Sjursen; Sverdrup, Line Emilie; Gudbrandsen, Marius; Reinecke, Sophiè A; Reinecke, Adriaan J; Stenersen, Jørgen

    2007-09-01

    Organophosphorus (OP) insecticides inhibit cholinesterase activity, an essential process in the nervous system of most animals. Re-establishment of active enzymes is slow and depends on elimination of the insecticide from the body followed by two lengthy processes: Reactivation and/or biosynthesis of new enzymes. Earthworms (Eisenia fetida) were exposed to either clean or chlorpyrifos-containing (240 mg/kg) soil for 48 h. After transfer to clean soil, we monitored two cholinesterases (E1 and E2) and chlorpyrifos content of the earthworms for 12 weeks. After 14 to 21 d of recovery, the exposed and control worms were indistinguishable in terms of appearance and behavior. Chemical analysis showed a rapid elimination of chlorpyrifos from the earthworms, with only minor levels detected after one week. The activities of E1 and E2 were measured spectrophotometrically in whole specimen homogenates using acetylthiocholine as the substrate. Carbaryl, which selectively inhibits E1, was used to discriminate the enzyme activities. Mean +/- standard error of mean of E1 and E2 activity in the controls immediately after exposure were 1.57 +/- 0.18 nanokatal (nkat)/mg protein (n = 3) and 0.95 +/- 0.07 nkat/mg protein, respectively, and 0.48 +/- 0.07 nkat/mg and 0.45 +/- 0.06 nkat/mg, respectively, in exposed worms. After three weeks, E1 had regained an activity comparable to the controls, whereas E2 remained depressed throughout the 12-week monitoring period. The non- or late recovery of E2 makes this enzyme a potential biomarker candidate for previous OP insecticide exposure in Eisenia fetida, provided the protocol for measurements is improved and standardized.

  4. Association of distinct α2 adrenoceptor and serotonin transporter polymorphisms with constipation and somatic symptoms in functional gastrointestinal disorders

    OpenAIRE

    Kim, H J; Camilleri, M; Carlson, P J; Cremonini, F; Ferber, I; Stephens, D; McKinzie, S; Zinsmeister, A R; Urrutia, R

    2004-01-01

    Background: The role of genetics in the phenotypic manifestations of irritable bowel syndrome (IBS) is unclear. Our aims were: (1) to compare the prevalence of polymorphisms of alpha 2 (α2) adrenoceptors, norepinephrine transporter, and serotonin transporter protein (soluble carrier protein member 4 (SLC6A4)) promoter in patients with lower functional gastrointestinal disorders (FGID) and in healthy controls; and (2) to test associations of these genetic variations with symptoms of IBS and hi...

  5. Comparative effects of chlorpyrifos in wild type and cannabinoid Cb1 receptor knockout mice

    Energy Technology Data Exchange (ETDEWEB)

    Baireddy, Praveena; Liu, Jing; Hinsdale, Myron; Pope, Carey, E-mail: carey.pope@okstate.edu

    2011-11-15

    Endocannabinoids (eCBs) modulate neurotransmission by inhibiting the release of a variety of neurotransmitters. The cannabinoid receptor agonist WIN 55.212-2 (WIN) can modulate organophosphorus (OP) anticholinesterase toxicity in rats, presumably by inhibiting acetylcholine (ACh) release. Some OP anticholinesterases also inhibit eCB-degrading enzymes. We studied the effects of the OP insecticide chlorpyrifos (CPF) on cholinergic signs of toxicity, cholinesterase activity and ACh release in tissues from wild type (+/+) and cannabinoid CB1 receptor knockout (-/-) mice. Mice of both genotypes (n = 5-6/treatment group) were challenged with CPF (300 mg/kg, 2 ml/kg in peanut oil, sc) and evaluated for functional and neurochemical changes. Both genotypes exhibited similar cholinergic signs and cholinesterase inhibition (82-95% at 48 h after dosing) in cortex, cerebellum and heart. WIN reduced depolarization-induced ACh release in vitro in hippocampal slices from wild type mice, but had no effect in hippocampal slices from knockouts or in striatal slices from either genotype. Chlorpyrifos oxon (CPO, 100 {mu}M) reduced release in hippocampal slices from both genotypes in vitro, but with a greater reduction in tissues from wild types (21% vs 12%). CPO had no significant in vitro effect on ACh release in striatum. CPF reduced ACh release in hippocampus from both genotypes ex vivo, but reduction was again significantly greater in tissues from wild types (52% vs 36%). In striatum, CPF led to a similar reduction (20-23%) in tissues from both genotypes. Thus, while CB1 deletion in mice had little influence on the expression of acute toxicity following CPF, CPF- or CPO-induced changes in ACh release appeared sensitive to modulation by CB1-mediated eCB signaling in a brain-regional manner. -- Highlights: Black-Right-Pointing-Pointer C57Bl/6 mice showed dose-related cholinergic toxicity following subcutaneous chlorpyrifos exposure. Black-Right-Pointing-Pointer Wild type and

  6. A novel role for antizyme inhibitor 2 as a regulator of serotonin and histamine biosynthesis and content in mouse mast cells.

    Science.gov (United States)

    Acosta-Andrade, Carlos; Lambertos, Ana; Urdiales, José L; Sánchez-Jiménez, Francisca; Peñafiel, Rafael; Fajardo, Ignacio

    2016-10-01

    Antizymes and antizyme inhibitors are key regulatory proteins of polyamine levels by affecting ornithine decarboxylase and polyamine uptake. Our previous studies indicated a metabolic interplay among polyamines, histamine and serotonin in mast cells, and demonstrated that polyamines are present in mast cell secretory granules, being important for histamine storage and serotonin levels. Recently, the novel antizyme inhibitor-2 (AZIN2) was proposed as a local regulator of polyamine biosynthesis in association with mast cell serotonin-containing granules. To gain insight into the role of AZIN2 in the biosynthesis and storage of serotonin and histamine, we have generated bone marrow derived mast cells (BMMCs) from both wild-type and transgenic Azin2 hypomorphic mice, and have analyzed polyamines, serotonin and histamine contents, and some elements of their metabolisms. Azin2 hypomorphic BMMCs did not show major mast cell phenotypic alterations as judged by morphology and specific mast cell proteases. However, compared to wild-type controls, these cells showed reduced spermidine and spermine levels, and diminished growth rate. Serotonin levels were also reduced, whereas histamine levels tended to increase. Accordingly, tryptophan hydroxylase-1 (TPH1; the key enzyme for serotonin biosynthesis) mRNA expression and protein levels were reduced, whereas histidine decarboxylase (the enzyme responsible for histamine biosynthesis) enzymatic activity was increased. Furthermore, microphtalmia-associated transcription factor, an element involved in the regulation of Tph1 expression, was reduced. Taken together, our results show, for the first time, an element of polyamine metabolism -AZIN2-, so far described as exclusively devoted to the control of polyamine concentrations, involved in regulating the biosynthesis and content of other amines like serotonin and histamine.

  7. Induction of VMAT-1 and TPH-1 expression induces vesicular accumulation of serotonin and protects cells and tissue from cooling/rewarming injury.

    Directory of Open Access Journals (Sweden)

    Fatemeh Talaei

    Full Text Available DDT₁ MF-2 hamster ductus deferens cells are resistant to hypothermia due to serotonin secretion from secretory vesicles and subsequent cystathionine beta synthase (CBS mediated formation of H₂S. We investigated whether the mechanism promoting resistance to hypothermia may be translationally induced in cells vulnerable to cold storage. Thus, VMAT-1 (vesicular monoamino transferase and TPH-1 (tryptophan hydroxylase were co-transfected in rat aortic smooth muscle cells (SMAC and kidney tissue to create a serotonin-vesicular phenotype (named VTSMAC and VTkidney, respectively. Effects on hypothermic damage were assessed. VTSMAC showed a vesicular phenotype and an 8-fold increase in serotonin content and 5-fold increase in its release upon cooling. Cooled VTSMAC produced up to 10 fold higher concentrations of H₂S, and were protected from hypothermia, as shown by a 50% reduction of caspase 3/7 activity and 4 times higher survival compared to SMAC. Hypothermic resistance was abolished by the inhibition of CBS activity or blockade of serotonin re-uptake. In VTkidney slices, expression of CBS was 3 fold increased in cold preserved kidney tissue, with two-fold increase in H₂S concentration. While cooling induced substantial damage to empty vector transfected kidney as shown by caspase 3/7 activity and loss of FABP1, VTkidney was fully protected and comparable to non-cooled control. Thus, transfection of VMAT-1 and TPH-1 induced vesicular storage of serotonin which is triggered release upon cooling and has protective effects against hypothermia. The vesicular serotonergic phenotype protects against hypothermic damage through re-uptake of serotonin inducing CBS mediated H₂S production both in cells and kidney slices.

  8. Induction of VMAT-1 and TPH-1 expression induces vesicular accumulation of serotonin and protects cells and tissue from cooling/rewarming injury.

    Science.gov (United States)

    Talaei, Fatemeh; Schmidt, Martina; Henning, Robert H

    2012-01-01

    DDT₁ MF-2 hamster ductus deferens cells are resistant to hypothermia due to serotonin secretion from secretory vesicles and subsequent cystathionine beta synthase (CBS) mediated formation of H₂S. We investigated whether the mechanism promoting resistance to hypothermia may be translationally induced in cells vulnerable to cold storage. Thus, VMAT-1 (vesicular monoamino transferase) and TPH-1 (tryptophan hydroxylase) were co-transfected in rat aortic smooth muscle cells (SMAC) and kidney tissue to create a serotonin-vesicular phenotype (named VTSMAC and VTkidney, respectively). Effects on hypothermic damage were assessed. VTSMAC showed a vesicular phenotype and an 8-fold increase in serotonin content and 5-fold increase in its release upon cooling. Cooled VTSMAC produced up to 10 fold higher concentrations of H₂S, and were protected from hypothermia, as shown by a 50% reduction of caspase 3/7 activity and 4 times higher survival compared to SMAC. Hypothermic resistance was abolished by the inhibition of CBS activity or blockade of serotonin re-uptake. In VTkidney slices, expression of CBS was 3 fold increased in cold preserved kidney tissue, with two-fold increase in H₂S concentration. While cooling induced substantial damage to empty vector transfected kidney as shown by caspase 3/7 activity and loss of FABP1, VTkidney was fully protected and comparable to non-cooled control. Thus, transfection of VMAT-1 and TPH-1 induced vesicular storage of serotonin which is triggered release upon cooling and has protective effects against hypothermia. The vesicular serotonergic phenotype protects against hypothermic damage through re-uptake of serotonin inducing CBS mediated H₂S production both in cells and kidney slices.

  9. Clemizole and modulators of serotonin signalling suppress seizures in Dravet syndrome.

    Science.gov (United States)

    Griffin, Aliesha; Hamling, Kyla R; Knupp, Kelly; Hong, SoonGweon; Lee, Luke P; Baraban, Scott C

    2017-03-01

    Dravet syndrome is a catastrophic childhood epilepsy with early-onset seizures, delayed language and motor development, sleep disturbances, anxiety-like behaviour, severe cognitive deficit and an increased risk of fatality. It is primarily caused by de novo mutations of the SCN1A gene encoding a neuronal voltage-activated sodium channel. Zebrafish with a mutation in the SCN1A homologue recapitulate spontaneous seizure activity and mimic the convulsive behavioural movements observed in Dravet syndrome. Here, we show that phenotypic screening of drug libraries in zebrafish scn1 mutants rapidly and successfully identifies new therapeutics. We demonstrate that clemizole binds to serotonin receptors and its antiepileptic activity can be mimicked by drugs acting on serotonin signalling pathways e.g. trazodone and lorcaserin. Coincident with these zebrafish findings, we treated five medically intractable Dravet syndrome patients with a clinically-approved serotonin receptor agonist (lorcaserin, Belviq®) and observed some promising results in terms of reductions in seizure frequency and/or severity. Our findings demonstrate a rapid path from preclinical discovery in zebrafish, through target identification, to potential clinical treatments for Dravet syndrome. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Measurements of Chlorpyrifos Levels in Forager Bees and Comparison with Levels that Disrupt Honey Bee Odor-Mediated Learning Under Laboratory Conditions.

    Science.gov (United States)

    Urlacher, Elodie; Monchanin, Coline; Rivière, Coraline; Richard, Freddie-Jeanne; Lombardi, Christie; Michelsen-Heath, Sue; Hageman, Kimberly J; Mercer, Alison R

    2016-02-01

    Chlorpyrifos is an organophosphate pesticide used around the world to protect food crops against insects and mites. Despite guidelines for chlorpyrifos usage, including precautions to protect beneficial insects, such as honeybees from spray drift, this pesticide has been detected in bees in various countries, indicating that exposure still occurs. Here, we examined chlorpyrifos levels in bees collected from 17 locations in Otago, New Zealand, and compared doses of this pesticide that cause sub-lethal effects on learning performance under laboratory conditions with amounts of chlorpyrifos detected in the bees in the field. The pesticide was detected at 17 % of the sites sampled and in 12 % of the colonies examined. Amounts detected ranged from 35 to 286 pg.bee(-1), far below the LD50 of ~100 ng.bee(-1). We detected no adverse effect of chlorpyrifos on aversive learning, but the formation and retrieval of appetitive olfactory memories was severely affected. Chlorpyrifos fed to bees in amounts several orders of magnitude lower than the LD50, and also lower than levels detected in bees, was found to slow appetitive learning and reduce the specificity of memory recall. As learning and memory play a central role in the behavioral ecology and communication of foraging bees, chlorpyrifos, even in sublethal doses, may threaten the success and survival of this important insect pollinator.

  11. Chlorpyrifos causes decreased organic matter decomposition by suppressing earthworm and termite communities in tropical soil

    Energy Technology Data Exchange (ETDEWEB)

    De Silva, P. Mangala C.S., E-mail: msilva@falw.vu.n [Department of Animal Ecology, VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Department of Zoology, Faculty of Science, University of Ruhuna, Matara (Sri Lanka); Pathiratne, Asoka [Department of Zoology, Faculty of Science, University of Kelaniya, Kelaniya (Sri Lanka); Straalen, Nico M. van; Gestel, Cornelis A.M. van [Department of Animal Ecology, VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands)

    2010-10-15

    Effects of pesticides on structural and functional properties of ecosystems are rarely studied under tropical conditions. In this study litterbag and earthworm field tests were performed simultaneously at the same tropical field site sprayed with chlorpyrifos (CPF). The recommended dose of CPF (0.6 kg a.i. ha{sup -1}) and two higher doses (4.4-8.8 kg a.i. ha{sup -1}) significantly decreased litter decomposition during the first 3 months after application, which could be explained from lower earthworm and termite abundances during this period. Species-specific effects of CPF on organism abundance and biomass were observed, with termites being mostly affected followed by the earthworm Perionyx excavatus; the earthworm Megascolex sp. was least affected. Recovery was completed within 6 months. Decomposition in the controls and lowest two treatments was completed within 4 months, which suggests the need for modification of standard test guidelines to comply with faster litter degradation under tropical conditions. - Effects of chlorpyrifos on functional and structural endpoints in soil.

  12. Serotonin Syndrome: Clinical Findings, Diagnosis, Management

    Directory of Open Access Journals (Sweden)

    Pedro Cintra

    2014-06-01

    Full Text Available The serotonin syndrome is a relatively infrequent clinical entity, but can have potentially lethal consequences. The spectrum of manifestations is highly variable, ranging from mild diarrhea to tremor and mental status changes, autonomic hyperactivity, hyperthermia and clonic contractions. Eighty-five percent of physicians are not familiar with the characteristics of the syndrome. We propose to briefly review its epidemiology, pathophysiology, clinical manifestations, diagnostic criteria and therapeutic, emphasizing practical aspects of clinical performance.

  13. Construction of a novel electrochemical sensor based on molecularly imprinted polymers for the selective determination of chlorpyrifos in real samples.

    Science.gov (United States)

    Xu, Wanzhen; Wang, Qingqing; Huang, Weihong; Yang, Wenming

    2017-12-01

    We present a novel electrochemical sensor based on an electrode modified with molecularly imprinted polymers for the detection of chlorpyrifos. The modified electrode was constructed by the synthesis of molecularly imprinted polymers by a precipitation method then coated on a glassy carbon electrode. The surface morphology of the modified electrode was characterized by using field-emission scanning electron microscopy and transmission electron microscopy. The performance of the imprinted sensor was thoroughly investigated by using cyclic voltammetry and differential pulse voltammetry. The imprinted electrochemical sensor displayed high repeatability, stability, and selectivity towards the template molecules. Under the optimal experimental conditions, the peak current response of the imprinted electrochemical sensor was linearly related to the concentration of chlorpyrifos over the range 1 × 10-10 -1 × 10-5  mol/L with a limit of detection of 4.08 × 10-9  mol/L (signal-to-noise ratio = 3). Furthermore, the proposed molecularly imprinted electrochemical sensor was applied to the determination of chlorpyrifos in the complicated matrixes of real samples with satisfactory results. Therefore, the molecularly imprinted polymers based electrochemical sensor might provide a highly selective, rapid, and cost-effective method for chlorpyrifos determination and related analysis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Dietary predictors of young children’s exposures to chlorpyrifos, permethrin, and 2,4-D using urinary biomonitoring

    Science.gov (United States)

    Few data exist on the association between dietary habits and urinary biomarker concentrations of pesticides in children. The objective was to examined the association between the weekly intake frequency of 65 food items and urinary biomarkers of exposure to chlorpyrifos (3,5,6-tr...

  15. Pharmacokinetics and effects on serum cholinesterase activities of organophosphorus pesticides acephate and chlorpyrifos in chimeric mice transplanted with human hepatocytes.

    Science.gov (United States)

    Suemizu, Hiroshi; Sota, Shigeto; Kuronuma, Miyuki; Shimizu, Makiko; Yamazaki, Hiroshi

    2014-11-01

    Organophosphorus pesticides acephate and chlorpyrifos in foods have potential to impact human health. The aim of the current study was to investigate the pharmacokinetics of acephate and chlorpyrifos orally administered at lowest-observed-adverse-effect-level doses in chimeric mice transplanted with human hepatocytes. Absorbed acephate and its metabolite methamidophos were detected in serum from wild type mice and chimeric mice orally administered 150mg/kg. Approximately 70% inhibition of cholinesterase was evident in plasma of chimeric mice with humanized liver (which have higher serum cholinesterase activities than wild type mice) 1day after oral administrations of acephate. Adjusted animal biomonitoring equivalents from chimeric mice studies were scaled to human biomonitoring equivalents using known species allometric scaling factors and in vitro metabolic clearance data with a simple physiologically based pharmacokinetic (PBPK) model. Estimated plasma concentrations of acephate and chlorpyrifos in humans were consistent with reported concentrations. Acephate cleared similarly in humans and chimeric mice but accidental/incidental overdose levels of chlorpyrifos cleared (dependent on liver metabolism) more slowly from plasma in humans than it did in mice. The data presented here illustrate how chimeric mice transplanted with human hepatocytes in combination with a simple PBPK model can assist evaluations of toxicological potential of organophosphorus pesticides. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Effects of the insecticide Dursban 4E (active ingredient chlorpyrifos) in outdoor experimental ditches: II. invertebrate community responses and recovery

    NARCIS (Netherlands)

    Brink, van den P.J.; Wijngaarden, van R.P.A.; Lucassen, W.G.H.; Brock, T.C.M.; Leeuwangh, P.

    1996-01-01

    This paper describes long-term effects of chlorpyrifos on macro-invertebrates and zooplankton after a single application. Crustaceans and insects showed a rapid, concentration-dependent decrease in numbers after application (direct effects). A significant increase in gastropods and oligochaetes was

  17. Effectiveness of personal protective equipment: Relevance of dermal and inhalation exposure to chlorpyrifos among pest control operators

    NARCIS (Netherlands)

    Jagt, K. van der; Tielemans, E.; Links, I.; Brouwer, D.; Hemmen, J. van

    2004-01-01

    This study assessed the effectiveness of a custom fit personal protective equipment (PPE) program aimed at reducing occupational exposure to pesticides. The intervention study was carried out on 15 pest control operators (PCOs) during mixing/loading and application of chlorpyrifos. Each worker was

  18. Peripheral Serotonin: a New Player in Systemic Energy Homeostasis.

    Science.gov (United States)

    Namkung, Jun; Kim, Hail; Park, Sangkyu

    2015-12-01

    Whole body energy balance is achieved through the coordinated regulation of energy intake and energy expenditure in various tissues including liver, muscle and adipose tissues. A positive energy imbalance by excessive energy intake or insufficient energy expenditure results in obesity and related metabolic diseases. Although there have been many obesity treatment trials aimed at the reduction of energy intake, these strategies have achieved only limited success because of their associated adverse effects. An ancient neurotransmitter, serotonin is among those traditional pharmacological targets for anti-obesity treatment because it exhibits strong anorectic effect in the brain. However, recent studies suggest the new functions of peripheral serotonin in energy homeostasis ranging from the endocrine regulation by gut-derived serotonin to the autocrine/paracrine regulation by adipocyte-derived serotonin. Here, we discuss the role of serotonin in the regulation of energy homeostasis and introduce peripheral serotonin as a possible target for anti-obesity treatment.

  19. Serotonin: a regulator of neuronal morphology and circuitry

    Science.gov (United States)

    Daubert, Elizabeth A.; Condron, Barry G.

    2010-01-01

    Serotonin is an important neuromodulator associated with a wide range of physiological effects in the central nervous system. The exact mechanisms for how serotonin influences brain development are not well understood, although studies in invertebrate and vertebrate model organisms are beginning to unravel a regulatory role for serotonin in neuronal morphology and circuit formation. Recent data suggests a developmental window during which altered serotonin levels permanently impact circuitry, however, the temporal constraints and molecular mechanisms responsible are still under investigation. Growing evidence suggests that alterations in early serotonin signaling contribute to a number of neurodevelopmental and neuropsychiatric disorders. Thus, understanding how altered serotonin signaling affects neuronal morphology and plasticity, and ultimately animal physiology and pathophysiology, will be of great significance. PMID:20561690

  20. MODULATION OF DEFENSIVE REFLEX CONDITIONING IN SNAILS BY SEROTONIN

    Directory of Open Access Journals (Sweden)

    Vyatcheslav V Andrianov

    2015-10-01

    Full Text Available We studied the role of serotonin in the mechanisms of learning in terrestrial snails. To produce a serotonin deficit, the neurotoxic analogues of serotonin, 5,6- or 5,7-dihydroxytryptamine (5,6/5,7-DHT were used. Injection of 5,6/5,7-DHT was found to disrupt defensive reflex conditioning. Within two weeks of neurotoxin application, the ability to learn had recovered. Daily injection of serotonin before a training session accelerated defensive reflex conditioning and daily injections of 5-HTP in snails with a deficiency of serotonin induced by 5,7-DHT restored the snail’s ability to learn. We discovered that injections of the neurotoxins 5,6/5,7-DHT as well as serotonin, caused a decrease in the resting and threshold potentials of the premotor interneurons LPa3 and RPa3.

  1. Serotonin transporter genotype x construction stress interaction in rats.

    Science.gov (United States)

    Schipper, Pieter; Nonkes, Lourens J P; Karel, Peter; Kiliaan, Amanda J; Homberg, Judith R

    2011-09-30

    A well-known example for gene x environment interactions in psychiatry is the one involving the low activity (s) allelic variant of the serotonin transporter (5-HTT) promoter polymorphism (5-HTTLPR) that in the context of stress increases risk for depression. In analogy, 5-HTT knockout rodents are highly responsive to early life, but also adult external stressors, albeit conflicting data have been obtained. In our study on emotion and cognition using homozygous 5-HTT knockout (5-HTT(-/-)) and wild-type (5-HTT(+/+)) rats we have been confronted with animal facility construction, which were associated with severe lifetime stress (noise and vibrations). To assess the impact of construction stress on well-established 5-HTT(-/-) rat phenotypes we conducted ad hoc analyses of 5-HTT(-/-) and 5-HTT(+/+) rats that grew up before and during the construction. The reproductive capacity of the parents of the experimental 5-HTT(+/-) rats was significantly decreased. Further, 5-HTT(-/-) anxiety-related phenotypes in the elevated plus maze and social interaction tests were abolished after construction noise exposure, due to increased anxiety in 5-HTT(+/+) rats and decreased anxiety in 5-HTT(-/-) rats (social interaction test only). In addition, reversal learning was improved in 5-HTT(+/+) and, to a milder extent, decreased in 5-HTT(-/-) rats. Finally, construction stress genotype-independently increased behavioural despair in the forced swim test. In conclusion, severe construction stress induces 5-HTT genotype-dependent 'for-better-and-for-worse' effects. These data importantly contribute to the understanding of 5-HTT gene x environment interactions and show the risk of losing genotype effects by construction stress. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Serotonin control of thermotaxis memory behavior in nematode Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Yinxia Li

    Full Text Available Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans.

  3. Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency

    Science.gov (United States)

    Weng, Rui; Shen, Sensen; Tian, Yonglu; Burton, Casey; Xu, Xinyuan; Liu, Yi; Chang, Cuilan; Bai, Yu; Liu, Huwei

    2015-07-01

    Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer’s disease and Parkinson’s disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency-associated mechanisms under multiple pathological states.

  4. Plasma serotonin in horses undergoing surgery for small intestinal colic

    Science.gov (United States)

    Torfs, Sara C.; Maes, An A.; Delesalle, Catherine J.; Pardon, Bart; Croubels, Siska M.; Deprez, Piet

    2015-01-01

    This study compared serotonin concentrations in platelet poor plasma (PPP) from healthy horses and horses with surgical small intestinal (SI) colic, and evaluated their association with postoperative ileus, strangulation and non-survival. Plasma samples (with EDTA) from 33 horses with surgical SI colic were collected at several pre- and post-operative time points. Serotonin concentrations were determined using liquid-chromatography tandem mass spectrometry. Results were compared with those for 24 healthy control animals. The serotonin concentrations in PPP were significantly lower (P serotonin was not a suitable prognostic factor in horses with SI surgical colic. PMID:25694668

  5. Molecular imaging of serotonin degeneration in mild cognitive impairment.

    Science.gov (United States)

    Smith, Gwenn S; Barrett, Frederick S; Joo, Jin Hui; Nassery, Najlla; Savonenko, Alena; Sodums, Devin J; Marano, Christopher M; Munro, Cynthia A; Brandt, Jason; Kraut, Michael A; Zhou, Yun; Wong, Dean F; Workman, Clifford I

    2017-09-01

    Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions and is found in high concentrations in the serotonergic cell bodies of origin of these projections (raphe nuclei). Twenty-eight participants with mild cognitive impairment (age 66.6±6.9, 16 males) and 28 healthy, cognitively normal, demographically matched controls (age 66.2±7.1, 15 males) underwent magnetic resonance imaging for measurement of grey matter volumes and high-resolution positron emission tomography with well-established radiotracers for the serotonin transporter and regional cerebral blood flow. Beta-amyloid imaging was performed to evaluate, in combination with the neuropsychological testing, the likelihood of subsequent cognitive decline in the participants with mild cognitive impairment. The following hypotheses were tested: 1) the serotonin transporter would be lower in mild cognitive impairment compared to controls in cortical and limbic regions, 2) in mild cognitive impairment relative to controls, the serotonin transporter would be lower to a greater extent and observed in a more widespread pattern than lower grey matter volumes or lower regional cerebral blood flow and 3) lower cortical and limbic serotonin transporters would be correlated with greater deficits in auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls. Reduced serotonin transporter availability was observed in mild cognitive impairment compared to controls in cortical and limbic

  6. Stimulation of aortic smooth muscle cell mitogenesis by serotonin

    Energy Technology Data Exchange (ETDEWEB)

    Nemecek, G.M.; Coughlin, S.R.; Handley, D.A.; Moskowitz, M.A.

    1986-02-01

    Bovine aortic smooth muscle cells in vitro responded to 1 nM to 10 ..mu..M serotonin with increased incorporation of (/sup 3/H)thymidine into DNA. The mitogenic effect of serotonin was half-maximal at 80 nM and maximal above 1 ..mu..M. At a concentration of 1 ..mu..M, serotonin stimulated smooth muscle cell mitogenesis to the same extent as human platelet-derived growth factor (PDGF) at 12 ng/ml. Tryptamine was approx. = 1/10th as potent as serotonin as a mitogen for smooth muscle cells. Other indoles that are structurally related to serotonin (D- and L-tryptophan, 5-hydroxy-L-tryptophan, N-acetyl-5-hydroxytryptamine, melatonin, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophol) and quipazine were inactive. The stimulatory effect of serotonin on smooth muscle cell DNA synthesis required prolonged (20-24 hr) exposure to the agonist and was attenuated in the presence of serotonin D receptor antagonists. When smooth muscle cells were incubated with submaximal concentrations of serotonin and PDGF, synergistic rather than additive mitogenic responses were observed. These data indicate that serotonin has a significant mitogenic effect on smooth muscle cells in vitro, which appears to be mediated by specific plasma membrane receptors.

  7. Effect of serotonin on small intestinal contractility in healthy volunteers

    DEFF Research Database (Denmark)

    Hansen, M.B.; Arif, F.; Gregersen, H.

    2008-01-01

    -duodeno-jejunal contractility in healthy human volunteers. Manometric recordings were obtained and the effects of either a standard meal, continuous intravenous infusion of serotonin (20 nmol/kg/min) or intraluminal bolus infusions of graded doses of serotonin (2.5, 25 or 250 nmol) were compared. In addition, platelet......-lived adverse effects following intraluminal serotonin stimulations. We conclude that exogenous serotonin in the lumen of the upper part of the small intestine does not seem to change antro-duodeno-jejunal contractility significantly in healthy adult volunteers Udgivelsesdato: 2008...

  8. Effects of acute exposure to chlorpyrifos on cholinergic and non-cholinergic targets in normal and high-fat fed male C57BL/6J mice.

    Science.gov (United States)

    Kondakala, Sandeep; Lee, Jung Hwa; Ross, Matthew K; Howell, George E

    2017-10-31

    The prevalence of obesity is increasing at an alarming rate in the United States with 36.5% of adults being classified as obese. Compared to normal individuals, obese individuals have noted pathophysiological alterations which may alter the toxicokinetics of xenobiotics and therefore alter their toxicities. However, the effects of obesity on the toxicity of many widely utilized pesticides has not been established. Therefore, the present study was designed to determine if the obese phenotype altered the toxicity of the most widely used organophosphate (OP) insecticide, chlorpyrifos (CPS). Male C57BL/6J mice were fed normal or high-fat diet for 4weeks and administered a single dose of vehicle or CPS (2.0mg/kg; oral gavage) to assess cholinergic (acetylcholinesterase activities) and non-cholinergic (carboxylesterase and endocannabinoid hydrolysis) endpoints. Exposure to CPS significantly decreased red blood cell acetylcholinesterase (AChE) activity, but not brain AChE activity, in both diet groups. Further, CPS exposure decreased hepatic carboxylesterase activity and hepatic hydrolysis of a major endocannabinoid, anandamide, in a diet-dependent manner with high-fat diet fed animals being more sensitive to CPS-mediated inhibition. These in vivo studies were corroborated by in vitro studies using rat primary hepatocytes, which demonstrated that fatty acid amide hydrolase and CES activities were more sensitive to CPS-mediated inhibition than 2-arachidonoylglycerol hydrolase activity. These data demonstrate hepatic CES and FAAH activities in high-fat diet fed mice were more potently inhibited than those in normal diet fed mice following CPS exposure, which suggests that the obese phenotype may exacerbate some of the non-cholinergic effects of CPS exposure. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. PON1 status does not influence cholinesterase activity in Egyptian agricultural workers exposed to chlorpyrifos

    Energy Technology Data Exchange (ETDEWEB)

    Ellison, Corie A., E-mail: cellison@buffalo.edu [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Crane, Alice L., E-mail: alcrane@buffalo.edu [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Bonner, Matthew R., E-mail: mrbonner@buffalo.edu [Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Knaak, James B., E-mail: jbknaak@aol.com [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Browne, Richard W., E-mail: rwbrowne@buffalo.edu [Department of Biotechnical and Clinical Laboratory Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Lein, Pamela J., E-mail: pjlein@ucdavis.edu [Department of Molecular Biosciences, University of California School of Veterinary Medicine, Davis, CA 95618 (United States); Olson, James R., E-mail: jolson@buffalo.edu [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY 14214 (United States)

    2012-12-15

    Animal studies have shown that paraoxonase 1 (PON1) genotype can influence susceptibility to the organophosphorus pesticide chlorpyrifos (CPF). However, Monte Carlo analysis suggests that PON1 genotype may not affect CPF-related toxicity at low exposure conditions in humans. The current study sought to determine the influence of PON1 genotype on the activity of blood cholinesterase as well as the effect of CPF exposure on serum PON1 in workers occupationally exposed to CPF. Saliva, blood and urine were collected from agricultural workers (n = 120) from Egypt's Menoufia Governorate to determine PON1 genotype, blood cholinesterase activity, serum PON1 activity towards chlorpyrifos-oxon (CPOase) and paraoxon (POase), and urinary levels of the CPF metabolite 3,5,6-trichloro-2-pyridinol (TCPy). The PON1 55 (P ≤ 0.05) but not the PON1 192 genotype had a significant effect on CPOase activity. However, both the PON1 55 (P ≤ 0.05) and PON1 192 (P ≤ 0.001) genotypes had a significant effect on POase activity. Workers had significantly inhibited AChE and BuChE after CPF application; however, neither CPOase activity nor POase activity was associated with ChE depression when adjusted for CPF exposure (as determined by urinary TCPy levels) and stratified by PON1 genotype. CPOase and POase activity were also generally unaffected by CPF exposure although there were alterations in activity within specific genotype groups. Together, these results suggest that workers retained the capacity to detoxify chlorpyrifos-oxon under the exposure conditions experienced by this study population regardless of PON1 genotype and activity and that effects of CPF exposure on PON1 activity are minimal. -- Highlights: ► CPF exposure resulted in an increase in TCPy and decreases in BuChE and AChE. ► CPOase activity decreased in subjects with the PON1 55LM and PON1 55 MM genotypes. ► Neither PON1 genotype nor CPOase activity had an effect on BuChE or AChE inhibition.

  10. Involvement of serotonin 2C receptor RNA editing in accumbal neuropeptide Y expression and behavioural despair.

    Science.gov (United States)

    Aoki, Miku; Watanabe, Yoshihisa; Yoshimoto, Kanji; Tsujimura, Atsushi; Yamamoto, Toshiro; Kanamura, Narisato; Tanaka, Masaki

    2016-05-01

    Serotonin 2C receptors (5-HT2 C Rs) are widely expressed in the central nervous system, and are associated with various neurological disorders. 5-HT2 C R mRNA undergoes adenosine-to-inosine RNA editing at five sites within its coding sequence, resulting in expression of 24 different isoforms. Several edited isoforms show reduced activity, suggesting that RNA editing modulates serotonergic systems in the brain with causative relevance to neuropsychiatric disorders. Transgenic mice solely expressing the non-edited 5-HT2 C R INI-isoform (INI) or the fully edited VGV-isoform exhibit various phenotypes including metabolic abnormalities, aggressive behaviour, anxiety-like behaviour, and depression-like behaviour. Here, we examined the behavioural phenotype and molecular changes of INI mice on a C57BL/6J background. INI mice showed an enhanced behavioural despair in the forced swimming test, elevated sensitivity to the tricyclic antidepressant desipramine, and significantly decreased serotonin in the nucleus accumbens (NAc), amygdala, and striatum. They also showed reduced expression of neuropeptide Y (NPY) mRNA in the NAc. In addition, by stereotactic injection of adeno-associated virus encoding NPY into the NAc, we demonstrated that accumbal NPY overexpression relieved behavioural despair. Our results suggest that accumbal NPY expression may be regulated by 5-HT2 C R RNA editing, and its impairment may be linked to mood disorders. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  11. Maternal 25-hydroxyvitamin D is inversely correlated with foetal serotonin.

    Science.gov (United States)

    Murthi, Padma; Davies-Tuck, Miranda; Lappas, Martha; Singh, Harmeet; Mockler, Joanne; Rahman, Rahana; Lim, Rebecca; Leaw, Bryan; Doery, James; Wallace, Euan M; Ebeling, Peter R

    2017-03-01

    Maternal vitamin D deficiency during pregnancy has been linked to impaired neurocognitive development in childhood. The mechanism by which vitamin D affects childhood neurocognition is unclear but may be via interactions with serotonin, a neurotransmitter involved in foetal brain development. In this study, we aimed to explore associations between maternal and foetal vitamin D concentrations, and foetal serotonin concentrations at term. Serum 25-hydroxyvitamin D (25(OH)D, nmol/l) and serotonin (5-HT, nmol/l) concentrations were measured in maternal and umbilical cord blood from mother-infant pairs (n = 64). Association between maternal 25(OH)D, cord 25(OH)D and cord serotonin was explored using linear regression, before and after adjusting for maternal serotonin levels. We also assessed the effects of siRNA knockdown of the vitamin D receptor (VDR) and administration of 10 nm 1,25-dihydroxyvitamin D3 on serotonin secretion in human umbilical vein endothelial cells (HUVECs) in vitro. We observed an inverse relationship between both maternal and cord 25(OH)D concentrations with cord serotonin concentrations. The treatment of HUVECs with 1,25-dihydroxyvitamin D3 in vitro decreased the release of serotonin (193·9 ±14·8 nmol/l vs 458·9 ± 317·5 nmol/l, control, P serotonin release in cultured HUVECs. These observations provide the first evidence of an inverse relationship between maternal 25(OH)D and foetal serotonin concentrations. We propose that maternal vitamin D deficiency increases foetal serotonin concentrations and thereby contributes to longer-term neurocognitive impairment in infants and children. © 2016 John Wiley & Sons Ltd.

  12. Relationship among phenotypic plasticity, phenotypic fluctuations ...

    Indian Academy of Sciences (India)

    Prakash

    These results provide quantitative formulation on canalization and genetic assimilation, in terms of fluctuations of gene expression levels. [Kaneko K 2009 Relationship among phenotypic plasticity, phenotypic fluctuations, robustness, and evolvability; Waddington's legacy revisited under the spirit of Einstein; J. Biosci.

  13. Mutational scanning of the human serotonin transporter reveals fast translocating serotonin transporter mutants

    DEFF Research Database (Denmark)

    Kristensen, Anders S; Larsen, Mads B; Johnsen, Laust B

    2004-01-01

    The serotonin transporter (SERT) belongs to a family of sodium-chloride-dependent transporters responsible for uptake of amino acids and biogenic amines from the extracellular space. SERT represents a major pharmacological target in the treatment of several clinical conditions, including depression...

  14. No link of serotonin 2C receptor editing to serotonin transporter genotype

    NARCIS (Netherlands)

    Lyddon, R.; Cuppen, E.; Haroutunian, V.; Siever, L.J.; Dracheva, S.

    2010-01-01

    RNA editing is a post-transcriptional process, which has the potential to alter the function of encoded proteins. In particular, serotonin 2C receptor (5-HT2cR) mRNA editing can produce 24 protein isoforms of varying functionality. Rodent studies have shown that 5-HT2cR editing is dynamically

  15. Chronic exposure to chlorpyrifos reveals two modes of action in the springtail Folsomia candida.

    Science.gov (United States)

    Jager, Tjalling; Crommentuijn, Trudie; van Gestel, Cornelis A M; Kooijman, Sebastiaan A L M

    2007-01-01

    Organophosphates are popular insecticides, but relatively little is known about their chronic effects on ecologically relevant endpoints. In this paper, we examine a life-cycle experiment with the springtail Folsomia candida, exposed via food to chlorpyrifos (CPF). The results for all endpoints (survival, growth and reproduction) were analyzed using the DEBtox model. Growth was unaffected by CPF, even at concentrations causing severe effects on survival and reproduction. Model analysis suggests that CPF directly affects the process of egg production. For the short-term response (45 days), this single mode of action accurately agreed with the data. However, the full data set (120 days) revealed a dose-related decrease in reproduction at low concentrations after prolonged exposure, not covered by the same mechanism. It appears that CPF interacts with senescence by increasing oxidative damage. This assumption fits the data well, but has little consequences for the predicted response at the population level.

  16. Integrating ecosystem services into risk management decisions: case study with Spanish citrus and the insecticide chlorpyrifos.

    Science.gov (United States)

    Deacon, Samantha; Norman, Steve; Nicolette, Joseph; Reub, Gregory; Greene, Gretchen; Osborn, Rachel; Andrews, Paul

    2015-02-01

    The European regulatory system for the approval of pesticides includes a thorough evaluation of risks to the environment and is designed to be protective of ecosystems. However, a decision to ban an agrochemical could also potentially have a negative impact on the value of ecosystem services, if resulting changes in crop management are damaging to ecosystems or result in negative socio-economic impacts. To support regulatory decision-making, consideration of ecosystem services to identify best environmental management options could be a way forward. There is generally a growing trend for the consideration of ecosystem services in decision making. Ecosystems provide the conditions for growing food, regulate water and provide wildlife habitats; these, amongst others, are known as ecosystem services. The objectives of this case study were to bring a holistic approach to decision making by valuing the environmental, social and economic benefits derived from the use of chlorpyrifos in Valencian citrus production. Spanish growers harvest between 5 and 6 milliont of citrus annually, worth an estimated €5 to 7 billion in food markets throughout Europe. The approach highlighted the potential for unintended negative consequences of regulatory decisions if the full context is not considered. In this study, rather than a regulatory restriction, the best option was the continued use of chlorpyrifos together with vegetated conservation patches as refuges for non-target insects. The conservation patches offset potential insecticidal impacts to insects whilst maintaining citrus production, farm income and the amenity value of the citrus landscape of Valencia. This was an initial proof-of-concept study and illustrates the importance of a wider perspective; other cases may have different outcomes depending on policies, the pesticide, crop scenarios, farm economics and the region. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Impact of Location, Cropping History, Tillage, and Chlorpyrifos on Soil Arthropods in Peanut.

    Science.gov (United States)

    Cardoza, Yasmin J; Drake, Wendy L; Jordan, David L; Schroeder-Moreno, Michelle S; Arellano, Consuelo; Brandenburg, Rick L

    2015-08-01

    Demand for agricultural production systems that are both economically viable and environmentally conscious continues to increase. In recent years, reduced tillage systems, and grass and pasture rotations have been investigated to help maintain or improve soil quality, increase crop yield, and decrease labor requirements for production. However, documentation of the effects of reduced tillage, fescue rotation systems as well as other management practices, including pesticides, on pest damage and soil arthropod activity in peanut production for the Mid-Atlantic US region is still limited. Therefore, this project was implemented to assess impacts of fescue-based rotation systems on pests and other soil organisms when compared with cash crop rotation systems over four locations in eastern North Carolina. In addition, the effects of tillage (strip vs. conventional) and soil chlorpyrifos application on pod damage and soil-dwelling organisms were also evaluated. Soil arthropod populations were assessed by deploying pitfall traps containing 50% ethanol in each of the sampled plots. Results from the present study provide evidence that location significantly impacts pest damage and soil arthropod diversity in peanut fields. Cropping history also influenced arthropod diversity, with higher diversity in fescue compared with cash crop fields. Corn rootworm damage to pods was higher at one of our locations (Rocky Mount) compared with all others. Cropping history (fescue vs. cash crop) did not have an effect on rootworm damage, but increased numbers of hymenopterans, acarina, heteropterans, and collembolans in fescue compared with cash crop fields. Interestingly, there was an overall tendency for higher number of soil arthropods in traps placed in chlorpyrifos-treated plots compared with nontreated controls. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Developmental neurotoxic effects of two pesticides: Behavior and biomolecular studies on chlorpyrifos and carbaryl.

    Science.gov (United States)

    Lee, Iwa; Eriksson, Per; Fredriksson, Anders; Buratovic, Sonja; Viberg, Henrik

    2015-11-01

    In recent times, an increased occurrence of neurodevelopmental disorders, such as neurodevelopmental delays and cognitive abnormalities has been recognized. Exposure to pesticides has been suspected to be a possible cause of these disorders, as these compounds target the nervous system of pests. Due to the similarities of brain development and composition, these pesticides may also be neurotoxic to humans. We studied two different pesticides, chlorpyrifos and carbaryl, which specifically inhibit acetylcholinesterase (AChE) in the nervous system. The aim of the study was to investigate if the pesticides can induce neurotoxic effects, when exposure occurs during a period of rapid brain growth and maturation. The results from the present study show that both compounds can affect protein levels in the developing brain and induce persistent adult behavior and cognitive impairments, in mice neonatally exposed to a single oral dose of chlorpyrifos (0.1, 1.0 or 5mg/kg body weight) or carbaryl (0.5, 5.0 or 20.0mg/kg body weight) on postnatal day 10. The results also indicate that the developmental neurotoxic effects induced are not related to the classical mechanism of acute cholinergic hyperstimulation, as the AChE inhibition level (8-12%) remained below the threshold for causing systemic toxicity. The neurotoxic effects are more likely caused by a disturbed neurodevelopment, as similar behavioral neurotoxic effects have been reported in studies with pesticides such as organochlorines, organophosphates, pyrethroids and POPs, when exposed during a critical window of neonatal brain development. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Removal of pesticides and ecotoxicological changes during the simultaneous treatment of triazines and chlorpyrifos in biomixtures.

    Science.gov (United States)

    Lizano-Fallas, Verónica; Masís-Mora, Mario; Espinoza-Villalobos, David; Lizano-Brenes, Michelle; Rodríguez-Rodríguez, Carlos E

    2017-09-01

    Biopurification systems constitute a biological approach for the treatment of pesticide-containing wastewaters produced in agricultural activities, and contain an active core called biomixture. This work evaluated the performance of a biomixture to remove and detoxify a combination of three triazine herbicides (atrazine/terbuthylazine/terbutryn) and one insecticide (chlorpyrifos), and this efficiency was compared with dissipation in soil alone. The potential enhancement of the process was also assayed by bioaugmentation with the ligninolytic fungi Trametes versicolor. Globally, the non-bioaugmented biomixture exhibited faster pesticide removal than soil, but only in the first stages of the treatment. After 20 d, the largest pesticide removal was achieved in the biomixture, while significant removal was detected only for chlorpyrifos in soil. However, after 60 d the removal values in soil matched those achieved in the biomixture for all the pesticides. The bioaugmentation failed to enhance, and even significantly decreased the biomixture removal capacity. Final removal values were 82.8% (non-bioaugmented biomixture), 43.8% (fungal bioaugmented biomixture), and 84.7% (soil). The ecotoxicological analysis revealed rapid detoxification (from 100 to 170 TU to pesticide removal. On the contrary, despite important herbicide elimination, no clear detoxification patterns were observed in the phytotoxicity towards Lactuca sativa. Findings suggest that the proposed biomixture is useful for fast removal of the target pesticides; even though soil also removes the agrochemicals, longer periods would be required. On the other hand, the use of fungal bioaugmentation is discouraged in this matrix. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Effects of Nicotine Exposure on In Vitro Metabolism of Chlorpyrifos in Male Sprague-Dawley Rats

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sookwang; Busby, Andrea L.; Timchalk, Charles; Poet, Torka S.

    2009-01-30

    Chlorpyrifos (CPF) is a common organophosphate (OP) insecticide which is metabolized by CYP450s to the neurotoxic metabolite, chlorpyrifos-oxon (CPF-oxon) and a non-toxic metabolite, 3,5,6-trichloro-2-pyridinol (TCP). The objective of this study was to quantify the effect of repeated in vivo nicotine exposures on CPF in vitro metabolism and marker substrate activities in rats. Male Sprague-Dawley rats were dosed subcutaneously with 1 mg nicotine/kg/, for up to 10 days. Animals showed signs of cholinergic crisis after the initial nicotine doses, but exhibited adaptation after a couple days of treatment. Rats were sacrificed on selected days 4 or 24 hr after the last nicotine-treatment. While CYP450 reduced CO spectra were not different across the treatments, the single nicotine dose group showed a 2-fold increase in CYP2E1 marker substrate (p-nitrophenol) activity 24 hr after a single nicotine treatment compared to saline controls. Conversely, repeated nicotine treatments resulted in decreased EROD marker substrate activity 4 hr after the 7th day of treatment. CPF-oxon Vmax and Km did not show significant changes across the different nicotine treatment groups. The Vmax describing the metabolism of CPF to TCP was increased on all groups (days 1, 7, and 10) 24 hr after nicotine treatment but were unchanged 4 hr after nicotine treatment. Results of this in vitro study suggest that repeated nicotine exposure (i.e., from smoking) may result in altered metabolism of CPF. Future in vivo experiments based on these results will be conducted to ascertain the impact of in vivo nicotine exposures on CPF metabolism in rats.

  1. A Visible-Light-Sensitive Caged Serotonin

    OpenAIRE

    Cabrera, R.; Filevich, O; Garcia-Acosta, B; Athilingam, J; Bender, KJ; Poskanzer, KE; R. Etchenique

    2017-01-01

    Serotonin, or 5-hydroxytryptamine (5HT), is an important neurotransmitter in the nervous system of both vertebrates and invertebrates. Deficits in 5HT signaling are responsible for many disabling psychiatric conditions, and its molecular machinery is the target of many pharmaceuticals. We present a new 5HT phototrigger, the compound [Ru(bpy)2(PMe3)(5HT)]2+, where PMe3 is trimethylphosphine. As with other ruthenium-bipyridyl based caged compounds, [Ru(bpy)2(PMe3)(5HT)]2+ presents activity in t...

  2. Serotonin Immunoreactive Cells and Nerve Fibers in the Mucosa of ...

    African Journals Online (AJOL)

    They appeared not to be in contact with the immunopositive endocrine and mast cells. The current study shows that serotonin may be released by the immunoreactive elements in the stomach and that future work is needed to characterize the ultrastructural features of serotonin positive nerve fibers in the pyloric mucosa.

  3. Serotonin: is it a marker for the diagnosis of hepatocellular ...

    African Journals Online (AJOL)

    Hoda Aly Abd El Moety

    2013-04-19

    Apr 19, 2013 ... Abstract Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer mortality among men worldwide. Serotonin is a biogenic amine, ligand of a family of 5-HT receptors that reflect the diversity of serotonergic actions. Majority of serotonin in body (90%) is synthesized by enterochromaffin ...

  4. Context-dependent modulation of auditory processing by serotonin

    Science.gov (United States)

    Hurley, L.M.; Hall, I.C.

    2011-01-01

    Context-dependent plasticity in auditory processing is achieved in part by physiological mechanisms that link behavioral state to neural responses to sound. The neuromodulator serotonin has many characteristics suitable for such a role. Serotonergic neurons are extrinsic to the auditory system but send projections to most auditory regions. These projections release serotonin during particular behavioral contexts. Heightened levels of behavioral arousal and specific extrinsic events, including stressful or social events, increase serotonin availability in the auditory system. Although the release of serotonin is likely to be relatively diffuse, highly specific effects of serotonin on auditory neural circuitry are achieved through the localization of serotonergic projections, and through a large array of receptor types that are expressed by specific subsets of auditory neurons. Through this array, serotonin enacts plasticity in auditory processing in multiple ways. Serotonin changes the responses of auditory neurons to input through the alteration of intrinsic and synaptic properties, and alters both short- and long-term forms of plasticity. The infrastructure of the serotonergic system itself is also plastic, responding to age and cochlear trauma. These diverse findings support a view of serotonin as a widespread mechanism for behaviorally relevant plasticity in the regulation of auditory processing. This view also accommodates models of how the same regulatory mechanism can have pathological consequences for auditory processing. PMID:21187135

  5. Serotonin synthesis rate and the tryptophan hydroxylase-2

    DEFF Research Database (Denmark)

    Furmark, Tomas; Marteinsdottir, Ina; Frick, Andreas

    2016-01-01

    It is disputed whether anxiety disorders, like social anxiety disorder, are characterized by serotonin over- or underactivity. Here, we evaluated whether our recent finding of elevated neural serotonin synthesis rate in patients with social anxiety disorder could be reproduced in a separate cohor...

  6. Serotonin: Is it a marker for the diagnosis of hepatocellular ...

    African Journals Online (AJOL)

    Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer mortality among men worldwide. Serotonin is a biogenic amine, ligand of a family of 5-HT receptors that reflect the diversity of serotonergic actions. Majority of serotonin in body (90%) is synthesized by enterochromaffin cells of the gastrointestinal ...

  7. Looking on the bright side of serotonin transporter gene variation.

    NARCIS (Netherlands)

    Homberg, J.R.; Lesch, K.P.

    2011-01-01

    Converging evidence indicates an association of the short (s), low-expressing variant of the repeat length polymorphism, serotonin transporter-linked polymorphic region (5-HTTLPR), in the human serotonin transporter gene (5-HTT, SERT, SLC6A4) with anxiety-related traits and increased risk for

  8. Dopamine and serotonin regulate tumor behavior by affecting angiogenesis

    NARCIS (Netherlands)

    Peters, Marloes; Walenkamp, Annemiek M. E.; Kema, Ido P.; Meijer, Coby; de Vries, Elisabeth G. E.; Oosting, Sjoukje F.

    2014-01-01

    The biogenic amines dopamine and serotonin are neurotransmitters and hormones, which are mainly produced in the central nervous system and in the gastro-intestinal tract. They execute local and systemic functions such as intestinal motility and tissue repair. Dopamine and serotonin are primarily

  9. Dissipation, half-lives, and mass spectrometric identification of chlorpyrifos and its two metabolites on field-grown collard and kale.

    Science.gov (United States)

    Antonious, George F; Turley, Eric T; Abubakari, Mutari; Snyder, John C

    2017-04-03

    The persistence and fate of chlorpyrifos and its two metabolites, chlorpyrifos-oxon and the 3, 5, 6-trichloro-2-pyridinol (TCP) break-down product were investigated on kale and collard leaves under field conditions. A simultaneous extraction and quantification procedure was developed for chrorpyrifos and its two main metabolites. Residues of chlorpyrifos, chlorpyrifos oxon, and TCP were determined using a gas chromatograph (GC) equipped with an electron capture detector (GC/ECD). Chlorpyrifos metabolites were detectable up to 23 days following application. Residues were confirmed using a GC equipped with a mass selective detector (GC/MSD) in total ion mode. Initial residues of chlorpyrifos were greater on collard (14.5 µg g-1) than kale (8.2 µg g-1) corresponding to half-lives (T1/2) values of 7.4 and 2.2 days, respectively. TCP, the hydrolysis product, was more persistent on collards with an estimated T1/2 of 6.5 days compared to kale (T1/2 of 1.9 days).

  10. Effects of chlorpyrifos and chlorantraniliprole on fermentation quality of alfalfa (Medicago sativa L.) silage inoculated with or without Lactobacillus plantarum LP.

    Science.gov (United States)

    Zhang, Qing; Yu, Zhu; Wang, Xianguo; Na, Risu

    2017-03-01

    The effects of pesticides and Lactobacillus plantarum (LP) on fermentation quality of alfalfa (Medicago sativa L.) silage were investigated. Chlorpyrifos and chlorantraniliprole were sprayed on the surface of alfalfa plants at 658.6 and 45.0 g active ingredient/ha, respectively. Alfalfa plants were harvested on day 5 post-application and ensiled with or without LP. Chlorpyrifos and chlorantraniliprole decreased the yeast count of alfalfa material (P < 0.05). Both pesticides increased the butyric acid content of alfalfa silage (P < 0.001). Chlorpyrifos increased pH and decreased lactic acid, acetic acid and short-chain fatty acid contents (P < 0.05). LP decreased pH and butyric acid content, and increased lactic acid and short-chain fatty acid contents of alfalfa silage treated with pesticides (P < 0.05). LP increased the concentration of chlorpyrifos residue in alfalfa silage (P < 0.05). Chlorpyrifos and chlorantraniliprole affected the microbial communities of the material before ensiling, especially coliform bacteria and yeast; the two pesticide residues were reduced after the fermentation of alfalfa silage and affected the fermentation process, whereas LP improved the fermentation quality of pesticides-contaminated alfalfa silage and slowed down the dissipation of chlorpyrifos. © 2016 Japanese Society of Animal Science.

  11. A specific role for serotonin in overcoming effort cost.

    Science.gov (United States)

    Meyniel, Florent; Goodwin, Guy M; Deakin, Jf William; Klinge, Corinna; MacFadyen, Christine; Milligan, Holly; Mullings, Emma; Pessiglione, Mathias; Gaillard, Raphaël

    2016-11-08

    Serotonin is implicated in many aspects of behavioral regulation. Theoretical attempts to unify the multiple roles assigned to serotonin proposed that it regulates the impact of costs, such as delay or punishment, on action selection. Here, we show that serotonin also regulates other types of action costs such as effort. We compared behavioral performance in 58 healthy humans treated during 8 weeks with either placebo or the selective serotonin reuptake inhibitor escitalopram. The task involved trading handgrip force production against monetary benefits. Participants in the escitalopram group produced more effort and thereby achieved a higher payoff. Crucially, our computational analysis showed that this effect was underpinned by a specific reduction of effort cost, and not by any change in the weight of monetary incentives. This specific computational effect sheds new light on the physiological role of serotonin in behavioral regulation and on the clinical effect of drugs for depression. ISRCTN75872983.

  12. Infrared Thermography in Serotonin-Induced Itch Model in Rats

    DEFF Research Database (Denmark)

    Jasemian, Yousef; Gazerani, Parisa; Dagnæs-Hansen, Frederik

    2012-01-01

    The study validated the application of infrared thermography in a serotonin-induced itch model in rats since the only available method in animal models of itch is the count of scratching bouts. Twenty four adult Sprague-Dawley male rats were used in 3 experiments: 1) local vasomotor response...... with no scratching reflex was investigated. Serotonin elicited significant scratching and lowered the local temperature at the site of injection. A negative dose-temperature relationship of serotonin was found by thermography. Vasoregulation at the site of serotonin injection took place in the absence of scratching...... reflexes. Thermography is a reliable, non-invasive, and objective method for assessment in serotonin-induced itch model in rat....

  13. Serotonin enhances solitariness in phase transition of the migratory locust

    Directory of Open Access Journals (Sweden)

    Xiaojiao eGuo

    2013-10-01

    Full Text Available The behavioral plasticity of locusts is a striking trait presented during the reversible phase transition between solitary and gregarious individuals. However, the results of serotonin as a neurotransmitter from the migratory locust Locusta migratoria in phase transition showed an alternative profile compared to the results from the desert locust Schistoserca gregaria. In this study, we investigated the roles of serotonin in the brain during the phase change of the migratory locust. During the isolation of gregarious nymphs, the concentration of serotonin in the brain increased significantly, whereas serotonin receptors (i.e. 5-HT1, 5-HT2 and 5-HT7 we identified here showed invariable expression patterns. Pharmacological intervention showed that serotonin injection in the brain of gregarious nymphs did not induced the behavior change toward solitariness, but injection of this chemical in isolated gregarious nymphs accelerated the behavioral change from gregarious to solitary phase. During the crowding of solitary nymphs, the concentration of serotonin in the brain remained unchanged, whereas 5-HT2 increased after 1 h of crowding and maintained stable expression level thereafter. Activation of serotonin-5-HT2 signaling with a pharmaceutical agonist inhibited the gregariousness of solitary nymphs in crowding treatment. These results indicate that the fluctuations of serotonin content and 5-HT2 expression are results of locust phase change. Overall, this study demonstrates that serotonin enhances the solitariness of the gregarious locusts. Serotonin may regulate the withdrawal-like behavioral pattern displayed during locust phase change and this mechanism is conserved in different locust species.

  14. A Dualistic Conformational Response to Substrate Binding in the Human Serotonin Transporter Reveals a High Affinity State for Serotonin*

    Science.gov (United States)

    Bjerregaard, Henriette; Severinsen, Kasper; Said, Saida; Wiborg, Ove; Sinning, Steffen

    2015-01-01

    Serotonergic neurotransmission is modulated by the membrane-embedded serotonin transporter (SERT). SERT mediates the reuptake of serotonin into the presynaptic neurons. Conformational changes in SERT occur upon binding of ions and substrate and are crucial for translocation of serotonin across the membrane. Our understanding of these conformational changes is mainly based on crystal structures of a bacterial homolog in various conformations, derived homology models of eukaryotic neurotransmitter transporters, and substituted cysteine accessibility method of SERT. However, the dynamic changes that occur in the human SERT upon binding of ions, the translocation of substrate, and the role of cholesterol in this interplay are not fully elucidated. Here we show that serotonin induces a dualistic conformational response in SERT. We exploited the substituted cysteine scanning method under conditions that were sensitized to detect a more outward-facing conformation of SERT. We found a novel high affinity outward-facing conformational state of the human SERT induced by serotonin. The ionic requirements for this new conformational response to serotonin mirror the ionic requirements for translocation. Furthermore, we found that membrane cholesterol plays a role in the dualistic conformational response in SERT induced by serotonin. Our results indicate the existence of a subpopulation of SERT responding differently to serotonin binding than hitherto believed and that membrane cholesterol plays a role in this subpopulation of SERT. PMID:25614630

  15. A dualistic conformational response to substrate binding in the human serotonin transporter reveals a high affinity state for serotonin

    DEFF Research Database (Denmark)

    Bjerregaard, Henriette; Severinsen, Kasper; Said, Saida

    2015-01-01

    that were sensitized to detect a more outward-facing conformation of SERT. We found a novel high affinity outward-facing conformational state of the human SERT induced by serotonin. The ionic requirements for this new conformational response to serotonin mirror the ionic requirements for translocation...

  16. Serotonin in the sudden infant death syndrome.

    Science.gov (United States)

    Waters, Karen

    2010-11-01

    It seems likely that some infants who die from sudden infant death syndrome (SIDS) have a brainstem abnormality of the serotonergic system. Evidence suggests that infants who died from SIDS had defective respiratory and/or autonomic responses that led to death instead of recovery after an acute insult. The serotonergic neuromodulator system has roles in the control of cardiac autonomic and respiratory function, as well as now being identified as abnormal in infants with SIDS. This manuscript reviews the multiple roles of serotonin with reference to the functional aspects of the relevant brain regions. Correlations with pre- or postnatal exposure to stressors, or an underlying genetic process are also reviewed. Together, these studies indicate that perturbed function of the serotonin system will have significant physiological impact during early development. Understanding the functional importance of these systems assists understanding of the pathogenesis of SIDS. In conclusion, whether an infant inherits serotonergic defects and is therefore "inherently vulnerable", or whether postnatal stressors can induce the abnormalities, any functional abnormalities of the serotonergic system that result are likely to be subclinical in the majority of cases and not easily detected with current medical tools. Copyright 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

  17. Acupuncture causes serotonin release by mast cells.

    Science.gov (United States)

    Dimitrov, Nikolay; Atanasova, Dimitrinka; Tomov, Nikola; Sivrev, Dimitar; Lazarov, Nikolai

    2017-01-01

    Mast cells (MCs) are important object in experimental acupuncture due to their putative involvement in local reactions to needling. In the rat, they are shown to contain in their granules, among other tissue mediators, serotonin, also called 5-hydroxytryptamine (5-HT). The aim of this study is to examine the normal distribution of 5-HT-containing MCs in soft tissues of Zusanli (ST36) acupuncture point (acupoint) and their morphological changes caused by experimental acupuncture. We observed 5-HT-immunopositive MCs in the tissues and in the vicinity of the needle tract formed after acupuncture. As a result of acupuncture needling, the tissue integrity is disrupted and certain folds are formed in the direction of the needle tract. Connective tissue in the vicinity of the needle tract gets compressed and displaced, together with the 5-HT-immunoreactive MCs seen there. Some of those 5-HT-immunopositive MCs showed signs of degranulation with numerous discharged granules, some of them found at a considerable distance form the cell. Furthermore, 5-HT-immunopositive MCs are unevenly distributed in soft tissues of ST36 acupoint. Larger numbers of 5-HT-containing MCs were visualized in subcutis and dermis, compared to the observed in striated muscles. Placing the acupuncture needle into the rat skin caused a formation of an apparent needle tract, tissue displacement and degranulation of 5-HT-immunopositive MCs. The demonstrated serotonin release by means of MC degranulation might be involved in the local tissue response to acupuncture.

  18. Efeito da interação do nicosulfuron e chlorpyrifos sobre o banco de sementes e os atributos microbianos do solo Effect of sequential nicosulfuron and chlorpyrifos application on seed bank and soil microbial characteristics

    Directory of Open Access Journals (Sweden)

    Taciane Almeida de Oliveira

    2009-06-01

    Full Text Available Considerando o período de competição de plantas daninhas e a incidência da lagarta-do-cartucho na cultura do milho, há necessidade de aplicação, em curto intervalo de tempo, de herbicidas e de inseticidas, principalmente o nicosulfuron e o chlorpyrifos. O objetivo deste estudo foi avaliar o efeito da aplicação sequencial do nicosulfuron e do chlorpyrifos sobre a emergência de plântulas do banco de sementes, a taxa de desprendimento de CO2 (respiração basal e o C da biomassa microbiana (CBM do solo. Foi realizada aplicação sequencial, em solo, do nicosulfuron (doses de 0 a 64 g ha-1 associado ou não ao chlorpyrifos (0 e 240 g ha-1. Aos 20, 40 e 60 dias após a aplicação (DAA dos produtos, todas as plântulas emergidas do banco de sementes foram identificadas em nível de espécie, sendo estimadas a frequência, densidade e abundância, além do índice de valor de importância (IVI. Aos 60 DAA, determinou-se também a taxa de desprendimento de CO2, o CBM e o quociente metabólico (qCO2, por meio da relação entre o CO2 acumulado e o CBM total do solo. A aplicação alterou severamente a massa de plântulas secas e o número de espécies nas doses superiores a 20 g ha-1 do nicosulfuron. Na presença do herbicida, as espécies com maior IVI foram Boehavia diffusa e Commelina benghalensis. Quanto aos bioindicadores do solo, foi observado decréscimo na taxa da respiração basal do solo com o aumento da dose aplicada do nicosulfuron associado ao chlorpyrifos, sem efeito na ausência do inseticida. Houve decréscimo linear no CBM em todos os casos, independentemente da aplicação do chlorpyrifos; entretanto, observou-se uma taxa de decréscimo 4,5 vezes maior para o solo que recebeu esse inseticida em conjunto com o nicosulfuron. A avaliação do qCO2 confirmou o efeito negativo da aplicação do inseticida e do herbicida. Conclui-se que a aplicação de chlorpyrifos + nicosulfuron promove impacto negativo sobre o banco de

  19. Plasma anti-serotonin and serotonin anti-idiotypic antibodies are elevated in panic disorder.

    Science.gov (United States)

    Coplan, J D; Tamir, H; Calaprice, D; DeJesus, M; de la Nuez, M; Pine, D; Papp, L A; Klein, D F; Gorman, J M

    1999-04-01

    The psychoneuroimmunology of panic disorder is relatively unexplored. Alterations within brain stress systems that secondarily influence the immune system have been documented. A recent report indicated elevations of serotonin (5-HT) and ganglioside antibodies in patients with primary fibromyalgia, a condition with documented associations with panic disorder. In line with our interest in dysregulated 5-HT systems in panic disorder (PD), we wished to assess if antibodies directed at the 5-HT system were elevated in patients with PD in comparison to healthy volunteers. Sixty-three patients with panic disorder and 26 healthy volunteers were diagnosed by the SCID. Employing ELISA, we measured anti-5-HT and 5-HT anti-idiotypic antibodies (which are directed at 5-HT receptors). To include all subjects in one experiment, three different batches were run during the ELISA. Plasma serotonin anti-idiotypic antibodies: there was a significant group effect [patients > controls (p = .007)] and batch effect but no interaction. The mean effect size for the three batches was .76. Following Z-score transformation of each separate batch and then combining all scores, patients demonstrated significantly elevated levels of plasma serotonin anti-idiotypic antibodies. Neither sex nor age as covariates affected the significance of the results. There was a strong correlation between anti-serotonin antibody and serotonin anti-idiotypic antibody measures. Plasma anti-serotonin antibodies: there was a significant diagnosis effect [patients > controls (p = .037)]. Mean effect size for the three batches was .52. Upon Z-score transformation, there was a diagnosis effect with antibody elevations in patients. Covaried for sex and age, the result falls below significance to trend levels. The data raise the possibility that psychoimmune dysfunction, specifically related to the 5-HT system, may be present in PD. Potential interruption of 5-HT neurotransmission through autoimmune mechanisms may be of

  20. Bioslurry phase remediation of chlorpyrifos contaminated soil: process evaluation and optimization by Taguchi design of experimental (DOE) methodology.

    Science.gov (United States)

    Venkata Mohan, S; Sirisha, K; Sreenivasa Rao, R; Sarma, P N

    2007-10-01

    Design of experimental (DOE) methodology using Taguchi orthogonal array (OA) was applied to evaluate the influence of eight biotic and abiotic factors (substrate-loading rate, slurry phase pH, slurry phase dissolved oxygen (DO), soil water ratio, temperature, soil microflora load, application of bioaugmentation and humic substance concentration) on the soil bound chlorpyrifos bioremediation in bioslurry phase reactor. The selected eight factors were considered at three levels (18 experiments) in the experimental design. Substrate-loading rate showed significant influence on the bioremediation process among the selected factors. Derived optimum operating conditions obtained by the methodology showed enhanced chlorpyrifos degradation from 1479.99 to 2458.33microg/g (over all 39.82% enhancement). The proposed method facilitated systematic mathematical approach to understand the complex bioremediation process and the optimization of near optimum design parameters, only with a few well-defined experimental sets.

  1. Serotonin at the Nexus of Impulsivity and Cue Reactivity in Cocaine Addiction

    Science.gov (United States)

    Cunningham, Kathryn A.; Anastasio, Noelle C.

    2014-01-01

    Cocaine abuse and addiction remain great challenges on the public health agendas in the U.S. and the world. Increasingly sophisticated perspectives on addiction to cocaine and other drugs of abuse have evolved with concerted research efforts over the last 30 years. Relapse remains a particularly powerful clinical problem as, even upon termination of drug use and initiation of abstinence, the recidivism rates can be very high. The cycling course of cocaine intake, abstinence and relapse is tied to a multitude of behavioral and cognitive processes including impulsivity (a predisposition toward rapid unplanned reactions to stimuli without regard to the negative consequences), and cocaine cue reactivity (responsivity to cocaine-associated stimuli) cited as two key phenotypes that contribute to relapse vulnerability even years into recovery. Preclinical studies suggest that serotonin (5-hydroxytryptamine; 5-HT) neurotransmission in key neural circuits may contribute to these interlocked phenotypes well as the altered neurobiological states evoked by cocaine that precipitate relapse events. As such, 5-HT is an important target in the quest to to understand the neurobiology of relapse-predictive phenotypes, to successfully treat this complex disorder and improve diagnostic and prognostic capabilities. This review emphasizes the role of 5-HT and its receptor proteins in key addiction phenotypes and the implications of current findings to the future of therapeutics in addiction. PMID:23850573

  2. Inulin Supplementation Lowered the Metabolic Defects of Prolonged Exposure to Chlorpyrifos from Gestation to Young Adult Stage in Offspring Rats

    OpenAIRE

    Reygner, Julie; Lichtenberger, Lydia; Elmhiri, Ghada; Dou, Samir; Bahi-Jaber, Narges; Rhazi, Larbi; Depeint, Flore; Bach, Veronique; Khorsi-Cauet, Hafida; Abdennebi-Najar, Latifa

    2016-01-01

    Increasing evidence indicates that chlorpyrifos (CPF), an organophosphorus insecticide, is involved in metabolic disorders. We assess the hypothesis whether supplementation with prebiotics from gestation to adulthood, through a modulation of microbiota composition and fermentative activity, alleviates CPF induced metabolic disorders of 60 days old offspring. 5 groups of Wistar rats, from gestation until weaning, received two doses of CPF pesticide: 1 mg/kg/day (CPF1) or 3.5 mg/kg/day (CPF3.5)...

  3. Chlorpyrifos pollution: its effect on brain acetylcholinesterase activity in rat and treatment of polluted soil by indigenous Pseudomonas sp.

    Science.gov (United States)

    Sharma, Shelly; Singh, Partap Bir; Chadha, Pooja; Saini, Harvinder Singh

    2017-01-01

    The study was aimed to evaluate the levels of chlorpyrifos (CPF) pollution in agricultural soil of Punjab, India, its detrimental effects on acetylcholinesterase (AChE) activity in rat brain and bioremediation of soils polluted with CPF using indigenous and adapted bacterial lab isolate. The analysis revealed that soil samples of Bathinda and Amritsar regions are highly contaminated with chlorpyrifos showing 19 to 175 mg/kg concentrations of CPF. The non-targeted animals may get poisoned with CPF by its indirect dermal absorption, inhalation of toxic fumes and regular consumption of soiled food grains. The study indicated that even the lowermost concentrations of CPF, 19 and 76 mg/kg of soil found in the Amritsar and Bathinda regions respectively can significantly inhibit the AChE activity in rat brain within 24 h of its treatment. This represents the antagonistic effect of CPF on AChE which is a prime neurotransmitter present in all living beings including humans. In light of this, an attempt was made to remediate the polluted soil, a major reservoir of CPF, using Pseudomonas sp. (ChlD), an indigenous bacterial isolate. The culture efficiently degraded 10 to 100 mg/kg chlorpyrifos supplemented in the soil and utilized it as sole source of carbon and energy for its growth. Thus, this study provides a detailed insight regarding the level of CPF pollution in Punjab, its detrimental effects on mammals and bio-based solution to remediate the sites polluted with CPF.

  4. Residual Toxicity of Abamectin, Chlorpyrifos, Cyromazine, Indoxacarb and Spinosad on Liriomyza trifolii (Burgess (Diptera: Agromyzidae in Greenhouse Conditions

    Directory of Open Access Journals (Sweden)

    Ghasem Askari Saryazdi

    2012-01-01

    Full Text Available Liriomyza trifolii is an important pest of vegetable crops in many parts of the worldincluding Iran. In this study potted bean plants were sprayed with recommended fieldrates of abamectin, chlorpyrifos, cyromazine, indoxacarb and spinosad. To assess the residualactivities of these insecticides, the plants were infested with L. trifolii adults 2 hours; 1, 3,5, 7, 10, 15, 20, 25 and 35 days after insecticidal treatments. The adults were allowed to stayon treated plants for eight hours. The treated plants were kept in a greenhouse. Numberof feeding stipples and larval mines on leaves, as well as pupation and adult eclosion rateswere assessed. Two-way ANOVA procedure of SAS was used for statistical analysis andthe treatment means were separated using Duncan’s multiple range test. Abamectin andspinosad severely affected egg hatching and embryonic development. Eggs oviposited inleaves with residues of chlorpyrifos up to 5 days old, had reduced hatching. Larval developmentwas also, affected by residues of chlorpyrifos up to four weeks old. Indoxacarbreduced larval development and adult eclosion in treatments with up to 20 days old residues.Cyromazine had no effect on the number of larval mines, but, pupation was severelyhampered and adult eclosion was completely ceased even in treatments with five weeksold residues. Determining the residual activity of insecticides used for controlling this pestis useful in avoiding unnecessary treatments.

  5. The Mechanism by Which Dodecyl Dimethyl Benzyl Ammonium Chloride Increased the Toxicity of Chlorpyrifos to Spodoptera exigua

    Directory of Open Access Journals (Sweden)

    Li Cui

    2017-07-01

    Full Text Available Beet armyworm, Spodoptera exigua (Hübner is one of the most destructive pests that causes significant losses in crops. Unfortunately, S. exigua have developed resistance toward the majority of insecticides. Synergists may provide an important choice to deal with the resistance problems. Dodecyl dimethyl benzyl ammonium chloride (DDBAC is a cationic surfactant, which displayed enhancement effect when combined with chlorpyrifos against S. exigua, giving enhancement factors of 1.50 and 1.57 at the concentrations of 90 and 810 mg L−1. In order to clarify the possible mechanisms, we investigate the effects of DDBAC on detoxification enzymes. However, DDBAC showed no inhibition on these enzymes activities. Meanwhile, scanning electron microscope images indicated DDBAC did not affect the cuticle super micro structure of S. exigua. The alterations in cuticular penetration rate have also been observed; indeed, it has been suggested that synergism is obtained by an acceleration of insecticide penetration through the cuticle. The chlorpyrifos penetration increased sharply when combined with 90 and 810 mg L−1 DDBAC, with only 12.6 and 8.5% of the initial chlorpyrifos recovered by external rinsing after 8 h. In contrast, when there was no DDBAC, more than 23.3% of the initial dose was recovered after 8 h.

  6. Serotonin 2c receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis

    Science.gov (United States)

    Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor a...

  7. Serotonin and the regulation of mammalian energy balance.

    Science.gov (United States)

    Donovan, Michael H; Tecott, Laurence H

    2013-01-01

    Maintenance of energy balance requires regulation of the amount and timing of food intake. Decades of experiments utilizing pharmacological and later genetic manipulations have demonstrated the importance of serotonin signaling in this regulation. Much progress has been made in recent years in understanding how central nervous system (CNS) serotonin systems acting through a diverse array of serotonin receptors impact feeding behavior and metabolism. Particular attention has been paid to mechanisms through which serotonin impacts energy balance pathways within the hypothalamus. How upstream factors relevant to energy balance regulate the release of hypothalamic serotonin is less clear, but work addressing this issue is underway. Generally, investigation into the central serotonergic regulation of energy balance has had a predominantly "hypothalamocentric" focus, yet non-hypothalamic structures that have been implicated in energy balance regulation also receive serotonergic innervation and express multiple subtypes of serotonin receptors. Moreover, there is a growing appreciation of the diverse mechanisms through which peripheral serotonin impacts energy balance regulation. Clearly, the serotonergic regulation of energy balance is a field characterized by both rapid advances and by an extensive and diverse set of central and peripheral mechanisms yet to be delineated.

  8. Association between salivary serotonin and the social sharing of happiness

    Science.gov (United States)

    Ishii, Keiko; Ohtsubo, Yohsuke; Noguchi, Yasuki; Ochi, Misaki; Yamasue, Hidenori

    2017-01-01

    Although human saliva contains the monoamine serotonin, which plays a key role in the modulation of emotional states, the association between salivary serotonin and empathic ability remains unclear. In order to elucidate the associations between salivary serotonin levels, trait empathy, and the sharing effect of emotions (i.e., sharing emotional experiences with others), we performed a vignette-based study. Participants were asked to evaluate their happiness when they experience several hypothetical life events, whereby we manipulated the valence of the imagined event (positive, neutral, or negative), as well as the presence of a friend (absent, positive, or negative). Results indicated that the presence of a happy friend significantly enhanced participants’ happiness. Correlation analysis demonstrated that salivary serotonin levels were negatively correlated with happiness when both the self and friend conditions were positive. Correlation analysis also indicated a negative relationship between salivary serotonin levels and trait empathy (particularly in perspective taking), which was measured by the Interpersonal Reactivity Index. Furthermore, an exploratory multiple regression analysis suggested that mothers’ attention during childhood predicted salivary serotonin levels. Our findings indicate that empathic abilities and the social sharing of happiness decreases as a function of salivary serotonin levels. PMID:28683075

  9. Association between salivary serotonin and the social sharing of happiness.

    Science.gov (United States)

    Matsunaga, Masahiro; Ishii, Keiko; Ohtsubo, Yohsuke; Noguchi, Yasuki; Ochi, Misaki; Yamasue, Hidenori

    2017-01-01

    Although human saliva contains the monoamine serotonin, which plays a key role in the modulation of emotional states, the association between salivary serotonin and empathic ability remains unclear. In order to elucidate the associations between salivary serotonin levels, trait empathy, and the sharing effect of emotions (i.e., sharing emotional experiences with others), we performed a vignette-based study. Participants were asked to evaluate their happiness when they experience several hypothetical life events, whereby we manipulated the valence of the imagined event (positive, neutral, or negative), as well as the presence of a friend (absent, positive, or negative). Results indicated that the presence of a happy friend significantly enhanced participants' happiness. Correlation analysis demonstrated that salivary serotonin levels were negatively correlated with happiness when both the self and friend conditions were positive. Correlation analysis also indicated a negative relationship between salivary serotonin levels and trait empathy (particularly in perspective taking), which was measured by the Interpersonal Reactivity Index. Furthermore, an exploratory multiple regression analysis suggested that mothers' attention during childhood predicted salivary serotonin levels. Our findings indicate that empathic abilities and the social sharing of happiness decreases as a function of salivary serotonin levels.

  10. Selective serotonin reuptake inhibitors and risk for gastrointestinal bleeding

    Directory of Open Access Journals (Sweden)

    Batić-Mujanović Olivera

    2014-01-01

    Full Text Available The most of the known effects of selective serotonin reuptake inhibitors, beneficial or harmful, are associated with the inhibitory action of the serotonin reuptake transporter. This mechanism is present not only in neurons, but also in other cells such as platelets. Serotoninergic mechanism seems to have an important role in hemostasis, which has long been underestimated. Abnormal activation may lead to a prothrombotic state in patients treated with selective serotonin reuptake inhibitors. On one hand there may be an increased risk of bleeding, and on the other hand reduction in thrombotic risk may be possible. Serotonin is critical to maintain a platelet haemostatic function, such as platelet aggregation. Evidences from the studies support the hypothesis that antidepressants with a relevant blockade of action of serotonin reuptake mechanism may increase the risk of bleeding, which can occur anywhere in the body. Epidemiological evidences are, however, the most robust for upper gastrointestinal bleeding. It is estimated that this bleeding can occur in 1 in 100 to 1 in 1.000 patient-years of exposure to the high-affinity selective serotonin reuptake inhibitors, with very old patients at the highest risk. The increased risk may be of particular relevance when selective serotonin reuptake inhibitors are taken simultaneously with nonsteroidal anti-inflammatory drugs, low dose of aspirin or warfarin.

  11. Association between salivary serotonin and the social sharing of happiness.

    Directory of Open Access Journals (Sweden)

    Masahiro Matsunaga

    Full Text Available Although human saliva contains the monoamine serotonin, which plays a key role in the modulation of emotional states, the association between salivary serotonin and empathic ability remains unclear. In order to elucidate the associations between salivary serotonin levels, trait empathy, and the sharing effect of emotions (i.e., sharing emotional experiences with others, we performed a vignette-based study. Participants were asked to evaluate their happiness when they experience several hypothetical life events, whereby we manipulated the valence of the imagined event (positive, neutral, or negative, as well as the presence of a friend (absent, positive, or negative. Results indicated that the presence of a happy friend significantly enhanced participants' happiness. Correlation analysis demonstrated that salivary serotonin levels were negatively correlated with happiness when both the self and friend conditions were positive. Correlation analysis also indicated a negative relationship between salivary serotonin levels and trait empathy (particularly in perspective taking, which was measured by the Interpersonal Reactivity Index. Furthermore, an exploratory multiple regression analysis suggested that mothers' attention during childhood predicted salivary serotonin levels. Our findings indicate that empathic abilities and the social sharing of happiness decreases as a function of salivary serotonin levels.

  12. Probable Tapentadol-Associated Serotonin Syndrome After Overdose.

    Science.gov (United States)

    Walczyk, Heather; Liu, Cheuk H Michael; Alafris, Antonia; Cohen, Henry

    2016-04-01

    Drug-induced serotonin syndrome is a potentially life-threatening condition. An Ovid MEDLINE, and PubMed search from 1950 to October 2015 revealed one published case report of suspected tapentadol-induced serotonin syndrome. We report a probable case of tapentadol-induced serotonin syndrome after overdose. A 48-year-old male was found unresponsive after a witnessed overdose of medications including tapentadol. After administration of naloxone by emergency medical services, the patient became combative and presented with altered mental status. He was managed with physical and pharmacologic restraints in the emergency department. Other medications that could be implicated in the patient's presentation include duloxetine and amitriptyline. It was suspected that the opioid properties of tapentadol were masking the patient's signs and symptoms of serotonin syndrome. The patient was admitted to the medical intensive care unit, remained stable, and was discharged 2 days later. Currently, there is one published case report of suspected tapentadol-induced serotonin syndrome after an overdose. The manufacturer of tapentadol reported no cases of serotonin syndrome during clinical trials, but there have been postmarketing cases reported with co-administration of other serotonergic drugs. We report a probable case of tapentadol-induced serotonin syndrome after overdose. Further research is needed to better understand the pharmacology and incidence behind this adverse event.

  13. Serotonin syndrome following methylene blue administration during cardiothoracic surgery.

    Science.gov (United States)

    Smith, Christina J; Wang, Dorothy; Sgambelluri, Anna; Kramer, Robert S; Gagnon, David J

    2015-04-01

    Despite its favorable safety profile, there have been reports of methylene blue-induced encephalopathy and serotonin syndrome in patients undergoing parathyroidectomy. We report a case of serotonin syndrome following methylene blue administration in a cardiothoracic surgery patient. A 59-year-old woman taking preoperative venlafaxine and trazodone was given a single dose of 2 mg/kg methylene blue (167 mg) during a planned coronary artery bypass and mitral valve repair. Postoperatively, she was febrile to 38.7°C and developed full-body tremors, rhythmic twitching of the perioral muscles, slow conjugate roving eye movements, and spontaneous movements of the upper extremities. Electroencephalography revealed generalized diffuse slowing consistent with toxic encephalopathy, and a computed tomography scan showed no acute process. The patient's symptoms were most consistent with a methylene blue-induced serotonin syndrome. Her motor symptoms resolved within 48 hours and she was eventually discharged home. Only 2 cases of methylene blue-induced serotonin syndrome during cardiothoracic surgery have been described in the literature, with this report representing the third case. Methylene blue and its metabolite, azure B, are potent, reversible inhibitors of monoamine oxidase A which is responsible for serotonin metabolism. Concomitant administration of methylene blue with serotonin-modulating agents may precipitate serotonin syndrome. © The Author(s) 2015.

  14. Serotonin Mechanisms in Heart Valve Disease I

    Science.gov (United States)

    Jian, Bo; Xu, Jie; Connolly, Jeanne; Savani, Rashmin C.; Narula, Navneet; Liang, Bruce; Levy, Robert J.

    2002-01-01

    Clinical disorders associated with increased serotonin [5-hydroxytryptamine (5-HT)] levels, such as carcinoid syndrome, and the use of serotonin agonists, such as fenfluoramine have been associated with a valvulopathy characterized by hyperplastic valvular and endocardial lesions with increased extracellular matrix. Furthermore, 5-HT has been demonstrated to up-regulate transforming growth factor (TGF)-β in mesangial cells via G-protein signal transduction. We investigated the hypothesis that increased exposure of heart valve interstitial cells to 5-HT may result in increased TGF-β1 expression and activity because of serotonin receptor-mediated signal transduction with activation of Gαq, and subsequently up-regulation of phospholipase C. Thus, in the present study we performed a clinical-pathological investigation of retrieved carcinoid and normal valve cusps using immunohistochemical techniques to detect the presence of TGF-β1 and other proteins associated with TGF-β expression, including TGF-β receptors I and II, latent TGF-β-associated peptide (LAP), and α-smooth muscle actin. Carcinoid valve cusps demonstrated the unusual finding of widespread smooth muscle actin involving the interstitial cells in the periphery of carcinoid nodules; these same cells were also positive for LAP. Normal valve cusps were only focally positive for smooth muscle actin and LAP. In sheep aortic valve interstitial cell cultures 5-HT induced TGF-β1 mRNA production and increased TGF-β1 activity. 5-HT also increased collagen biosynthesis at the dosages studied. Furthermore, TGF-β1 added to SAVIC cultures increased the production of sulfated glycan and hyaluronic acid. In addition, overexpression of Gαq using an adenoviral expression vector for a constitutively active Gαq mutant (Q209L-Gαq) resulted in increased phospholipase C activity as well as up-regulation of TGF-β expression and activity. These results strongly support the view that G-protein-related signal

  15. Remediation of Chlorpyrifos-Contaminated Soils by Laboratory-Synthesized Zero-Valent Nano Iron Particles: Effect of pH and Aluminium Salts

    Directory of Open Access Journals (Sweden)

    A. Vijaya Bhaskar Reddy

    2013-01-01

    Full Text Available Degradation of the insecticide chlorpyrifos in contaminated soils was investigated using laboratory synthesized zero-valent nano iron (ZVNI particles. The synthesized ZVNI particles were characterized as nanoscale sized by scanning electron microscopy (SEM and transmission electron microscopy (TEM. The zero-valent state (Fe0 of iron was confirmed by EDAX analysis and the morphology of the ZVNI particles was studied by XRD. Batch experiments were conducted by treating the chlorpyrifos contaminated soil with ZVNI, our results indicate that 90% of chlorpyrifos was degraded after 10 days of incubation. Only 32% degradation was observed with micro zero-valent iron (mZVI and no considerable degradation was attained without ZVNI. The degradation of chlorpyrifos followed the first-order kinetics with a rate constant and a half-life of 0.245 day−1 and 2.82 days, respectively. Degradation was monitored at two different pH values, that is, pH 10 and pH 4. Chlorpyrifos degradation rate constant increased as the pH decreases from 10 to 4. The corresponding rate constant and half-lives were 0.43 day−1 and 1.57days for pH 4, 0.18 day−1 and 3.65 days for pH 10. In addition, an attempt was made by augmenting Al2(SO43 with ZVNI and it was found that the degradation rate of chlorpyrifos was greatly enhanced and the rate constant was rapidly increased from 0.245 day−1 to 0.60 day−1. Hydrolysis and stepwise dechlorination pathway of chlorpyrifos with ZVNI was the dominant reaction.

  16. Serotonin syndrome:case report and current concepts.

    LENUS (Irish Health Repository)

    Fennell, J

    2005-05-01

    Selective serotonin reuptake inhibitors (SSRI\\'s) are increasingly being used as the first line therapeutic agent for the depression. It is therefore not unusual to see a case of overdose with these agents. More commonly an adverse drug reaction may be seen among the older patients who are particularly vulnerable to the serotonin syndrome due to multiple co-morbidity and polypharmacy. The clinical picture of serotonin syndrome (SS) is non-specific and there is no confirmatory test. SS may go unrecognized because it is often mistaken for a viral illness, anxiety, neurological disorder or worsening psychiatric condition.

  17. Serotonin as a Biomarker: Stress Resilience among Battlefield Airmen Trainees

    Science.gov (United States)

    2016-05-21

    Depression -Dejection 0.310 0.358 Fatigue 0.929 0.384 Friendliness 0.295 0.046 Serotonin 0.281 0.489 Tension-Anxiety 0.789 0.912 Total Distress...Discriminant analysis showed that subjects with increased serotonin levels were more likely to SIE. Confusion-bewilderment, depression -dejection, and...and that NPY may be a protective factor during acute stress [10]. Studies have established that low levels of serotonin are associated with depression

  18. Hippocampal volume and serotonin transporter polymorphism in major depressive disorder

    DEFF Research Database (Denmark)

    Ahdidan, Jamila; Foldager, Leslie; Rosenberg, Raben

    2013-01-01

    Objective: The main aim of the present study was to replicate a previous finding in major depressive disorder (MDD) of association between reduced hippocampal volume and the long variant of the di- and triallelic serotonin transporter polymorphism in SLC6A4 on chromosome 17q11.2. Secondarily, we...... that we aimed to replicate, and no significant associations with the serotonin transporter polymorphism were found. Conclusions: The present quantitative and morphometric MRI study was not able to replicate the previous finding of association between reduced hippocampal volume in depressed patients...... and the serotonin transporter polymorphism....

  19. Serotonin syndrome associated with MDPV use: a case report.

    Science.gov (United States)

    Mugele, Josh; Nañagas, Kristine A; Tormoehlen, Laura M

    2012-07-01

    Serotonin syndrome is associated with use of certain street drugs, including methamphetamine, cocaine, and ecstasy. We describe a case of a woman who developed clinical findings consistent with serotonin syndrome after insufflation of 3,4-methylenedioxypyrovalerone (MDPV), a synthetic amphetamine. MDPV belongs to a group of substances called phenylethylamines, which are β-ketone analogs of other drugs of abuse, such as amphetamines and 3,4-methylenedioxymethamphetamine. She also received fentanyl initially during her hospitalization, which has also been associated with serotonin syndrome. In addition to benzodiazepines and supportive care, she was treated with cyproheptadine for 8 days, with slow resolution of her symptoms. Copyright © 2011. Published by Mosby, Inc.

  20. Serotonin Deficiency Rescues Lactation on Day 1 in Mice Fed a High Fat Diet.

    Directory of Open Access Journals (Sweden)

    Samantha R Weaver

    Full Text Available Obesity is an inflammatory state associated with delayed lactogenesis stage II and altered mammary gland morphology. Serotonin mediates inflammation and mammary gland involution. The objective of this study was to determine if a genetic deficiency of tryptophan hydroxylase 1, the rate-limiting enzyme in peripheral serotonin synthesis, would result in an improved ability to lactate in dams fed a high fat diet. Twenty-six female mice were fed a high (HFD or low fat (LFD diet throughout pregnancy and lactation. Fourteen mice were genetically deficient for Tph1 (Tph1-/-, and twelve were wild type. Milk yield, pup mortality, and dam weights were recorded and milk samples were collected. On day 10 of lactation, dams were sacrificed and mammary glands were harvested for RT-PCR and histological evaluation. HFD dams weighed more than LFD dams at the onset of lactation. WT HFD dams were unable to lactate on day 1 of lactation and exhibited increased pup mortality relative to all other treatments, including Tph1-/- HFD dams. mRNA expression of immune markers C-X-C motif chemokine 5 and tumor necrosis factor alpha were elevated in WT HFD mammary glands. Mammary gland histology showed a reduced number of alveoli in WT compared to Tph1-/- dams, regardless of diet, and the alveoli of HFD dams were smaller than those of LFD dams. Finally, fatty acid profile in milk was dynamic in both early and peak lactation, with reduced de novo synthesis of fatty acids on day 10 of lactation in the HFD groups. Administration of a HFD to C57BL/6 dams produced an obese phenotype in the mammary gland, which was alleviated by a genetic deficiency of Tph1. Serotonin may modulate the effects of obesity on the mammary gland, potentially contributing to the delayed onset of lactogenesis seen in obese women.

  1. Serotonin Deficiency Rescues Lactation on Day 1 in Mice Fed a High Fat Diet.

    Science.gov (United States)

    Weaver, Samantha R; Bohrer, Justin C; Prichard, Allan S; Perez, Paola K; Streckenbach, Liana J; Olson, Jake M; Cook, Mark E; Hernandez, Laura L

    2016-01-01

    Obesity is an inflammatory state associated with delayed lactogenesis stage II and altered mammary gland morphology. Serotonin mediates inflammation and mammary gland involution. The objective of this study was to determine if a genetic deficiency of tryptophan hydroxylase 1, the rate-limiting enzyme in peripheral serotonin synthesis, would result in an improved ability to lactate in dams fed a high fat diet. Twenty-six female mice were fed a high (HFD) or low fat (LFD) diet throughout pregnancy and lactation. Fourteen mice were genetically deficient for Tph1 (Tph1-/-), and twelve were wild type. Milk yield, pup mortality, and dam weights were recorded and milk samples were collected. On day 10 of lactation, dams were sacrificed and mammary glands were harvested for RT-PCR and histological evaluation. HFD dams weighed more than LFD dams at the onset of lactation. WT HFD dams were unable to lactate on day 1 of lactation and exhibited increased pup mortality relative to all other treatments, including Tph1-/- HFD dams. mRNA expression of immune markers C-X-C motif chemokine 5 and tumor necrosis factor alpha were elevated in WT HFD mammary glands. Mammary gland histology showed a reduced number of alveoli in WT compared to Tph1-/- dams, regardless of diet, and the alveoli of HFD dams were smaller than those of LFD dams. Finally, fatty acid profile in milk was dynamic in both early and peak lactation, with reduced de novo synthesis of fatty acids on day 10 of lactation in the HFD groups. Administration of a HFD to C57BL/6 dams produced an obese phenotype in the mammary gland, which was alleviated by a genetic deficiency of Tph1. Serotonin may modulate the effects of obesity on the mammary gland, potentially contributing to the delayed onset of lactogenesis seen in obese women.

  2. Characterization and expression analysis of peroxiredoxin family genes from the silkworm Bombyx mori in response to phoxim and chlorpyrifos.

    Science.gov (United States)

    Shi, Gui-Qin; Zhang, Ze; Jia, Kun-Lun; Zhang, Kun; An, Dong-Xu; Wang, Gang; Zhang, Bao-Long; Yin, He-Nan

    2014-09-01

    The organophosphorus pesticide poisoning of the silkworm Bombyx mori is one of the major events causing serious damage to sericulture. Some antioxidant enzymes play roles in regulating generation of reactive oxygen species (ROS) by pesticides including phoxim and chlorpyrifos, but relatively little is known about their effects on the silkworm peroxiredoxin family genes. Here, five peroxiredoxin (Prx) genes have been identified in silkworm genome, and Prx genes of silkworm and mammalian homologs have apparent ortholog relationship. Based on the genomic DNA sequence, putative 5'-flanking region of five BmPrxs were obtained and the transcription factor binding sites were predicted. Their expression profiles exposed to different concentrations of phoxim and chlorpyrifos for 24 h, 48 h and 72 h in midgut of silkworm were investigated using quantitative RT-PCR (qRT-PCR). The results showed that five BmPrxs and dual oxidase (BmDUOX) gene were all expressed in midgut of silkworm. After feeding with 0.375 mg/L and 0.75 mg/L phoxim, the transcription levels of BmPrx3 and BmPrx5 that can be located in mitochondria reached their peak levels at an early time point (24h). However, the transcription levels of BmPrx4 and BmPrx6 that can be addressed to secrete from the cell and cytosol, respectively, reached their peak levels at a later time point (72 h). Similar to expose to phoxim, the transcription levels of BmPrx3 and BmPrx5 that can be located in mitochondria reached their peak levels at an early time point (24 h) under chlorpyrifos stress. However, the transcription levels of BmPrx4 and BmPrx6 that can be addressed to secrete from the cell and cytosol, respectively, reached their peak levels at a later time point (72 h) under chlorpyrifos stress. These results revealed that BmPrxs that can be located in mitochondria were able to protect cells even more efficiently than cytosolic from an oxidative stress caused by OP. In addition, BmDUOX was also induced by phomix and

  3. The Role of Serotonin beyond the Central Nervous System during Embryogenesis

    OpenAIRE

    Lv, Junhua; Liu, Feng

    2017-01-01

    Serotonin, or 5-hydroxytryptamine (5-HT), is a well-known neurotransmitter that plays vital roles in neural activities and social behaviors. Clinically, deficiency of serotonin is linked with many psychiatric disorders. Interestingly, a large proportion of serotonin is also produced outside the central nervous system (CNS). There is increasing evidence demonstrating important roles of serotonin in the peripheral tissues. Here, we will describe the multiple biological functions of serotonin in...

  4. Autophagy regulates chlorpyrifos-induced apoptosis in SH-SY5Y cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jae Hyeon [Department of Pharmacology, College of Medicine, Hanyang University (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); Lee, Jeong Eun [Department of Pharmacology, College of Medicine, Hanyang University (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Shin, In Chul [Department of Pharmacology, College of Medicine, Hanyang University (Korea, Republic of); Koh, Hyun Chul, E-mail: hckoh@hanyang.ac.kr [Department of Pharmacology, College of Medicine, Hanyang University (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of)

    2013-04-01

    Recent studies have shown that up-regulation of autophagy may be a tractable therapeutic intervention for clearing disease-causing proteins, including α-synuclein, ubiquitin, and other misfolded or aggregated proteins in pesticide-induced neurodegeneration. In a previous study, we reported that chlorpyrifos (CPF)-induced mitochondria-dependent apoptosis is mediated through reactive oxygen species in SH-SY5Y cells. In this study, we explored a novel pharmacotherapeutic approach to prevent CPF neurotoxicity involving the regulation of autophagy. We investigated the modulation of CPF-induced apoptosis according to autophagy regulation. We found that CPF induced apoptosis in SH-SY5Y cells, as demonstrated by the activation of caspase-3 and nuclear condensation. In addition, we observed that cells treated with CPF underwent autophagic cell death by monitoring the expression of LC3-II and p62. Pretreatment with the autophagy inducer rapamycin significantly enhanced the cell viability of CPF-exposed cells, and the enhancement of cell viability was partially due to alleviation of CPF-induced apoptosis via a decrease in levels of cleaved caspase-3. Specifically, rapamycin pretreatment decreased Bax and increased Bcl-2 expression in mitochondria. In addition, rapamycin significantly decreased cytochrome c release in from mitochondria into the cytosol. However, pretreatment of cells with the autophagy inhibitor, 3-methyladenine (3MA), remarkably increased CPF toxicity in these cells; this with correlated with increased expression of Bax and decreased expression of Bcl-2 in mitochondria. Our results suggest that CPF-induced cytotoxicity is modified by autophagy regulation and that rapamycin protects against CPF-induced apoptosis by enhancing autophagy. Pharmacologic induction of autophagy by rapamycin may be a useful treatment strategy in neurodegenerative disorders. - Highlights: ► Chlorpyrifos (CPF) is cytotoxic to SH-SY5Y cells ► CPF-induced cytotoxicity is mediated by

  5. Effect of in vivo nicotine exposure on chlorpyrifos pharmacokinetics and pharmacodynamics in rats

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Soo Kwang; Poet, Torka S.; Smith, Jordan N.; Busby-Hjerpe, Andrea L.; Timchalk, Charles

    2010-03-30

    Chlorpyrifos (CPF) is one of the most studied and widely used broad spectrum organophosphorus (OP) insecticides. The neurotoxicity of CPF results from inhibition of cholinesterase (ChE) by its metabolite, chlorpyrifos-oxon (CPF-oxon), which subsequently leads to cholinergic hyperstimulation. The routine consumption of alcoholic beverages and tobacco products will modify a number of metabolic and physiological processes which may impact the metabolism and pharmacokinetics of other xenobiotics including pesticides. The objective of this study was to evaluate the influence of repeated ethanol and nicotine co-exposure on in vivo CPF pharmacokinetics and pharmacodynamics. The major CPF metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urine along with changes in plasma and brain AChE activities were measured in male Sprague-Dawley (S-D) rats. Animals were repeatedly treated with either saline or ethanol (1 g/kg/day, po) and nicotine (1 mg/kg/day, sc) in addition to CPF (1 or 5 mg/kg/day, po) for 7 days. Rats were sacrificed at times from 1 to 24 hr post-last dosing of CPF. There were apparent differences in blood TCPy pharmacokinetics following ethanol and nicotine pretreatments in both CPF dose groups, which showed higher TCPy peak concentrations and increased blood TCPy AUC in ethanol and nicotine groups over CPF-only (~1.8- and 3.8-fold at 1 and 5 mg CPF doses, respectively). Brain acetylcholinesterase (AChE) activities from both ethanol and nicotine-treated groups showed substantially less inhibition following repeated 5 mg CPF/kg dosing compared to CPF-only controls (96 ± 13 and 66 ± 7% of naïve at 4 hr post-last CPF dosing, respectively). Inhibition of brain AChE activities was minimal in both 1 mg CPF/kg/day dosing groups, but a similar trend indicating less inhibition following ethanol/nicotine pretreatment was apparent. No differences were observed in plasma ChE activities due to the combined alcohol and nicotine treatments. In vitro, CPF

  6. Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Tingting; Zhao, Ling; Liu, Mengyu; Xie, Fei; Ma, Xuemei, E-mail: xmma@bjut.edu.cn; Zhao, Pengxiang; Liu, Yunqi; Li, Jiala; Wang, Minglian; Yang, Zhaona; Zhang, Yutong

    2014-10-01

    Chronic exposure to low-levels of organophosphate (OP) compounds, such as chlorpyrifos (CPF), induces oxidative stress and could be related to neurological disorders. Hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. We explore whether intake of hydrogen-rich water (HRW) can protect Wistar rats from CPF-induced neurotoxicity. Rats were gavaged daily with 6.75 mg/kg body weight (1/20 LD{sub 50}) of CPF and given HRW by oral intake. Nissl staining and electron microscopy results indicated that HRW intake had protective effects on the CPF-induced damage of hippocampal neurons and neuronal mitochondria. Immunostaining results showed that the increased glial fibrillary acidic protein (GFAP) expression in astrocytes induced by CPF exposure can be ameliorated by HRW intake. Moreover, HRW intake also attenuated CPF-induced oxidative stress as evidenced by enhanced level of MDA, accompanied by an increase in GSH level and SOD and CAT activity. Acetylcholinesterase (AChE) activity tests showed significant decrease in brain AChE activity after CPF exposure, and this effect can be ameliorated by HRW intake. An in vitro study demonstrated that AChE activity was more intense in HRW than in normal water with or without chlorpyrifos-oxon (CPO), the metabolically-activated form of CPF. These observations suggest that HRW intake can protect rats from CPF-induced neurotoxicity, and the protective effects of hydrogen may be mediated by regulating the oxidant and antioxidant status of rats. Furthermore, this work defines a novel mechanism of biological activity of hydrogen by directly increasing the AChE activity. - Highlights: • Hydrogen molecules protect rats from CPF-induced damage of hippocampal neurons. • The increased GFAP expression induced by CPF can also be ameliorated by hydrogen. • Hydrogen molecules attenuated the increase in CPF-induced oxidative stress. • Hydrogen molecules attenuated AChE inhibition in vivo

  7. Agonist-directed signaling of serotonin 5-HT2C receptors: differences between serotonin and lysergic acid diethylamide (LSD).

    Science.gov (United States)

    Backstrom, J R; Chang, M S; Chu, H; Niswender, C M; Sanders-Bush, E

    1999-08-01

    For more than 40 years the hallucinogen lysergic acid diethylamide (LSD) has been known to modify serotonin neurotransmission. With the advent of molecular and cellular techniques, we are beginning to understand the complexity of LSD's actions at the serotonin 5-HT2 family of receptors. Here, we discuss evidence that signaling of LSD at 5-HT2C receptors differs from the endogenous agonist serotonin. In addition, RNA editing of the 5-HT2C receptor dramatically alters the ability of LSD to stimulate phosphatidylinositol signaling. These findings provide a unique opportunity to understand the mechanism(s) of partial agonism.

  8. Serotonin-Sensitive Adenylate Cyclase in Neural Tissue and Its Similarity to the Serotonin Receptor: A Possible Site of Action of Lysergic Acid Diethylamide

    Science.gov (United States)

    Nathanson, James A.; Greengard, Paul

    1974-01-01

    An adenylate cyclase (EC 4.6.1.1) that is activated specifically by low concentrations of serotonin has been identified in homogenates of the thoracic ganglia of an insect nervous system. The activation of this enzyme by serotonin was selectively inhibited by extremely low concentrations of D-lysergic acid diethylamide (LSD), 2-bromo-LSD, and cyproheptadine, agents which are known to block certain serotonin receptors in vivo. The inhibition was competitive with respect to serotonin, and the calculated inhibitory constant of LSD for this serotonin-sensitive adenylate cyclase was 5 nM. The data are consistent with a model in which the serotonin receptor of neural tissue is intimately associated with a serotonin-sensitive adenylate cyclase which mediates serotonergic neurotransmission. The results are also compatible with the possibility that some of the physiological effects of LSD may be mediated through interaction with serotonin-sensitive adenylate cyclase. PMID:4595572

  9. An autism-associated serotonin transporter variant disrupts multisensory processing

    National Research Council Canada - National Science Library

    J K Siemann; C L Muller; C G Forsberg; R D Blakely; J Veenstra-vanderweele; M T Wallace

    2017-01-01

    ... (that is, multisensory function). The serotonin system has an important role in sensory development and function, and alterations of serotonergic signaling have been suggested to have a role in ASD...

  10. Serotonin blockade delays learning performance in a cooperative fish.

    Science.gov (United States)

    Soares, Marta C; Paula, José R; Bshary, Redouan

    2016-09-01

    Animals use learning and memorizing to gather information that will help them to make ecologically relevant decisions. Neuro-modulatory adjustments enable them to make associations between stimuli and appropriate behavior. A key candidate for the modulation of cooperative behavior is serotonin. Previous research has shown that modulation of the serotonergic system spontaneously affects the behavior of the cleaner wrasse Labroides dimidiatus during interactions with so-called 'client' reef fish. Here, we asked whether shifts in serotonin function affect the cleaners' associative learning abilities when faced with the task to distinguish two artificial clients that differ in their value as a food source. We found that the administration of serotonin 1A receptor antagonist significantly slowed learning speed in comparison with saline treated fish. As reduced serotonergic signaling typically enhances fear, we discuss the possibility that serotonin may affect how cleaners appraise, acquire information and respond to client-derived stimuli via manipulation of the perception of danger.

  11. Antidepressants differentially affect striatal amphetamine-stimulated dopamine and serotonin release in rats with high and low novelty-oriented behaviour.

    Science.gov (United States)

    O'Leary, Aet; Kõiv, Kadri; Raudkivi, Karita; Harro, Jaanus

    2016-11-01

    In the studies of depression pathogenesis and antidepressant action, the monoaminergic hypothesis of depression has mainly focused on the serotonergic and noradrenergic mechanisms. However, dopaminergic neurotransmission is also linked to both depressive symptomatology as well as antidepressant effects. We have previously shown that persistent inter-individual differences in the rat behavioural activity in novel environments is associated with differences in the striatal extracellular levels of dopamine and serotonin, depressive-like behaviour and the expression of several depression-related genes. The aim of the current study was to investigate the relative potency of the tricyclic antidepressant imipramine, the selective serotonin re-uptake inhibitor fluoxetine, and the selective noradrenaline re-uptake inhibitor reboxetine (all drugs administered in the dose of 10mg/kg, i.p.) to enhance amphetamine-stimulated dopamine and serotonin release in the striatum using in vivo microdialysis in awake, freely-moving rats, categorized into high explorers (HE) and low explorers (LE) based on their spontaneous novelty-oriented behaviour. The basal extracellular dopamine and serotonin concentration in the striatum did not differ between the LE- and HE-rats. None of the antidepressants alone were able to modify baseline striatal dopamine levels, but the amphetamine-stimulated dopamine release was significantly higher in the HE-rats after acute and chronic imipramine (but not fluoxetine or reboxetine). Acute imipramine and fluoxetine, but not reboxetine, increased both the basal and amphetamine-stimulated levels of serotonin in the striatum. Again, the HE-rats had higher amphetamine-stimulated serotonin release after fluoxetine administration. These findings suggest that rats with depressive-like phenotype are less sensitive to the neurochemical effects of antidepressants in the striatum. These results may have relevance in understanding the neurobiological bases for inter

  12. Determination of selected pesticides in water samples adjacent to agricultural fields and removal of organophosphorus insecticide chlorpyrifos using soil bacterial isolates

    Science.gov (United States)

    Hossain, M. S.; Chowdhury, M. Alamgir Zaman; Pramanik, Md. Kamruzzaman; Rahman, M. A.; Fakhruddin, A. N. M.; Alam, M. Khorshed

    2015-06-01

    The use of pesticide for crops leads to serious environmental pollution, therefore, it is essential to monitor and develop approaches to remove pesticide from contaminated environment. In this study, water samples were collected to monitor pesticide residues, and degradation of chlorpyrifos was also performed using soil bacteria. Identification of pesticide residues and determination of their levels were performed by high-performance liquid chromatography with photodiode array detector. Among 12 samples, 10 samples were found contaminated with pesticides. Chlorpyrifos was detected in four tested samples and concentrations ranged from 3.27 to 9.31 μg/l whereas fenitrothion ranging from (Below Detection Limit, removal of 50 mg/l chlorpyrifos. Chlorpyrifos degradation rates were found maximum by all three isolates at 2nd day of incubation for both tested concentrations. The results of the present study suggest the need for regular monitoring of pesticide residues in water, to protect the aquatic environment. Chlorpyrifos degrading bacterial isolates can be used to clean up environmental samples contaminated with the organophosphate pesticides.

  13. In vivo imaging of cerebral serotonin transporter and serotonin(2A) receptor binding in 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") and hallucinogen users

    DEFF Research Database (Denmark)

    Erritzoe, David; Frøkjær, Vibe; Holst, Klaus K

    2011-01-01

    Both hallucinogens and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin.......Both hallucinogens and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin....

  14. Divergent Roles of Central Serotonin in Adult Hippocampal Neurogenesis

    OpenAIRE

    Song, Ning-Ning; Huang, Ying; Yu, Xin; Lang, Bing; Ding, Yu-Qiang; Zhang, Lei

    2017-01-01

    The central serotonin (5-HT) system is the main target of selective serotonin reuptake inhibitors (SSRIs), the first-line antidepressants widely used in current general practice. One of the prominent features of chronic SSRI treatment in rodents is the enhanced adult neurogenesis in the hippocampus, which has been proposed to contribute to antidepressant effects. Therefore, tremendous effort has been made to decipher how central 5-HT regulates adult hippocampal neurogenesis. In this paper, we...

  15. Genetics of premenstrual syndrome: investigation of specific serotonin receptor polymorphisms

    OpenAIRE

    Dhingra, Vandana

    2014-01-01

    Premenstrual dysphoric disorder (PMDD) is a distressing and disabling syndrome causing a significant degree of impairment on daily functioning and interpersonal relationships in 3-8% of the women. With the convincing evidence that PMS is inheritable and that serotonin is important in the pathogenesis of PMS, and failure of initial studies to demonstrate significant associations between key genes controlling the synthesis, reuptake and catabolism of serotonin and PMDD, the main aim of this the...

  16. SEP-225289 serotonin and dopamine transporter occupancy: a PET study.

    Science.gov (United States)

    DeLorenzo, Christine; Lichenstein, Sarah; Schaefer, Karen; Dunn, Judith; Marshall, Randall; Organisak, Lisa; Kharidia, Jahnavi; Robertson, Brigitte; Mann, J John; Parsey, Ramin V

    2011-07-01

    SEP-225289 is a novel compound that, based on in vitro potencies for transporter function, potentially inhibits reuptake at dopamine, norepinephrine, and serotonin transporters. An open-label PET study was conducted during the development of SEP-225289 to investigate its dopamine and serotonin transporter occupancy. Different single doses of SEP-225289 were administered to healthy volunteers in 3 cohorts: 8 mg (n = 7), 12 mg (n = 5), and 16 mg (n = 7). PET was performed before and approximately 24 h after oral administration of SEP-225289, to assess occupancy at trough levels. Dopamine and serotonin transporter occupancies were estimated from PET using (11)C-N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane ((11)C-PE2I) and (11)C-N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine ((11)C-DASB), respectively. Plasma concentration of SEP-225289 was assessed before ligand injection, and subjects were monitored for adverse events. Average dopamine and serotonin transporter occupancies increased with increasing doses of SEP-225289. Mean dopamine and serotonin transporter occupancies were 33% ± 11% and 2% ± 13%, respectively, for 8 mg; 44% ± 4% and 9% ± 10%, respectively, for 12 mg; and 49% ± 7% and 14% ± 15%, respectively, for 16 mg. On the basis of the relationship between occupancy and plasma concentration, dopamine transporter IC(50) (the plasma concentration of drug at 50% occupancy) was determined (4.5 ng/mL) and maximum dopamine transporter occupancy was extrapolated (85%); however, low serotonin transporter occupancy prevented similar serotonin transporter calculations. No serious adverse events were reported. At the doses evaluated, occupancy of the dopamine transporter was significantly higher than that of the serotonin transporter, despite similar in vitro potencies, confirming that, in addition to in vitro assays, PET occupancy studies can be instrumental to the drug development process by informing early decisions about

  17. Gestational/perinatal chlorpyrifos exposure is not associated with autistic-like behaviors in rodents.

    Science.gov (United States)

    Williams, Amy Lavin; DeSesso, John M

    2014-07-01

    Although animal models cannot exactly replicate human psychiatric disorders, they may be useful to investigate whether the behaviors associated with certain exposures in animals parallel those observed in people. According to the most current version of the Diagnostic and Statistical Manual of Mental Disorders, autism is diagnosed based on (1) persistent deficits in social communication and social interaction; and (2) the presence of restricted, repetitive patterns of behavior, interests and activities. To address whether developmental chlorpyrifos (CPF) exposure was associated with the development of autistic behaviors, a literature search was conducted to identify studies in rats and mice involving gestational or early postnatal exposure to CPF or CPF oxon (CPO, the active metabolite of CPF) and subsequent behavioral testing to assess behaviors related to autism. A total of 13 studies conducted in six different laboratories were identified. Analysis of these studies found that perinatal CPF exposure was generally associated with (1) no effect or increased social communications; (2) no effect or increased social encounters; (3) no effect, reduced stereotypies, or conflicting findings on stereotypic behaviors; and (4) no effect or increased preference for novelty and reduced anxiety in novel environments. These behavioral findings are generally inconsistent with the types of behaviors that would be expected in children with clinical autism. Based on the results of this analysis of rodent model studies involving CPF/CPO exposure, it cannot be concluded that gestational and/or perinatal CPF exposure is likely to be associated with the development of autism-like behaviors in humans.

  18. Characterization of the interaction between cadmium and chlorpyrifos with integrative techniques in incurring synergistic hepatoxicity.

    Directory of Open Access Journals (Sweden)

    Liqun Chen

    Full Text Available Mixture toxicity is an important issue for the risk assessment of environmental pollutants, for which an extensive amount of data are necessary in evaluating their potential adverse health effects. However, it is very hard to decipher the interaction between compounds due to limited techniques. Contamination of heavy metals and organophosphoric insecticides under the environmental and biological settings poses substantial health risk to humans. Although previous studies demonstrated the co-occurrence of cadmium (Cd and chlorpyrifos (CPF in environmental medium and food chains, their interaction and potentially synergistic toxicity remain elusive thus far. Here we integrated the approaches of thin-layer chromatography and (1H NMR to study the interaction between Cd(2+ and CPF in inducing hepatoxicity. A novel interaction was identified between Cd(2+ and CPF, which might be the bonding between Cd(2+ and nitrogen atom in the pyridine ring of CPF, or the chelation formation between one Cd(2+ and two CPF molecules. The Cd-CPF complex was conferred with distinct biological fate and toxicological performances from its parental components. We further demonstrated that the joint hepatoxicity of Cd ion and CPF was chiefly due to the Cd-CPF complex-facilitated intracellular transport associated with oxidative stress.

  19. Modulation of macrophage functionality induced in vitro by chlorpyrifos and carbendazim pesticides.

    Science.gov (United States)

    Helali, Imen; Ferchichi, Saiida; Maaouia, Amal; Aouni, Mahjoub; Harizi, Hedi

    2016-09-01

    The immune response is the first defense against pathogens; however, it is very sensitive and can be impacted on by agrochemicals such as carbamate and organophosphate pesticides widely present in the environment. To understand how pesticides can affect immune cell function in vitro, this study investigated the effects of chlorpyrifos (CPF) and carbendazim (CBZ), the most commonly used pesticides worldwide, on murine immune cell (i.e. macrophage) functions, including lysosomal enzyme activity and pro-inflammatory cytokines (IL-1β and TNFα) and nitric oxide (NO) production by isolated mouse peritoneal macrophages. This study showed for the first time that CPF and CBZ dose-relatedly reduced macrophage lysosomal enzyme activity and LPS-induced production of IL-1β, TNFα and NO. In general, the effects caused by CPF appeared more pronounced than those by CBZ. Collectively, these results demonstrated that CPF and CBZ exhibited marked immunomodulatory effects and could act as potent immunosuppressive factors in vitro. This inhibition of macrophage pro-inflammatory function may be an integral part of the underlying mode of action related to pesticide-induced immunosuppression.

  20. Dose-dependent regional brain acetylcholinesterase and acylpeptide hydrolase inhibition without cell death after chlorpyrifos administration.

    Science.gov (United States)

    Cardona, Diana; López-Granero, Caridad; Cañadas, Fernando; Llorens, Jordi; Flores, Pilar; Pancetti, Floria; Sánchez-Santed, Fernando

    2013-01-01

    Organophosphates (OPs) are important toxic compounds commonly used for a variety of purposes in agriculture, industry and household settings. It has been well established that the main mechanism of acute toxic action of OP is the inhibition of acetylcholinesterase (AChE). However, we observed long term deficit after acute subcutaneous exposure to Chlorpyrifos (CPF) even when AChE activity is restored. In fact, besides AChE inhibition, non-AChE targets have also been proposed as an alternative mechanism involved in the acute lethal action and side effects of short or long-term exposure. In this context, our main aim in this research was to establish a dose-response curve of Acylpeptide hydrolase (APH) and AChE regional brain activity after acute CPF administration that could explain these long term effects observed in the literature. Moreover, since available data suggest that long term effects of OPs exposure could involve neuronal cell death, our second aim was to evaluate, assessing by Fluoro-Jade B (FJB) staining, whether CPF produces induced cell death. Our results show that an acute exposure to 250 mg/kg CPF does not induce neuronal death as measured by FJB but produces highest AChE regional brain inhibition after administration. In addition, APH seems to be more sensitive than AChE to CPF exposure because after 31 days of exposure, complete recovery was seen only for APH activity at Frontal Cortex, Cerebellum and Brain Stem.

  1. The effect of chlorpyrifos on thermogenic capacity of bank voles selected for increased aerobic exercise metabolism.

    Science.gov (United States)

    Dheyongera, Geoffrey; Grzebyk, Katherine; Rudolf, Agata M; Sadowska, Edyta T; Koteja, Paweł

    2016-04-01

    Agro-chemicals potentially cause adverse effects in non-target organisms. The rate of animal energy metabolism can influence their susceptibility to pesticides by influencing food consumption, biotransformation and elimination rates of toxicants. We used experimental evolution to study the effects of inherent differences in energy metabolism rate and exposure to the organophosphate insecticide, chlorpyrifos (CPF) on thermogenic capacity in a wild rodent, the bank vole (Myodes = Clethrionomys glareolus). The voles were sampled from four replicate lines selected for high swim-induced aerobic metabolism (A) and four unselected control (C) lines. Thermogenic capacity, measured as the maximum cold-induced rate of oxygen consumption (VO2cold), was higher in the A - than C lines, and it decreased after continuous exposure to CPF via food or after a single dose administered via oral gavage, but only when measured shortly after exposure. VO2cold measured 24 h after repeated exposure was not affected. In addition, gavage with a single dose led to decreased food consumption and loss in body mass. Importantly, the adverse effects of CPF did not differ between the selected and control lines. Therefore, exposure to CPF has adverse effects on thermoregulatory performance and energy balance in this species. The effects are short-lived and their magnitude is not associated with the inherent level of energy metabolism. Even without severe symptoms of poisoning, fitness can be compromised under harsh environmental conditions, such as cold and wet weather. Copyright © 2016. Published by Elsevier Ltd.

  2. ChpR is a chlorpyrifos-responsive transcription regulator in Sinorhizobium meliloti.

    Science.gov (United States)

    Whangsuk, Wirongrong; Dubbs, James M; Sallabhan, Ratiboot; Somsongkul, Kumpanart; Mongkolsuk, Skorn; Loprasert, Suvit

    2010-01-01

    The broad-spectrum organophosphate insecticide chlorpyrifos (CPF)-inducible locus, chpAB, was identified on the endogenous plasmid pSymB in Sinorhizobium meliloti. The S. meliloti chpA promoter was highly induced by CPF and was induced at much lower levels by diazinon and ethion. Transcription of chpA was dependent on chpR, a CadC family transcriptional regulator located upstream of, and divergently transcribed from, chpAB. ChpR was able to mediate the CPF-inducible expression of the S. melilotichpA promoter in Escherichia coli through direct interaction with the chpAB promoter. The chpR-chpA intergenic regions of several bacterial chpRAB operons were aligned and a putative ChpR-binding sequence was proposed. Both the ChpR transcription factor and chpA promoter constitute a good candidate system for genetic-based biosensor development. 2010 S. Karger AG, Basel.

  3. Thermoactivated persulfate oxidation of pesticide chlorpyrifos in aquatic system: kinetic and mechanistic investigations.

    Science.gov (United States)

    Zhou, Lei; Zhang, Ya; Ying, Rongrong; Wang, Guoqing; Long, Tao; Li, Jianhua; Lin, Yusuo

    2017-04-01

    The widespread occurrence of organophosphorus pesticides (OPPs) in the environment poses risks to both ecologic system as well as human health. This study investigated the oxidation kinetics of chlorpyrifos (CP), one of the typical OPPs, by thermoactivated persulfate (PS) oxidation process, and evaluated the influence of key kinetic factors, such as PS concentrations, pH, temperature, bicarbonate, and chloride ions. The reaction pathways and mechanisms were also proposed based on products identification by LC-MS techniques. Our results revealed that increasing initial PS concentration and temperature favored the decomposition of CP, whereas the oxidation efficiency was not affected by pH change ranging from 3 to 11. Bicarbonate was found to play a detrimental role on CP removal rates, while chloride showed no effect. The oxidation pathways including initial oxidation of P=S bond to P=O, dechlorination, dealkylation, and the dechlorination-hydroxylation were proposed, and the detailed underlying mechanisms were also discussed. Molecular orbital (MO) calculations indicated that P=S bond was the most favored oxidation site of the molecule. The toxicity of reaction solution was believed to increase due to the formation of products with P=O structures. This work demonstrates that OPPs can readily react with SO4·- and provides important information for further research on the oxidation of these contaminants.

  4. How safe is the use of chlorpyrifos: Revelations through its effect on layer birds

    Directory of Open Access Journals (Sweden)

    P. P. Singh

    2016-07-01

    Full Text Available Aim: The present study was aimed to investigate the immunological competence of chlorpyrifos (CPF insecticide after oral administration in layer chickens. Materials and Methods: A total of 20 White Leghorn birds were given CPF in drinking water at 0.3 ppm/bird/day (no observable effect level dose for a period of 3-month. Immune competence status of layer birds and chicks hatched from CPF-treated birds were estimated at 15 days interval in layer birds and monthly interval in chicks using immunological and biochemical parameters. Results: There was a significant decrease in values of total leukocytes count, absolute lymphocyte count, absolute heterophil count, total serum protein, serum albumin, serum globulin, and serum gamma globulin in the birds treated with CPF as compared to control. Similarly, immune competence tests such as lymphocyte stimulation test, oxidative burst assay, and enzyme-linked immunosorbent assay tests indicated lower immunity in birds treated with CPF as compared to control. Subsequently, chicks produced from CPF-treated birds were also examined for immune competence, but no significant difference was observed between chicks of both the groups. Conclusion: The exposure to CPF produced hemo-biochemical and other changes that could be correlated with changes in the immunological profile of layer chickens suggesting total stoppage of using CPF in poultry sheds.

  5. Immunoprotective activity and antioxidant properties of cactus (Opuntia ficus indica) extract against chlorpyrifos toxicity in rats.

    Science.gov (United States)

    Smida, Amani; Ncibi, Saida; Taleb, Jihen; Ben Saad, Anouar; Ncib, Sana; Zourgui, Lazhar

    2017-04-01

    Opuntia ficus indica (family Cactaceae) is a typical Mediterranean plant, mainly used in food and traditional folk medicine. The present study was designed to evaluate the protective effect of Opuntia ficus indica extract against chlorpyrifos (CPF)-induced immunotoxicity in rats. The experimental animals consisted of four groups of Wistar rats (5-6 weeks old) of eight each: a control group, a group treated with CPF (10mg/kg), a group treated with Opuntia ficus indica extract (100mg/kg), and a group treated with cactus extract then treated with CPF. These components were daily administered by gavage for 30days. After treatment, immunotoxicity was estimated by a count of thymocytes, splenocytes, stem cells in the bone marrow, relative weights of thymus and spleen, DNA aspects, and oxidative stress status in these organs. Results showed that CPF could induce thymus atrophy, splenomegaly, and a decrease in the cell number in the bone marrow. It also increased the oxidative stress markers resulting in elevated levels of the lipid peroxidation with a concomitant decrease in the levels of enzymatic antioxidants (SOD, CAT, GPx) in both spleen and thymus, and also degradation of thymocyte and splenocyte DNA. Consistent histological changes were found in the spleen and thymus under CPF treatment. However, administration of Opuntia ficus indica extract was found to alleviate this CPF-induced damage. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. Chlorpyrifos exposure in common carp (Cyprinus carpio L.) leads to oxidative stress and immune responses.

    Science.gov (United States)

    Zhang, Ziwei; Liu, Qi; Cai, Jingzeng; Yang, Jie; Shen, Qiang; Xu, Shiwen

    2017-08-01

    Chlorpyrifos (CPF) is an environmental pollutant with increasing importance due to its high toxicity to fish and aquatic animals. To understand how CPF impacts immune response and oxidative stress in common carp (Cyprinus carpio L.), we investigated the transcriptomic profiles of the head kidneys from common carp exposed to CPF for 15days. A total of 52, 297, 928 and 52, 273, 784 high quality clean reads were obtained from CPF exposure groups, 44,677,578 and 44,106,696 high quality clean reads were obtained from corresponding control groups. Among them, 456 genes were differentially expressed, including 246 up-regulated genes and 210 down-regulated genes identified and enriched in databases of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Antioxidant systems, and immune response genes and pathways were verified by quantitative real-time RT-PCR. We found that CPF-induced ROS regulates immune response by stimulating the antigen-presenting ability of head kidney in carp. These results provide new insights for unveiling the biological effects of CPF in common carp. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Relative susceptibility of stream macroinvertebrates to temephos and chlorpyrifos, determined in laboratory continuous-flow systems.

    Science.gov (United States)

    Muirhead-Thomson, R C

    1978-01-01

    Laboratory techniques are described for evaluating the lethal and behavioral impact of pesticides on a range of stream macroinvertebrates under continuous through-flow and simulated stream conditions. The same basic test unit has been used, with slight modifications, to study the reactions of both Simulium larvae and non-target stream invertebrates. On the basis of a standard 1-hr exposure period to different concentrations followed by a 24-hr holding period in a continuous flow of clean water, different test organisms showed wide and consistent differences in tolerance to each of the two insecticides tested. The widest difference between two organisms occurred in the case of the Amphipod, Gammarus pulex (LC90-95, greater than 1 ppm) which was found to be about 5000 x more tolerant to temephos than are nymphs of the mayfly, Baetis rhodani. (LC 90-95, 0.001-0.002 ppm) The widest difference in the reactions of any one species is shown on the part of Gammarus which is about 100 times more susceptible to chlorpyrifos (LC 90-95, 0.05-0.1 ppm) than to temephos. The susceptibility levels of other indicator species such as Agrion, Hydropsyche, Brachycentrus, Ephemera, etc. are discussed in relation to susceptibility levels of Simulium larvae under the same test conditions, and also in relation to current field dosages of the two insecticides in practical and experimental Simulium control.

  8. Multiple cellular responses to serotonin contribute to epithelial homeostasis.

    Directory of Open Access Journals (Sweden)

    Vaibhav P Pai

    Full Text Available Epithelial homeostasis incorporates the paradoxical concept of internal change (epithelial turnover enabling the maintenance of anatomical status quo. Epithelial cell differentiation and cell loss (cell shedding and apoptosis form important components of epithelial turnover. Although the mechanisms of cell loss are being uncovered the crucial triggers that modulate epithelial turnover through regulation of cell loss remain undetermined. Serotonin is emerging as a common autocrine-paracine regulator in epithelia of multiple organs, including the breast. Here we address whether serotonin affects epithelial turnover. Specifically, serotonin's roles in regulating cell shedding, apoptosis and barrier function of the epithelium. Using in vivo studies in mouse and a robust model of differentiated human mammary duct epithelium (MCF10A, we show that serotonin induces mammary epithelial cell shedding and disrupts tight junctions in a reversible manner. However, upon sustained exposure, serotonin induces apoptosis in the replenishing cell population, causing irreversible changes to the epithelial membrane. The staggered nature of these events induced by serotonin slowly shifts the balance in the epithelium from reversible to irreversible. These finding have very important implications towards our ability to control epithelial regeneration and thus address pathologies of aberrant epithelial turnover, which range from degenerative disorders (e.g.; pancreatitis and thyrioditis to proliferative disorders (e.g.; mastitis, ductal ectasia, cholangiopathies and epithelial cancers.

  9. Central serotonin neurons are required for arousal to CO2.

    Science.gov (United States)

    Buchanan, Gordon F; Richerson, George B

    2010-09-14

    There is a long-standing controversy about the role of serotonin in sleep/wake control, with competing theories that it either promotes sleep or causes arousal. Here, we show that there is a marked increase in wakefulness when all serotonin neurons are genetically deleted in mice hemizygous for ePet1-Cre and homozygous for floxed Lmx1b (Lmx1b(f/f/p)). However, this only occurs at cool ambient temperatures and can be explained by a thermoregulatory defect that leads to an increase in motor activity to generate heat. Because some serotonin neurons are stimulated by CO(2), and serotonin activates thalamocortical networks, we hypothesized that serotonin neurons cause arousal in response to hypercapnia. We found that Lmx1b(f/f/p) mice completely lacked any arousal response to inhalation of 10% CO(2) (with 21% O(2) in balance N(2)) but had normal arousal responses to hypoxia, sound, and air puff. We propose that serotonin neurons mediate the potentially life-saving arousal response to hypercapnia. Impairment of this response may contribute to sudden unexpected death in epilepsy, sudden infant death syndrome, and sleep apnea.

  10. Serotonin receptors in depression: from A to B

    Science.gov (United States)

    Nautiyal, Katherine M.; Hen, René

    2017-01-01

    The role of serotonin in major depressive disorder (MDD) is the focus of accumulating clinical and preclinical research. The results of these studies reflect the complexity of serotonin signaling through many receptors, in a large number of brain regions, and throughout the lifespan. The role of the serotonin transporter in MDD has been highlighted in gene by environment association studies as well as its role as a critical player in the mechanism of the most effective antidepressant treatments – selective serotonin reuptake inhibitors. While the majority of the 15 known receptors for serotonin have been implicated in depression or depressive-like behavior, the serotonin 1A (5-HT 1A) and 1B (5-HT 1B) receptors are among the most studied. Human brain imaging and genetic studies point to the involvement of 5-HT 1A and 5-HT 1B receptors in MDD and the response to antidepressant treatment. In rodents, the availability of tissue-specific and inducible knockout mouse lines has made possible the identification of the involvement of 5-HT 1A and 5-HT 1B receptors throughout development and in a cell-type specific manner. This, and other preclinical pharmacology work, shows that autoreceptor and heteroreceptor populations of these receptors have divergent roles in modulating depression-related behavior as well as responses to antidepressants and also have different functions during early postnatal development compared to during adulthood. PMID:28232871

  11. Serotonin Regulates the Feeding and Reproductive Behaviors of Pratylenchus penetrans.

    Science.gov (United States)

    Han, Ziduan; Boas, Stephanie; Schroeder, Nathan E

    2017-07-01

    The success of all plant-parasitic nematodes is dependent on the completion of several complex behaviors. The lesion nematode Pratylenchus penetrans is an economically important parasite of a diverse range of plant hosts. Unlike the cyst and root-knot nematodes, P. penetrans moves both within and outside of the host roots and can feed from both locations. Adult females of P. penetrans require insemination by actively moving males for reproduction and can lay eggs both within and outside of the host roots. We do not have a complete understanding of the molecular basis for these behaviors. One candidate modulator of these behaviors is the neurotransmitter serotonin. Previous research demonstrated an effect of exogenously applied serotonin on the feeding and male mating behaviors of cyst and root-knot nematodes. However, there are no data on the role of exogenous serotonin on lesion nematodes. Similarly, there are no data on the presence and function of endogenous serotonin in any plant-parasitic nematode. Here, we establish that exogenous serotonin applied to P. penetrans regulates both feeding and sex-specific behaviors. Furthermore, using immunohistochemistry and pharmacological assays, our data suggest that P. penetrans utilizes endogenous serotonin to regulate both feeding and sex-specific behaviors.

  12. Increased hypothalamic serotonin turnover in inflammation-induced anorexia.

    Science.gov (United States)

    Dwarkasing, J T; Witkamp, R F; Boekschoten, M V; Ter Laak, M C; Heins, M S; van Norren, K

    2016-05-20

    Anorexia can occur as a serious complication of disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. First, we investigated the response of two hypothalamic neuronal cell lines to TNFα, IL-6 and LPS. Next, we studied transcriptomic changes and serotonergic activity in the hypothalamus of mice after intraperitoneal injection with TNFα, IL-6 or a combination of TNFα and IL-6. In vitro, we showed that hypothalamic neurons responded to inflammatory mediators by releasing cytokines. This inflammatory response was associated with an increased serotonin release. Mice injected with TNFα and IL-6 showed decreased food intake, associated with altered expression of inflammation-related genes in the hypothalamus. In addition, hypothalamic serotonin turnover showed to be elevated in treated mice. Overall, our results underline that peripheral inflammation reaches the hypothalamus where it affects hypothalamic serotoninergic metabolism. These hypothalamic changes in serotonin pathways are associated with decreased food intake, providing evidence for a role of serotonin in inflammation-induced anorexia.

  13. Effect of endurance training on hypothalamic serotonin concentration and performance.

    Science.gov (United States)

    Caperuto, E C; dos Santos, R V T; Mello, M T; Costa Rosa, L F B P

    2009-02-01

    1. Serotonin is a neurotransmitter that modulates several functions, such as food intake, energy expenditure, motor activity, mood and sleep. Acute exhaustive endurance exercise increases the synthesis, concentration and metabolism of serotonin in the brain. This phenomenon could be responsible for central fatigue after prolonged and exhaustive exercise. However, the effect of chronic exhaustive training on serotonin is not known. The present study was conducted to examine the effect of exhaustive endurance training on performance and serotonin concentrations in the hypothalamus of trained rats. 2. Rats were divided into three groups: sedentary rats (SED), moderately trained rats (MOD) and exhaustively trained rats (EXT), with an increase of 200% in the load carried during the final week of training. 3. Hypothalamic serotonin concentrations were similar between the SED and MOD groups, but were higher in the EXT group (P MOD group (P < 0.05). 4. Thus, the present study demonstrates that exhaustive training increases serotonin concentrations in the hypothalamus, together with decreased endurance performance after inadequate recovery time. However, the mechanism underlying these changes remains unknown.

  14. Brain serotonin content regulates the manifestation of tramadol-induced seizures in rats: disparity between tramadol-induced seizure and serotonin syndrome.

    Science.gov (United States)

    Fujimoto, Yohei; Funao, Tomoharu; Suehiro, Koichi; Takahashi, Ryota; Mori, Takashi; Nishikawa, Kiyonobu

    2015-01-01

    Tramadol-induced seizures might be pathologically associated with serotonin syndrome. Here, the authors investigated the relationship between serotonin and the seizure-inducing potential of tramadol. Two groups of rats received pretreatment to modulate brain levels of serotonin and one group was treated as a sham control (n = 6 per group). Serotonin modulation groups received either para-chlorophenylalanine or benserazide + 5-hydroxytryptophan. Serotonin, dopamine, and histamine levels in the posterior hypothalamus were then measured by microdialysis, while simultaneously infusing tramadol until seizure onset. In another experiment, seizure threshold with tramadol was investigated in rats intracerebroventricularly administered with either a serotonin receptor antagonist (methysergide) or saline (n = 6). Pretreatment significantly affected seizure threshold and serotonin fluctuations. The threshold was lowered in para-chlorophenylalanine group and raised in benserazide + 5-hydroxytryptophan group (The mean ± SEM amount of tramadol needed to induce seizures; sham: 43.1 ± 4.2 mg/kg, para-chlorophenylalanine: 23.2 ± 2.8 mg/kg, benserazide + 5-hydroxytryptophan: 59.4 ± 16.5 mg/kg). Levels of serotonin at baseline, and their augmentation with tramadol infusion, were less in the para-chlorophenylalanine group and greater in the benserazide + 5-hydroxytryptophan group. Furthermore, seizure thresholds were negatively correlated with serotonin levels (correlation coefficient; 0.71, P seizure threshold (P seizures, and that serotonin concentrations were negatively associated with seizure thresholds. Moreover, serotonin receptor antagonism precipitated seizure manifestation, indicating that tramadol-induced seizures are distinct from serotonin syndrome.

  15. INFLUENCE OF A SEROTONIN-RICH AND DOPAMINE-RICH DIET ON PLATELET SEROTONIN CONTENT AND URINARY-EXCRETION OF BIOGENIC-AMINES AND THEIR METABOLITES

    NARCIS (Netherlands)

    KEMA, IP; SCHELLINGS, AMJ; MEIBORG, G; HOPPENBROUWERS, CJM; MUSKIET, FAJ

    Using high-performance liquid chromatography and gas chromatography, we reevaluated the 24-h influence of a serotonin- and dopamine-rich diet on platelet serotonin and serotonin, 5-hydroxyindoleacetic acid (5-HIAA), and major catecholamine metabolites in the urine of 15 healthy adults. Although

  16. Developmental Effects of Serotonin 1A Autoreceptors on Anxiety and Social Behavior

    Science.gov (United States)

    Donaldson, Zoe R; Piel, David A; Santos, Tabia L; Richardson-Jones, Jesse; Leonardo, E David; Beck, Sheryl G; Champagne, Frances A; Hen, René

    2014-01-01

    The serotonin 1A receptor (5-HT1A) has a major role in modulating the effects of serotonin on mood and behavior. Previous studies have shown that knockout of 5-HT1A selectively in the raphe leads to higher levels of anxiety during adulthood. However, it remains unclear whether this phenotype is due to variation in receptor levels specifically during development or throughout life. To test the hypothesis that developmental sensitivity may underlie the effects of 5-HT1A on anxiety, we used an inducible transgenic system to selectively suppress 5-HT1A levels in serotonergic raphe neurons from post-natal days (P) 14 to P30, with a maximal reduction of 40% at P21 and return to regular levels by P30. This developmental decrease in receptor levels has long-lasting consequences, increasing anxiety and decreasing social investigation in adulthood. In addition, post-natal knockdown of autoreceptors leads to long-term increases in the excitability of serotonergic neurons, which may represent a mechanism underlying the effects of post-natal receptor variation on behavior later in life. Finally, we also examined the interplay between receptor variation and juvenile exposure to stress (applied from P14 to P21). Similar to receptor knockdown, juvenile exposure to stress led to increased anxiety phenotypes but did not exacerbate 5-HT1A knockdown-mediated anxiety levels. This work indicates that the effects of 5-HT1A autoreceptors on anxiety and social behaviors are developmentally mediated and suggests that natural variations in the expression of 5-HT1A may act during development to influence individual anxiety levels and contribute to susceptibility to anxiety disorders. PMID:23907404

  17. Female, but not male, serotonin reuptake transporter (5-HTT) knockout mice exhibit bladder instability.

    Science.gov (United States)

    Cornelissen, L L; Brooks, D P; Wibberley, A

    2005-10-30

    Correlations exist between the incidence of depression, irritable bowel syndrome (IBS) and overactive bladder [Masand, P.S., Kaplan, D.S., Gupta, S., Bhandary, A.N., Nasra, G.S., Kline, M.D., Margo, K.L., 1995. Major depression and irritable bowel syndrome: is there a relationship? J. Clin. Psychiatry 56, 363-367.; Cukier, J.M., Cortina-Borja, M., Brading, A.F., 1997. A case-control study to examine any association between idiopathic detrusor instability and gastrointestinal tract disorder, and between irritable bowel syndrome and urinary tract disorder. Br. J. Urol. 79, 865-878.; Monga, A.K., Marrero, J.M., Stanton, S.L., Lemieux, M.C., Maxwell, J.D., 1997. Is there an irritable bladder in the irritable bowel syndrome? Br. J. Obstet. Gynaecol. 104, 1409-1412.; Zorn, B.H., Montgomery, H., Pieper, K., Gray, M., Steers, W.D., 1999. Urinary incontinence and depression. J. Urol. 162, 82-84.]. Furthermore, alterations in serotonergic neurotransmission may play a common role in the etiology of these disorders. Serotonin reuptake transporter knockout mice (5-HTT(-/-)) display phenotypes consistent with clinical features of mood and bowel disorders including anxiety and abnormal gastrointestinal motility [Holmes, A., Murphy, D.L., Crawley, J.N., 2003. Abnormal behavioral phenotypes of serotonin transporter knockout mice: parallels with human anxiety and depression. Biol. Psychiatry 54, 953-959.]. In the present study, we evaluated bladder function in 5-HTT(-/-) mice. We have found that female 5-HTT(-/-) mice exhibit bladder dysfunction, characterized by significant increases in the frequency of spontaneous non-voiding bladder contractions and decreases in void volume compared to control female mice. These differences were not observed in male knockout mice. These studies provide significant supporting data for a mechanistic link between alterations in 5-HT, depression, IBS and overactive bladder in women.

  18. An approach for serotonin depletion in pigs: effects on serotonin receptor binding

    DEFF Research Database (Denmark)

    Ettrup, Anders; Kornum, Birgitte R; Weikop, Pia

    2011-01-01

    Depletion of central serotonin (5-HT) levels and dysfunction in serotonergic transmission are implicated in a variety of human CNS disorders. The mechanisms behind these serotonergic deficits have been widely studied using rodent models, but only to a limited extent in larger animal models. The pig...... concentrations of 5-HT in seven distinct brain structures from one hemisphere: frontal and occipital cortex, striatum, hippocampus, cerebellum, rostral, and caudal brain stem, were determined. The other hemisphere was processed for receptor autoradiography. Treatments with 50 mg/kg and 100 mg/kg pCPA caused...

  19. The Effect of Early Trauma Exposure on Serotonin Type 1B Receptor Expression Revealed by Reduced Selective Radioligand Binding

    Science.gov (United States)

    Murrough, James W.; Czermak, Christoph; Henry, Shannan; Nabulsi, Nabeel; Gallezot, Jean-Dominique; Gueorguieva, Ralitza; Planeta-Wilson, Beata; Krystal, John H.; Neumaier, John F.; Huang, Yiyun; Ding, Yu-Shin; Carson, Richard E.; Neumeister, Alexander

    2011-01-01

    Context Serotonergic dysfunction is implicated in the pathogenesis of posttraumatic stress disorder (PTSD), and recent animal models suggest that disturbances in serotonin type 1B receptor function, in particular, may contribute to chronic anxiety. However, the specific role of the serotonin type 1B receptor has not been studied in patients with PTSD. Objective To investigate in vivo serotonin type 1B receptor expression in individuals with PTSD, trauma-exposed control participants without PTSD (TC), and healthy (non–trauma-exposed) control participants (HC) using positron emission tomography and the recently developed serotonin type 1B receptor selective radiotracer [11C]P943. Design Cross-sectional positron emission tomography study under resting conditions. Setting Academic and Veterans Affairs medical centers. Participants Ninety-six individuals in 3 study groups: PTSD (n=49), TC (n=20), and HC (n=27). Main Outcome Measure Regional [11C]P943 binding potential (BPND) values in an a priori–defined limbic corticostriatal circuit investigated using multivariate analysis of variance and multiple regression analysis. Results A history of severe trauma exposure in the PTSD and TC groups was associated with marked reductions in [11C]P943 BPND in the caudate, the amygdala, and the anterior cingulate cortex. Participant age at first trauma exposure was strongly associated with low [11C]P943 BPND. Developmentally earlier trauma exposure also was associated with greater PTSD symptom severity and major depression comorbidity. Conclusions These data suggest an enduring effect of trauma history on brain function and the phenotype of PTSD. The association of early age at first trauma and more pronounced neurobiological and behavioral alterations in PTSD suggests a developmental component in the cause of PTSD. PMID:21893657

  20. Gastric pentadecapeptide BPC 157 effective against serotonin syndrome in rats.

    Science.gov (United States)

    Boban Blagaic, Alenka; Blagaic, Vladimir; Mirt, Mirela; Jelovac, Nikola; Dodig, Goran; Rucman, Rudolf; Petek, Marijan; Turkovic, Branko; Anic, Tomislav; Dubovecak, Miroslav; Staresinic, Mario; Seiwerth, Sven; Sikiric, Predrag

    2005-04-11

    Serotonin syndrome commonly follows irreversible monoamine oxidase (MAO)-inhibition and subsequent serotonin (5-HT) substrate (in rats with fore paw treading, hind limbs abduction, wet dog shake, hypothermia followed by hyperthermia). A stable gastric pentadecapeptide BPC 157 with very safe profile (inflammatory bowel disease clinical phase II, PL-10, PLD-116, PL-14736, Pliva) reduced the duration of immobility to a greater extent than imipramine, and, given peripherally, has region specific influence on brain 5-HT synthesis (alpha-[14C]methyl-L-tryptophan autoradiographic measurements) in rats, different from any other serotonergic drug. Thereby, we investigate this peptide (10 microg, 10 ng, 10 pg/kg i.p.) in (i) full serotonin syndrome in rat combining pargyline (irreversible MAO-inhibition; 75 mg/kg i.p.) and subsequent L-tryptophan (5-HT precursor; 100 mg/kg i.p.; BPC 157 as a co-treatment), or (ii, iii) using pargyline or L-tryptophan given separately, as a serotonin-substrate with (ii) pargyline (BPC 157 as a 15-min posttreatment) or as a potential serotonin syndrome inductor with (iii) L-tryptophan (BPC 157 as a 15 min-pretreatment). In all experiments, gastric pentadecapeptide BPC 157 contrasts with serotonin-syndrome either (i) presentation (i.e., particularly counteracted) or (ii) initiation (i.e., neither a serotonin substrate (counteraction of pargyline), nor an inductor for serotonin syndrome (no influence on L-tryptophan challenge)). Indicatively, severe serotonin syndrome in pargyline + L-tryptophan rats is considerably inhibited even by lower pentadecapeptide BPC 157 doses regimens (particularly disturbances such as hyperthermia and wet dog shake thought to be related to stimulation of 5-HT2A receptors), while the highest pentadecapeptide dose counteracts mild disturbances present in pargyline rats (mild hypothermia, feeble hind limbs abduction). Thereby, in severe serotonin syndrome, gastric pentadecapeptide BPC 157 (alone, no behavioral or

  1. Phytotoxicity of Chlorpyrifos to White Mustard (Sinapis alba L. and Maize (Zea mays L.: Potential Indicators of Insecticide Presence in Water

    Directory of Open Access Journals (Sweden)

    Sonja Gvozdenac

    2013-12-01

    Full Text Available Chlorpyrifos is a hazardous insecticide and important pollutant of the environment. The EU Directive 2008/105/EC lists it as one of the priority water pollutants. Its presence is mainly detected by chemical methods but, since biological tests have gained in importance in the last few years, this study aimed to assess the potentials of white mustard (Sinapis alba L. and maize (Zea mays L. as indicators of water pollution. The phytotoxic effects of chlorpyrifos (rates 0.05-10μg a.i./l were assessed based on physiological (germination energy and germination and morphological traits (root and shoot length, fresh and dry weights of the tested species. A slightly modified filter paper method was used and the results were processed by Duncan`s multiple range test and Probit analysis (EC50. According to the Directive, the maximal allowable concentration (MAC of chlorpyrifos in water is 0.1μg a.i./l. When applied at the MAC value, chlorpyrifos inhibited germination energy and germination (11.25% of white mustard, as compared to the control (91.5; 93.5%, and its hypocotyls and epicotyls failed to form. At the rates 50% below the MAC, germination energy and germination (87.75; 88.25% were significanty inhibited, as well as root and shoot growth of seedlings. Chlorpyrofos did not affect the germination energy and germination of maize, while all morphological traits were significantly reduced by chlorpyrifos at the MAC rate. The EC50 of chlorpyrifos was 0.09μg a.i./l for germination of white mustard and 3.21μg a.i./l for maize.

  2. Serotonin and migraine: biology and clinical implications.

    Science.gov (United States)

    Hamel, E

    2007-11-01

    Migraine is the most frequent neurological disorder in the adult population worldwide, affecting up to 12% of the general population and more frequent in women ( approximately 25%). It has a high impact on our society due to its disabling nature and, therein, reduced quality of life and increased absenteeism from work. Headache is the primary clinical manifestation and it has been associated with 'a hereditary or predisposed sensitivity of neurovascular reactions to certain stimuli or to cyclic changes in the central nervous system' (1). Amongst the many neurotransmitters in the brain, the serotonergic (serotonin, 5-HT) system from the brainstem raphe nucleus has been most convincingly implicated in migraine pathophysiology. The documented changes in 5-HT metabolism and in the processing of central 5-HT-mediated responses during and in between migraine attacks have led to the suggestion that migraine is a consequence of a central neurochemical imbalance that involves a low serotonergic disposition. Although the exact cascade of events that link abnormal serotonergic neurotransmission to the manifestation of head pain and the accompanying symptoms has yet to be fully understood, recent evidence suggests that a low 5-HT state facilitates activation of the trigeminovascular nociceptive pathway, as induced by cortical spreading depression. In this short review, we present and discuss the original and most recent findings that support a role for altered serotonergic neurotransmission in the manifestation of migraine headache.

  3. Fitness Effects of Chlorpyrifos in the Damselfly Enallagma cyathigerum Strongly Depend upon Temperature and Food Level and Can Bridge Metamorphosis.

    Directory of Open Access Journals (Sweden)

    Lizanne Janssens

    Full Text Available Interactions between pollutants and suboptimal environmental conditions can have severe consequences for the toxicity of pollutants, yet are still poorly understood. To identify patterns across environmental conditions and across fitness-related variables we exposed Enallagma cyathigerum damselfly larvae to the pesticide chlorpyrifos at two food levels or at two temperatures and quantified four fitness-related variables (larval survival, development time, mass at emergence and adult cold resistance. Food level and temperature did not affect survival in the absence of the pesticide, yet the pesticide reduced survival only at the high temperature. Animals reacted to the pesticide by accelerating their development but only at the high food level and at the low temperature; at the low food level, however, pesticide exposure resulted in a slower development. Chlorpyrifos exposure resulted in smaller adults except in animals reared at the high food level. Animals reared at the low food level and at the low temperature had a higher cold resistance which was not affected by the pesticide. In summary our study highlight that combined effects of exposure to chlorpyrifos and the two environmental conditions (i were mostly interactive and sometimes even reversed in comparison with the effect of the environmental condition in isolation, (ii strongly differed depending on the fitness-related variable under study, (iii were not always predictable based on the effect of the environmental condition in isolation, and (iv bridged metamorphosis depending on which environmental condition was combined with the pesticide thereby potentially carrying over from aquatic to terrestrial ecosystems. These findings are relevant when extrapolating results of laboratory tests done under ideal environmental conditions to natural communities.

  4. A new method for setting guidelines to protect human health from agricultural exposure by using chlorpyrifos as an example

    Directory of Open Access Journals (Sweden)

    Dung Tri Phung

    2015-05-01

    Full Text Available Introduction and objectives. Guidelines set by various agencies for the control and management of chlorpyrifos cover a wide range of values reflecting difficulties in the procedures for their development. To overcome these difficulties a new method to set guidelines would be developed. Published data derived from epidemiological investigations on human populations would be used to develop a dose-response relationship for chlorpyrifos allowing the calculation of threshold values which can be used as guidelines. Materials and Method. Data from the scientific literature on human populations were collected to evaluate the adverse response doses for a range of health effects. The Cumulative Frequency Distribution (CFD for the minimum levels of adverse effects measured in terms of the Lifetime Average Daily Dose (LADD[sub]D[/sub] and the Absorbed Daily Dose for neurological (ADD[sub]DN[/sub] and non-neurological effects were used. Results. Linear regression equations were fitted to the CFD plots giving R 2 values of 0.93 and 0.86 indicating a normal distribution of the data. Using these CFD plots, the chronic and acute threshold values were calculated at the 5% cumulative frequency level for chlorpyrifos exposure giving values at 0.5 µg/kg/d and 3 µg/kg/d respectively. Conclusions. Guidelines set using this technique at the values at 0.5 µg/kg/d and 3 µg/kg/d for chronic and acute exposure respectively provide an alternative to the currently used biological endpoint and safety factor method.

  5. Prenatal naled and chlorpyrifos exposure is associated with deficits in infant motor function in a cohort of Chinese infants.

    Science.gov (United States)

    Silver, Monica K; Shao, Jie; Zhu, Binquan; Chen, Minjian; Xia, Yankai; Kaciroti, Niko; Lozoff, Betsy; Meeker, John D

    2017-09-01

    Organophosphate insecticides (OPs) are used worldwide, yet despite nearly ubiquitous exposure in the general population, few have been studied outside the laboratory. Fetal brains undergo rapid growth and development, leaving them susceptible to long-term effects of neurotoxic OPs. The objective here was to investigate the extent to which prenatal exposure to OPs affects infant motor development. 30 OPs were measured in umbilical cord blood using gas chromatography tandem mass spectrometry in a cohort of Chinese infants. Motor function was assessed at 6-weeks and 9-months using Peabody Developmental Motor Scales 2nd edition (PDMS-2) (n=199). Outcomes included subtest scores: reflexes, stationary, locomotion, grasping, visual-motor integration (V-M), composite scores: gross (GM), fine (FM), total motor (TM), and standardized motor quotients: gross (GMQ), fine (FMQ), total motor (TMQ). Naled, methamidophos, trichlorfon, chlorpyrifos, and phorate were detected in ≥10% of samples. Prenatal naled and chlorpyrifos were associated with decreased 9-month motor function. Scores were 0.55, 0.85, and 0.90 points lower per 1ng/mL increase in log-naled, for V-M (p=0.04), FM (p=0.04), and FMQ (p=0.08), respectively. For chlorpyrifos, scores were 0.50, 1.98, 0.80, 1.91, 3.49, 2.71, 6.29, 2.56, 2.04, and 2.59 points lower for exposed versus unexposed infants, for reflexes (p=0.04), locomotion (p=0.02), grasping (p=0.05), V-M (pGM (p=0.007), FM (p=0.002), TM (pmosquitoes carrying Zika virus, yet this is the first non-occupational human study of its health effects. Delays in early-motor skill acquisition may be detrimental for downstream development and cognition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. A probabilistic risk assessment for the Kirtland's warbler potentially exposed to chlorpyrifos and malathion during the breeding season and migration.

    Science.gov (United States)

    Moore, Dwayne Rj; Priest, Colleen D; Olson, Adric D; Teed, R Scott

    2017-11-04

    Two organophosphate pesticides, chlorpyrifos and malathion, are currently undergoing reregistration in the United States and were recently used by the US Environmental Protection Agency (USEPA) as case studies to develop a national procedure for evaluating risks to endangered species. One of the endangered bird species considered by the USEPA was the Kirtland's warbler (Setophaga kirtlandii). The Kirtland's warbler is an endangered migratory species that nests exclusively in young jack pine stands in Michigan and Wisconsin, and winters in the Bahamas. We developed probabilistic models to assess the risks of chlorpyrifos and malathion to Kirtland's warblers during the breeding season and the spring and fall migrations. The breeding area model simulates acute and chronic exposure and risk to each of 10 000 birds over a 60-d period following initial pesticide application. The model is highly species specific with regard to the foraging behavior of Kirtland's warblers during the breeding season. We simulated the maximum application rate and number of applications allowed on the labels for representative use patterns that could be found within 3 km of the breeding areas of Kirtland's warbler. The migration model simulates 10 000 birds during the course of their 12- to 23-d migration between their breeding area and the Bahamas. The model takes advantage of more than a century of observations of when, where, and for how long Kirtland's warblers forage in different habitats during the course of their migration. The data indicate that warblers only infrequently stop over in habitats that could be treated with chlorpyrifos and malathion. The breeding area and migration models resulted in predictions of very low acute and chronic risk for both pesticides to Kirtland's warblers. These results were expected, given that field observations indicate that the Kirtland's warbler has dramatically increased in abundance in recent decades. Integr Environ Assess Manag 2017

  7. Effects of a wood-based biochar on the leaching of pesticides chlorpyrifos, diuron, glyphosate and MCPA.

    Science.gov (United States)

    Cederlund, Harald; Börjesson, Elisabet; Stenström, John

    2017-04-15

    We studied the ability of a wood-based biochar to reduce the leaching of the pesticides chlorpyrifos, diuron, glyphosate and MCPA in a sand column test system. In addition, time-dependent adsorption of the pesticides to the biochar and to the sand used in the columns was determined. The sorption kinetics was shown to be controlled by the log K ow -values of the pesticides and sorption rates varied in the order: chlorpyrifos (log K ow  = 4.7) > diuron (log K ow  = 2.87) > MCPA (log K ow  = -0.8) > glyphosate (log K ow  = -3.2). Glyphosate sorbed very weakly to the biochar but strongly to the sand. Biochar was most effective at retaining the pesticides if applied as a distinct layer rather than mixed with the sand. Leaching of diuron and MCPA was reduced by biochar application, and the retention was linearly related to the thickness of the biochar layers. However, leaching of chlorpyrifos and glyphosate was not affected by biochar addition. Leaching was low for all pesticides when the pesticides were added directly to biochar that was then added to the column. Together, our results suggest that a viable strategy for using biochar as a means to mitigate leaching of pesticides may be to use it as an adsorptive layer directly on or close to the soil surface. This would be especially useful in areas where pesticides are routinely handled and potentially spilled. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Effects of selective serotonin reuptake inhibition on neural activity related to risky decisions and monetary rewards in healthy males

    DEFF Research Database (Denmark)

    Macoveanu, Julian; Fisher, Patrick M; Haahr, Mette E

    2014-01-01

    Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are commonly prescribed antidepressant drugs targeting the dysfunctional serotonin (5-HT) system, yet little is known about the functional effects of prolonged serotonin reuptake inhibition in healthy individuals. Here we used...

  9. SEROTONIN, CATECHOLAMINES, HISTAMINE, AND THEIR METABOLITES IN URINE, PLATELETS, AND TUMOR-TISSUE OF PATIENTS WITH CARCINOID-TUMORS

    NARCIS (Netherlands)

    KEMA, IP; DEVRIES, EGE; SLOOFF, MJH; BIESMA, B; MUSKIET, FAJ

    We monitored long-term (median 11 months) concentrations of platelet serotonin and urinary serotonin, 5-hydroxyindoleacetic acid, and seven catecholamine metabolites in 44 patients with carcinoid tumors. Tumor serotonin and catecholamine contents (11 patients) and urinary histamine and

  10. Comparative effects of parathion and chlorpyrifos on extracellular endocannabinoid levels in rat hippocampus: Influence on cholinergic toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jing [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK (United States); Parsons, Loren [Committee on Neurobiology of Affective Disorders, The Scripps Research Institute, La Jolla, CA (United States); Pope, Carey, E-mail: carey.pope@okstate.edu [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK (United States)

    2013-11-01

    Parathion (PS) and chlorpyrifos (CPF) are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). Endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) can modulate neurotransmission by inhibiting neurotransmitter release. We proposed that differential inhibition of eCB-degrading enzymes (fatty acid amide hydrolase, FAAH, and monoacylglycerol lipase, MAGL) by PS and CPF leads to differences in extracellular eCB levels and toxicity. Microdialysis cannulae were implanted into hippocampus of adult male rats followed by treatment with vehicle (peanut oil, 2 ml/kg, sc), PS (27 mg/kg) or CPF (280 mg/kg) 6–7 days later. Signs of toxicity, AChE, FAAH and MAGL inhibition, and extracellular levels of AEA and 2AG were measured 2 and 4 days later. Signs were noted in PS-treated rats but not in controls or CPF-treated rats. Cholinesterase inhibition was extensive in hippocampus with PS (89–90%) and CPF (78–83%) exposure. FAAH activity was also markedly reduced (88–91%) by both OPs at both time-points. MAGL was inhibited by both OPs but to a lesser degree (35–50%). Increases in extracellular AEA levels were noted after either PS (about 2-fold) or CPF (about 3-fold) while lesser treatment-related 2-AG changes were noted. The cannabinoid CB1 receptor antagonist/inverse agonist AM251 (3 mg/kg, ip) had no influence on functional signs after CPF but markedly decreased toxicity in PS-treated rats. The results suggest that extracellular eCBs levels can be markedly elevated by both PS and CPF. CB1-mediated signaling appears to play a role in the acute toxicity of PS but the role of eCBs in CPF toxicity remains unclear. - Highlights: • Chlorpyrifos and parathion both extensively inhibited hippocampal cholinesterase. • Functional signs were only noted with parathion. • Chlorpyrifos and parathion increased hippocampal extracellular anandamide levels. • 2-Arachidonoylglycerol levels were

  11. Effects of selective serotonin reuptake inhibitors on platelet serotonin parameters in major depressive disorder.

    Science.gov (United States)

    Bakish, D; Cavazzoni, P; Chudzik, J; Ravindran, A; Hrdina, P D

    1997-01-15

    The effects of treatment with serotonin (5-HT) reuptake inhibitors on platelet 5-HT2 receptors, 5-HT reuptake sites an 5-HT uptake were studied in a double-blind trial comparing two selective serotonin reuptake inhibitors (SSRI), paroxetine, and fluoxetine, for the treatment of major depression. Hamilton Depression Rating Scale (HAM-D) scores and platelet 5-HT parameters were determined in 21 depressed patients at baseline, after 4 and 8 weeks of treatment, and were compared to 21 healthy controls. Antidepressant treatment did not significantly alter the density of 5-HT reuptake sites, labelled with [3H]paroxetine, or 5-HT2 receptors, labelled with [3H]LSD. However, a strong correlation was observed between the HAM-D suicidality item and 5-HT2 receptor density at baseline. A marked increase in platelet 5-HT2 receptors at baseline was observed in suicidal depressed patients compared to those with no suicidal ideation and healthy controls. Changes in [3H]paroxetine Bmax and in [3H]5-HT uptake significantly correlated with change in HAM-D score at 4 and 8 weeks respectively. These results confirm previous reports of an association between suicidality and platelet 5-HT2 receptor upregulation. Our data also lends support to the use of platelet 5-HT parameters as indicators of antidepressant efficacy, particularly in suicidal depressed patients.

  12. Serotonin transporter gene polymorphisms: Relation with platelet serotonin level in patients with primary Sjogren's syndrome.

    Science.gov (United States)

    Markeljevic, J; Sarac, H; Bozina, N; Henigsberg, N; Simic, M; Cicin Sain, L

    2015-05-15

    Significantly lower platelet serotonin level (PSL) in patients with primary Sjogren's syndrome (pSS) than in healthy controls has been reported in our prior studies. In the present report, we demonstrated effect of functional polymorphisms in the serotonin transporter gene (5-HTT) on PSL. We describe a group of 61 pSS patients and 100 healthy individuals subjects, who received PSL measurement in our prior study. All subjects were genotyped for the promoter 5-HTTLPR (L/S), rs25531 (A/G) and intronic 5-HTTVNTRin2 (l/s) polymorphisms. Overall, the presence of 5-HTTVNTRin2 ss genotype was associated with significantly lower PSL in pSS patients, not in healthy controls. Reduced PSL in pSS patients is in line with hypothesis of association between chronic immunoinflammation and 5-HT system dysregulation, identifying additional mechanisms such as altered 5-HT transport as potential genetic factor contributing to PSL depletion. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Co-treatment of chlorpyrifos and lead induce serum lipid disorders in rats: Alleviation by taurine.

    Science.gov (United States)

    Akande, Motunrayo G; Aliu, Yusuf O; Ambali, Suleiman F; Ayo, Joseph O

    2016-07-01

    The aim of this study was to investigate the effects of taurine (TA) on serum lipid profiles following chronic coadministration of chlorpyrifos (CP) and lead acetate (Pb) in male Wistar rats. Fifty rats randomly distributed into five groups served as subjects. Distilled water (DW) was given to DW group, while soya oil (SO; 1 mL kg(-1)) was given to SO group. The TA group was treated with TA (50 mg kg(-1)). The CP + Pb group was administered sequentially with CP (4.25 mg kg(-1); 1/20th median lethal dose (LD50)) and Pb at 233.25 mg kg(-1) (1/20th LD50), while the TA + CP + Pb group received TA (50 mg kg(-1)), CP (4.25 mg kg(-1)), and Pb (233.25 mg kg(-1)) sequentially. The treatments were administered once daily by oral gavage for 16 weeks. The rats were euthanised, and the blood samples were collected at the termination of the study. Sera obtained from the blood samples were analyzed for total cholesterol, high-density lipoprotein cholesterol, triglycerides, and malondialdehyde, and also the activities of serum antioxidant enzymes including superoxide dismutase, catalase and glutathione peroxidase were analyzed. The low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and atherogenic index were calculated. The results showed that CP and Pb induced alterations in the serum lipid profiles and evoked oxidative stress. TA alleviated the disruptions in the serum lipid profiles of the rats partially by mitigating oxidative stress. It was concluded that TA may be used for prophylaxis against serum lipid disorders in animals that were constantly co-exposed to CP and Pb in the environment. © The Author(s) 2014.

  14. Prenatal chlorpyrifos leads to autism-like deficits in C57Bl6/J mice.

    Science.gov (United States)

    Lan, Anat; Kalimian, Michal; Amram, Benjamin; Kofman, Ora

    2017-05-02

    Children are at daily risk for exposure to organophosphate insecticides, of which the most common is chlorpyrifos (CPF). Exposure of pregnant women to CPF was linked to decreased birth weight, abnormal reflexes, reduction in IQ, as well as increased maternal reports of signs of pervasive developmental disorder. The aim of current study was to examine the long term effects of prenatal exposure to CPF in C57BL/6 J (B6) mice with specific focus on social and repetitive behavior. B6 female mice were treated with vehicle, 2.5 mg/kg CPF or 5 mg/kg of CPF on gestational days 12-15 by oral gavage. On postnatal days (PND's) 6-12 early development and neuromotor ability were assessed by measuring 3 neonatal reflexes in the offspring. In adulthood, PND 90, social behavior was investigated using the social preference, social novelty and social conditioned place preference tasks. Object recognition and restricted interest, measured by the repetitive novel object contact task (RNOC), were also assessed on PN D 90. In order to rule out the possibility that CPF administration induced alterations in maternal care, the dams' behavior was evaluated via the maternal retrieval task. CPF treatment resulted in delayed development of neonatal reflexes on PND's 6-12. On PND 90, mice treated prenatally with the 5.0 mg/kg dose exhibited reduced preference towards an unfamiliar conspecific in the social preference test and reduced social conditioned place preference. In the RNOC task, mice exposed prenatally to 2.5 mg/kg dose of CPF showed enhanced restricted interest. CPF administration did not impair dams' behavior and did not cause memory or recognition deficit as was observed in the object recognition task. Our data indicate that gestational exposure to CPF has long-term deleterious effects on social behavior and limits exploration of novel objects.

  15. Spatial learning impairment in prepubertal guinea pigs prenatally exposed to the organophosphorus pesticide chlorpyrifos: Toxicological implications.

    Science.gov (United States)

    Mamczarz, Jacek; Pescrille, Joseph D; Gavrushenko, Lisa; Burke, Richard D; Fawcett, William P; DeTolla, Louis J; Chen, Hegang; Pereira, Edna F R; Albuquerque, Edson X

    2016-09-01

    Exposure of the developing brain to chlorpyrifos (CPF), an organophosphorus (OP) pesticide used extensively in agriculture worldwide, has been associated with increased prevalence of cognitive deficits in children, particularly boys. The present study was designed to test the hypothesis that cognitive deficits induced by prenatal exposure to sub-acute doses of CPF can be reproduced in precocial small species. To address this hypothesis, pregnant guinea pigs were injected daily with CPF (25mg/kg,s.c.) or vehicle (peanut oil) for 10days starting on presumed gestation day (GD) 53-55. Offspring were born around GD 65, weaned on postnatal day (PND) 20, and subjected to behavioral tests starting around PND 30. On the day of birth, butyrylcholinesterase (BuChE), an OP bioscavenger used as a biomarker of OP exposures, and acetylcholinesterase (AChE), a major molecular target of OP compounds, were significantly inhibited in the blood of CPF-exposed offspring. In their brains, BuChE, but not AChE, was significantly inhibited. Prenatal CPF exposure had no significant effect on locomotor activity or on locomotor habituation, a form of non-associative memory assessed in open fields. Spatial navigation in the Morris water maze (MWM) was found to be sexually dimorphic among guinea pigs, with males outperforming females. Prenatal CPF exposure impaired spatial learning more significantly among male than female guinea pigs and, consequently, reduced the sexual dimorphism of the task. The results presented here, which strongly support the test hypothesis, reveal that the guinea pig is a valuable animal model for preclinical assessment of the developmental neurotoxicity of OP pesticides. These findings are far reaching as they lay the groundwork for future studies aimed at identifying therapeutic interventions to treat and/or prevent the neurotoxic effects of CPF in the developing brain. Copyright © 2016. Published by Elsevier B.V.

  16. Species traits as predictors for intrinsic sensitivity of aquatic invertebrates to the insecticide chlorpyrifos.

    Science.gov (United States)

    Rubach, Mascha N; Baird, Donald J; Boerwinkel, Marie-Claire; Maund, Stephen J; Roessink, Ivo; Van den Brink, Paul J

    2012-10-01

    Ecological risk assessment (ERA) has followed a taxonomy-based approach, making the assumption that related species will show similar sensitivity to toxicants, and using safety factors or species sensitivity distributions to extrapolate from tested to untested species. In ecology it has become apparent that taxonomic approaches may have limitations for the description and understanding of species assemblages in nature. Therefore it has been proposed that the inclusion of species traits in ERA could provide a useful and alternative description of the systems under investigation. At the same time, there is a growing recognition that the use of mechanistic approaches in ERA, including conceptual and quantitative models, may improve predictive and extrapolative power. Purposefully linking traits with mechanistic effect models could add value to taxonomy-based ERA by improving our understanding of how structural and functional system facets may facilitate inter-species extrapolation. Here, we explore whether and in what ways traits can be linked purposefully to mechanistic effect models to predict intrinsic sensitivity using available data on the acute sensitivity and toxicokinetics of a range of freshwater arthropods exposed to chlorpyrifos. The results of a quantitative linking of seven different endpoints and twelve traits demonstrate that while quantitative links between traits and/or trait combinations and process based (toxicokinetic) model parameters can be established, the use of simple traits to predict classical sensitivity endpoints yields little insight. Remarkably, neither of the standard sensitivity values, i.e. the LC(50) or EC(50), showed a strong correlation with traits. Future research in this area should include a quantitative linking of toxicodynamic parameter estimations and physiological traits, and requires further consideration of how mechanistic trait-process/parameter links can be used for prediction of intrinsic sensitivity across species for

  17. Increased gut permeability and bacterial translocation after chronic chlorpyrifos exposure in rats.

    Directory of Open Access Journals (Sweden)

    Claire Joly Condette

    Full Text Available The epithelium's barrier function is crucial for maintaining homeostasis and preventing the passage of food antigens and luminal bacteria. This function is essentially subserved by tight junctions (TJs, multiprotein complexes located in the most apical part of the lateral membrane. Some gastrointestinal disease states are associated with elevated intestinal permeability to macromolecules. In a study on rats, we determined the influence of chronic, daily ingestion of chlorpyrifos (CPF, a pesticide that crosses the placental barrier during pre- and postnatal periods on intestinal permeability and TJ characteristics in the pups. Fluorescein isothiocyanate (FITC-dextran was used as a marker of paracellular transport and mucosal barrier dysfunction. Pups were gavaged with FITC-dextran solution and blood samples were collected every 30 min for 400 min and analyzed spectrofluorimetrically. At sacrifice, different intestinal segments were resected and prepared for analysis of the transcripts (qPCR and localization (using immunofluorescence of ZO-1, occludin and claudins (scaffolding proteins that have a role in the constitution of TJs. In rats that had been exposed to CPF in utero and after birth, we observed a progressive increase in FITC-dextran passage across the epithelial barrier from 210 to 325 min at day 21 after birth (weaning but not at day 60 (adulthood. At both ages, there were significant changes in intestinal TJ gene expression, with downregulation of ZO-1 and occludin and upregulation of claudins 1 and 4. In some intestinal segments, there were changes in the cellular localization of ZO-1 and claudin 4 immunostaining. Lastly, bacterial translocation to the spleen was also observed. The presence of CPF residues in food may disturb epithelial homeostasis in rats. Changes in TJ protein expression and localization may be involved in gut barrier dysfunction in this model. Uncontrolled passage of macromolecules and bacteria across the intestinal

  18. Influence of diphenyl diselenide on chlorpyrifos-induced toxicity in Drosophila melanogaster.

    Science.gov (United States)

    Adedara, Isaac A; Klimaczewski, Claudia V; Barbosa, Nilda B V; Farombi, Ebenezer O; Souza, Diogo O; Rocha, Joao B T

    2015-10-01

    Exposure to chlorpyrifos (CPF) poses several harmful effects to human and animal health. The present study investigated the influence of diphenyl diselenide (DPDS) on CPF-induced toxicity in Drosophila melanogaster. Firstly, the time course lethality response of virgin flies (2- to 3-day-old) to CPF (0.075-0.6μg/g) and DPDP (5-40μmol/kg) in the diet for 28 consecutive days were investigated. Subsequently, the protective effect of DPDS (10, 20 and 40μmol/kg) on CPF (0.15μg/g)-induced mortality, locomotor deficits, neurotoxicity and oxidative stress was assessed in a co-exposure paradigm for 7 days. Results showed that CPF exposure significantly decreased the percent live flies in a time- and concentration-dependent manner, whereas the percent live flies with DPDS treatment was not statistically different from control following 28 days of treatment. In the co-exposure study, CPF significantly increased flies mortality while the survivors exhibited significant locomotor deficits with decreased acetylcholinesterase (AChE) activity. Dietary supplementation with DPDS was associated with marked decrease in mortality, improvement in locomotor activity and restoration of AChE activity in CPF-exposed flies. Moreover, CPF exposure significantly decreased catalase and glutathione-S-transferase activities, total thiol level with concomitant significant elevation in the levels of reactive oxygen species and thiobarbituric acid reactive substances in the head and body regions of the treated flies. Dietary supplementation with DPDS significantly improved the antioxidant status and prevented CPF-induced oxidative stress, thus demonstrating the protective effect of DPDS in CPF-treated flies. Copyright © 2015 Elsevier GmbH. All rights reserved.

  19. Comparative Pharmacokinetics of Chlorpyrifos versus its Major Metabolites Following Oral Administration in the Rat

    Energy Technology Data Exchange (ETDEWEB)

    Busby-Hjerpe, Andrea L.; Campbell, James A.; Smith, Jordan N.; Lee, Sookwang; Poet, Torka S.; Barr, Dana; Timchalk, Charles

    2010-01-31

    Chlorpyrifos (CPF) is a commonly used diethylphosphorothionate organophosphorus (OP) insecticide. Diethylphosphate (DEP), diethylthiophosphate (DETP) and 3,5,6-trichloro-2-pyridinol (TCPy) are products of in vivo metabolism and environmental degradation of CPF and are routinely measured in urine as biomarkers of exposure. Hence, urinary biomonitoring of TCPy, DEP and DETP may be reflective of an individual’s contact with both the parent pesticide and exposure to these metabolites. In the current study, simultaneous dosing of 13C- or 2H- isotopically labeled CPF (13Clabeled CPF, 5 13C on the TCPy ring; or 2H-labeled CPF, diethyl-D10 (deuterium labeled) on the side chain) were exploited to directly compare the pharmacokinetics and metabolism of CPF with TCPy, and DETP. Individual metabolites were co-administered (oral gavage) with the parent compound at equal molar doses (14 μmol/kg; ~5mg/kg CPF). The key objective in the current study was to quantitatively evaluate the pharmacokinetics of the individual metabolites relative to their formation following a dose of CPF. Major differences in the pharmacokinetics between CPF and metabolites doses were observed within the first 3 h of exposure, due to the required metabolism of CPF to initially form TCPy and DETP. Nonetheless, once a substantial amount of CPF has been metabolized (≥ 3 h post-dosing) pharmacokinetics for both treatment groups and metabolites were very comparable. Urinary excretion rates for orally administered TCPy and DETP relative to 13C-CPF or 2H-CPF derived 13C-TCPy and 2H-DETP were consistent with blood pharmacokinetics, and the urinary clearance of metabolite dosed groups were comparable with the results for the 13C- and 2H-CPF groups. Since the pharmacokinetics of the individual metabolites were not modified by co-exposure to 3 CPF; it suggests that environmental exposure to low dose mixtures of pesticides and metabolites will not impact the pharmacokinetics of either.

  20. Chronic dietary chlorpyrifos causes long-term spatial memory impairment and thigmotaxic behavior.

    Science.gov (United States)

    López-Granero, Caridad; Ruiz-Muñoz, Ana M; Nieto-Escámez, Francisco A; Colomina, María T; Aschner, Michael; Sánchez-Santed, Fernando

    2016-03-01

    Little is known about the long-term effects of chronic exposure to low-level organophosphate (OP) pesticides, and the role of neurotransmitter systems, other than the cholinergic system, in mediating OP neurotoxicity. In this study, rats were administered 5mg/kg/day of chlorpyrifos (CPF) for 6 months commencing at 3-months-of-age. The animals were examined 7 months later (at 16-months-of-age) for spatial learning and memory in the Morris water maze (MWM) and locomotor activity. In addition, we assessed the chronic effects of CPF on glutamatergic and gamma-aminobutyric acid (GABAergic) function using pharmacological challenges with dizocilpine (MK801) and diazepam. Impaired performance related to altered search patterns, including thigmotaxis and long-term spatial memory was noted in the MWM in animals exposed to CPF, pointing to dietary CPF-induced behavioral disturbances, such as anxiety. Twenty-four hours after the 31st session of repeated acquisition task, 0.1mg/kg MK801, an N-methyl-d-aspartate (NMDA) antagonist was intraperitoneally (i.p.) injected for 4 consecutive days. Decreased latencies in the MWM in the control group were noted after two sessions with MK801 treatment. Once the MWM assessment was completed, animals were administered 0.1 or 0.2mg/kg of MK801 and 1 or 3mg/kg of diazepam i.p., and tested for locomotor activity. Both groups, the CPF dietary and control, displayed analogous performance in motor activity. In conclusion, our data point to a connection between the long-term spatial memory, thigmotaxic response and CPF long after the exposure ended. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Voltammetric and Mathematical Evidence for Dual Transport Mediation of Serotonin Clearance In Vivo

    Science.gov (United States)

    Wood, Kevin M.; Zeqja, Anisa; Nijhout, H. Frederik; Reed, Michael C.; Best, Janet; Hashemi, Parastoo

    2014-01-01

    The neurotransmitter serotonin underlies many of the brain’s functions. Understanding serotonin neurochemistry is important for improving treatments for neuropsychiatric disorders such as depression. Antidepressants commonly target serotonin clearance via serotonin transporters (SERTs) and have variable clinical effects. Adjunctive therapies, targeting other systems including serotonin autoreceptors, also vary clinically and carry adverse consequences. Fast scan cyclic voltammetry (FSCV) is particularly well suited for studying antidepressant effects on serotonin clearance and autoreceptors by providing real-time chemical information on serotonin kinetics in vivo. However, the complex nature of in vivo serotonin responses makes it difficult to interpret experimental data with established kinetic models. Here, we electrically stimulated the mouse medial forebrain bundle (MFB) to provoke and detect terminal serotonin in the substantia nigra reticulata (SNr). In response to MFB stimulation we found three dynamically distinct serotonin signals. To interpret these signals we developed a computational model that supports two independent serotonin reuptake mechanisms (high affinity, low efficiency reuptake mechanism and low affinity, high efficiency reuptake system) and bolsters an important inhibitory role for the serotonin autoreceptors. Our data and analysis, afforded by the powerful combination of voltammetric and theoretical methods, gives new understanding of the chemical heterogeneity of serotonin dynamics in the brain. This diverse serotonergic matrix likely contributes to clinical variability of antidepressants. PMID:24702305

  2. Updates on the biology of serotonin and tryptophan hydroxylase.

    Science.gov (United States)

    Swami, Tara; Weber, H Christian

    2018-02-01

    To summarize the most recent findings relevant to the biology of serotonin (5-hydroxytryptamine; 5-HT) and the enzyme tryptophan hydroxylase (TPH) in human gastrointestinal disease. Serotonin is synthesized in the central nervous system (CNS) and the gastrointestinal tract where it is secreted from enteroendocrine cells. Its biosynthesis is regulated by two isoforms of the enzyme TPH of which TPH1 is localized predominantly in gastrointestinal enteroendocrine cells. Serotonin activates the peristaltic reflexes, regulates gastrointestinal motility, and has a role in intestinal inflammation. Inhibition of TPH with novel molecules represents a new pharmacological tool in the successful management of carcinoid syndrome in patients with gastrointestinal neuroendocrine tumors (GI-NETs). Certain 5-HT receptor subtype agonists and antagonists are useful in the treatment of functional gastrointestinal disorders. The gastrointestinal tract is the largest storage organ for serotonin where its biosynthesis is regulated by TPH1. It has several important functions in gastrointestinal motility, secretion, and inflammation. Furthermore, TPH represents a target for inhibitory pharmacological therapy of serotonin access states such as the carcinoid syndrome.

  3. Major depressive disorder and diabetes: does serotonin bridge the gap?

    Science.gov (United States)

    De Long, Nicole E; Stepita, Rebecca A; Taylor, Valerie H; Holloway, Alison C

    2015-01-01

    Major depressive disorder (MDD) is one of the most common psychiatric illnesses worldwide, with reported prevalence rates ranging between 10% and 19%. Pharmacotherapy is a first-line option for the management of MDD and, as a result, the use of antidepressants has increased 4 fold in the last 20 years. Serotonin is the most commonly dysregulated neurotransmitter in the etiology of MDD and this system is the primary focus of most medications used in the treatment of illness. Although antidepressant use in adults increases the risk of developing new onset type 2 diabetes, the mechanisms underlying this association are poorly defined. This review will focus on 1) the evidence from human and animal studies suggesting a link between the use of antidepressants that target serotonin signaling (i.e., SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), serotonin antagonist and reuptake inhibitors (SARIs), and noradrenergic and specific serotonergic antidepressants (NaSSAs)) and increased risk of diabetes, and 2) the mechanisms by which alterations in serotonin signalling by antidepressants can affect glucose homeostasis.

  4. Serotonin inhibits low-threshold spike interneurons in the striatum

    Science.gov (United States)

    Cains, Sarah; Blomeley, Craig P; Bracci, Enrico

    2012-01-01

    Low-threshold spike interneurons (LTSIs) are important elements of the striatal architecture and the only known source of nitric oxide in this nucleus, but their rarity has so far prevented systematic studies. Here, we used transgenic mice in which green fluorescent protein is expressed under control of the neuropeptide Y (NPY) promoter and striatal NPY-expressing LTSIs can be easily identified, to investigate the effects of serotonin on these neurons. In sharp contrast with its excitatory action on other striatal interneurons, serotonin (30 μm) strongly inhibited LTSIs, reducing or abolishing their spontaneous firing activity and causing membrane hyperpolarisations. These hyperpolarisations persisted in the presence of tetrodotoxin, were mimicked by 5-HT2C receptor agonists and reversed by 5-HT2C antagonists. Voltage-clamp slow-ramp experiments showed that serotonin caused a strong increase in an outward current activated by depolarisations that was blocked by the specific M current blocker XE 991. In current-clamp experiments, XE 991 per se caused membrane depolarisations in LTSIs and subsequent application of serotonin (in the presence of XE 991) failed to affect these neurons. We concluded that serotonin strongly inhibits striatal LTSIs acting through postsynaptic 5-HT2C receptors and increasing an M type current. PMID:22495583

  5. Serotonin inhibits low-threshold spike interneurons in the striatum.

    Science.gov (United States)

    Cains, Sarah; Blomeley, Craig P; Bracci, Enrico

    2012-05-15

    Low-threshold spike interneurons (LTSIs) are important elements of the striatal architecture and the only known source of nitric oxide in this nucleus, but their rarity has so far prevented systematic studies. Here, we used transgenic mice in which green fluorescent protein is expressed under control of the neuropeptide Y (NPY) promoter and striatal NPY-expressing LTSIs can be easily identified, to investigate the effects of serotonin on these neurons. In sharp contrast with its excitatory action on other striatal interneurons, serotonin (30 μM) strongly inhibited LTSIs, reducing or abolishing their spontaneous firing activity and causing membrane hyperpolarisations.These hyperpolarisations persisted in the presence of tetrodotoxin, were mimicked by 5-HT(2C) receptor agonists and reversed by 5-HT(2C) antagonists. Voltage-clamp slow-ramp experiments showed that serotonin caused a strong increase in an outward current activated by depolarisations that was blocked by the specific M current blocker XE 991. In current-clamp experiments,XE 991 per se caused membrane depolarisations in LTSIs and subsequent application of serotonin (in the presence of XE 991) failed to affect these neurons.We concluded that serotonin strongly inhibits striatal LTSIs acting through postsynaptic 5-HT(2C) receptors and increasing an M type current.

  6. Transient Serotonin Toxicity Evoked by Combination of Electroconvulsive Therapy and Fluoxetine

    Directory of Open Access Journals (Sweden)

    René Klysner

    2014-01-01

    Full Text Available The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine.

  7. Organization of Monosynaptic Inputs to the Serotonin and Dopamine Neuromodulatory Systems

    Directory of Open Access Journals (Sweden)

    Sachie K. Ogawa

    2014-08-01

    Full Text Available Serotonin and dopamine are major neuromodulators. Here, we used a modified rabies virus to identify monosynaptic inputs to serotonin neurons in the dorsal and median raphe (DR and MR. We found that inputs to DR and MR serotonin neurons are spatially shifted in the forebrain, and MR serotonin neurons receive inputs from more medial structures. Then, we compared these data with inputs to dopamine neurons in the ventral tegmental area (VTA and substantia nigra pars compacta (SNc. We found that DR serotonin neurons receive inputs from a remarkably similar set of areas as VTA dopamine neurons apart from the striatum, which preferentially targets dopamine neurons. Our results suggest three major input streams: a medial stream regulates MR serotonin neurons, an intermediate stream regulates DR serotonin and VTA dopamine neurons, and a lateral stream regulates SNc dopamine neurons. These results provide fundamental organizational principles of afferent control for serotonin and dopamine.

  8. Genotype to phenotype

    National Research Council Canada - National Science Library

    Malcolm, Sue; Goodship, Timothy H. J

    2001-01-01

    ... Disorders Molecular Genetics of Hypertension Human Gene EvolutionAnalysis of Multifactorial Disease Transcription Factors Molecular Genetics of Cancer, Second edition Genotype to Phenotype, second e...

  9. Chlorpyrifos-induced oxidative damage is reduced under warming and predation risk: Explaining antagonistic interactions with a pesticide.

    Science.gov (United States)

    Janssens, Lizanne; Stoks, Robby

    2017-07-01

    Interactions with pollutants and environmental factors are poorly studied for physiological traits. Yet physiological traits are important for explaining and predicting interactions at higher levels of organization. We investigated the single and combined impact of the pesticide chlorpyrifos, predation risk and warming on endpoints related to oxidative stress in the damselfly Enallagma cyathigerum. We thereby integrated information on reactive oxygen species (ROS), antioxidant enzymes and oxidative damage. All three treatments impacted the oxidative stress levels and for most traits the pesticide interacted antagonistically with warming or predation risk. Chlorpyrifos exposure resulted in increased ROS levels, decreased antioxidant defence and increased oxidative damage compared to the control situation. Under warming, the pesticide-induced increase in oxidative stress was less strong and the investment in antioxidant defence higher. Although both the pesticide and predation risk increased oxidative damage, the effects of the pesticide on oxidative damage were less strong in the presence of predator cues (at 20 °C). Despite the weaker pesticide-induced effects under predation risk, the combination of the pesticide and predator cues consistently caused the highest ROS levels, the lowest antioxidant defence and the highest oxidative damage, indicating the importance of cumulative stressor effects for impairing fitness. Our results provide the first evidence for antagonistic interactions of warming and predation risk with a pollutant for physiological traits. We identified two general mechanisms that may generate antagonistic interactions for oxidative stress: cross-tolerance and the maximum cumulative levels of damage. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Inhibition, recovery and oxime-induced reactivation of muscle esterases following chlorpyrifos exposure in the earthworm Lumbricus terrestris

    Energy Technology Data Exchange (ETDEWEB)

    Collange, B. [Universite d' Avignon et des Pays de Vaucluse, UMR 406 Abeilles et Environnement, Site AGROPARC, F-84914, Avignon Cede 09 (France); Wheelock, C.E. [Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 171 77, Stockholm (Sweden); Rault, M.; Mazzia, C. [Universite d' Avignon et des Pays de Vaucluse, UMR 406 Abeilles et Environnement, Site AGROPARC, F-84914, Avignon Cede 09 (France); Capowiez, Y. [INRA, Unite PSH, Site AGROPARC, F-84914 Avignon Cedex 09 (France); Sanchez-Hernandez, J.C., E-mail: juancarlos.sanchez@uclm.e [Laboratory of Ecotoxicology, Faculty of Environmental Science, University of Castilla-La Mancha, Avda. Carlos III s/n, 45071, Toledo (Spain)

    2010-06-15

    Assessment of wildlife exposure to organophosphorus (OP) pesticides generally involves the measurement of cholinesterase (ChE) inhibition, and complementary biomarkers (or related endpoints) are rarely included. Herein, we investigated the time course inhibition and recovery of ChE and carboxylesterase (CE) activities in the earthworm Lumbricus terrestris exposed to chlorpyrifos, and the ability of oximes to reactivate the phosphorylated ChE activity. Results indicated that these esterase activities are a suitable multibiomarker scheme for monitoring OP exposure due to their high sensitivity to OP inhibition and slow recovery to full activity levels following pesticide exposure. Moreover, oximes reactivated the inhibited ChE activity of the earthworms exposed to 12 and 48 mg kg{sup -1} chlorpyrifos during the first week following pesticide exposure. This methodology is useful for providing evidence for OP-mediated ChE inhibition in individuals with a short history of OP exposure (<=1 week); resulting a valuable approach for assessing multiple OP exposure episodes in the field. - Esterase inhibition combined with oxime reactivation methods is a suitable approach for monitoring organophosphate contamination

  11. Prenatal Exposure of Guinea Pigs to the Organophosphorus Pesticide Chlorpyrifos Disrupts the Structural and Functional Integrity of the Brain

    Science.gov (United States)

    Mullins, Roger J.; Xu, Su; Pereira, Edna F.R.; Pescrille, Joseph D.; Todd, Spencer W.; Mamczarz, Jacek; Albuquerque, Edson X.; Gullapalli, Rao P.

    2015-01-01

    This study was designed to test the hypothesis that prenatal exposure of guinea pigs to the organophosphorus (OP) pesticide chlorpyrifos (CPF) disrupts the structural and functional integrity of the brain. Pregnant guinea pigs were injected with chlorpyrifos (20 mg/kg, s.c.) or vehicle (peanut oil) once per day for ten consecutive days, starting approximately on the 50th day of gestation. Cognitive behavior of female offspring was examined starting at 40–45 post-natal days (PND) using the Morris Water Maze (MWM), and brain structural integrity was analyzed at PND 70 using magnetic resonance imaging (MRI) methods, including T2-weighted anatomical scans and Diffusion Kurtosis Imaging (DKI). The offspring of exposed mothers had significantly decreased body weight and brain volume, particularly in the frontal regions of the brain including the striatum. Furthermore, the offspring demonstrated significant spatial learning deficits in MWM recall compared to the vehicle group. Diffusion measures revealed reduced white matter integrity within the striatum and amygdala that correlated with spatial learning performance. These findings reveal the lasting effect of pre-natal exposure to CPF as well as the danger of mother to child transmission of CPF in the environment. PMID:25704171

  12. Behavior of pyrimethanil, pyraclostrobin, boscalid, cypermethrin and chlorpyrifos residues on raspberry fruit and leaves of Laszka variety.

    Science.gov (United States)

    Sadło, Stanisław; Szpyrka, Ewa; Stawarczyk, Michał; Piechowicz, Bartosz

    2014-01-01

    The purpose of the research conducted was to investigate and evaluate the behavior of pyrimethanil, pyraclostrobin, boscalid, cypermethrin and chlorpyrifos, the active ingredients of selected fungicides and insecticides, on ripe fruit and in fully developed leaves of raspberry of the Laszka variety. The field trial was carried out in the period of one month starting from the first fruit picking. The results obtained indicated that residue levels on the day of the first crop picking did not even approximate the corresponding EU-MRLs (http://ec.europa.eu/sanco_pesticides). Individual substances in raspberry fruits and leaves disappeared at a similar rate. As a result of chlorpyrifos application to the soil, its residue in fruits and leaves occurred for the whole period of fruit bearing, though in fruit they dropped successively. To produce raspberries with residues below or equal to 0.01 μg g(-1), the application of pesticides should be stopped at least 2-3 weeks before the first crop picking, and on condition that an appropriate preparation (active in low doses) is applied to the last treatments.

  13. Genome-wide gene expression analysis in response to organophosphorus pesticide chlorpyrifos and diazinon in C. elegans.

    Directory of Open Access Journals (Sweden)

    Ana Viñuela

    Full Text Available Organophosphorus pesticides (OPs were originally designed to affect the nervous system by inhibiting the enzyme acetylcholinesterase, an important regulator of the neurotransmitter acetylcholine. Over the past years evidence is mounting that these compounds affect many other processes. Little is known, however, about gene expression responses against OPs in the nematode Caenorhabditis elegans. This is surprising because C. elegans is extensively used as a model species in toxicity studies. To address this question we performed a microarray study in C. elegans which was exposed for 72 hrs to two widely used Ops, chlorpyrifos and diazinon, and a low dose mixture of these two compounds. Our analysis revealed transcriptional responses related to detoxification, stress, innate immunity, and transport and metabolism of lipids in all treatments. We found that for both compounds as well as in the mixture, these processes were regulated by different gene transcripts. Our results illustrate intense, and unexpected crosstalk between gene pathways in response to chlorpyrifos and diazinon in C. elegans.

  14. Efficacy of Ganoderma sp. JAS4 in bioremediation of chlorpyrifos and its hydrolyzing metabolite TCP from agricultural soil.

    Science.gov (United States)

    Silambarasan, Sivagnanam; Abraham, Jayanthi

    2014-01-01

    A novel fungal strain JAS4 was isolated from agricultural soil and was found to be highly effective in degrading chlorpyrifos and its major degradation product 3,5,6-trichloro-2-pyridinol (TCP). The molecular characterization based on 18S rRNA sequence analysis, revealed strain JAS4 as Ganoderma sp. which could able to degrade chlorpyrifos and its metabolite in an aqueous medium with rate constant of 0.8460 day(-1), following first order rate kinetics, and the time in which the initial insecticide concentration was reduced by 50% (DT(50)) was 0.81 days. Studies on biodegradation in soil with nutrients showed that JAS4 strain exhibited efficient degradation of insecticide with a rate constant of 0.9 day(-1), and DT(50) was 0.73 day. In contrast, degradation of insecticide in soil without nutrients was characterized by a rate constant of 0.7576 day(-1) and the DT(50) was 0.91 day. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Sex Differences in Serotonin 1 Receptor Binding in Rat Brain

    Science.gov (United States)

    Fischette, Christine T.; Biegon, Anat; McEwen, Bruce S.

    1983-10-01

    Male and female rats exhibit sex differences in binding by serotonin 1 receptors in discrete areas of the brain, some of which have been implicated in the control of ovulation and of gonadotropin release. The sex-specific changes in binding, which occur in response to the same hormonal (estrogenic) stimulus, are due to changes in the number of binding sites. Castration alone also affects the number of binding sites in certain areas. The results lead to the conclusion that peripheral hormones modulate binding by serotonin 1 receptors. The status of the serotonin receptor system may affect the reproductive capacity of an organism and may be related to sex-linked emotional disturbances in humans.

  16. Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas

    DEFF Research Database (Denmark)

    Casar-Borota, Olivera; Botling, Johan; Granberg, Dan

    2017-01-01

    Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker...... in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown. Facing a difficult diagnostic...... case of an invasive serotonin and adrenocorticotroph hormone immunoreactive NET in the sellar region, we explored the immunohistochemical expression of serotonin, ATRX, and DAXX in a large series of pituitary endocrine tumors of different types from 246 patients and in 2 corticotroph carcinomas. None...

  17. Protonated serotonin: Geometry, electronic structures and photophysical properties

    Science.gov (United States)

    Omidyan, Reza; Amanollahi, Zohreh; Azimi, Gholamhassan

    2017-07-01

    The geometry and electronic structures of protonated serotonin have been investigated by the aim of MP2 and CC2 methods. The relative stabilities, transition energies and geometry of sixteen different protonated isomers of serotonin have been presented. It has been predicted that protonation does not exhibit essential alteration on the S1 ← S0 electronic transition energy of serotonin. Instead, more complicated photophysical nature in respect to its neutral analogue is suggested for protonated system owing to radiative and non-radiative deactivation pathways. In addition to hydrogen detachment (HD), hydrogen/proton transfer (H/PT) processes from ammonium to indole ring along the NH+⋯ π hydrogen bond have been predicted as the most important photophysical consequences of SERH+ at S1 excited state. The PT processes is suggested to be responsible for fluorescence of SERH+ while the HD driving coordinate is proposed for elucidation of its nonradiative deactivation mechanism.

  18. Effects of ageing on serotonin transporters in healthy females

    Energy Technology Data Exchange (ETDEWEB)

    Kuikka, J.T. [Dept. of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital (Finland); Dept. of Forensic Psychiatry, University of Kuopio and Niuvanniemi Hospital, Kuopio (Finland); Tammela, L.; Karhunen, L.; Uusitupa, M. [Dept. of Clinical Nutrition, University of Kuopio and Kuopio University Hospital, Kuopio (Finland); Bergstroem, K.A. [Dept. of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital (Finland); Tiihonen, J. [Dept. of Forensic Psychiatry, University of Kuopio and Niuvanniemi Hospital, Kuopio (Finland)

    2001-07-01

    The effect of ageing on brain serotonin transporters was evaluated in 19 healthy female volunteers (age range 22-74 years) using single-photon emission tomography and [{sup 123}I] nor-{beta}-CIT. The study subjects were scanned 0.3, 3, 6 and 23 h after injection of 185 MBq of [{sup 123}I] nor-{beta}-CIT. The ratio of the distribution volume for tracer in the midbrain to that in the cerebellum minus 1 was used as an index for serotonin transporter binding. An age-related decline of 2% per decade (r=-0.47; P<0.05) was found in the midbrain. The decline in [{sup 123}I] nor-{beta}-CIT binding in the serotonin transporter-rich area is much less than that in dopamine transporters in the striatum (6% per decade). (orig.)

  19. Mechanism of Paroxetine (Paxil) Inhibition of the Serotonin Transporter.

    Science.gov (United States)

    Davis, Bruce A; Nagarajan, Anu; Forrest, Lucy R; Singh, Satinder K

    2016-04-01

    The serotonin transporter (SERT) is an integral membrane protein that exploits preexisting sodium-, chloride-, and potassium ion gradients to catalyze the thermodynamically unfavorable movement of synaptic serotonin into the presynaptic neuron. SERT has garnered significant clinical attention partly because it is the target of multiple psychoactive agents, including the antidepressant paroxetine (Paxil), the most potent selective serotonin reuptake inhibitor known. However, the binding site and orientation of paroxetine in SERT remain controversial. To provide molecular insight, we constructed SERT homology models based on the Drosophila melanogaster dopamine transporter and docked paroxetine to these models. We tested the predicted binding configurations with a combination of radioligand binding and flux assays on wild-type and mutant SERTs. Our data suggest that the orientation of paroxetine, specifically its fluorophenyl ring, in SERT's substrate binding site directly depends on this pocket's charge distribution, and thereby provide an avenue toward understanding and enhancing high-affinity antidepressant activity.

  20. Transient Serotonin Toxicity Evoked by Combination of Electroconvulsive Therapy and Fluoxetine

    DEFF Research Database (Denmark)

    Klysner, René; Bjerg Bendsen, Birgitte; Hansen, Maja Soon

    2014-01-01

    The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine.......The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine....

  1. Age-related effect of serotonin transporter genotype on amygdala and prefrontal cortex function in adolescence

    OpenAIRE

    Wiggins, Jillian Lee; Bedoyan, Jirair K.; Carrasco, Melisa; Swartz, Johnna R.; Martin, Donna M.; Monk, Christopher S.

    2012-01-01

    The S and LG alleles of the serotonin transporter-linked polymorphic region (5-HTTLPR) lower serotonin transporter expression. These low expressing alleles are linked to increased risk for depression and brain activation patterns found in depression (increased amygdala activation and decreased amygdala-prefrontal cortex connectivity). Paradoxically, serotonin transporter blockade relieves depression symptoms. Rodent models suggest that decreased serotonin transporter in early life produces de...

  2. Phenotypic malignant changes and untargeted lipidomic analysis of long-term exposed prostate cancer cells to endocrine disruptors

    Energy Technology Data Exchange (ETDEWEB)

    Bedia, Carmen, E-mail: carmen.bedia@idaea.csic.es; Dalmau, Núria, E-mail: nuria.dalmau@idaea.csic.es; Jaumot, Joaquim, E-mail: joaquim.jaumot@idaea.csic.es; Tauler, Romà, E-mail: roma.tauler@idaea.csic.es

    2015-07-15

    Endocrine disruptors (EDs) are a class of environmental toxic molecules able to interfere with the normal hormone metabolism. Numerous studies involve EDs exposure to initiation and development of cancers, including prostate cancer. In this work, three different EDs (aldrin, aroclor 1254 and chlorpyrifos (CPF)) were investigated as potential inducers of a malignant phenotype in DU145 prostate cancer cells after a chronic exposure. Epithelial to mesenchymal transition (EMT) induction, proliferation, migration, colony formation and release of metalloproteinase 2 (MMP-2) were analyzed in 50-day exposed cells to the selected EDs. As a result, aldrin and CPF exposure led to an EMT induction (loss of 16% and 14% of E-cadherin levels, respectively, compared to the unexposed cells). Aroclor and CPF presented an increased migration (134% and 126%, respectively), colony formation (204% and 144%, respectively) and MMP-2 release (137% in both cases) compared to the unexposed cells. An untargeted lipidomic analysis was performed to decipher the lipids involved in the observed transformations. As general results, aldrin exposure showed a global decrease in phospholipids and sphingolipids, and aroclor and CPF showed an increase of certain phospholipids, glycosphingolipids as well as a remarkable increase of some cardiolipin species. Furthermore, the three exposures resulted in an increase of some triglyceride species. In conclusion, some significant changes in lipids were identified and thus we postulate that some lipid compounds and lipid metabolic pathways could be involved in the acquisition of the malignant phenotype in exposed prostate cancer cells to the selected EDs. - Highlights: • Aldrin, aroclor and chlorpyrifos induced an aggressive phenotype in DU145 cells. • An untargeted lipidomic analysis has been performed on chronic exposed cells. • Lipidomic results showed changes in specific lipid species under chronic exposure. • These lipids may have a role in the

  3. [Serotonin dysfunctions in the background of the seven deadly sins].

    Science.gov (United States)

    Janka, Zoltán

    2003-11-20

    The symbolic characters of the Seven Deadly Sins can be traced from time to time in the cultural history of human mankind, being directly specified in certain artistic products. Such are, among others, the painting entitled "The Seven Deadly Sins and the Four Lost Things" by Hieronymus Bosch and the poems Divina Commedia and The Foerie Queene by Dante Alighieri and Edmund Spenser, respectively. However, there are several paragraphs referring to these behaviours of the Seven Deadly Sins in the Bible and in the dramas of William Shakespeare. The objective of the present review is to propose that dysfunctions in the central serotonergic system might be involved in the neurobiology of these 'sinful' behaviour patterns. Evidences indicate that behaviour traits such as Accidia (Sloth), Luxuria (Lust, Lechery), Superbia (Pride), Ira (Wrath, Anger), Invidia (Envy), Avaritia (Greed, Avarice), and Gula (Gluttony) can relate to the functional alterations of serotonin in the brain. Results of biochemical and molecular genetic (polymorphism) studies on the human serotonergic system (receptor, transporter, enzyme), findings of functional imaging techniques, effects of depletion (or supplementation) of the serotonin precursor tryptophan, data of challenge probe investigations directed to testing central serotonergic functions, alterations in the peripheral serotonin measures (platelet), and the changes in the CSF 5-hydroxy-indoleacetic acid content indicate such serotonergic involvement. Furthermore, results of animal experiments on behaviour change (aggressive, dominant or submissive, appetite, alcohol preference) attributed to serotonin status modification and the clinically evidenced therapeutic efficacy of pharmacological interventions, based on the modulation and perturbation of the serotonergic system (e.g. selective serotonin reuptake inhibitors), in treating the 'sinful' behaviour forms and analogous pathological states reaching the severity of psychiatric disorders

  4. Controlled release study on microencapsulated mixture of fipronil and chlorpyrifos for the management of white grubs (Holotrichia parallela) in peanuts (Arachis hypogaea L.).

    Science.gov (United States)

    Yang, Daibin; Li, Guangxing; Yan, Xiaojing; Yuan, Huizhu

    2014-11-05

    This study was conducted to determine the release dynamics of a microencapsulated mixture of fipronil and chlorpyrifos in peanut fields and its efficacy against white grubs. The results indicated that microencapsulation significantly stabilized this mixture against degradation in the environment so that a single dose of this microencapsulated formulation applied through seed treatment effectively controlled white grubs throughout the entire growing season. During the experimental course, the concentration of chlorpyrifos in the soil with the microencapsulated formulation was 13.6 ± 9.9 (n = 6) times that of the conventional formulation, and the concentration of fipronil was at least 2.2 times that of the conventional formulation in the soil and peanut roots. However, the residue risks of chlorpyrifos and fipronil in the kernels were different. At harvest, there was a low risk that the residual chlorpyrifos in the kernels exceeded the MRLs (maximum residue limit). In contrast, the amount of residual fipronil in some kernel samples reached the statutory MRL set by the European Union, which suggested that a higher application rate or the repeated application of the microencapsulated fipronil formulation would not be acceptable.

  5. The use of self-reported symptoms as a proxy for acute organophosphate poisoning after exposure to chlorpyrifos 50% plus cypermethrin 5% among Nepali farmers

    DEFF Research Database (Denmark)

    Kofod, Dea Haagensen; Jørs, Erik; Varma, Anshu

    2016-01-01

    in response to occupational acute organophosphate exposure. Methods: We performed a randomized, double-blind, placebo-controlled, crossover trial among 42 Nepali commercial vegetable farmers. The farmers were randomly assigned (ratio 1:1) to a 2-h organophosphate (chlorpyrifos 50% plus cypermethrin 5...

  6. Both synthesis and reuptake are critical for replenishing the releasable serotonin pool in Drosophila

    Science.gov (United States)

    Borue, Xenia; Condron, Barry; Venton, B. Jill

    2010-01-01

    The two main sources of serotonin available for release are expected to be newly synthesized serotonin and serotonin recycled after reuptake by the serotonin transporter (SERT). However, their relative importance for maintaining release and the time course of regulation are unknown. We studied serotonin signaling in the ventral nerve cord of the larval Drosophila central nervous system. Fast-scan cyclic voltammetry at implanted microelectrodes was used to detect serotonin elicited by channelrhodopsin2-mediated depolarization. The effects of reuptake were probed by incubating in cocaine, which is selective for the serotonin transporter in Drosophila. p-chlorophenylalanine (PCPA), an inhibitor of tryptophan hydroxylase2, was used to investigate the effects of synthesis. Stimulations were repeated at various intervals to assess the time course of recovery of the releasable pool. Reuptake is important for the rapid replenishment of the releasable pool, on the 1 minute time scale. Synthesis is critical to the longer-term replenishment (10 min) of the releasable pool, especially when reuptake is also inhibited. Concurrent synthesis and reuptake inhibition decreased both serotonin tissue content measured by immunohistochemistry (by 50%) and the initial amount of evoked serotonin (by 65%). Decreases in evoked serotonin are rescued by inhibiting action potential propagation with tetrodotoxin, implicating endogenous activity in the depletion. These results show synthesis is necessary to replenish part of the releasable serotonin pool that is depleted after reuptake inhibition, suggesting that regulation of synthesis may modulate the effects of serotonin reuptake inhibitors. PMID:20070864

  7. Coaction of Stress and Serotonin Transporter Genotype in Predicting Aggression at the Transition to Adulthood

    Science.gov (United States)

    Conway, Christopher C.; Keenan-Miller, Danielle; Hammen, Constance; Lind, Penelope A.; Najman, Jake M.; Brennan, Patricia A.

    2012-01-01

    Despite consistent evidence that serotonin functioning affects stress reactivity and vulnerability to aggression, research on serotonin gene-stress interactions (G x E) in the development of aggression remains limited. The present study investigated variation in the promoter region of the serotonin transporter gene (5-HTTLPR) as a moderator of the…

  8. Serum serotonin concentration associated with bone mineral density in Chinese postmenopausal women.

    Science.gov (United States)

    Wei, Qiu-Shi; Chen, Zhen-Qiu; Tan, Xin; Kang, Lu-Chen; Jiang, Xiao-Bing; Liang, Jiang; He, Wei; Deng, Wei-Min

    2017-02-01

    Recent studies have shown that circulating serotonin plays a potential role in bone metabolism. However, conflicting results have been reported for the relationship between serum serotonin concentrations and bone mineral density (BMD). We investigated whether the serum serotonin concentrations related to BMD in Chinese postmenopausal women. Serum serotonin and bone turnover concentrations of 117 premenopausal women and 262 asymptomatic postmenopausal women were analyzed by enzyme-linked immunosorbent assay. BMD at the lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry. The relationship between serotonin and BMD was investigated. The postmenopausal women had lower mean serum serotonin concentrations compared to the premenopausal women. Serotonin concentrations were negatively associated with age, weight, BMI, fat mass, and β-CTX concentrations in postmenopausal women. No significant correlations were found between serotonin and these parameters in premenopausal women. In postmenopausal women, age- and BMI-adjusted serotonin concentrations were positively correlated with BMD of the lumbar spine and femoral neck. Multiple regression analyses showed serum serotonin and β-CTX were the predictors for lumbar spine BMD. Only serum serotonin was the determinant for femoral neck BMD. In conclusion, lower serum serotonin concentrations are linked to low lumbar spine and femoral neck BMD in postmenopausal women.

  9. 21 CFR 862.1390 - 5-Hydroxyindole acetic acid/serotonin test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false 5-Hydroxyindole acetic acid/serotonin test system... Test Systems § 862.1390 5-Hydroxyindole acetic acid/serotonin test system. (a) Identification. A 5-hydroxyindole acetic acid/serotonin test system is a device intended to measure 5-hydroxyindole acetic acid...

  10. Interaction of antidepressants with the serotonin and norepinephrine transporters

    DEFF Research Database (Denmark)

    Sørensen, Lena; Andersen, Jacob; Thomsen, Mette

    2012-01-01

    The serotonin transporter (SERT) and the norepinephrine transporter (NET) are sodium-dependent neurotransmitter transporters responsible for reuptake of released serotonin and norepinephrine, respectively, into nerve terminals in the brain. A wide range of inhibitors of SERT and NET are used...... as treatment of depression and anxiety disorders or as psychostimulant drugs of abuse. Despite their clinical importance, the molecular mechanisms by which various types of antidepressant drugs bind and inhibit SERT and NET are still elusive for the majority of the inhibitors, including the molecular basis...

  11. Functional characterization of serotonin receptor subtypes in human duodenal secretion

    DEFF Research Database (Denmark)

    Engelmann, Bodil Elisabeth; Bindslev, Niels; Poulsen, Steen Seier

    2006-01-01

    Serotonin (5-HT) stimulates ion secretion in the gastrointestinal tract and the sensitivity for 5-HT might be altered in dyspeptic patients infected with Helicobacter pylori. The purpose of the present study was to characterize the 5-HT-induced electrogenic ion transport in the duodenum of dyspep......Serotonin (5-HT) stimulates ion secretion in the gastrointestinal tract and the sensitivity for 5-HT might be altered in dyspeptic patients infected with Helicobacter pylori. The purpose of the present study was to characterize the 5-HT-induced electrogenic ion transport in the duodenum...

  12. Serotonin transporter evolution and impact of polymorphic transcriptional regulation

    DEFF Research Database (Denmark)

    Søeby, Karen; Larsen, Svend Ask; Olsen, Line

    2005-01-01

    The serotonin transporter (SERT) is the primary drug target in the current antidepressant therapy. A functional polymorphism in the 2nd intron of the 5HTT gene encoding the SERT has been identified and associated with susceptibility to affective disorders and treatment response to antidepressants...... in the VNTRs of all mammalian SERT genes. The number of these putative binding sites varies proportionally to the length of the VNTR. We propose that the intronic VNTR have been selectively targeted through mammalian evolution to finetune transcriptional regulation of the serotonin expression....

  13. Mutations in the Caenorhabditis elegans serotonin reuptake transporter MOD-5 reveal serotonin-dependent and -independent activities of fluoxetine.

    Science.gov (United States)

    Ranganathan, R; Sawin, E R; Trent, C; Horvitz, H R

    2001-08-15

    We isolated two mutants defective in the uptake of exogenous serotonin (5-HT) into the neurosecretory motor neurons of Caenorhabditis elegans. These mutants were hypersensitive to exogenous 5-HT and hyper-responsive in the experience-dependent enhanced slowing response to food modulated by 5-HT. The two allelic mutations defined the gene mod-5 (modulation of locomotion defective), which encodes the only serotonin reuptake transporter (SERT) in C. elegans. The selective serotonin reuptake inhibitor fluoxetine (Prozac) potentiated the enhanced slowing response, and this potentiation required mod-5 function, establishing a 5-HT- and SERT-dependent behavioral effect of fluoxetine in C. elegans. By contrast, other responses of C. elegans to fluoxetine were independent of MOD-5 SERT and 5-HT. Further analysis of the MOD-5-independent behavioral effects of fluoxetine could lead to the identification of novel targets of fluoxetine and could facilitate the development of more specific human pharmaceuticals.

  14. Serotonin, Amygdala and Fear: Assembling the Puzzle.

    Science.gov (United States)

    Bocchio, Marco; McHugh, Stephen B; Bannerman, David M; Sharp, Trevor; Capogna, Marco

    2016-01-01

    The fear circuitry orchestrates defense mechanisms in response to environmental threats. This circuitry is evolutionarily crucial for survival, but its dysregulation is thought to play a major role in the pathophysiology of psychiatric conditions in humans. The amygdala is a key player in the processing of fear. This brain area is prominently modulated by the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). The 5-HT input to the amygdala has drawn particular interest because genetic and pharmacological alterations of the 5-HT transporter (5-HTT) affect amygdala activation in response to emotional stimuli. Nonetheless, the impact of 5-HT on fear processing remains poorly understood.The aim of this review is to elucidate the physiological role of 5-HT in fear learning via its action on the neuronal circuits of the amygdala. Since 5-HT release increases in the basolateral amygdala (BLA) during both fear memory acquisition and expression, we examine whether and how 5-HT neurons encode aversive stimuli and aversive cues. Next, we describe pharmacological and genetic alterations of 5-HT neurotransmission that, in both rodents and humans, lead to altered fear learning. To explore the mechanisms through which 5-HT could modulate conditioned fear, we focus on the rodent BLA. We propose that a circuit-based approach taking into account the localization of specific 5-HT receptors on neurochemically-defined neurons in the BLA may be essential to decipher the role of 5-HT in emotional behavior. In keeping with a 5-HT control of fear learning, we review electrophysiological data suggesting that 5-HT regulates synaptic plasticity, spike synchrony and theta oscillations in the BLA via actions on different subcellular compartments of principal neurons and distinct GABAergic interneuron populations. Finally, we discuss how recently developed optogenetic tools combined with electrophysiological recordings and behavior could progress the knowledge of the mechanisms underlying 5

  15. Serotonin hypothesis and pulmonary artery hypertension

    Directory of Open Access Journals (Sweden)

    Monika Kloza

    2014-06-01

    Full Text Available Tętnicze nadciśnienie płucne jest postępującą chorobą, prowadzącą do niewydolności prawej komory serca i przedwczesnej śmierci. Charakteryzuje się podwyższonym ciśnieniem w tętnicy płucnej, zwiększeniem oporu naczyniowego, przebudową naczyń płucnych oraz dysfunkcją śródbłonka. Patomechanizm tej choroby jest wciąż nieznany. Sugeruje się, że dysfunkcja śródbłonka zaburza równowagę między czynnikami wazodylatacyjnymi a wazokonstrykcyjnymi, w tym np. serotoniną (5-HT. Pierwotnie teorię serotoninową tętniczego nadciśnienia płucnego powiązano z przyjmowaniem leków anoreksygennych, pochodnych fenfluraminy, hamujących wychwyt zwrotny 5-HT. Obecnie potwierdzono zaangażowanie wszystkich składowych układu serotoninergicznego w krążeniu płucnym w tym patomechanizm. W komórkach śródbłonka tętnicy płucnej, hydroksylaza tryptofanu 1 katalizuje reakcję syntezy serotoniny z tryptofanu. 5-HT kurczy naczynia płucne przez pobudzenie receptorów serotoninowych, głównie 5-HT1B i 5-HT2A, a także jest transportowana przez transporter serotoniny (SERT do wnętrza komórki mięśni gładkich tętnicy płucnej, a następnie działając przez kinazę Rho (ROCK lub reaktywne formy tlenu powoduje skurcz naczyń i/lub wzrost aktywacji czynników transkrypcyjnych i proliferację. Potwierdzono interakcję między receptorem 5-HT1B i SERT w modulowaniu skurczu naczyń płucnych i ich proliferacji. W pracy omówiono dowody wpływu 5-HT na rozwój tętniczego nadciśnienia płucnego i możliwe cele terapeutyczne w obrębie układu serotoninergicznego.

  16. Decreased anxiety in juvenile rats following exposure to low levels of chlorpyrifos during development.

    Science.gov (United States)

    Carr, Russell L; Armstrong, Nathan H; Buchanan, Alenda T; Eells, Jeffrey B; Mohammed, Afzaal N; Ross, Matthew K; Nail, Carole A

    2017-03-01

    Exposure to chlorpyrifos (CPF) during the late preweanling period in rats inhibits the endocannabinoid metabolizing enzymes fatty acid hydrolase (FAAH) and monoacylglycerol lipase (MAGL), resulting in accumulation of their respective substrates anandamide (AEA) and 2-arachidonylglycerol (2-AG). This occurs at 1.0mg/kg, but at a lower dosage (0.5mg/kg) only FAAH and AEA are affected with no measurable inhibition of either cholinesterase (ChE) or MAGL. The endocannabinoid system plays a vital role in nervous system development and may be an important developmental target for CPF. The endocannabinoid system plays an important role in the regulation of anxiety and, at higher dosages, developmental exposure to CPF alters anxiety-like behavior. However, it is not clear whether exposure to low dosages of CPF that do not inhibit ChE will cause any persistent effects on anxiety-like behavior. To determine if this occurs, 10-day old rat pups were exposed daily for 7 days to either corn oil or 0.5, 0.75, or 1.0mg/kg CPF by oral gavage. At 12h following the last CPF administration, 1.0mg/kg resulted in significant inhibition of FAAH, MAGL, and ChE, whereas 0.5 and 0.75mg/kg resulted in significant inhibition of only FAAH. AEA levels were significantly elevated in all three treatment groups as were palmitoylethanolamide and oleoylethanolamide, which are also substrates for FAAH. 2-AG levels were significantly elevated by 0.75 and 1.0mg/kg but not 0.5mg/kg. On day 25, the latency to emerge from a dark container into a highly illuminated novel open field was measured as an indicator of anxiety. All three CPF treatment groups spent significantly less time in the dark container prior to emerging as compared to the control group, suggesting a decreased level of anxiety. This demonstrates that repeated preweanling exposure to dosages of CPF that do not inhibit brain ChE can induce a decline in the level of anxiety that is detectable during the early postweanling period. Copyright

  17. Clinical phenotypes of asthma

    NARCIS (Netherlands)

    Bel, Elisabeth H.

    2004-01-01

    PURPOSE OF REVIEW: Asthma is a phenotypically heterogeneous disorder and, over the years, many different clinical subtypes of asthma have been described. A precise definition of asthma phenotypes is now becoming more and more important, not only for a better understanding of pathophysiologic

  18. Serotonin transporter gene polymorphisms and brain function during emotional distraction from cognitive processing in posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Hauser Michael A

    2011-05-01

    Full Text Available Abstract Background Serotonergic system dysfunction has been implicated in posttraumatic stress disorder (PTSD. Genetic polymorphisms associated with serotonin signaling may predict differences in brain circuitry involved in emotion processing and deficits associated with PTSD. In healthy individuals, common functional polymorphisms in the serotonin transporter gene (SLC6A4 have been shown to modulate amygdala and prefrontal cortex (PFC activity in response to salient emotional stimuli. Similar patterns of differential neural responses to emotional stimuli have been demonstrated in PTSD but genetic factors influencing these activations have yet to be examined. Methods We investigated whether SLC6A4 promoter polymorphisms (5-HTTLPR, rs25531 and several downstream single nucleotide polymorphisms (SNPs modulated activity of brain regions involved in the cognitive control of emotion in post-9/11 veterans with PTSD. We used functional MRI to examine neural activity in a PTSD group (n = 22 and a trauma-exposed control group (n = 20 in response to trauma-related images presented as task-irrelevant distractors during the active maintenance period of a delayed-response working memory task. Regions of interest were derived by contrasting activation for the most distracting and least distracting conditions across participants. Results In patients with PTSD, when compared to trauma-exposed controls, rs16965628 (associated with serotonin transporter gene expression modulated task-related ventrolateral PFC activation and 5-HTTLPR tended to modulate left amygdala activation. Subsequent to combat-related trauma, these SLC6A4 polymorphisms may bias serotonin signaling and the neural circuitry mediating cognitive control of emotion in patients with PTSD. Conclusions The SLC6A4 SNP rs16965628 and 5-HTTLPR are associated with a bias in neural responses to traumatic reminders and cognitive control of emotions in patients with PTSD. Functional MRI may help identify

  19. Spinach or amaranth contains highest residue of metalaxyl, fluazifop-P-butyl, chlorpyrifos, and lambda-cyhalothrin on six leaf vegetables upon open field application.

    Science.gov (United States)

    Fan, Sufang; Zhang, Fengzu; Deng, Kailin; Yu, Chuanshan; Liu, Shaowen; Zhao, Pengyue; Pan, Canping

    2013-03-06

    To select representative leaf vegetables which may contain the highest residue, field experiments of metalaxyl, fluazifop-P-butyl, chlorpyrifos, and lambda-cyhalothrin on six crops including pakchoi, rape, crown daisy, amaranth, spinach, and lettuce were designed and conducted. In this study, a high-performance liquid chromatograph and electrospray ionization tandem mass spectrometer with multiple reaction monitoring was used to simultaneously determine metalaxyl and fluazifop-P-butyl residue in various samples, and a gas chromatograph with electron capture detector was used to detect chlorpyrifos and lambda-cyhalothrin. The limits of quantification (LOQ) of metalaxyl, fluazifop-P-butyl, chlorpyrifos, and lambda-cyhalothrin were in the range of 0.001-0.01 mg kg(-1) for all samples, and the average recoveries of all pesticides ranged from 67.6 to 119.1% at spiked levels of 0.01-0.1 mg kg(-1). In supervised field trials, the half-lives of metalaxyl, fluazifop-P-butyl, chlorpyrifos, and lambda-cyhalothrin were in the range of 1.11-3.79 days, 1.11-2.27 days, 1.13-5.17 days, and 1.77-6.24 days. It was also found that all pesticide residues in spinach and/or amaranth were higher than others after application. It is recommended that spinach or amaranth can be selected as a representative crop of leaf vegetables in studying systemic fungicide, insecticides, and herbicides with similarity as metalaxyl, fluazifop-P-butyl, chlorpyrifos, and lambda-cyhalothrin.

  20. Ti/IrO2/SnO2 anode for electrochemical degradation of chlorpyrifos in water: optimization and degradation performances

    Science.gov (United States)

    Pathiraja, G. C.; Wijesingha, M. S.; Nanayakkara, N.

    2017-05-01

    Chlorpyrifos, a widely used organophosphate pesticide which can be found in surface water bodies, is harmful for human body. Thus, treating water contaminated with chlorpyrifos is important. In our previous studies, novel Ti/IrO2-SnO2 anode was successfully developed for electrochemical degradation of chlorpyrifos in chloride free water. In this study, optimization of previously developed Ti/IrO2-SnO2 anode for mineralization of chlorpyrifos was successfully performed through response surface methodology. During the optimization study, two-level factorial design was used to determine the optimal coating solutions concentration for developing the Ti/IrO2-SnO2 anode. Cyclic voltammetry and open circuit potential were performed to investigate the electrochemically active surface area and stability of these anodes. The response surface and contour plots show that 0.3 M of [Ir] and 7.5 mM of [Sn] coated electrode has both highest anodic charge and stability. Scanning Electron Microscopic (SEM) images show the evidence of having both compact and porous regions in the surface of the thin film, resulting larger surface area. Within 6 h, the best result for mineralization (55.56%) of chlorpyrifos was obtained with 0.3 M of [Ir] and 7.5 mM of [Sn] coated anode using Total organic Carbon (TOC) analyzer. Therefore, the optimum coating concentration was found as 0.3 M of [Ir] and 7.5 mM of [Sn]. It would require an energy consumption of 6 kWhm-3.

  1. Serotonin modifies corticotropin-releasing factor-induced behaviors of chicks.

    Science.gov (United States)

    Zhang, Rong; Tachibana, Tetsuya; Takagi, Tomo; Koutoku, Tomoyuki; Denbow, D Michael; Furuse, Mitsuhiro

    2004-05-05

    Glucagon-like peptide-1 (GLP-1) decreased corticotropin-releasing factor (CRF)-induced behaviors in neonatal chicks, and serotonin is one of the possible mechanisms through which GLP-1 affects CRF-induced behaviors. The present experiments were conducted to confirm the effect of serotonin on CRF-induced behaviors. In Experiment 1, chicks were intracerebroventricularly injected with either saline, 0.1 microg of CRF, 5.0 microg of serotonin, or 0.1 microg of CRF plus 5.0 microg of serotonin. Injection of CRF caused excitation as evidenced by increased spontaneous activities and distress vocalizations (DVs) compared to the control group. The effect of CRF was attenuated by serotonin since chicks became quiet after given CRF with serotonin. Sleep-like behaviors were observed in the serotonin group. The number of defecations was increased by CRF and decreased by serotonin. Both CRF and serotonin increased plasma corticosterone, and the effect was synergistic. Serotonin dose-dependently decreased locomotor activities of chicks after central administration of 0.1 microg of CRF, 0.1 microg of CRF plus 2.5, 5.0, or 10.0 microg of serotonin in Experiment 2. CRF-induced DVs were modified by serotonin. Instead of DVs, tender and low-pitched vocalizations were observed in chicks treated with CRF plus serotonin, the voice frequencies of which were less than 10 kHz. In conclusion, serotonin attenuated the CRF-induced behaviors while stimulating corticosterone release. These results indicate that the role of serotonin is dependent on the behaviors being measured. Copyright 2003 Elsevier B.V.

  2. Single nucleotide polymorphisms (SNPs in coding regions of canine dopamine- and serotonin-related genes

    Directory of Open Access Journals (Sweden)

    Lingaas Frode

    2008-01-01

    Full Text Available Abstract Background Polymorphism in genes of regulating enzymes, transporters and receptors of the neurotransmitters of the central nervous system have been associated with altered behaviour, and single nucleotide polymorphisms (SNPs represent the most frequent type of genetic variation. The serotonin and dopamine signalling systems have a central influence on different behavioural phenotypes, both of invertebrates and vertebrates, and this study was undertaken in order to explore genetic variation that may be associated with variation in behaviour. Results Single nucleotide polymorphisms in canine genes related to behaviour were identified by individually sequencing eight dogs (Canis familiaris of different breeds. Eighteen genes from the dopamine and the serotonin systems were screened, revealing 34 SNPs distributed in 14 of the 18 selected genes. A total of 24,895 bp coding sequence was sequenced yielding an average frequency of one SNP per 732 bp (1/732. A total of 11 non-synonymous SNPs (nsSNPs, which may be involved in alteration of protein function, were detected. Of these 11 nsSNPs, six resulted in a substitution of amino acid residue with concomitant change in structural parameters. Conclusion We have identified a number of coding SNPs in behaviour-related genes, several of which change the amino acids of the proteins. Some of the canine SNPs exist in codons that are evolutionary conserved between five compared species, and predictions indicate that they may have a functional effect on the protein. The reported coding SNP frequency of the studied genes falls within the range of SNP frequencies reported earlier in the dog and other mammalian species. Novel SNPs are presented and the results show a significant genetic variation in expressed sequences in this group of genes. The results can contribute to an improved understanding of the genetics of behaviour.

  3. Psychopathic traits mediate the association of serotonin transporter genotype and child externalizing behavior.

    Science.gov (United States)

    Brammer, Whitney A; Jezior, Kristen L; Lee, Steve S

    2016-09-01

    Although the promoter polymorphism of the serotonin transporter (5-HTTLPR) gene is associated with externalizing behavior, its mediating pathways are unknown. Given their sensitivity to serotonin neurotransmission and unique association with attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD), we tested callous-unemotional (CU) traits and narcissism as separate mediators of the association of 5-HTTLPR with ADHD and ODD. We evaluated 209 5-9 year-old children with and without ADHD at baseline; approximately 2 years later (i.e., Wave 2), parents and teachers separately rated ADHD and ODD symptoms and youth self-reported antisocial behavior. Controlling for race-ethnicity and baseline ADHD/ODD, narcissism uniquely mediated predictions of multi-informant rated Wave 2 ADHD and ODD from variation in 5-HTTLPR; CU traits mediated predictions of Wave 2 ADHD from variations in 5-HTTLPR, but did not mediate the associations of 5-HTTLPR with ODD or youth self-reported antisocial behavior. Specifically, the number of 5-HTTLPR long alleles positively predicted CU traits and narcissism; narcissism was positively associated with Wave 2 ADHD and ODD symptoms, whereas CU traits were positively associated with Wave 2 ADHD. Child sex also moderated indirect effects of CU traits and narcissism, such that narcissism mediated predictions of ADHD/ODD in girls but not boys. Psychopathic traits may represent a relevant pathway underlying predictions of prospective change in ADHD and ODD from 5-HTTLPR, particularly in girls. We consider the role of psychopathic traits as a potential intermediate phenotype in genetically sensitive studies of child psychopathology. Aggr. Behav. 42:455-470, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Serotonin Potentiates Transforming Growth Factor-beta3 Induced Biomechanical Remodeling in Avian Embryonic Atrioventricular Valves

    Science.gov (United States)

    Buskohl, Philip R.; Sun, Michelle L.; Thompson, Robert P.; Butcher, Jonathan T.

    2012-01-01

    Embryonic heart valve primordia (cushions) maintain unidirectional blood flow during development despite an increasingly demanding mechanical environment. Recent studies demonstrate that atrioventricular (AV) cushions stiffen over gestation, but the molecular mechanisms of this process are unknown. Transforming growth factor-beta (TGFβ) and serotonin (5-HT) signaling modulate tissue biomechanics of postnatal valves, but less is known of their role in the biomechanical remodeling of embryonic valves. In this study, we demonstrate that exogenous TGFβ3 increases AV cushion biomechanical stiffness and residual stress, but paradoxically reduces matrix compaction. We then show that TGFβ3 induces contractile gene expression (RhoA, aSMA) and extracellular matrix expression (col1α2) in cushion mesenchyme, while simultaneously stimulating a two-fold increase in proliferation. Local compaction increased due to an elevated contractile phenotype, but global compaction appeared reduced due to proliferation and ECM synthesis. Blockade of TGFβ type I receptors via SB431542 inhibited the TGFβ3 effects. We next showed that exogenous 5-HT does not influence cushion stiffness by itself, but synergistically increases cushion stiffness with TGFβ3 co-treatment. 5-HT increased TGFβ3 gene expression and also potentiated TGFβ3 induced gene expression in a dose-dependent manner. Blockade of the 5HT2b receptor, but not 5-HT2a receptor or serotonin transporter (SERT), resulted in complete cessation of TGFβ3 induced mechanical strengthening. Finally, systemic 5-HT administration in ovo induced cushion remodeling related defects, including thinned/atretic AV valves, ventricular septal defects, and outflow rotation defects. Elevated 5-HT in ovo resulted in elevated remodeling gene expression and increased TGFβ signaling activity, supporting our ex-vivo findings. Collectively, these results highlight TGFβ/5-HT signaling as a potent mechanism for control of biomechanical remodeling of

  5. Serotonin potentiates transforming growth factor-beta3 induced biomechanical remodeling in avian embryonic atrioventricular valves.

    Directory of Open Access Journals (Sweden)

    Philip R Buskohl

    Full Text Available Embryonic heart valve primordia (cushions maintain unidirectional blood flow during development despite an increasingly demanding mechanical environment. Recent studies demonstrate that atrioventricular (AV cushions stiffen over gestation, but the molecular mechanisms of this process are unknown. Transforming growth factor-beta (TGFβ and serotonin (5-HT signaling modulate tissue biomechanics of postnatal valves, but less is known of their role in the biomechanical remodeling of embryonic valves. In this study, we demonstrate that exogenous TGFβ3 increases AV cushion biomechanical stiffness and residual stress, but paradoxically reduces matrix compaction. We then show that TGFβ3 induces contractile gene expression (RhoA, aSMA and extracellular matrix expression (col1α2 in cushion mesenchyme, while simultaneously stimulating a two-fold increase in proliferation. Local compaction increased due to an elevated contractile phenotype, but global compaction appeared reduced due to proliferation and ECM synthesis. Blockade of TGFβ type I receptors via SB431542 inhibited the TGFβ3 effects. We next showed that exogenous 5-HT does not influence cushion stiffness by itself, but synergistically increases cushion stiffness with TGFβ3 co-treatment. 5-HT increased TGFβ3 gene expression and also potentiated TGFβ3 induced gene expression in a dose-dependent manner. Blockade of the 5HT2b receptor, but not 5-HT2a receptor or serotonin transporter (SERT, resulted in complete cessation of TGFβ3 induced mechanical strengthening. Finally, systemic 5-HT administration in ovo induced cushion remodeling related defects, including thinned/atretic AV valves, ventricular septal defects, and outflow rotation defects. Elevated 5-HT in ovo resulted in elevated remodeling gene expression and increased TGFβ signaling activity, supporting our ex-vivo findings. Collectively, these results highlight TGFβ/5-HT signaling as a potent mechanism for control of biomechanical

  6. Effects of Postnatal Serotonin Agonism on Fear Response and Memory

    Science.gov (United States)

    The neurotransmitter serotonin (5-HT) also acts as a neurogenic compound in the developing brain. Early administration of a 5-HT agonist could alter the development of the serotonergic circuitry, altering behaviors mediated by 5-HT signaling, such as memory, fear and aggression. White leghorn chicks...

  7. Perinatal vs genetic programming of serotonin states associated with anxiety.

    Science.gov (United States)

    Altieri, Stefanie C; Yang, Hongyan; O'Brien, Hannah J; Redwine, Hannah M; Senturk, Damla; Hensler, Julie G; Andrews, Anne M

    2015-05-01

    Large numbers of women undergo antidepressant treatment during pregnancy; however, long-term consequences for their offspring remain largely unknown. Rodents exposed to serotonin transporter (SERT)-inhibiting antidepressants during development show changes in adult emotion-like behavior. These changes have been equated with behavioral alterations arising from genetic reductions in SERT. Both models are highly relevant to humans yet they vary in their time frames of SERT disruption. We find that anxiety-related behavior and, importantly, underlying serotonin neurotransmission diverge between the two models. In mice, constitutive loss of SERT causes life-long increases in anxiety-related behavior and hyperserotonemia. Conversely, early exposure to the antidepressant escitalopram (ESC; Lexapro) results in decreased anxiety-related behavior beginning in adolescence, which is associated with adult serotonin system hypofunction in the ventral hippocampus. Adult behavioral changes resulting from early fluoxetine (Prozac) exposure were different from those of ESC and, although somewhat similar to SERT deficiency, were not associated with changes in hippocampal serotonin transmission in late adulthood. These findings reveal dissimilarities in adult behavior and neurotransmission arising from developmental exposure to different widely prescribed antidepressants that are not recapitulated by genetic SERT insufficiency. Moreover, they support a pivotal role for serotonergic modulation of anxiety-related behavior.

  8. The genetics of the serotonin transporter and irritable bowel syndrome.

    Science.gov (United States)

    Colucci, Rocchina; Blandizzi, Corrado; Bellini, Massimo; Ghisu, Narcisa; Tonini, Marcello; Del Tacca, Mario

    2008-07-01

    Serotonin transporter (SERT) mediates the intracellular reuptake of released serotonin, thus regulating its biological functions. Abnormalities in serotonin reuptake can alter enteric serotonergic signalling, leading to sensory, motor and secretory gut dysfunctions, which contribute to the pathophysiology of irritable bowel syndrome (IBS). This relationship has fostered the use of selective serotonin reuptake inhibitors (SSRIs) in the treatment of IBS. Current data on the efficacy of SSRIs in IBS, association of the SERT gene promoter polymorphism 5-HTTLPR with IBS and the expression pattern of SERT in the intestinal mucosa of IBS patients are conflicting. Recent molecular studies have raised critical questions about multiple SERT mRNA transcripts in the human gut, the role of polymorphic SERT promoter in the regulation of enteric SERT expression and the ability of 5-HTTLPR to affect human SERT gene transcription. The present review highlights recent advances in SERT genetics, discusses their implications for potential therapeutic applications of SSRIs in IBS and presents original suggestions for future investigations.

  9. Serotonin Transporter Gene, Depressive Symptoms, and Interleukin-6

    NARCIS (Netherlands)

    Su, Shaoyong; Zhao, Jinying; Bremner, J. Douglas; Miller, Andrew H.; Tang, Weining; Bouzyk, Mark; Snieder, Harold; Novik, Olga; Afzal, Nadeem; Goldberg, Jack; Vaccarino, Viola

    2009-01-01

    Background-We explored the relationship of genetic variants of the serotonin transporter gene SLC6A4, a key regulator of the serotonergic neurotransmission, with both depressive symptoms and plasma interleukin-6 (IL-6) levels. Methods and Results-We genotyped 20 polymorphisms in 360 male twins (mean

  10. Selective serotonin reuptake inhibitors for depression in pregnancy.

    Science.gov (United States)

    Susser, Leah C; Sansone, Stephanie A; Hermann, Alison D

    2016-12-01

    Perinatal depression is associated with a high risk of morbidity and mortality and may have long-term consequences on child development. The US Preventive Services Task Force has recently recognized the importance of identifying and treating women with depression in the perinatal period. However, screening and accessing appropriate treatment come with logistical challenges. In many areas, there may not be sufficient access to psychiatric care, and, until these resources develop, the burden may inadvertently fall on obstetricians. As a result, understanding the risks of perinatal depression in comparison with the risks of treatment is important. Many studies of selective serotonin reuptake inhibitors in pregnancy fail to control for underlying depressive illness, which can lead to misinterpretation of selective serotonin reuptake inhibitor risk by clinicians. This review discusses the risks and benefits of selective serotonin reuptake inhibitor treatment in pregnancy within the context of perinatal depression. Whereas selective serotonin reuptake inhibitors may be associated with certain risks, the absolute risks are low and may be outweighed by the risks of untreated depression for many women and their offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Buspirone is an effective augmenting agent of serotonin selective re ...

    African Journals Online (AJOL)

    Background. Buspirone has previously been reported to be effective in the augmentation of the antidepressant effect of serotonin selective re-uptake inhibitors (SSRls) in depressed outpatients. We report on buspirone augmentation of SSRls in severe treatment-refractory depression in inpatients. Methods. A retrospective ...

  12. Serotonin receptors: Subtypes, functional responses and therapeutic relevance

    NARCIS (Netherlands)

    P.R. Saxena (Pramod Ranjan)

    1995-01-01

    textabstractRecent, rapid progress in the molecular biology of serotonin (5-HT) receptors requires conceptual re-thinking with respect to receptor classification. Thus, based on operational criteria (agonist and antagonist rank order), as well as transduction mechanisms involved and the structure of

  13. Serotonin 2A receptor antagonists for treatment of schizophrenia

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn Hylsebeck; Rasmussen, Hans; Arnt, Jørn

    2011-01-01

    : Preclinical, clinical and post-mortem studies of the serotonin 5-HT2A system in schizophrenia are reviewed. The implications of a combined D2 and 5-HT2A receptor blockade, which is obtained by several current antipsychotic drugs, are discussed, and the rationale for the development of more selective 5-HT2A...

  14. A role for serotonin in piglet preweaning mortality

    Science.gov (United States)

    Improving piglet survivability rate is of high priority for swine production as well as for piglet well-being. Dysfunction in the serotonin system has been associated with growth deficiencies, infant mortality or failure to thrive (FTT) in human infants. The aim of this study was to examine the role...

  15. Serotonin transporter genotype x construction stress interaction in rats

    NARCIS (Netherlands)

    Schipper, P.; Nonkes, L.J.P.; Karel, P.G.A.; Kiliaan, A.J.; Homberg, J.R.

    2011-01-01

    A well-known example for gene x environment interactions in psychiatry is the one involving the low activity (s) allelic variant of the serotonin transporter (5-HTT) promoter polymorphism (5-HTTLPR) that in the context of stress increases risk for depression. In analogy, 5-HTT knockout rodents are

  16. Serotonin 5-HT(3) receptors in the central nervous system

    NARCIS (Netherlands)

    Chameau, P.J.P.; van Hooft, J.A.

    2006-01-01

    The 5-HT(3) receptor is a ligand-gated ion channel activated by serotonin (5-HT). Although originally identified in the peripheral nervous system, the 5-HT(3) receptor is also ubiquitously expressed in the central nervous system. Sites of expression include several brain stem nuclei and higher

  17. Serotonin and noradrenaline reuptake inhibitors improve micturition control in mice.

    Directory of Open Access Journals (Sweden)

    Marco Redaelli

    Full Text Available Poor micturition control may cause profound distress, because proper voiding is mandatory for an active social life. Micturition results from the subtle interplay of central and peripheral components. It involves the coordination of autonomic and neuromuscular activity at the brainstem level, under the executive control of the prefrontal cortex. We tested the hypothesis that administration of molecules acting as reuptake inhibitors of serotonin, noradrenaline or both may exert a strong effect on the control of urine release, in a mouse model of overactive bladder. Mice were injected with cyclophosphamide (40 mg/kg, to increase micturition acts. Mice were then given one of four molecules: the serotonin reuptake inhibitor imipramine, its metabolite desipramine that acts on noradrenaline reuptake, the serotonin and noradrenaline reuptake inhibitor duloxetine or its active metabolite 4-hydroxy-duloxetine. Cyclophosphamide increased urine release without inducing overt toxicity or inflammation, except for increase in urothelium thickness. All the antidepressants were able to decrease the cyclophosphamide effects, as apparent from longer latency to the first micturition act, decreased number of urine spots and volume of released urine. These results suggest that serotonin and noradrenaline reuptake inhibitors exert a strong and effective modulatory effect on the control of urine release and prompt to additional studies on their central effects on brain areas involved in the social and behavioral control of micturition.

  18. Brief Report: Platelet-Poor Plasma Serotonin in Autism

    Science.gov (United States)

    Anderson, George M.; Hertzig, Margaret E.; McBride, P. A.

    2012-01-01

    Possible explanations for the well-replicated platelet hyperserotonemia of autism include an alteration in the platelet's handling of serotonin (5-hydroxyserotonin, 5-HT) or an increased exposure of the platelet to 5-HT. Measurement of platelet-poor plasma (PPP) levels of 5-HT appears to provide the best available index of in vivo exposure of the…

  19. Serotonin modulates striatal responses to fairness and retaliation in humans

    Science.gov (United States)

    Crockett, MJ; Apergis-Schoute, AM; Herrmann, B; Lieberman, MD; Müller, U; Robbins, TW; Clark, L

    2013-01-01

    Humans are willing to incur personal costs to punish others who violate social norms. Such ‘costly punishment’ is an important force for sustaining human cooperation, but the causal neurobiological determinants of punishment decisions remain unclear. Using a combination of behavioral, pharmacological and neuroimaging techniques, we show that manipulating the serotonin system in humans alters costly punishment decisions by modulating responses to fairness and retaliation in the striatum. Following dietary depletion of the serotonin precursor tryptophan, participants were more likely to punish those who treated them unfairly, and were slower to accept fair exchanges. Neuroimaging data revealed activations in the ventral and dorsal striatum that were associated with fairness and punishment, respectively. Depletion simultaneously reduced ventral striatal responses to fairness and increased dorsal striatal responses during punishment, an effect that predicted its influence on punishment behavior. Finally, we provide behavioral evidence that serotonin modulates specific retaliation, rather than general norm enforcement: depleted participants were more likely to punish unfair behavior directed toward themselves, but not unfair behavior directed toward others. Our findings demonstrate that serotonin modulates social value processing in the striatum, producing context-dependent effects on social behavior. PMID:23426678

  20. Plasma serotonin in horses undergoing surgery for small intestinal colic

    NARCIS (Netherlands)

    Torfs, Sara C; Maes, An A; Delesalle, Catherine J; Pardon, Bart; Croubels, Siska M; Deprez, Piet

    This study compared serotonin concentrations in platelet poor plasma (PPP) from healthy horses and horses with surgical small intestinal (SI) colic, and evaluated their association with postoperative ileus, strangulation and non-survival. Plasma samples (with EDTA) from 33 horses with surgical SI

  1. Mood state moderates the role of serotonin in cognitive biases

    NARCIS (Netherlands)

    Robinson, O.; Cools, R.; Crockett, M.; Sahakian, B.

    2010-01-01

    Reduction of the monoamine serotonin (5-HT) via the dietary manipulation of tryptophan (acute tryptophan depletion; ATD) has been shown to induce negative cognitive biases similar to those found in depression in healthy individuals. However, evidence also indicates that there can be positive effects

  2. Mood state moderates the role of serotonin in cognitive biases.

    NARCIS (Netherlands)

    Robinson, O.J.; Cools, R.; Crockett, M.J.; Sahakian, B.J.

    2010-01-01

    Reduction of the monoamine serotonin (5-HT) via the dietary manipulation of tryptophan (acute tryptophan depletion; ATD) has been shown to induce negative cognitive biases similar to those found in depression in healthy individuals. However, evidence also indicates that there can be positive effects

  3. Serotonin Transporter Gene: Will Epigenetics Prove Less Depressing Than Genetics?

    NARCIS (Netherlands)

    de Geus, E.J.C.; Middeldorp, C.M.

    2013-01-01

    The serotonin transporter gene has been hypothesized to influence, possibly in interaction with environmental factors, the vulnerability for depression. So far, genetic studies have tested the association of the repeat polymorphism (5-HTTLPR) with depression and whether it is moderated by exposure

  4. Alterations to embryonic serotonin change aggression and fearfulness

    Science.gov (United States)

    Prenatal environment, including maternal hormones, affects the development of the serotonin (5-HT) system, with long-lasting effects on mood and behavioral exhibition in children and adults. The chicken provides a unique animal model to study the effects of embryonic development on childhood and ado...

  5. How the cerebral serotonin homeostasis predicts environmental changes

    DEFF Research Database (Denmark)

    Kalbitzer, Jan; Kalbitzer, Urs; Knudsen, Gitte Moos

    2013-01-01

    Molecular imaging studies with positron emission tomography have revealed that the availability of serotonin transporter (5-HTT) in the human brain fluctuates over the course of the year. This effect is most pronounced in carriers of the short allele of the 5-HTT promoter region (5-HTTLPR), which...

  6. Kynurenine and serotonin pathways: A review | Adegbusi | Bayero ...

    African Journals Online (AJOL)

    Serotonin, a major bioactive end-product of SP is a potent neurotransmitter, vasoconstrictor, regulation of intestinal motility and a player in cognitive function. Foods that give an increased ratio of tryptophan to phenylalanine and leucine such as nuts of walnut, plantains, bananas, dates, pineapples and tomatoes are good ...

  7. Síndrome serotoninérgica associada ao uso de paroxetina: relato de caso Serotonin syndrome associated to the use of paroxetine: case report

    Directory of Open Access Journals (Sweden)

    LUÍS OTÁVIO CAVALLAZZI

    1999-09-01

    Full Text Available Relatamos um caso de síndrome serotoninérgica pelo uso de inibidor da recaptação da serotonina, a paroxetina. Tal síndrome por esta droga, sem combinações, ainda não tinha sido descrita na literatura.We report on a case of serotonin syndrome associated to the use of the paroxetine, a serotonin reuptake inhibitor drug. Serotonin syndrome related to this drug not combined with other drugs had not yet been described in literature.

  8. Oxytocin and Serotonin Brain Mechanisms in the Nonhuman Primate.

    Science.gov (United States)

    Lefevre, Arthur; Richard, Nathalie; Jazayeri, Mina; Beuriat, Pierre-Aurélien; Fieux, Sylvain; Zimmer, Luc; Duhamel, Jean-René; Sirigu, Angela

    2017-07-12

    Oxytocin (OT) is increasingly studied for its therapeutic potential in psychiatric disorders, which are associated with the deregulation of several neurotransmission systems. Studies in rodents demonstrated that the interaction between OT and serotonin (5-HT) is critical for several aspects of social behavior. Using PET scan in humans, we have recently found that 5-HT 1A receptor (5-HT 1A R) function is modified after intranasal oxytocin intake. However, the underlying mechanism between OT and 5-HT remains unclear. To understand this interaction, we tested 3 male macaque monkeys using both [ 11 C]DASB and [ 18 F]MPPF, two PET radiotracers, marking the serotonin transporter and the 5-HT 1A R, respectively. Oxytocin (1 IU in 20 μl of ACSF) or placebo was injected into the brain lateral ventricle 45 min before scans. Additionally, we performed postmortem autoradiography. Compared with placebo, OT significantly reduced [ 11 C]DASB binding potential in right amygdala, insula, and hippocampus, whereas [ 18 F]MPPF binding potential increased in right amygdala and insula. Autoradiography revealed that [ 11 C]DASB was sensitive to physiological levels of 5-HT modification, and that OT does not act directly on the 5-HT 1A R. Our results show that oxytocin administration in nonhuman primates influences serotoninergic neurotransmission via at least two ways: (1) by provoking a release of serotonin in key limbic regions; and (2) by increasing the availability of 5-HT 1A R receptors in the same limbic areas. Because these two molecules are important for social behavior, our study sheds light on the specific nature of their interaction, therefore helping to develop new mechanisms-based therapies for psychiatric disorders. SIGNIFICANCE STATEMENT Social behavior is largely controlled by brain neuromodulators, such as oxytocin and serotonin. While these are currently targeted in the context of psychiatric disorders such as autism and schizophrenia, a new promising pharmaceutical

  9. Non-conventional features of peripheral serotonin signalling - the gut and beyond.

    Science.gov (United States)

    Spohn, Stephanie N; Mawe, Gary M

    2017-07-01

    Serotonin was first discovered in the gut, and its conventional actions as an intercellular signalling molecule in the intrinsic and extrinsic enteric reflexes are well recognized, as are a number of serotonin signalling pharmacotherapeutic targets for treatment of nausea, diarrhoea or constipation. The latest discoveries have greatly broadened our understanding of non-conventional actions of peripheral serotonin within the gastrointestinal tract and in a number of other tissues. For example, it is now clear that bacteria within the lumen of the bowel influence serotonin synthesis and release by enterochromaffin cells. Also, serotonin can act both as a pro-inflammatory and anti-inflammatory signalling molecule in the intestinal mucosa via activation of serotonin receptors (5-HT7 or 5-HT4 receptors, respectively). For decades, serotonin receptors have been known to exist in a variety of tissues other than the gut, but studies have now provided strong evidence for physiological roles of serotonin in several important processes, including haematopoiesis, metabolic homeostasis and bone metabolism. Furthermore, evidence for serotonin synthesis in peripheral tissues outside of the gut is emerging. In this Review, we expand the discussion beyond gastrointestinal functions to highlight the roles of peripheral serotonin in colitis, haematopoiesis, energy and bone metabolism, and how serotonin is influenced by the gut microbiota.

  10. [On the role of gene of SER-4 serotonin receptor in thermotolerance of Caenorhabditis elegans behavior].

    Science.gov (United States)

    Kalinnikova, T B; Kolsanova, R R; Shagidullin, R R; Osipova, E B; Gaĭnutdinov, M Kh

    2013-03-01

    Serotonin reduces the behavior tolerance of Caenorhabditis elegans of the N2 wild-type strain (swimming induced by the mechanical stimulus) to a temperature of 36 degrees C. The sensitivity to the serotonin influence on the behavior thermotolerance remains intact in strains with null mutations of mod-1 (ok103) and ser-1 (ok345) serotonin receptor genes, and is almost completely lost in the ser-4 (ok512) strain with null mutation in the gene of the SER-4 serotonin receptor, which is a homologue of 5-HT1 mammalian serotonin receptor. In addition, nematodes of the ser-4 (ok512) strain have high behavior thermotolerance in the absence of the exogenous serotonin compared to the N2 strain. These data indicate the involvement of the ser-4 gene in the serotonin regulation of the tolerance of C. elegance nervous system functions to hyperthermia.

  11. Association between serotonin transporter gene polymorphism and recurrent aphthous stomatitis.

    Science.gov (United States)

    Manchanda, Aastha; Iyengar, Asha R; Patil, Seema

    2016-01-01

    Anxiety-related traits have been attributed to sequence variability in the genes coding for serotonin transmission in  the brain. Two alleles, termed long (L) and short (S) differing by 44 base pairs, are found in a polymorphism identified in the promoter region of serotonin transporter gene. The presence of the short allele  and SS and LS genotypes is found to be associated with the reduced expression of this gene decreasing the uptake of serotonin in the brain leading to various anxiety-related traits. Recurrent aphthous stomatitis (RAS) is an oral mucosal disease with varied etiology including the presence of stress, anxiety, and genetic influences. The present study aimed to determine this serotonin transporter gene polymorphism in patients with RAS and compare it with normal individuals. This study included 20 subjects with various forms of RAS and 20 normal healthy age- and gender-matched individuals. Desquamated oral mucosal cells were collected for DNA extraction and subjected to polymerase chain reaction for studying insertion/deletion in the 5-HTT gene-linked polymorphic region. Cross tabulations followed by Chi-square tests were performed to compare the significance of findings, P aphthous stomatitis (60%) and controls (40%). The total percentage of LS and SS genotypes and the frequency of S allele were found to be higher in the subjects with aphthous stomatitis as compared to the control group although a statistically significant correlation could not be established, P = 0.144 and 0.371, respectively. Within the limitations of this study, occurrence of RAS was not found to be associated with polymorphic promoter region in serotonin transporter gene.

  12. Exercise and sleep in aging: emphasis on serotonin.

    Science.gov (United States)

    Melancon, M O; Lorrain, D; Dionne, I J

    2014-10-01

    Reductions in central serotonin activity with aging might be involved in sleep-related disorders in later life. Although the beneficial effects of aerobic exercise on sleep are not new, sleep represents a complex recurring state of unconsciousness involving many lines of transmitters which remains only partly clear despite intense ongoing research. It is known that serotonin released into diencephalon and cerebrum might play a key inhibitory role to help promote sleep, likely through an active inhibition of supraspinal neural networks. Several lines of evidence support the stimulatory effects of exercise on higher serotonergic pathways. Hence, exercise has proved to elicit acute elevations in forebrain serotonin concentrations, an effect that waned upon cessation of exercise. While adequate exercise training might lead to adaptations in higher serotonergic networks (desensitization of forebrain receptors), excessive training has been linked to serious brain serotonergic maladaptations accompanied by insomnia. Dietary supplementation of tryptophan (the only serotonin precursor) is known to stimulate serotonergic activity and promote sleep, whereas acute tryptophan depletion causes deleterious effects on sleep. Regarding sleep-wake regulation, exercise has proved to accelerate resynchronization of the biological clock to new light-dark cycles following imposition of phase shifts in laboratory animals. Noteworthy, the effect of increased serotonergic transmission on wake state appears to be biphasic, i.e. promote wake and thereafter drowsiness. Therefore, it might be possible that acute aerobic exercise would act on sleep by increasing activity of ascending brain serotonergic projections, though additional work is warranted to better understand the implication of serotonin in the exercise-sleep axis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  13. Developmental exposure to fluoxetine modulates the serotonin system in hypothalamus.

    Directory of Open Access Journals (Sweden)

    Cecilia Berg

    Full Text Available The selective serotonin reuptake inhibitor (SSRI fluoxetine (FLU, Prozac® is commonly prescribed for depression in pregnant women. This results in SSRI exposure of the developing fetus. However, there are knowledge gaps regarding the impact of SSRI exposure during development. Given the role of serotonin in brain development and its cross-talk with sex hormone function, we investigated effects of developmental exposure to pharmacologically relevant concentrations of FLU (3 and 30 nM (measured on brain neurotransmitter levels, gonadal differentiation, aromatase activity in brain and gonads, and the thyroid system, using the Xenopus tropicalis model. Tadpoles were chronically exposed (8 weeks until metamorphosis. At metamorphosis brains were cryosectioned and levels of serotonin, dopamine, norepinephrine, and their metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were measured in discrete regions (telencephalon, hypothalamus and the reticular formation of the cryosections using high-performance liquid chromatography. Exposure to 30 nM FLU increased the concentration of 5-hydroxyindoleacetic acid in hypothalamus compared with controls. FLU exposure did not affect survival, time to metamorphosis, thyroid histology, gonadal sex differentiation, or aromatase activity implying that the effect on the serotonergic neurotransmitter system in the hypothalamus region was specific. The FLU concentration that impacted the serotonin system is lower than the concentration measured in umbilical cord serum, suggesting that the serotonin system of the developing brain is highly sensitive to in utero exposure to FLU. To our knowledge this is the first study showing effects of developmental FLU exposure on brain neurochemistry. Given that SSRIs are present in the aquatic environment the current results warrant further investigation into the neurobehavioral effects of SSRIs in aquatic wildlife.

  14. Optogenetic Control of Serotonin and Dopamine Release in Drosophila Larvae

    Science.gov (United States)

    2014-01-01

    Optogenetic control of neurotransmitter release is an elegant method to investigate neurobiological mechanisms with millisecond precision and cell type-specific resolution. Channelrhodopsin-2 (ChR2) can be expressed in specific neurons, and blue light used to activate those neurons. Previously, in Drosophila, neurotransmitter release and uptake have been studied after continuous optical illumination. In this study, we investigated the effects of pulsed optical stimulation trains on serotonin or dopamine release in larval ventral nerve cords. In larvae with ChR2 expressed in serotonergic neurons, low-frequency stimulations produced a distinct, steady-state response while high-frequency patterns were peak shaped. Evoked serotonin release increased with increasing stimulation frequency and then plateaued. The steady-state response and the frequency dependence disappeared after administering the uptake inhibitor fluoxetine, indicating that uptake plays a significant role in regulating the extracellular serotonin concentration. Pulsed stimulations were also used to evoke dopamine release in flies expressing ChR2 in dopaminergic neurons and similar frequency dependence was observed. Release due to pulsed optical stimulations was modeled to determine the uptake kinetics. For serotonin, Vmax was 0.54 ± 0.07 μM/s and Km was 0.61 ± 0.04 μM; and for dopamine, Vmax was 0.12 ± 0.03 μM/s and Km was 0.45 ± 0.13 μM. The amount of serotonin released per stimulation pulse was 4.4 ± 1.0 nM, and the amount of dopamine was 1.6 ± 0.3 nM. Thus, pulsed optical stimulations can be used to mimic neuronal firing patterns and will allow Drosophila to be used as a model system for studying mechanisms underlying neurotransmission. PMID:24849718

  15. Serotonin, tryptophan metabolism and the brain-gut-microbiome axis.

    Science.gov (United States)

    O'Mahony, S M; Clarke, G; Borre, Y E; Dinan, T G; Cryan, J F

    2015-01-15

    The brain-gut axis is a bidirectional communication system between the central nervous system and the gastrointestinal tract. Serotonin functions as a key neurotransmitter at both terminals of this network. Accumulating evidence points to a critical role for the gut microbiome in regulating normal functioning of this axis. In particular, it is becoming clear that the microbial influence on tryptophan metabolism and the serotonergic system may be an important node in such regulation. There is also substantial overlap between behaviours influenced by the gut microbiota and those which rely on intact serotonergic neurotransmission. The developing serotonergic system may be vulnerable to differential microbial colonisation patterns prior to the emergence of a stable adult-like gut microbiota. At the other extreme of life, the decreased diversity and stability of the gut microbiota may dictate serotonin-related health problems in the elderly. The mechanisms underpinning this crosstalk require further elaboration but may be related to the ability of the gut microbiota to control host tryptophan metabolism along the kynurenine pathway, thereby simultaneously reducing the fraction available for serotonin synthesis and increasing the production of neuroactive metabolites. The enzymes of this pathway are immune and stress-responsive, both systems which buttress the brain-gut axis. In addition, there are neural processes in the gastrointestinal tract which can be influenced by local alterations in serotonin concentrations with subsequent relay of signals along the scaffolding of the brain-gut axis to influence CNS neurotransmission. Therapeutic targeting of the gut microbiota might be a viable treatment strategy for serotonin-related brain-gut axis disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children.

    Science.gov (United States)

    Chugani, D C; Muzik, O; Behen, M; Rothermel, R; Janisse, J J; Lee, J; Chugani, H T

    1999-03-01

    Serotonin content, serotonin uptake sites, and serotonin receptor binding measured in animal studies are all higher in the developing brain, compared with adult values, and decline before puberty. Furthermore, a disruption of synaptic connectivity in sensory cortical regions can result from experimental increase or decrease of brain serotonin before puberty. The purpose of the present study was to determine whether brain serotonin synthesis capacity is higher in children than in adults and whether there are differences in serotonin synthesis capacity between autistic and nonautistic children. Serotonin synthesis capacity was measured in autistic and nonautistic children at different ages, using alpha[11C]methyl-L-tryptophan and positron emission tomography. Global brain values for serotonin synthesis capacity (K complex) were obtained for autistic children (n = 30), their nonautistic siblings (n = 8), and epileptic children without autism (n = 16). K-complex values were plotted according to age and fitted to linear and five-parameter functions, to determine developmental changes and differences in serotonin synthesis between groups. For nonautistic children, serotonin synthesis capacity was more than 200% of adult values until the age of 5 years and then declined toward adult values. Serotonin synthesis capacity values declined at an earlier age in girls than in boys. In autistic children, serotonin synthesis capacity increased gradually between the ages of 2 years and 15 years to values 1.5 times adult normal values and showed no sex difference. Significant differences were detected between the autistic and epileptic groups and between the autistic and sibling groups for the change with age in the serotonin synthesis capacity. These data suggest that humans undergo a period of high brain serotonin synthesis capacity during childhood, and that this developmental process is disrupted in autistic children.

  17. Combined effect of environmental pollutants (nickel, chlorpyrifos) and temperature on the ground beetle, Pterostichus oblongopunctatus (Coleoptera: Carabidae).

    Science.gov (United States)

    Bednarska, Agnieszka J; Portka, Iwona; Kramarz, Paulina E; Laskowski, Ryszard

    2009-04-01

    Terrestrial organisms in the field often are exposed to a combination of stress factors of various origins, but little is known about interactions between different types of stressors. In the present study, we demonstrate the results of a study on interactions between Ni, chlorpyrifos (CPF), and temperature in the ground beetle, Pterostichus oblongopunctatus. The results revealed that all factors, and their interactions, influenced life-cycle parameters of the beetles (survival and reproduction). Significant three-factor interactions were found for effects on beetle survival, indicating that the combined negative effect of Ni and CPF was temperature dependent. In addition, significant effects of body mass were found: The survival of beetles treated with CPF and the reproduction of beetles exposed to Ni were positively correlated with body mass. All studied endpoints were affected by temperature. The results indicate that understanding interactions between temperature and toxicants, as well as among chemicals themselves, is essential for proper ecological risk assessment.

  18. Role of the serotonin transporter gene locus in the response to SSRI treatment of major depressive disorder in late life.

    Science.gov (United States)

    Seripa, Davide; Pilotto, Andrea; Paroni, Giulia; Fontana, Andrea; D'Onofrio, Grazia; Gravina, Carolina; Urbano, Maria; Cascavilla, Leandro; Paris, Francesco; Panza, Francesco; Padovani, Alessandro; Pilotto, Alberto

    2015-05-01

    It has been suggested that the serotonin or 5-hydroxytriptamine (5-HT) transporter (5-HTT) and its gene-linked polymorphic region (5-HTTLPR) are selective serotonin reuptake inhibitor (SSRI) response modulators in late-life depression (LLD), and particularly in late-life major depressive disorder (MDD). Previous studies differed in design and results. Our study aimed to investigate the solute carrier family 6 (neurotransmitter transporter and serotonin) member 4 (SLC6A4) gene locus, encoding 5-HTT and SSRI treatment response in late-life MDD. For a prospective cohort study, we enrolled 234 patients with late-life MDD to be treated with escitalopram, sertraline, paroxetine or citalopram for 6 months. The SLC6A4 polymorphisms rs4795541 (5-HTTLPR), rs140701 and rs3813034 genotypes spanning the SLC6A4 locus were investigated in blinded fashion. No placebo group was included. We assessed responder or non-responder phenotypes according to a reduction in the 21-item version of the Hamilton Depression Rating Scale (HDRS-21) score of ⩾ 50%. At follow-up, 30% of the late-life MDD patients were non-responders to SSRI treatment. No time-course of symptoms and responses was made. A poor response was associated with a higher baseline HDRS-21 score. We observed a significant over-representation of the rs4795541-S allele in the responder patients (0.436 versus 0.321; p = 0.023). The single S-allele dose-additive effect had OR = 1.74 (95% CI 1.12-2.69) in the additive regression model. Our findings suggested a possible influence of 5-HTTLPR on the SSRI response in patients with late-life MDD, which is potentially useful in identifying the subgroups of LLD patients whom need a different pharmacological approach. © The Author(s) 2015.

  19. An Age-Dependent Physiologically-Based Pharmacokinetic/Pharmacodynamic Model for the Organophosphorus Insecticide Chlorpyrifos in the Preweanling Rat

    Energy Technology Data Exchange (ETDEWEB)

    Timchalk, Chuck; Kousba, Ahmed A.; Poet, Torka S.

    2007-08-01

    Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to chlorpyrifos-oxon (CPF-oxon) and trichloropyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. In the current study, a modified physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model incorporating age-dependent changes in CYP450, PON-1, and tissue ChE levels for rats was developed. In this model, age was used as a dependent function to estimate body weight which was then used to allometrically scale both metabolism and tissue ChE levels. Model simulations suggest that preweanling rats are particularly sensitive to CPF toxicity, with levels of CPF-oxon in blood and brain disproportionately increasing, relative to the response in adult rats. This age-dependent non-linear increase in CPF-oxon concentration may potentially result from the depletion of non-target B-esterases, and a lower PON-1 metabolic capacity in younger animals. These results indicate that the PBPK/PD model behaves consistently with the general understanding of CPF toxicity, pharmacokinetics and tissue ChE inhibition in neonatal and adult rats. Hence, this model represents an important starting point for developing a computational model to assess the neurotoxic potential of environmentally relevant organophosphate exposures in infants and children.

  20. Tramadol and another atypical opioid meperidine have exaggerated serotonin syndrome behavioural effects, but decreased analgesic effects, in genetically deficient serotonin transporter (SERT) mice.

    Science.gov (United States)

    Fox, Meredith A; Jensen, Catherine L; Murphy, Dennis L

    2009-09-01

    The serotonin syndrome is a potential side-effect of serotonin-enhancing drugs, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs). We recently reported a genetic mouse model for the serotonin syndrome, as serotonin transporter (SERT)-deficient mice have exaggerated serotonin syndrome behavioural responses to the MAOI tranylcypromine and the serotonin precursor 5-hydroxy-l-tryptophan (5-HTP). As numerous case reports implicate the atypical opioids tramadol and meperidine in the development of the human serotonin syndrome, we examined tramadol and meperidine as possible causative drugs in the rodent model of the serotonin syndrome in SERT wild-type (+/+), heterozygous (+/-) and knockout (-/-) mice. Comparisons were made with SERT mice treated with either vehicle or morphine, an opioid not implicated in the serotonin syndrome in humans. Here we show that tramadol and meperidine, but not morphine, induce serotonin syndrome-like behaviours in mice, and we show that this response is exaggerated in mice lacking one or two copies of SERT. The exaggerated response to tramadol in SERT-/- mice was blocked by pretreatment with the 5-HT1A antagonist WAY 100635. Further, we show that morphine-, meperidine- and tramadol-induced analgesia is markedly decreased in SERT-/- mice. These studies suggest that caution seems warranted in prescribing or not warning patients receiving SSRIs or MAOIs that dangerous side-effects may occur during concurrent use of tramadol and similar agents. These findings suggest that it is conceivable that there might be increased vulnerability in individuals with SERT polymorphisms that may reduce SERT by more than 50%, the level in SERT+/- mice.

  1. Influence of menstrual cycle on platelet serotonin uptake site and serotonin2A receptor binding.

    Science.gov (United States)

    Wihlbäck, Anna-Carin; Sundström Poromaa, Inger; Bixo, Marie; Allard, Per; Mjörndal, Tom; Spigset, Olav

    2004-07-01

    Depression and anxiety are common health problems affecting women, particularly during the reproductive years. Major depression is two to three times as common in women than in men. Neuroendocrine factors are likely to contribute to this overall increased risk for developing mood disorders in women, and the neuroendocrine influence is most obviously seen in women with premenstrual dysphoric disorder (PMDD) as these women experience depressed mood and anxiety premenstrually only during ovulatory cycles. Moreover, dysfunction of serotonergic transmission has been regarded as an important mechanism in several psychiatric disorders and ovarian steroids have been shown to profoundly influence the activity of the serotonergic system. Given these facts, the purpose of this study was to examine whether binding of [3H]paroxetine to the platelet serotonin transporter or binding of [3H]lysergic acid diethylamide ([3H]LSD) to the platelet 5-HT2A receptor are influenced by the cyclical changes in circulating estradiol and progesterone that occur during the menstrual cycle. We examined 28 healthy women, without oral contraceptives and with regular menstrual cycles. In the late follicular phase, Bmax for [3H]paroxetine binding was significantly higher than in the ovulatory (pLSD binding was significantly higher in the early follicular phase and the early luteal phase compared to the mid-luteal phase (pLSD binding were found (p<0.05, respectively).

  2. Ontogeny of serotonin and serotonin2A receptors in rat auditory cortex.

    Science.gov (United States)

    Basura, Gregory J; Abbas, Atheir I; O'Donohue, Heather; Lauder, Jean M; Roth, Bryan L; Walker, Paul D; Manis, Paul B

    2008-10-01

    Maturation of the mammalian cerebral cortex is, in part, dependent upon multiple coordinated afferent neurotransmitter systems and receptor-mediated cellular linkages during early postnatal development. Given that serotonin (5-HT) is one such system, the present study was designed to specifically evaluate 5-HT tissue content as well as 5-HT(2A) receptor protein levels within the developing auditory cortex (AC). Using high performance liquid chromatography (HPLC), 5-HT and the metabolite, 5-hydroxyindoleacetic acid (5-HIAA), was measured in isolated AC, which demonstrated a developmental dynamic, reaching young adult levels early during the second week of postnatal development. Radioligand binding of 5-HT(2A) receptors with the 5-HT(2A/2C) receptor agonist, (125)I-DOI ((+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl; in the presence of SB206553, a selective 5-HT(2C) receptor antagonist, also demonstrated a developmental trend, whereby receptor protein levels reached young adult levels at the end of the first postnatal week (P8), significantly increased at P10 and at P17, and decreased back to levels not significantly different from P8 thereafter. Immunocytochemical labeling of 5-HT(2A) receptors and confocal microscopy revealed that 5-HT(2A) receptors are largely localized on layer II/III pyramidal cell bodies and apical dendrites within AC. When considered together, the results of the present study suggest that 5-HT, likely through 5-HT(2A) receptors, may play an important role in early postnatal AC development.

  3. Non-target effect of continuous application of chlorpyrifos on soil microbes, nematodes and its persistence under sub-humid tropical rice-rice cropping system.

    Science.gov (United States)

    Kumar, Upendra; Berliner, J; Adak, Totan; Rath, Prakash C; Dey, Avro; Pokhare, Somnath S; Jambhulkar, Nitiprasad N; Panneerselvam, P; Kumar, Anjani; Mohapatra, Shyamranjan D

    2017-01-01

    Application of pesticide in agricultural fields is "unnecessary evil" for non-target microflora and fauna. Hence, to identify the safer pesticide molecules against non-target microbes, a long-term pesticide experiment was initiated at National Rice Research Institute, Cuttack, India. In the present study, the effect of continuous application of chlorpyrifos (0.5kgha -1 ) in rice fields on non-target groups of soil microbes and nematodes was studied for seven seasons (four wet and three dry seasons) during 2009-2013. Treatments were arranged in a randomized complete block design with four replications of chlorpyrifos-treated (0.5kg a.i. ha -1 ) (CT) and untreated control (UT) plots. During seven seasons of experimentation, regular application of chlorpyrifos had no significant effect on population of heterotrophic aerobic, anaerobic, oligotrophic and copiotrophic bacteria in CT compared to UT, whereas, population of asymbiotic aerobic nitrogen fixer, nitrifiers, denitrifiers, gram positive and spore-forming bacteria were significantly reduced by nearly 0.25-2 fold in CT than UT. However, comparatively less deviation in population of actinomycetes, fungi, phosphate solubilizing and sulfur oxidizing bacteria were observed in CT than UT. Significant interactions were found between effects of chlorpyrifos with time in population dynamics of microbes. In plant parasitic nematode species, Meloidogyne graminicola (RRKN) and Hirschmanniella spp. (RRN), were significantly lower (p<0.01) in CT compared to UT after first year onwards. The overall observation of five years data indicated that the RRKN population showed a decreasing trend (R 2 =0.644) whereas RRN showed increasing trend (R 2 =0.932) in CT. The drastic chlorpyrifos dissipation was noticed after 15 days of application from the initial residue of 0.25mgkg -1 soil, which indicated that chlorpyrifos residue in rice field soil was not persistent and its half-life was found to be 4.02 days. Overall, the present

  4. Selective serotonin reuptake inhibitors for fibromyalgia syndrome

    Directory of Open Access Journals (Sweden)

    Brian Walitt

    Full Text Available ABSTRACT BACKGROUND: Fibromyalgia is a clinically well-defined chronic condition with a biopsychosocial aetiology. Fibromyalgia is characterized by chronic widespread musculoskeletal pain, sleep problems, cognitive dysfunction, and fatigue. Patients often report high disability levels and poor quality of life. Since there is no specific treatment that alters the pathogenesis of fibromyalgia, drug therapy focuses on pain reduction and improvement of other aversive symptoms. OBJECTIVES: To assess the benefits and harms of selective serotonin reuptake inhibitors (SSRIs in the treatment of fibromyalgia. METHODS: Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 5, MEDLINE (1966 to June 2014, EMBASE (1946 to June 2014, and the reference lists of reviewed articles. Selection criteria: We selected all randomized, double-blind trials of SSRIs used for the treatment of fibromyalgia symptoms in adult participants. We considered the following SSRIs in this review: citalopram, fluoxetine, escitalopram, fluvoxamine, paroxetine, and sertraline. Data collection and analysis: Three authors extracted the data of all included studies and assessed the risks of bias of the studies. We resolved discrepancies by discussion. MAIN RESULTS: The quality of evidence was very low for each outcome. We downgraded the quality of evidence to very low due to concerns about risk of bias and studies with few participants. We included seven placebo-controlled studies, two with citalopram, three with fluoxetine and two with paroxetine, with a median study duration of eight weeks (4 to 16 weeks and 383 participants, who were pooled together. All studies had one or more sources of potential major bias. There was a small (10% difference in patients who reported a 30% pain reduction between SSRIs (56/172 (32.6% and placebo (39/171 (22.8% risk difference (RD 0.10, 95% confidence interval (CI 0.01 to 0.20; number needed to treat for an

  5. Selective serotonin reuptake inhibitors for fibromyalgia syndrome

    Science.gov (United States)

    Walitt, Brian; Urrútia, Gerard; Nishishinya, María Betina; Cantrell, Sarah E; Häuser, Winfried

    2016-01-01

    Background Fibromyalgia is a clinically well-defined chronic condition with a biopsychosocial aetiology. Fibromyalgia is characterized by chronic widespread musculoskeletal pain, sleep problems, cognitive dysfunction, and fatigue. Patients often report high disability levels and poor quality of life. Since there is no specific treatment that alters the pathogenesis of fibromyalgia, drug therapy focuses on pain reduction and improvement of other aversive symptoms. Objectives The objective was to assess the benefits and harms of selective serotonin reuptake inhibitors (SSRIs) in the treatment of fibromyalgia. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 5), MEDLINE (1966 to June 2014), EMBASE (1946 to June 2014), and the reference lists of reviewed articles. Selection criteria We selected all randomized, double-blind trials of SSRIs used for the treatment of fibromyalgia symptoms in adult participants. We considered the following SSRIs in this review: citalopram, fluoxetine, escitalopram, fluvoxamine, paroxetine, and sertraline. Data collection and analysis Three authors extracted the data of all included studies and assessed the risks of bias of the studies. We resolved discrepancies by discussion. Main results The quality of evidence was very low for each outcome. We downgraded the quality of evidence to very low due to concerns about risk of bias and studies with few participants. We included seven placebo-controlled studies, two with citalopram, three with fluoxetine and two with paroxetine, with a median study duration of eight weeks (4 to 16 weeks) and 383 participants, who were pooled together. All studies had one or more sources of potential major bias. There was a small (10%) difference in patients who reported a 30% pain reduction between SSRIs (56/172 (32.6%)) and placebo (39/171 (22.8%)) risk difference (RD) 0.10, 95% confidence interval (CI) 0.01 to 0.20; number needed to treat for an additional

  6. Decreased exploratory activity in a mouse model of 15q duplication syndrome; implications for disturbance of serotonin signaling.

    Directory of Open Access Journals (Sweden)

    Kota Tamada

    Full Text Available Autism spectrum disorders (ASDs have garnered significant attention as an important grouping of developmental brain disorders. Recent genomic studies have revealed that inherited or de novo copy number variations (CNVs are significantly involved in the pathophysiology of ASDs. In a previous report from our laboratory, we generated mice with CNVs as a model of ASDs, with a duplicated mouse chromosome 7C that is orthologous to human chromosome 15q11-13. Behavioral analyses revealed paternally duplicated (patDp/+ mice displayed abnormal behaviors resembling the symptoms of ASDs. In the present study, we extended these findings by performing various behavioral tests with C57BL/6J patDp/+ mice, and comprehensively measuring brain monoamine levels with ex vivo high performance liquid chromatography. Compared with wild-type controls, patDp/+ mice exhibited decreased locomotor and exploratory activities in the open field test, Y-maze test, and fear-conditioning test. Furthermore, their decreased activity levels overcame increased appetite induced by 24 hours of food deprivation in the novelty suppressed feeding test. Serotonin levels in several brain regions of adult patDp/+ mice were lower than those of wild-type control, with no concurrent changes in brain levels of dopamine or norepinephrine. Moreover, analysis of monoamines in postnatal developmental stages demonstrated reduced brain levels of serotonin in young patDp/+ mice. These findings suggest that a disrupted brain serotonergic system, especially during postnatal development, may generate the phenotypes of patDp/+ mice.

  7. Gene structure and expression of serotonin receptor HTR2C in hypothalamic samples from infanticidal and control sows

    Directory of Open Access Journals (Sweden)

    Quilter Claire R

    2012-04-01

    Full Text Available Abstract Background The serotonin pathways have been implicated in behavioural phenotypes in a number of species, including human, rat, mouse, dog and chicken. Components of the pathways, including the receptors, are major targets for drugs used to treat a variety of physiological and psychiatric conditions in humans. In our previous studies we have identified genetic loci potentially contributing to maternal infanticide in pigs, which includes a locus on the porcine X chromosome long arm. The serotonin receptor HTR2C maps to this region, and is therefore an attractive candidate for further study based on its function and its position in the genome. Results In this paper we describe the structure of the major transcripts produced from the porcine HTR2C locus using cDNA prepared from porcine hypothalamic and pooled total brain samples. We have confirmed conservation of sites altered by RNA editing in other mammalian species, and identified polymorphisms in the gene sequence. Finally, we have analysed expression and editing of HTR2C in hypothalamus samples from infanticidal and control animals. Conclusions The results confirm that although the expression of the long transcriptional variant of HTR2C is raised in infanticidal animals, the overall patterns of editing in the hypothalamus are similar between the two states. Sequences associated with the cDNA and genomic structures of HTR2C reported in this paper are deposited in GenBank under accession numbers FR720593, FR720594 and FR744452.

  8. Impaired fear extinction as displayed by serotonin transporter knockout rats housed in open cages is disrupted by IVC cage housing.

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    Ling Shan

    Full Text Available Anxiety disorders are influenced by both environmental and genetic factors. A well-known example for gene x environment interactions in psychiatry is the low activity (s allelic variant of the serotonin transporter (5-HTT promoter polymorphism (5-HTTLPR that in the context of stress increases risk for depression and post-traumatic stress disorder (PTSD. Previously, we observed robust anxiety-related phenotypes, such as an impairment in fear extinction, in 5-HTT knockout (5-HTT-/- versus wild-type (5-HTT+/+ rats housed in open cages. Recently, housing conditions were changed from open cages to individually ventilated cages (IVC, which are associated with a high ventilation fold and noise. This switch in housing conditions prompted an unplanned 5-HTT gene x environment interaction study in our rats. The current study shows that lifetime stress by means of IVC cage housing abolished genotype differences in fear extinction between 5-HTT-/- and 5-HTT+/+ rats. Although this effect was not attributed specifically to either the 5-HTT+/+ or the 5-HTT-/- genotype, the findings are in agreement with the modulatory role of serotonin in the processing of environmental stimuli. Our findings also underline the possibility that housing conditions confound the interpretation of anxiety-related behaviours in rodents.

  9. Prenatal fluoxetine exposure induces life-long serotonin 5-HT₃ receptor-dependent cortical abnormalities and anxiety-like behaviour.

    Science.gov (United States)

    Smit-Rigter, Laura A; Noorlander, Cornelle W; von Oerthel, Lars; Chameau, Pascal; Smidt, Marten P; van Hooft, Johannes A

    2012-02-01

    Selective serotonin reuptake inhibitors (SSRIs) are the first choice of drugs to treat depression and anxiety during pregnancy. However, there is evidence that in utero exposure to SSRIs leads to adverse effects in offspring. Here we show that in mice, the adverse effects of the widely used antidepressant and SSRI fluoxetine are critically dependent on the 5-HT(3) receptor, the only ligand-gated ion channel in the family of serotonin receptors. In utero exposure to fluoxetine induces anxiety-like behavior in wildtype, but not in mice lacking the 5-HT(3) receptor. In addition to this behavioral phenotype, these mice show life-long abnormalities of cortical cytoarchitecture, which can be reversed in vitro by pharmacological block of 5-HT(3) receptors. Moreover, the effect of fluoxetine on the development of cortical neurons is absent in 5-HT(3) receptor knockout mice. These findings pinpoint the pivotal role of serotonergic signaling during development and provide a novel basis to investigate the adverse effects of the use of fluoxetine during pregnancy. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Decreased Exploratory Activity in a Mouse Model of 15q Duplication Syndrome; Implications for Disturbance of Serotonin Signaling

    Science.gov (United States)

    Tamada, Kota; Tomonaga, Shozo; Hatanaka, Fumiyuki; Nakai, Nobuhiro; Takao, Keizo; Miyakawa, Tsuyoshi; Nakatani, Jin; Takumi, Toru

    2010-01-01

    Autism spectrum disorders (ASDs) have garnered significant attention as an important grouping of developmental brain disorders. Recent genomic studies have revealed that inherited or de novo copy number variations (CNVs) are significantly involved in the pathophysiology of ASDs. In a previous report from our laboratory, we generated mice with CNVs as a model of ASDs, with a duplicated mouse chromosome 7C that is orthologous to human chromosome 15q11-13. Behavioral analyses revealed paternally duplicated (patDp/+) mice displayed abnormal behaviors resembling the symptoms of ASDs. In the present study, we extended these findings by performing various behavioral tests with C57BL/6J patDp/+ mice, and comprehensively measuring brain monoamine levels with ex vivo high performance liquid chromatography. Compared with wild-type controls, patDp/+ mice exhibited decreased locomotor and exploratory activities in the open field test, Y-maze test, and fear-conditioning test. Furthermore, their decreased activity levels overcame increased appetite induced by 24 hours of food deprivation in the novelty suppressed feeding test. Serotonin levels in several brain regions of adult patDp/+ mice were lower than those of wild-type control, with no concurrent changes in brain levels of dopamine or norepinephrine. Moreover, analysis of monoamines in postnatal developmental stages demonstrated reduced brain levels of serotonin in young patDp/+ mice. These findings suggest that a disrupted brain serotonergic system, especially during postnatal development, may generate the phenotypes of patDp/+ mice. PMID:21179543

  11. Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice

    Science.gov (United States)

    Suidan, Georgette L.; Demers, Melanie; Herr, Nadine; Carbo, Carla; Brill, Alexander; Cifuni, Stephen M.; Mauler, Maximilian; Cicko, Sanja; Bader, Michael; Idzko, Marco; Bode, Christoph

    2013-01-01

    The majority of peripheral serotonin is stored in platelets, which secrete it on activation. Serotonin releases Weibel-Palade bodies (WPBs) and we asked whether absence of platelet serotonin affects neutrophil recruitment in inflammatory responses. Tryptophan hydroxylase (Tph)1–deficient mice, lacking non-neuronal serotonin, showed mild leukocytosis compared with wild-type (WT), primarily driven by an elevated neutrophil count. Despite this, 50% fewer leukocytes rolled on unstimulated mesenteric venous endothelium of Tph1−/− mice. The velocity of rolling leukocytes was higher in Tph1−/− mice, indicating fewer selectin-mediated interactions with endothelium. Stimulation of endothelium with histamine, a secretagogue of WPBs, or injection of serotonin normalized the rolling in Tph1−/− mice. Diminished rolling in Tph1−/− mice resulted in reduced firm adhesion of leukocytes after lipopolysaccharide treatment. Blocking platelet serotonin uptake with fluoxetine in WT mice reduced serum serotonin by > 80% and similarly reduced leukocyte rolling and adhesion. Four hours after inflammatory stimulation, neutrophil extravasation into lung, peritoneum, and skin wounds was reduced in Tph1−/− mice, whereas in vitro neutrophil chemotaxis was independent of serotonin. Survival of lipopolysaccharide-induced endotoxic shock was improved in Tph1−/− mice. In conclusion, platelet serotonin promotes the recruitment of neutrophils in acute inflammation, supporting an important role for platelet serotonin in innate immunity. PMID:23243271

  12. Serotonin-immunoreactive sensory neurons in the antenna of the cockroach Periplaneta americana.

    Science.gov (United States)

    Watanabe, Hidehiro; Shimohigashi, Miki; Yokohari, Fumio

    2014-02-01

    The antennae of insects contain a vast array of sensory neurons that process olfactory, gustatory, mechanosensory, hygrosensory, and thermosensory information. Except those with multimodal functions, most sensory neurons use acetylcholine as a neurotransmitter. Using immunohistochemistry combined with retrograde staining of antennal sensory neurons in the cockroach Periplaneta americana, we found serotonin-immunoreactive sensory neurons in the antenna. These were selectively distributed in chaetic and scolopidial sensilla and in the scape, the pedicel, and first 15 segments of the flagellum. In a chaetic sensillum, A single serotonin-immunoreactive sensory neuron cohabited with up to four serotonin-negative sensory neurons. Based on their morphological features, serotonin-immunopositive and -negative sensory neurons might process mechanosensory and contact chemosensory modalities, respectively. Scolopidial sensilla constitute the chordotonal and Johnston's organs within the pedicel and process antennal vibrations. Immunoelectron microscopy clearly revealed that serotonin-immunoreactivities selectively localize to a specific type of mechanosensory neuron, called type 1 sensory neuron. In a chordotonal scolopidial sensillum, a serotonin-immunoreactive type 1 neuron always paired with a serotonin-negative type 1 neuron. Conversely, serotonin-immunopositive and -negative type 1 neurons were randomly distributed in Johnston's organ. In the deutocerebrum, serotonin-immunoreactive sensory neuron axons formed three different sensory tracts and those from distinct types of sensilla terminated in distinct brain regions. Our findings indicate that a biogenic amine, serotonin, may act as a neurotransmitter in peripheral mechanosensory neurons. Copyright © 2013 Wiley Periodicals, Inc.

  13. The serotonin system in autism spectrum disorder: from biomarker to animal models

    Science.gov (United States)

    Muller, Christopher L.; Anacker, Allison M.J.; Veenstra-VanderWeele, Jeremy

    2015-01-01

    Elevated whole blood serotonin, or hyperserotonemia, was the first biomarker identified in autism spectrum disorder (ASD) and is present in more than 25% of affected children. The serotonin system is a logical candidate for involvement in ASD due to its pleiotropic role across multiple brain systems both dynamically and across development. Tantalizing clues connect this peripheral biomarker with changes in brain and behavior in ASD, but the contribution of the serotonin system to ASD pathophysiology remains incompletely understood. Studies of whole blood serotonin levels in ASD and in a large founder population indicate greater heritability than for the disorder itself and suggest an association with recurrence risk. Emerging data from both neuroimaging and postmortem samples also indicate changes in the brain serotonin system in ASD. Genetic linkage and association studies of both whole blood serotonin levels and of ASD risk point to the chromosomal region containing the serotonin transporter (SERT) gene in males but not in females. In ASD families with evidence of linkage to this region, multiple rare SERT amino acid variants lead to a convergent increase in serotonin uptake in cell models. A knock-in mouse model of one of these variants, SERT Gly56Ala, recapitulates the hyperserotonemia biomarker and shows increased brain serotonin clearance, increased serotonin receptor sensitivity, and altered social, communication, and repetitive behaviors. Data from other rodent models also suggest an important role for the serotonin system in social behavior, in cognitive flexibility, and in sensory development. Recent work indicates that reciprocal interactions between serotonin and other systems, such as oxytocin, may be particularly important for social behavior. Collectively, these data point to the serotonin system as a prime candidate for treatment development in a subgroup of children defined by a robust, heritable biomarker. PMID:26577932

  14. Divergent Roles of Central Serotonin in Adult Hippocampal Neurogenesis

    Directory of Open Access Journals (Sweden)

    Ning-Ning Song

    2017-06-01

    Full Text Available The central serotonin (5-HT system is the main target of selective serotonin reuptake inhibitors (SSRIs, the first-line antidepressants widely used in current general practice. One of the prominent features of chronic SSRI treatment in rodents is the enhanced adult neurogenesis in the hippocampus, which has been proposed to contribute to antidepressant effects. Therefore, tremendous effort has been made to decipher how central 5-HT regulates adult hippocampal neurogenesis. In this paper, we review how changes in the central serotonergic system alter adult hippocampal neurogenesis. We focus on data obtained from three categories of genetically engineered mouse models: (1 mice with altered central 5-HT levels from embryonic stages, (2 mice with deletion of 5-HT receptors from embryonic stages, and (3 mice with altered central 5-HT system exclusively in adulthood. These recent findings provide unique insights to interpret the multifaceted roles of central 5-HT on adult hippocampal neurogenesis and its associated effects on depression.

  15. Does serotonin play a role in entrance into hibernation?

    Science.gov (United States)

    Canguilhem, B; Miro, J L; Kempf, E; Schmitt, P

    1986-10-01

    To study the role of brain serotonin in entrance into hibernation, intraventricular injections of 5,7-dihydroxytryptamine, electrolytic lesions of small parts of the median raphe nucleus, and chemical lesions of the same nucleus were undertaken on the European hamster in winter. All the lesions led to a variable decrease of serotonin levels in all parts of the brain areas examined. However, hibernation was suppressed only in those animals whose serotonergic neurons were destroyed in a small anterior part of the median raphe nucleus. Electrolytic lesions as well as chemical lesions in the other parts of the median raphe nucleus or the 5,7-dihydroxytryptamine injections into lateral ventricles do not prevent hibernation. These data suggest that in the European hamster only a specific group of serotonergic neurons of the median raphe nucleus are involved in the process of entrance into hibernation.

  16. Unifying concept of serotonin transporter-associated currents.

    Science.gov (United States)

    Schicker, Klaus; Uzelac, Zeljko; Gesmonde, Joan; Bulling, Simon; Stockner, Thomas; Freissmuth, Michael; Boehm, Stefan; Rudnick, Gary; Sitte, Harald H; Sandtner, Walter

    2012-01-02

    Serotonin (5-HT) uptake by the human serotonin transporter (hSERT) is driven by ion gradients. The stoichiometry of transported 5-HT and ions is predicted to result in electroneutral charge movement. However, hSERT mediates a current when challenged with 5-HT. This discrepancy can be accounted for by an uncoupled ion flux. Here, we investigated the mechanistic basis of the uncoupled currents and its relation to the conformational cycle of hSERT. Our observations support the conclusion that the conducting state underlying the uncoupled ion flux is in equilibrium with an inward facing state of the transporter with K+ bound. We identified conditions associated with accumulation of the transporter in inward facing conformations. Manipulations that increased the abundance of inward facing states resulted in enhanced steady-state currents. We present a comprehensive kinetic model of the transport cycle, which recapitulates salient features of the recorded currents. This study provides a framework for exploring transporter-associated currents.

  17. Embryo development, stress protein (Hsp70) responses, and histopathology in zebrafish (Danio rerio) following exposure to nickel chloride, chlorpyrifos, and binary mixtures of them.

    Science.gov (United States)

    Scheil, Volker; Zürn, Alexandra; Köhler, Heinz-R; Triebskorn, Rita

    2010-02-01

    Two different classes of chemicals were tested in a multilevel approach in this study: NiCl(2) as a representative for heavy metals and chlorpyrifos, a pesticide. Both, the single substances and mixtures of them were investigated for their effects on embryonic development, histological alterations, and the stress protein (Hsp70) response in the zebrafish Danio rerio. Fishes were exposed from fertilization of eggs up to a maximum of 168 h post fertilization, depending on the investigated endpoint. NiCl(2) led to effects in all tests which, however, were less severe at the histopathological level than in developmental (hatching success) and stress protein studies. Chlorpyrifos did not lead to developmental alterations but it was found to induce the Hsp70 response as well as histopathological damages. Mixtures of both substances resulted in similar results as the single substances; the results suggest an independent mode of action of these two substances and additivity of their effects.

  18. Bioremediation of chlorpyrifos contaminated soil by two phase bioslurry reactor: Processes evaluation and optimization by Taguchi's design of experimental (DOE) methodology.

    Science.gov (United States)

    Pant, Apourv; Rai, J P N

    2018-04-15

    Two phase bioreactor was constructed, designed and developed to evaluate the chlorpyrifos remediation. Six biotic and abiotic factors (substrate-loading rate, slurry phase pH, slurry phase dissolved oxygen (DO), soil water ratio, temperature and soil micro flora load) were evaluated by design of experimental (DOE) methodology employing Taguchi's orthogonal array (OA). The selected six factors were considered at two levels L-8 array (2^7, 15 experiments) in the experimental design. The optimum operating conditions obtained from the methodology showed enhanced chlorpyrifos degradation from 283.86µg/g to 955.364µg/g by overall 70.34% of enhancement. In the present study, with the help of few well defined experimental parameters a mathematical model was constructed to understand the complex bioremediation process and optimize the approximate parameters upto great accuracy. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Solubilization of serotonin-1a and serotonin-1b binding sites from bovine brain

    Energy Technology Data Exchange (ETDEWEB)

    Asarch, K.B.; Shih, J.C.

    1987-05-01

    Serotonin1 (5-hydroxytryptamine1, 5-HT1) binding sites have been solubilized from bovine brain cortex using a mixture of 0.1% Nonidet P-40 and 0.3% digitonin in a low-salt buffer containing 0.1% ascorbic acid. The affinity of (/sup 3/H)5-HT for the soluble cortical binding sites (2.1 nM) is identical to its affinity at membrane-bound binding sites (2.1 nM). (/sup 3/H)8-Hydroxy-2-(di-n-propylamino)tetralin ((/sup 3/H)DPAT), a selective 5-HT1a radioligand, also binds to soluble cortical binding sites with high affinity (1.8 nM) comparable with its affinity in the crude membranes (1.7 nM). A significant correlation exists in the rank order potency of serotonergic agents for (/sup 3/H)5-HT binding and for (/sup 3/H)DPAT binding to crude and soluble membranes. The density of (/sup 3/H)DPAT binding sites relative to the (/sup 3/H)5-HT sites in the solubilized cortical membranes (35%) corresponds well with the proportion of 5-HT1a sites in the crude membranes determined by spiperone displacement (33%), suggesting that both the 5-HT1a and 5-HT1b binding sites have been cosolubilized. (/sup 3/H)5-HT binding in the soluble preparations was inhibited by GTP, suggesting that a receptor complex may have been solubilized. (/sup 3/H)Spiperone-specific binding was not detectable in this preparation, suggesting that 5-HT2 sites were not cosolubilized.

  20. Serotonin receptor modulators in the treatment of irritable bowel syndrome

    Directory of Open Access Journals (Sweden)

    Mohammad Fayyaz

    2008-03-01

    Full Text Available Mohammad Fayyaz, Jeffrey M LacknerDivision of Gastroenterology, Department of Medicine, University at Buffalo School of Medicine, SUNY, Buffalo, NY, USAAbstract: The aim of this article is to review the pathophysiology and clinical role of serotonin receptor modulators used in the treatment of irritable bowel syndrome. Serotonin is an important monoamine neurotransmitter that plays a key role in the initiation of peristaltic and secretory reflexes, and in modulation of visceral sensations. Several serotonin receptor subtypes have been characterized, of which 5HT3, 5HT4, and 5HT1b are the most important for GI function. 5HT4 agonists (eg, tegaserod potentiate peristalsis initiated by 5HT1 receptor stimulation. 5HT4 agonists are therefore useful in constipation predominant form of IBS and in chronic constipation. 5HT3 antagonists (Alosetron and Cilansetron prevent the activation of 5HT3 receptors on extrinsic afferent neurons and can decrease the visceral pain associated with IBS. These agents also retard small intestinal and colonic transit, and are therefore useful in diarrhea-predominant IBS. Tegaserod has been demonstrated in several randomized, placebo controlled trials to relieve global IBS symptoms as well as individual symptoms of abdominal discomfort, number of bowel movements and stool consistency. Several randomized, controlled trials have shown that alosetron relieves pain, improves bowel function, and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome. However, ischemic colitis and severe complications of constipation have been major concerns leading to voluntary withdrawal of Alosetron from the market followed by remarketing with a comprehensive risk management program.Keywords: serotonin, irritable bowel syndrome, tegaserod

  1. Revisiting the Serotonin Hypothesis: Implications for Major Depressive Disorders.

    Science.gov (United States)

    Fakhoury, Marc

    2016-07-01

    Major depressive disorder (MDD) is a heritable neuropsychiatric disease associated with severe changes at cellular and molecular levels. Its diagnosis mainly relies on the characterization of a wide range of symptoms including changes in mood and behavior. Despite the availability of antidepressant drugs, 10 to 30 % of patients fail to respond after a single or multiple treatments, and the recurrence of depression among responsive patients is very high. Evidence from the past decades suggests that the brain neurotransmitter serotonin (5-HT) is incriminated in MDD, and that a dysfunction of 5-HT receptors may play a role in the genesis of this disease. The 5-HT membrane transporter protein (SERT), which helps regulate the serotonergic transmission, is also implicated in MDD and is one of the main targets of antidepressant therapy. Although a number of behavioral tests and animal models have been developed to study depression, little is known about the neurobiological bases of MDD. Understanding the role of the serotonergic pathway will significantly help improve our knowledge of the pathophysiology of depression and may open up avenues for the development of new antidepressant drugs. The overarching goal of this review is to present recent findings from studies examining the serotonergic pathway in MDD, with a focus on SERT and the serotonin 1A (5-HT1A), serotonin 1B (5-HT1B), and serotonin 2A (5-HT2A) receptors. This paper also describes some of the main molecules involved in the internalization of 5-HT receptors and illustrates the changes in 5-HT neurotransmission in knockout mice and animal model of depression.

  2. Selective serotonin reuptake inhibitorprescribing before, during and after pregnancy

    DEFF Research Database (Denmark)

    Charlton, Ra; Jordan, S; Pierini, A

    2015-01-01

    OBJECTIVE: To explore the prescribing patterns of selective serotonin reuptake inhibitors (SSRIs) before, during and after pregnancy in six European population-based databases. DESIGN: Descriptive drug utilisation study. SETTING: Six electronic healthcare databases in Denmark, the Netherlands...... prescribed in the Netherlands and Italian regions than in Denmark and the UK. CONCLUSIONS: The higher SSRI prescribing rates in the UK, compared with other European regions, raise questions about differences in the prevalence and severity of depression and its management in pregnancy across Europe....

  3. Molecular cloning, expression and characterization of a bovine serotonin transporter

    DEFF Research Database (Denmark)

    Mortensen, O V; Kristensen, A S; Rudnick, G

    1999-01-01

    The serotonin transporter (SERT) is a member of a highly homologous family of sodium/chloride dependent neurotransmitter transporters responsible for reuptake of biogenic amines from the extracellular fluid. SERT constitutes the pharmacological target of several clinically important antidepressan......-methylenedioxymethamphetamine (MDMA) was mainly unchanged. RT-PCR amplification of RNA from different tissues demonstrated expression of SERT in placenta, brain stem, bone marrow, kidney, lung, heart, adrenal gland, liver, parathyroid gland, thyroid gland, small intestine and pancreas....

  4. Dissipation of chlorantraniliprole, chlorpyrifos-methyl and indoxacarb-insecticides used to control codling moth (Cydia Pomonella L.) and leafrollers (Tortricidae) in apples for production of baby food.

    Science.gov (United States)

    Szpyrka, Ewa; Matyaszek, Aneta; Słowik-Borowiec, Magdalena

    2017-05-01

    Dissipations of three insecticides: chlorantraniliprole, chlorpyrifos-methyl and indoxacarb in apples were studied following their foliar application on apples intended for production of baby food. The apples were sprayed with formulations for control of codling moth (Cydia Pomonella L.) and leafrollers (Tortricidae). Six experiments were conducted; each insecticide was applied individually on dessert apples. A validated gas chromatography-based method with simultaneous electron capture and nitrogen-phosphorus detection (GC-ECD/NPD) was used for the residue analysis. The analytical performance of the method was satisfactory, with expanded uncertainties ≤36% (a coverage factor, k = 2, and a confidence level of 95%). The dissipations of insecticides were studied in pseudo-first-order kinetic models (for which the coefficient of determination, R 2 , ranged between 0.9188 and 0.9897). Residues of studied insecticides were below their maximum residue limits of 0.5 mg/kg at an early stage of growth of the fruit. The half-lives of chlorantraniliprole, chlorpyrifos-methyl and indoxacarb were 16-17, 4-6 and 20-24 days, respectively. The initial residue levels declined gradually and reached the level of 0.01 mg/kg in 1 month for chlorpyrifos-methyl, 2 months for chlorantraniliprole and 2.5 months for indoxacarb. To obtain the insecticide residue levels below 0.01 mg/kg, which is the default MRL for food intended for infants and young children, the application of the studied insecticides should be carried out at recommended doses not later then: 1 month before harvest for chlorpyrifos-methyl, 2 months for chlorantraniliprole and 2.5 months for indoxacarb.

  5. Isolation and Molecular Characterization of Novel Chlorpyrifos and 3,5,6-trichloro-2-pyridinol-degrading Bacteria from Sugarcane Farm Soils

    OpenAIRE

    Rayu, Smriti; Nielsen, Uffe N.; Nazaries, Loïc; Singh, Brajesh K.

    2017-01-01

    Chlorpyrifos (CP) is one of the most widely used organophosphate pesticides in agriculture worldwide, but its extensive use has led to the contamination of various soil and water systems. Microbial bioremediation is considered to be one of the most viable options for the removal of CP from the environment; however, little is known about the soil bacterial diversity that degrade CP. Sequential soil and liquid culture enrichments enabled the isolation of bacterial CP degraders with sequence hom...

  6. Induction by chlorpyrifos, of the confusion of males in discriminating female sexual pheromones used for mate finding by two sympatric trichogramma species (Hymenoptera: Trichogrammatidae).

    Science.gov (United States)

    Dupont, C; Allemand, R; Delpuech, J M

    2010-04-01

    Chlorpyrifos is one of the most widely used insecticides worldwide. It has been shown to have deleterious effects on survival of nontarget insects, but its impact on behavior has received less attention. In this study, we investigated the sublethal effects of this insecticide on sexual pheromone discrimination in two Trichogramma species. In these species, sexual pheromones arrest partners belonging to the same species. This specificity is important for reproduction efficacy because interspecific matings are sterile. We used two sympatric and closely related species of Trichogramma to study how two doses (LD 20 and LD 0.1) of chlorpyrifos can alter the discrimination by males and the emission by females of pheromones from both species. When exposed to the LD 20, the males of both species showed a decrease in the discrimination of conspecific sexual pheromones. For one of the two species (T. evanescens Westwood), this decrease even led to a total annihilation of discrimination. A dose as low as the LD 0.1, inducing no apparent mortality, induced the same decrease in pheromone discrimination for T. semblidis Aurivillius males. However, no effect was observed on the discrimination by males of sexual pheromones emitted by females either exposed to an LD 20 or an LD 0.1 of chlorpyrifos. By decreasing the discrimination by males of sexual pheromones, chlorpyrifos may induce interspecific interactions and attempts at copulating that would decrease the fitness of parasitoids. The implications of these results in relation to environmental pollution, the mode of action of the insecticide and the status of natural enemy of Trichogramma are discussed.

  7. Crystal Structure of an LSD-Bound Human Serotonin Receptor

    Energy Technology Data Exchange (ETDEWEB)

    Wacker, Daniel; Wang, Sheng; McCorvy, John D.; Betz, Robin M.; Venkatakrishnan, A.J.; Levit, Anat; Lansu, Katherine; Schools, Zachary L.; Che, Tao; Nichols, David E.; Shoichet, Brian K.; Dror, Ron O.; Roth, Bryan L. (UNCSM); (UNC); (Stanford); (Stanford-MED); (UCSF)

    2017-01-01

    The prototypical hallucinogen LSD acts via serotonin receptors, and here we describe the crystal structure of LSD in complex with the human serotonin receptor 5-HT2B. The complex reveals conformational rearrangements to accommodate LSD, providing a structural explanation for the conformational selectivity of LSD’s key diethylamide moiety. LSD dissociates exceptionally slow from both 5-HT2BR and 5-HT2AR—a major target for its psychoactivity. Molecular dynamics (MD) simulations suggest that LSD’s slow binding kinetics may be due to a “lid” formed by extracellular loop 2 (EL2) at the entrance to the binding pocket. A mutation predicted to increase the mobility of this lid greatly accelerates LSD’s binding kinetics and selectively dampens LSD-mediated β-arrestin2 recruitment. This study thus reveals an unexpected binding mode of LSD; illuminates key features of its kinetics, stereochemistry, and signaling; and provides a molecular explanation for LSD’s actions at human serotonin receptors.

  8. Serotonin 6 receptor controls alzheimer’s disease and depression

    Science.gov (United States)

    Kim, Eun-Cheol; Kim, Sanghyeon; Hong, Jin Tae

    2015-01-01

    Alzheimer’s disease (AD) and depression in late life are one of the most severe health problems in the world disorders. Serotonin 6 receptor (5-HT6R) has caused much interest for potential roles in AD and depression. However, a causative role of perturbed 5-HT6R function between two diseases was poorly defined. In the present study, we found that a 5-HT6R antagonist, SB271036 rescued memory impairment by attenuating the generation of Aβ via the inhibition of γ-secretase activity and the inactivation of astrocytes and microglia in the AD mouse model. It was found that the reduction of serotonin level was significantly recovered by SB271036, which was mediated by an indirect regulation of serotonergic neurons via GABA. Selective serotonin reuptake inhibitor (SSRI), fluoxetine significantly improved cognitive impairment and behavioral changes. In human brain of depression patients, we then identified the potential genes, amyloid beta (A4) precursor protein-binding, family A, member 2 (APBA2), well known AD modulators by integrating datasets from neuropathology, microarray, and RNA seq. studies with correlation analysis tools. And also, it was demonstrated in mouse models and patients of AD. These data indicate functional network of 5-HT6R between AD and depression. PMID:26449188

  9. Platelet serotonin transporter function predicts default-mode network activity.

    Directory of Open Access Journals (Sweden)

    Christian Scharinger

    Full Text Available The serotonin transporter (5-HTT is abundantly expressed in humans by the serotonin transporter gene SLC6A4 and removes serotonin (5-HT from extracellular space. A blood-brain relationship between platelet and synaptosomal 5-HT reuptake has been suggested, but it is unknown today, if platelet 5-HT uptake can predict neural activation of human brain networks that are known to be under serotonergic influence.A functional magnetic resonance study was performed in 48 healthy subjects and maximal 5-HT uptake velocity (Vmax was assessed in blood platelets. We used a mixed-effects multilevel analysis technique (MEMA to test for linear relationships between whole-brain, blood-oxygen-level dependent (BOLD activity and platelet Vmax.The present study demonstrates that increases in platelet Vmax significantly predict default-mode network (DMN suppression in healthy subjects independent of genetic variation within SLC6A4. Furthermore, functional connectivity analyses indicate that platelet Vmax is related to global DMN activation and not intrinsic DMN connectivity.This study provides evidence that platelet Vmax predicts global DMN activation changes in healthy subjects. Given previous reports on platelet-synaptosomal Vmax coupling, results further suggest an important role of neuronal 5-HT reuptake in DMN regulation.

  10. Crystal Structure of an LSD-Bound Human Serotonin Receptor.

    Science.gov (United States)

    Wacker, Daniel; Wang, Sheng; McCorvy, John D; Betz, Robin M; Venkatakrishnan, A J; Levit, Anat; Lansu, Katherine; Schools, Zachary L; Che, Tao; Nichols, David E; Shoichet, Brian K; Dror, Ron O; Roth, Bryan L

    2017-01-26

    The prototypical hallucinogen LSD acts via serotonin receptors, and here we describe the crystal structure of LSD in complex with the human serotonin receptor 5-HT2B. The complex reveals conformational rearrangements to accommodate LSD, providing a structural explanation for the conformational selectivity of LSD's key diethylamide moiety. LSD dissociates exceptionally slow from both 5-HT2BR and 5-HT2AR-a major target for its psychoactivity. Molecular dynamics (MD) simulations suggest that LSD's slow binding kinetics may be due to a "lid" formed by extracellular loop 2 (EL2) at the entrance to the binding pocket. A mutation predicted to increase the mobility of this lid greatly accelerates LSD's binding kinetics and selectively dampens LSD-mediated β-arrestin2 recruitment. This study thus reveals an unexpected binding mode of LSD; illuminates key features of its kinetics, stereochemistry, and signaling; and provides a molecular explanation for LSD's actions at human serotonin receptors. PAPERCLIP. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Serotonin-promoted elevation of ROS levels may lead to cardiac pathologies in diabetic rat

    Directory of Open Access Journals (Sweden)

    Ali Tahir

    2015-01-01

    Full Text Available Patients with diabetes mellitus (DM develop tendencies toward heart disease. Hyperglycemia induces the release of serotonin from enterochromaffin cells (EC. Serotonin was observed to elevate reactive oxygen species (ROS and downregulate antioxidant enzymes. As a result, elevated levels of serotonin could contribute to diabetic complications, including cardiac hypertrophy. In the present study, diabetes mellitus was induced in rats by alloxan administration; this was followed by the administration of serotonin to experimental animals. ROS, catalase (CAT, superoxide dismutase (SOD, B-type natriuretic peptide (BNP expression, and histopathological assessments were performed. Elevated ROS concentrations and decreased antioxidant enzyme activities were detected. Further, we observed an increase in cell surface area and elevated BNP expression which suggests that events associated with cardiac hypertrophy were increased in serotonin-administered diabetic rats. We conclude that serotonin secretion in diabetes could contribute to diabetic complications, including cardiac hypertrophy, through enhanced ROS production.

  12. Influence of the pesticides glyphosate, chlorpyrifos and atrazine on growth parameters of nonochratoxigenic Aspergillus section Nigri strains isolated from agricultural soils.

    Science.gov (United States)

    Carranza, Cecilia S; Barberis, Carla L; Chiacchiera, Stella M; Magnoli, Carina E

    2014-01-01

    This investigation was undertake to determine the effect of glyphosate, chlorpyrifos and atrazine on the lag phase and growth rate of nonochratoxigenic A. niger aggregate strains growing on soil extract medium at -0.70, -2.78 and -7.06 MPa. Under certain conditions, the glyphosate concentrations used significantly increased micelial growth as compared to control. An increase of about 30% was observed for strain AN 251 using 5 and 20 mg L(-1) of glyphosate at -2.78 MPa. The strains behaved differently in the presence of the insecticide chlorpyrifos. A significant decrease in growth rate, compared to control, was observed for all strains except AN 251 at -2.78 MPa with 5 mg L(-1). This strain showed a significant increase in growth rate. With regard to atrazine, significant differences were observed only under some conditions compared to control. An increase in growth rate was observed for strain AN 251 at -2.78 MPa with 5 and 10 mg L(-1) of atrazine. By comparison, a reduction of 25% in growth rate was observed at -7.06 MPa and higher atrazine concentrations. This study shows that glyphosate, chlorpyrifos and atrazine affect the growth parameters of nonochratoxigenic A. niger aggregate strains under in vitro conditions.

  13. Sublethal effects of diazinon, fenitrothion and chlorpyrifos on the functional response of predatory bug, Andrallus spinidens Fabricius (Hem.: Pentatomidae in the laboratory conditions

    Directory of Open Access Journals (Sweden)

    Moloud GholamzadehChitgar

    2014-04-01

    Full Text Available The sublethal effects of diazinon, fenitrothion and chlorpyrifos on the functional response of predatory bug, Andrallus spinidens Fabricius (Hem.: Pentatomidae, a potential biological control agent, were studied on 5th-instar nymphs. The experiment was conducted in varying densities (2, 4, 8, 16, 32 and 64 of last instars larvae of Chilo suppressalis Walker (Lepidoptera: Pyralidae as prey at 25 ± 2 °C, 60% ± 10% relative humidity (RH and a photoperiod of 16:8 h (L: D. The results of logistic regressions revealed a type II functional response in the control and all insecticide treatments. Comparison of functional response curves revealed that tested insecticides markedly decreased the mean of preys consumed by A. spinidens. Among them, functional response curve of A. spinidens in chlorpyrifos treatment was significantly lower than the other treatments. In this study, application of insecticides caused a decrease in the attack rate and an increase in the handling time of exposed bugs compared with the control. The longest handling time (3.97 ± 0.62 and the lowest attack rate (0.023 ± 0.007 were observed in chlorpyrifos and fenitrothion treatments, respectively. The results suggested that the adverse effect of these insecticides on A. spinidens should be considered in integrated pest management programs (IPM.

  14. Mixture and single-substance toxicity of selective serotonin reuptake inhibitors toward algae and crustaceans

    DEFF Research Database (Denmark)

    Christensen, Anne Munch; Faaborg-Andersen, S.; Ingerslev, Flemming

    2007-01-01

    Selective serotonin reuptake inhibitors (SSRIs) are used as antidepressant medications. primarily in the treatment of clinical depression. They are among the pharmaceuticals most often Prescribed in the industrialized countries. Selective serotonin reuptake inhibitors are compounds...... with an identical mechanism of action in mammals (inhibit reuptake of serotonin), and they have been found in different aqeous as well as biological samples collected in the environment. In the present study, we tested the toxicities of five SSRIs (citalopram, fluoxetine, fluoxamine, paroxetine, and sertraline...

  15. Characterization and regulation of (/sup 3/H)-serotonin uptake and release in rodent spinal

    Energy Technology Data Exchange (ETDEWEB)

    Stauderman, K.A.

    1986-01-01

    The uptake and release of (/sup 3/H)-serotonin were investigated in rat spinal cord synaptosomes. In the uptake experiments, sodium-dependent and sodium-independent (/sup 3/H)-serotonin accumulation processes were found. Sodium-dependent (/sup 3/H)-serotonin accumulation was: linear with sodium concentrations up to 180 mM; decreased by disruption of membrane integrity or ionic gradients; associated with purified synaptosomal fractions; and reduced after description of descending serotonergic neurons in the spinal cord. Of the uptake inhibitors tested, the most potent was fluoxetine (IC/sub 50/ 75 nM), followed by desipramine (IC/sub 50/ 430 nM) and nomifensine (IC/sub 50/ 950 nM). The sodium-independent (/sup 3/H)-serotonin accumulation process was insensitive to most treatments and probably represents nonspecific membrane binding. Thus, only sodium-dependent (/sup 3/H)-serotonin uptake represents the uptake process of serotonergic nerve terminals in rat spinal cord homogenates. In the release experiments, K/sup +/-induced release of previously accumulated (/sup 3/H)-serotonin was Ca/sup 2 +/-dependent, and originated from serotonergic synaptosomes. Exogenous serotonin and 5-methyoxy-N,N-dimethyltryptamine inhibited (/sup 3/H)-serotonin release in a concentration-dependent way. Of the antagonists tested, only methiothepin effectively blocked the effect of serotonin. These data support the existence of presynaptic serotonin autoreceptors on serotonergic nerve terminals in the rat spinal cord that act to inhibit a voltage and Ca/sup 2 +/-sensitive process linked to serotonin release. Alteration of spinai cord serotonergic function may therefore be possible by drugs acting on presynaptic serotonin autoreceptors in the spinal cord.

  16. Exocytosis of serotonin from the neuronal soma is sustained by a serotonin and calcium-dependent feedback loop

    Science.gov (United States)

    Leon-Pinzon, Carolina; Cercós, Montserrat G.; Noguez, Paula; Trueta, Citlali; De-Miguel, Francisco F.

    2014-01-01

    The soma of many neurons releases large amounts of transmitter molecules through an exocytosis process that continues for hundreds of seconds after the end of the triggering stimulus. Transmitters released in this way modulate the activity of neurons, glia and blood vessels over vast volumes of the nervous system. Here we studied how somatic exocytosis is maintained for such long periods in the absence of electrical stimulation and transmembrane Ca2+ entry. Somatic exocytosis of serotonin from dense core vesicles could be triggered by a train of 10 action potentials at 20 Hz in Retzius neurons of the leech. However, the same number of action potentials produced at 1 Hz failed to evoke any exocytosis. The 20-Hz train evoked exocytosis through a sequence of intracellular Ca2+ transients, with each transient having a different origin, timing and intracellular distribution. Upon electrical stimulation, transmembrane Ca2+ entry through L-type channels activated Ca2+-induced Ca2+ release. A resulting fast Ca2+ transient evoked an early exocytosis of serotonin from sparse vesicles resting close to the plasma membrane. This Ca2+ transient also triggered the transport of distant clusters of vesicles toward the plasma membrane. Upon exocytosis, the released serotonin activated autoreceptors coupled to phospholipase C, which in turn produced an intracellular Ca2+ increase in the submembrane shell. This localized Ca2+ increase evoked new exocytosis as the vesicles in the clusters arrived gradually at the plasma membrane. In this way, the extracellular serotonin elevated the intracellular Ca2+ and this Ca2+ evoked more exocytosis. The resulting positive feedback loop maintained exocytosis for the following hundreds of seconds until the last vesicles in the clusters fused. Since somatic exocytosis displays similar kinetics in neurons releasing different types of transmitters, the data presented here contributes to understand the cellular basis of paracrine neurotransmission

  17. Serotonin Coordinates Responses to Social Stress—What We Can Learn from Fish

    Directory of Open Access Journals (Sweden)

    Tobias Backström

    2017-10-01

    Full Text Available Social interaction is stressful and subordinate individuals are often subjected to chronic stress, which greatly affects both their behavior and physiology. In teleost fish the social position of an individual may have long-term effects, such as effects on migration, age of sexual maturation or even sex. The brain serotonergic system plays a key role in coordinating autonomic, behavioral and neuroendocrine stress responses. Social subordination results in a chronic activation of the brain serotonergic system an effect, which seems to be central in the subordinate phenotype. However, behavioral effects of short-term acute activation of the serotonergic system are less obvious. As in other vertebrates, divergent stress coping styles, often referred to as proactive and reactive, has been described in teleosts. As demonstrated by selective breeding, stress coping styles appear to be partly heritable. However, teleost fish are characterized by plasticity, stress coping style being affected by social experience. Again, the brain serotonergic system appears to play an important role. Studies comparing brain gene expression of fish of different social rank and/or displaying divergent stress coping styles have identified several novel factors that seem important for controlling aggressive behavior and stress coping, e.g., histamine and hypocretin/orexin. These may also interact with brain monoaminergic systems, including serotonin.

  18. Immune System Activation and Depression: Roles of Serotonin in the Central Nervous System and Periphery.

    Science.gov (United States)

    Robson, Matthew J; Quinlan, Meagan A; Blakely, Randy D

    2017-05-17

    Serotonin (5-hydroxytryptamine, 5-HT) has long been recognized as a key contributor to the regulation of mood and anxiety and is strongly associated with the etiology of major depressive disorder (MDD). Although more known for its roles within the central nervous system (CNS), 5-HT is recognized to modulate several key aspects of immune system function that may contribute to the development of MDD. Copious amounts of research have outlined a connection between alterations in immune system function, inflammation status, and MDD. Supporting this connection, peripheral immune activation results in changes in the function and/or expression of many components of 5-HT signaling that are associated with depressive-like phenotypes. How 5-HT is utilized by the immune system to effect CNS function and ultimately behaviors related to depression is still not well understood. This Review summarizes the evidence that immune system alterations related to depression affect CNS 5-HT signaling that can alter MDD-relevant behaviors and that 5-HT regulates immune system signaling within the CNS and periphery. We suggest that targeting the interrelationships between immune and 5-HT signaling may provide more effective treatments for subsets of those suffering from inflammation-associated MDD.

  19. The association between serotonin-related gene polymorphisms and panic disorder.

    Science.gov (United States)

    Yoon, Ho-Kyoung; Yang, Jong-Chul; Lee, Heon-Jeong; Kim, Yong-Ku

    2008-12-01

    Dysfunction of the serotonergic system has been hypothesized to play an important role in panic disorder. We investigated the 5-HT2A receptor (5HTR2A) and tryptophan hydroxylase (TPH) genes for an association with panic disorder (PD). Patients with PD (n=107) and control subjects (n=161) were genotyped for 5HTR2A 1438A/G, 5HTR2A 102T/C, and TPH218 A/C. The severity of their symptoms was measured using the Spielberger State-Trait Anxiety Inventory (STAI), Panic Disorder Severity Scale (PDSS), Anxiety Sensitivity Index (ASI), Acute Panic Inventory (API), and Hamilton's Rating Scale for Depression (HAMD). There were no significant differences in the genotype distributions or allelic frequencies in the three serotonergic polymorphisms between PD patients and normal controls. However, we found a significant difference in symptom severity among the genotypes of both the 5HTR2A 1438A/G and 102T/C polymorphisms. Although there were no significant differences in the genotype and allele distributions, we found a significant association between panic symptom severity and the serotonin 2A receptor gene. This result suggests that 5HTR2A 1438A/G and 102T/C polymorphic regions can be associated with the phenotype or the pathogenesis of panic disorder.

  20. Face and emotion expression processing and the serotonin transporter polymorphism 5-HTTLPR/rs22531.

    Science.gov (United States)

    Hildebrandt, A; Kiy, A; Reuter, M; Sommer, W; Wilhelm, O

    2016-06-01

    Face cognition, including face identity and facial expression processing, is a crucial component of socio-emotional abilities, characterizing humans as highest developed social beings. However, for these trait domains molecular genetic studies investigating gene-behavior associations based on well-founded phenotype definitions are still rare. We examined the relationship between 5-HTTLPR/rs25531 polymorphisms - related to serotonin-reuptake - and the ability to perceive and recognize faces and emotional expressions in human faces. For this aim we conducted structural equation modeling on data from 230 young adults, obtained by using a comprehensive, multivariate task battery with maximal effort tasks. By additionally modeling fluid intelligence and immediate and delayed memory factors, we aimed to address the discriminant relationships of the 5-HTTLPR/rs25531 polymorphisms with socio-emotional abilities. We found a robust association between the 5-HTTLPR/rs25531 polymorphism and facial emotion perception. Carriers of two long (L) alleles outperformed carriers of one or two S alleles. Weaker associations were present for face identity perception and memory for emotional facial expressions. There was no association between the 5-HTTLPR/rs25531 polymorphism and non-social abilities, demonstrating discriminant validity of the relationships. We discuss the implications and possible neural mechanisms underlying these novel findings. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  1. Serotonin transporter genotype linked to adolescent substance use treatment outcome through externalizing behavior

    Directory of Open Access Journals (Sweden)

    Tammy eChung

    2014-07-01

    Full Text Available Meta-analyses suggest that the serotonin transporter linked polymorphic region (5-HTTLPR short (S allele, relative to the long (L allele, is associated with risk for alcohol dependence, particularly among individuals with early onset antisocial alcoholism. Youth in substance use treatment tend to show antisocial or externalizing behaviors, such as conduct problems, which predict worse treatment outcome. This study examined a pathway in which 5-HTTLPR genotype is associated with externalizing behavior, and the intermediate phenotype of externalizing behavior serves as a link between 5-HTTLPR genotype and substance use treatment outcome in youth. Adolescents (n=142 who were recruited from addictions treatment were genotyped for 5-HTTLPR polymorphisms (S and LG carriers vs. LALA, assessed for externalizing and internalizing behaviors shortly after starting treatment, and followed over 6-months. 5-HTTLPR genotype was not associated with internalizing behaviors, and was not directly associated with 6-month substance use outcomes. However, 5-HTTLPR genotype was associated with externalizing behaviors (S and LG > LALA, and externalizing behaviors predicted alcohol and marijuana problem severity at 6-month follow-up. Results indicated an indirect (p<.05 and non-specific (i.e., both alcohol and marijuana severity effect of 5-HTTLPR genotype on youth substance use treatment outcomes, with externalizing behaviors as an important linking factor. Adolescents in substance use treatment with low expressing (S and LG 5-HTTLPR alleles and externalizing behavior might benefit from intervention that addresses serotonergic functioning, externalizing behaviors, and substance use to improve outcomes.

  2. Serotonin transporter gene polymorphism and treatment response to serotonin reuptake inhibitor (escitalopram) in depression: An open pilot study

    Science.gov (United States)

    Margoob, Mushtaq A.; Mushtaq, Dhuha; Murtza, Imtiyaz; Mushtaq, Huda; Ali, Arif

    2008-01-01

    Background: Blocking of the serotonin transporter is the main mechanism of action of SSRIs; therefore, the gene encoding this protein is a strong candidate for a possible genetic influence on the treatment response. Aim: To evaluate relationship between serotonin transporter gene promoter region polymorphism and the efficacy of SSRI (escitalopram) treatment in depression. Materials and Methods: Fifty-seven consecutive patients with unipolar depressive episode (DSM IV criteria) were genotyped for the SERT gene polymorphism and treated with escitalopram 20 mg/day. Weekly assessment (HAM-D-21) was made for treatment response up to 6 weeks. Results: Significant (P > 0.0001) difference between groups (ll vs. ss or ls) in response to treatment by escitalopram was revealed by our study. However, no difference with respect to age, gender, or onset of illness was observed between genotype subgroups. Conclusion: The study suggests that serotonin transporter gene polymorphism may have an influence on the effectiveness of SSRI treatment in depressive disorders, irrespective of clinical variables. Further controlled studies are required to validate these results PMID:19771307

  3. Down Syndrome: Cognitive Phenotype

    Science.gov (United States)

    Silverman, Wayne

    2007-01-01

    Down syndrome is the most prevalent cause of intellectual impairment associated with a genetic anomaly, in this case, trisomy of chromosome 21. It affects both physical and cognitive development and produces a characteristic phenotype, although affected individuals vary considerably with respect to severity of specific impairments. Studies…

  4. The DFNA10 phenotype.

    NARCIS (Netherlands)

    Leenheer, E. de; Huygen, P.L.M.; Wayne, S.; Smith, R.J.H.; Cremers, C.W.R.J.

    2001-01-01

    We present a detailed analysis of the DFNA10 phenotype based on data from 25 hearing-impaired persons coming from a large American pedigree segregating for deafness at the DFNA10 locus (chromosome 6q22.3-23.2). Cross-sectional analysis of air conduction threshold-on-age data from all available

  5. COPD: Definition and Phenotypes

    DEFF Research Database (Denmark)

    Vestbo, J.

    2014-01-01

    particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. The evolution of this definition and the diagnostic criteria currently in use are discussed. COPD is increasingly divided in subgroups or phenotypes based on specific features and association...

  6. Serotonin induces ecdysteroidogenesis and methyl farnesoate synthesis in the mud crab, Scylla serrata.

    Science.gov (United States)

    Girish, B P; Swetha, C H; Reddy, P Sreenivasula

    2017-09-02

    In the current study, we have examined the role of serotonin in regulating the levels of methyl farnesoate and ecdysteroids in the giant mud crab Scylla serrata and validated that serotonin indeed is a reproductive hormone. Administration of serotonin elevated circulatory levels of methyl farnesoate and ecdysteroids in crabs. Since methyl farnesoate and ecdysteroid act through retinoid X receptor (RXR) and ecdysteroid receptor (EcR) respectively and these receptors are involved in the regulation of reproduction in crustaceans, we have determined the mRNA levels of RXR and EcR in hepatopancreas and ovary after serotonin administration. The expression levels of both RXR and EcR increased significantly in the hepatopancreas and ovary of serotonin injected crabs when compared to the controls. In vitro organ culture studies revealed that incubation of Y-orgas and mandibular organ explants in the presence of serotonin resulted in a significant increase in the secretion of ecdysteroids by Y-organs, but without alterations in MF synthesis in mandibular organs. From the above studies it is evident that serotonin stimulates Y organs resulting in increased ecdysteroidogenesis. Though the circulatory levels methyl farnesoate elevated after serotonin administration, organ culture studies revealed serotonin mediated methyl farnesaote synthesis is indirect probably by inhibiting release of mandibular organ inhibiting hormone from eyestalks. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Cerebral serotonin release correlates with [(11)C]AZ10419369 PET measures of 5-HT1B receptor binding in the pig brain

    DEFF Research Database (Denmark)

    Jørgensen, Louise M; Weikop, Pia; Svarer, Claus

    2017-01-01

    of extracellular serotonin levels with microdialysis after various acute interventions (saline, escitalopram, fenfluramine). The interventions increased the cerebral extracellular serotonin levels to two to six times baseline, with fenfluramine being the most potent pharmacological enhancer of serotonin release...

  8. Phenotypic integration: studying the ecology and evolution of complex phenotypes

    National Research Council Canada - National Science Library

    Pigliucci, Massimo; Preston, Katherine

    2004-01-01

    .... Studying the Plasticity of Phenotypic Integration in a Model Organism, 155 Massimo Pigliucci 8. Integrating Phenotypic Plasticity When Death Is on the Line: Insights from Predator-Prey Systems...

  9. From metabolome to phenotype

    DEFF Research Database (Denmark)

    Khakimov, Bekzod; Rasmussen, Morten Arendt; Kannangara, Rubini Maya

    2017-01-01

    The development of crop varieties tolerant to growth temperature fluctuations and improved nutritional value is crucial due to climate change and global population growth. This study investigated the metabolite patterns of developing barley seed as a function of genotype and growth temperature fo...... their successful application to link genetic and environmental factors with the seed phenotype of unique and agro-economically important barley models for optimal vegetable protein and dietary fibre production....

  10. Amphetamine Action at the Cocaine- and Antidepressant-Sensitive Serotonin Transporter Is Modulated by αCaMKII

    DEFF Research Database (Denmark)

    Steinkellner, Thomas; Montgomery, Therese R; Hofmaier, Tina

    2015-01-01

    Serotonergic neurotransmission is terminated by reuptake of extracellular serotonin (5-HT) by the high-affinity serotonin transporter (SERT). Selective 5-HT reuptake inhibitors (SSRIs) such as fluoxetine or escitalopram inhibit SERT and are currently the principal treatment for depression...

  11. Biochemical and behavioral effects of long-term citalopram administration and discontinuation in rats Role of serotonin synthesis

    NARCIS (Netherlands)

    Bosker, Fokko J.; Tanke, Marit A. C.; Jongsma, Minke E.; Cremers, Thomas I. F. H.; Jagtman, Evelien; Pietersen, Charmaine Y.; van der Hart, Marieke G. C.; Gladkevich, Anatoliy V.; Kema, Ido P.; Westerink, Ben H. C.; Korf, Jakob; den Boer, Johan A.

    2010-01-01

    We have investigated effects of continuous SSRI administration and abrupt discontinuation on biochemical and behavioral indices of rat brain serotonin function and attempted to identify underlying mechanisms Biochemistry of serotonin was assessed with brain tissue assays and microdialysis behavior

  12. Cognitive function is related to fronto-striatal serotonin transporter levels--a brain PET study in young healthy subjects

    DEFF Research Database (Denmark)

    Madsen, Karine; Erritzøe, David Frederik; Mortensen, Erik Lykke

    2011-01-01

    Pharmacological manipulation of serotonergic neurotransmission in healthy volunteers impacts on cognitive test performance. Specifically, markers of serotonin function are associated with attention and executive functioning, long-term memory, and general cognitive ability. The serotonin transporter...

  13. Histological alterations of a combination of Chlorpyrifos and Cypermethrin (Nurocombi insecticide in the fresh water crab, Paratelphusa jacquemontii (Rathbun

    Directory of Open Access Journals (Sweden)

    A. Maharajan

    2015-10-01

    Full Text Available Chlorpyrifos (CPF and Cypermethrin (CPM are toxic and subject to long-term in vivo accumulation in different aquatic species throughout the world. The purpose of the present study was to examine the combined CPF/CPM (Nurocombi exposure on histology in various tissues of Paratelphusa jacquemontii. The crabs were exposed to combined CPF/CPM concentrations of 0.0187 ppm and 0.0374 ppm (sub lethal for 28 days with parallel untreated control. The experimental gill tissue exhibited epithelial lifting, edema, necrosis, fusion of secondary lamellae and hemorrhage. The deceased hepatopancreas revealed infiltration, formation of large lumen and disappearance of haemocytes. The pathologic symptoms like atrophy, necrosis, wavy appearance, accumulation of granular material in between muscle fibers, fragmentation, loss of muscle structure, appearance of basophilic deposits were displayed in the muscle tissue. The vas deferens showed remarkable epithelial vacuolar degeneration, irregular appearance of spermatophore matrix associated with reduction in the number of spermatophores and dehiscence of most of the spermatophores. It is concluded that histological biomarkers provide reliable and discriminatory data to augment pesticide pollution and therefore, long-term monitoring is necessary to assess the eco-health of the mangrove system.

  14. Changes in Composition and Function of Human Intestinal Microbiota Exposed to Chlorpyrifos in Oil as Assessed by the SHIME® Model

    Directory of Open Access Journals (Sweden)

    Julie Reygner

    2016-11-01

    Full Text Available The presence of pesticide residues in food is a public health problem. Exposure to these substances in daily life could have serious effects on the intestine—the first organ to come into contact with food contaminants. The present study investigated the impact of a low dose (1 mg/day in oil of the pesticide chlorpyrifos (CPF on the community structure, diversity and metabolic response of the human gut microbiota using the SHIME® model (six reactors, representing the different parts of the gastrointestinal tract. The last three reactors (representing the colon were inoculated with a mixture of feces from human adults. Three time points were studied: immediately before the first dose of CPF, and then after 15 and 30 days of CPF-oil administration. By using conventional bacterial culture and molecular biology methods, we showed that CPF in oil can affect the gut microbiota. It had the greatest effects on counts of culturable bacteria (with an increase in Enterobacteria, Bacteroides spp. and clostridia counts, and a decrease in bifidobacterial counts and fermentative activity, which were colon-segment-dependent. Our results suggest that: (i CPF in oil treatment affects the gut microbiota (although there was some discordance between the culture-dependent and culture-independent analyses; (ii the changes are “SHIME®-compartment” specific; and (iii the changes are associated with minor alterations in the production of short-chain fatty acids and lactate.

  15. Fish larval recruitment to reefs is a thyroid hormone-mediated metamorphosis sensitive to the pesticide chlorpyrifos

    Science.gov (United States)

    Lambert, Anne; François, Loïc; Barth, Paul; Gillet, Benjamin; Hughes, Sandrine; Piganeau, Gwenaël; Leulier, Francois; Viriot, Laurent

    2017-01-01

    Larval recruitment, the transition of pelagic larvae into reef-associated juveniles, is a critical step for the resilience of marine fish populations but its molecular control is unknown. Here, we investigate whether thyroid-hormones (TH) and their receptors (TR) coordinate the larval recruitment of the coral-reef-fish Acanthurus triostegus. We demonstrate an increase of TH-levels and TR-expressions in pelagic-larvae, followed by a decrease in recruiting juveniles. We generalize these observations in four other coral reef-fish species. Treatments with TH or TR-antagonist, as well as relocation to the open-ocean, disturb A. triostegus larvae transformation and grazing activity. Likewise, chlorpyrifos, a pesticide often encountered in coral-reefs, impairs A. triostegus TH-levels, transformation, and grazing activity, hence diminishing this herbivore’s ability to control the spread of reef-algae. Larval recruitment therefore corresponds to a TH-controlled metamorphosis, sensitive to endocrine disruption. This provides a framework to understand how larval recruitment, critical to reef-ecosystems maintenance, is altered by anthropogenic stressors. PMID:29083300

  16. Chlorpyrifos Induces the Expression of the Epstein-Barr Virus Lytic Cycle Activator BZLF-1 via Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Ling Zhao

    2015-01-01

    Full Text Available Organophosphate pesticides (OPs are among the most widely used synthetic chemicals for the control of a wide variety of pests, and reactive oxygen species (ROS caused by OPs may be involved in the toxicity of various pesticides. Previous studies have demonstrated that a reactivation of latent Epstein-Barr virus (EBV could be induced by oxidative stress. In this study, we investigated whether OPs could reactivate EBV through ROS accumulation. The Raji cells were treated with chlorpyrifos (CPF, one of the most commonly used OPs. Oxidative stress indicators and the expression of the EBV immediate-early gene BZLF-1 were determined after CPF treatment. Our results show that CPF induces oxidative stress as evidenced by decreased malondialdehyde (MDA level, accompanied by an increase in ROS production, DNA damage, glutathione (GSH level, and superoxide dismutase (SOD and catalase (CAT activity. Moreover, CPF treatment significantly enhances the expression of BZLF-1, and the increased BZLF-1 expression was ameliorated by N-acetylcysteine (NAC incubation. These results suggest that OPs could contribute to the reactivation of the EBV lytic cycle through ROS induction, a process that may play an important role in the development of EBV-associated diseases.

  17. Chlorpyrifos Exposure During Perinatal Period Affects Intestinal Microbiota Associated With Delay of Maturation of Digestive Tract in Rats.

    Science.gov (United States)

    Joly Condette, Claire; Bach, Véronique; Mayeur, Camille; Gay-Quéheillard, Jérôme; Khorsi-Cauet, Hafida

    2015-07-01

    Pesticide exposure via residues in food may be especially harmful when it takes place in the developing child. The present study was designed to assess the impact of perinatal exposure to chlorpyrifos (CPF, an insecticide known to cross the placental barrier). Female rats were exposed to oral CPF (1 or 5 mg kg day vs vehicle controls) from gestation onset up to weaning of the pups that were individually gavaged (CPF or vehicle) thereafter. Two developmental time points were studied: weaning (day 21) and adulthood (day 60). After sacrifice, samples from the intestinal tract and other organs underwent microbiological and histological analyses. Rat pups exposed to 5 mg kg day CPF were both significantly smaller (body length) and lighter than controls. Exposure to CPF was associated with changes in the histological structures (shorter and thinner intestinal villosities), an intestinal microbial dysbiosis, and increased bacterial translocation in the spleen and liver. These significant microbial changes in the gut were associated with impaired epithelium protection (mucin-2) and microbial pattern recognition receptor (Toll-like 2 and 4) gene expression. Exposure to CPF during gestation and development affected the pups' intestinal development, with morphological alteration of the structures involved in nutrient absorption, intestinal microbial dysbiosis, alteration of mucosal barrier (mucin-2), stimulation of the innate immune system, and increased bacterial translocation. Perinatal exposure to CPF may therefore have short- and long-term impacts on the digestive tract.

  18. Pro- and anti-inflammatory cytokine expression in immune organs of the common carp exposed to atrazine and chlorpyrifos.

    Science.gov (United States)

    Chen, Dechun; Zhang, Ziwei; Yao, Haidong; Cao, Ye; Xing, Houjuan; Xu, Shiwen

    2014-09-01

    Atrazine (ATR) and chlorpyrifos (CPF) are toxic and subject to long-term in vivo accumulation in different aquatic species throughout the world. The purpose of the present study was to examine the effect of ATR, CPF and combined ATR/CPF exposure on cytokines in the head kidney and spleen of common carp (Cyprinus carpio L.). The carp were sampled after a 40-d exposure to CPF and ATR, individually or in combination, followed by a 40-d recovery to measure the mRNA expression of IL-6fam (IL-6), IL-8, TNF-α, IL-10 and TGF-β1 (TGF-β) in the head kidney and spleen tissues. These results showed that the expression of cytokines IL-6, IL-8 and TNF-α in the head kidney and spleen was upregulated following ATR, CPF and mixed ATR/CPF exposure compared with the control group. The expression of IL-10 and TGF-β mRNA was significantly inhibited in both head kidney and spleen of carp exposed to ATR, CPF and the ATR/CPF mixture. The results suggested that long-term exposure of ATR, CPF and the ATR/CPF mixture in aquatic environments can induce the dysregulation of pro-/anti-inflammatory cytokine expression. The information regarding the effects of ATR and CPF on cytokine mRNA expression generated in this study will be important information for pesticides toxicology evaluation. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. The effect of HMGB1 on sub-toxic chlorpyrifos exposure-induced neuroinflammation in amygdala of neonatal rats.

    Science.gov (United States)

    Tian, Jing; Dai, Hongmei; Deng, Yuanying; Zhang, Jie; Li, Ying; Zhou, Jun; Zhao, Mingyi; Zhao, Mengwen; Zhang, Chen; Zhang, Yuxi; Wang, Peipei; Bing, Guoying; Zhao, Lingling

    2015-12-02

    Chlorpyrifos (CPF), one of organophosphorus pesticides (OPs), is associated with developmental neurotoxicity. Inflammatory response is closely related with CPF-induced neurotoxicity. The present study aimed at exploring whether sub-toxic CPF exposure on neonatal rats results in neuroinflammation that mediated by HMGB1/TLR4/NF-κB signaling pathway in the amygdala. The neonatal rats were subcutaneously injected with 5mg/kg CPF for 4 consecutive days (postnatal day 11-14) with or without HMGB1 inhibitor, glycyrrhizin. We assessed the levels of pro-inflammatory cytokines at 12, 24, and 72 h after CPF exposure. The role of HMGB1 on neuroinflammation in sub-toxic exposure during brain development was studied. CPF-treated neonatal rats exhibited a significant increase in the expression of pro-inflammatory cytokines, such as IL-6, TNF-α and HMGB1, and a significant increase in the activation of NF-κB in the amygdala after CPF exposure. Inhibited HMGB1 reduced the release of IL-6 and TNF-α, and inhibited activation of NF-κB. Our findings indicate that CPF exposure on developmental brain might induce the activation of neuroinflammation mediated by HMGB1/TLR4/NF-κB pathway in the amygdala. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  20. Tissue distribution, isozyme abundance and sensitivity to chlorpyrifos-oxon of carboxylesterases in the earthworm Lumbricus terrestris

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez-Hernandez, Juan C. [Laboratory of Ecotoxicology, Faculty of Environmental Science, University of Castilla-La Mancha, Avda. Carlos III, 45071 Toledo (Spain)], E-mail: juancarlos.sanchez@uclm.es; Wheelock, Craig E. [Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 171 77, Stockholm (Sweden)

    2009-01-15

    A laboratory-based study was conducted to determine the basal carboxylesterase (CbE) activity in different tissues of the earthworm Lumbricus terrestris, and its sensitivity to the organophosphate (OP) pesticide chlorpyrifos-oxon (CPx). Carboxylesterase activity was found in the pharynx, crop, gizzard, anterior intestine, wall muscle and reproductive tissues of L. terrestris, and multiple tissue-specific isozymes were observed by native gel electrophoresis. Esterase activity and sensitivity to CPx inhibition varied on a tissue- and substrate-specific basis, suggesting isoforms-specific selectivity to OP-mediated inhibition. Three practical issues are recommended for the use of earthworm CbE activity as a biomarker of pesticide exposure: (i) CbE should be measured using several routine substrates, (ii) it should be determined in selected tissues instead of whole organism homogenate, and (iii) earthworm CbE activity should be used in conjuncture with other common biomarkers (e.g., ChE) within a multibiomarker approach to assess field exposure of OPs, and potentially other agrochemicals. - The measurement of carboxylesterase inhibition in earthworm is a sensitive and complementary biomarker of pesticide exposure.

  1. Investigation of in vitro effects of ethephon and chlorpyrifos, either alone or in combination, on rat intestinal muscle contraction

    Science.gov (United States)

    Çetinkaya, Mustafa Alp; Baydan, Emine

    2010-01-01

    A range of pesticides is widely used in pest management and the chances of exposure to multiple organophosphorus (OP) compounds simultaneously are high, especially from dietary and other sources. Although health hazards of individual OP insecticides have been relatively well characterized, there is lesser information on the interactive toxicity of multiple OP insecticides. The aim of this study is to elicit the possible interactions in case combined exposure of an OP pesticide chlorpyrifos (CPF) and a plant growth regulator ethephon (ETF) which are used worldwide. The ileum segments of 3 months old Wistar Albino male rats were used in isolated organ bath containing Tyrode solution. ETF and CPF were incubated (10−7 M concentration) separately or in combination with each other to ileum and their effects on acetylcholine-induced contractions were studied. The data obtained from this study show that, single and combined exposure to the agents caused agonistic interactions with regard to potency of ACh whereas they caused a decrease on Emax value of ACh. These findings suggest that exposure to these agents which have direct and indirect cholinergic effects, may cause developing clinical responses with small doses and earlier but the extent of toxicity will be lower. PMID:21217869

  2. Differential sensitivity of barley (Hordeum vulgare L.) to chlorpyrifos and propiconazole: Morphology, cytogenetic assay and photosynthetic pigments.

    Science.gov (United States)

    Dubey, Pragyan; Mishra, Amit Kumar; Shukla, Pratiksha; Singh, Ashok Kumar

    2015-10-01

    The present investigation was performed to evaluate the effects of an insecticide and fungicide, namely, chlorpyrifos (CP) and propiconazole (PZ) on barley (Hordeum vulgare L. variety Karan-16). The seeds were treated with three concentrations of CP and PZ, i.e., 0.05%, 0.1% and 0.5% for 6 hours after different pre-soaking durations of 7, 17 and 27 hours. Different pre-soaking durations (7, 17 and 27 h) represent three phases of the cell cycle i.e., G1, S and G2, respectively. Double distilled water and ethyl methane sulfonate were used as negative and positive controls, respectively. As compared to their respective controls, treated root tip meristematic cells of barley showed significant reductions in the germination percentage, seedling height, mitotic index and comparative increase in chromosomal aberrations against both the pesticides, and the magnitude was higher in CP. After treatment with the pesticides, chlorophyll and carotenoid contents increased up to 0.1% but reduced at 0.5% and the decrease was more prominent in CP as compared to PZ. In treated cells, fragmentation, stickiness, bridges, multipolar anaphase and diagonal anaphase were observed as aberrations. As compared to control, chromosomal aberrations were higher in CP as compared to PZ. The results of the present study concluded that CP induced chromosomal aberrations were more frequent than PZ; hence it has higher probability to cause genotoxicity in barley. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. A Review of Vilazodone, Serotonin, and Major Depressive Disorder

    Science.gov (United States)

    Thase, Michael E.

    2014-01-01

    Objective: To review the mechanism of selective serotonin reuptake inhibitor (SSRI)–mediated serotonergic neurotransmission, focusing on serotonin 1A (5-HT1A) autoreceptors, which are proposed to be involved in delaying therapeutic efficacy. Vilazodone was specifically designed to function both as an SSRI and a partial agonist at 5-HT1A receptors. This combined mechanism is proposed to decrease time to efficacy, minimize sexual side effects, and provide concomitant anxiolytic properties. Data Sources: A PubMed search of all English-language articles from January 1990 to January 2013 was conducted using the search terms depression and 5-HT1A, depression and buspirone, depression and pindolol, and vilazodone. Study Selection: We found 47 articles and abstracts that were selected for inclusion on the basis of information about the pharmacology of 5-HT1A receptors and the clinical data on pindolol, buspirone, and vilazodone in depression. Data Extraction: This review summarizes current literature involving antidepressant activity, the role of 5-HT1A autoreceptors, and clinical trials involving serotonin reuptake inhibition in conjunction with 5-HT1A agonists and partial agonists, with a focus on vilazodone. Results:Vilazodone has demonstrated efficacy in 2 large, randomized, double-blind, placebo-controlled trials in major depressive disorder. Results suggest that vilazodone has a low incidence of sexual side effects and is effective in patients with high levels of anxiety. A pooled analysis shows evidence of significant symptom reduction after only 1 week of therapy. Conclusions: If future studies corroborate the clinical benefits attributed to its mechanism of action, vilazodone may show potential advantages in terms of onset of action, sexual side effects, and anxiolytic activity in patients with major depressive disorder. PMID:24940527

  4. Serotonin and brain function: a tale of two receptors

    Science.gov (United States)

    Carhart-Harris, RL; Nutt, DJ

    2017-01-01

    Previous attempts to identify a unified theory of brain serotonin function have largely failed to achieve consensus. In this present synthesis, we integrate previous perspectives with new and older data to create a novel bipartite model centred on the view that serotonin neurotransmission enhances two distinct adaptive responses to adversity, mediated in large part by its two most prevalent and researched brain receptors: the 5-HT1A and 5-HT2A receptors. We propose that passive coping (i.e. tolerating a source of stress) is mediated by postsynaptic 5-HT1AR signalling and characterised by stress moderation. Conversely, we argue that active coping (i.e. actively addressing a source of stress) is mediated by 5-HT2AR signalling and characterised by enhanced plasticity (defined as capacity for change). We propose that 5-HT1AR-mediated stress moderation may be the brain’s default response to adversity but that an improved ability to change one’s situation and/or relationship to it via 5-HT2AR-mediated plasticity may also be important – and increasingly so as the level of adversity reaches a critical point. We propose that the 5-HT1AR pathway is enhanced by conventional 5-HT reuptake blocking antidepressants such as the selective serotonin reuptake inhibitors (SSRIs), whereas the 5-HT2AR pathway is enhanced by 5-HT2AR-agonist psychedelics. This bipartite model purports to explain how different drugs (SSRIs and psychedelics) that modulate the serotonergic system in different ways, can achieve complementary adaptive and potentially therapeutic outcomes. PMID:28858536

  5. Serotonin noradrenaline reuptake inhibitors: Logical evolution of antidepressant development.

    Science.gov (United States)

    Montgomery, Stuart

    2006-01-01

    Although considerable progress has been made in improving the tolerability of antidepressant drugs, the classical tricyclic antidepressants (TCA) are still a standard for efficacy. The selective serotonin reuptake inhibitors (SSRI) are much better tolerated than the TCAs, but their antidepressant efficacy is, at best, equivalent and probably inferior to the TCA, clomipramine, in many situations. The introduction of the SSRIs naturally focussed both fundamental and clinical research effort on the role of serotonin (5-HT) in the pharmacogenesis and pharmacotherapy of depression. More recently the probable role of noradrenaline (NA) has been "rediscovered" and increasingly both 5-HT and NA dysfunctions are seen as fundamental to depressive illness. The therapeutic importance of this has been underlined by studies showing the increased antidepressant efficacy obtained when selective serotonergic drugs have been used in conjunction with selective noradrenergic drugs. The development of the new class of serotonin and noradrenaline reuptake inhibitors (SNRI) was a logical extension of these ideas. Compounds of this class, which currently comprises venlafaxine, milnacipran and duloxetine, act to inhibit the reuptake of both monoamines with no direct actions at postsynaptic receptors. Although, by definition all three SNRIs have actions on both 5-HT and NA neurotransmission, they do not all have equal potency for both transmitters. Venlafaxine has a 30-fold higher affinity for 5-HT than NA while duloxetine has a 10-fold selectivity for 5-HT. Only milnacipran is balanced between the two neurotransmitters with an approximately equal potency for the inhibition of reuptake of 5-HT and NA both in vitro and in vivo. At high doses venlafaxine and duloxetine appear to be superior to SSRIs but not at lower doses. Duloxetine is, however, not licensed in the EU at these higher doses. Milnacipran at usual doses appears more effective than SSRIs with efficacy which is similar to TCAs

  6. Looking on the bright side of serotonin transporter gene variation.

    Science.gov (United States)

    Homberg, Judith R; Lesch, Klaus-Peter

    2011-03-15

    Converging evidence indicates an association of the short (s), low-expressing variant of the repeat length polymorphism, serotonin transporter-linked polymorphic region (5-HTTLPR), in the human serotonin transporter gene (5-HTT, SERT, SLC6A4) with anxiety-related traits and increased risk for depression in interaction with psychosocial adversity across the life span. However, genetically driven deficient serotonin transporter (5-HTT) function would not have been maintained throughout evolution if it only exerted negative effects without conveying any gain of function. Here, we review recent findings that humans and nonhuman primates carrying the s variant of the 5-HTTLPR outperform subjects carrying the long allele in an array of cognitive tasks and show increased social conformity. In addition, studies in 5-HTT knockout rodents are included that provide complementary insights in the beneficial effects of the 5-HTTLPR s-allele. We postulate that hypervigilance, mediated by hyperactivity in corticolimbic structures, may be the common denominator in the anxiety-related traits and (social) cognitive superiority of s-allele carriers and that environmental conditions determine whether a response will turn out to be negative (emotional) or positive (cognitive, in conformity with the social group). Taken together, these findings urge for a conceptual change in the current deficit-oriented connotation of the 5-HTTLPR variants. In fact, these factors may counterbalance or completely offset the negative consequences of the anxiety-related traits. This notion may not only explain the modest effect size of the 5-HTTLPR and inconsistent reports but may also lead to a more refined appreciation of allelic variation in 5-HTT function. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  7. High brain serotonin levels in migraine between attacks

    DEFF Research Database (Denmark)

    Deen, Marie; Hansen, Hanne D.; Hougaard, Anders

    2017-01-01

    Objectives To investigate brain 5-HT4-receptor binding with positron emission tomography (PET) as a proxy of serotonin (5-hydroxytryptamine, 5-HT) levels in migraine patients between attacks. Methods Brain 5-HT4-receptor binding, assessed with PET imaging of the specific 5-HT4-receptor radioligand...... episodically high brain 5-HT-level. Our finding is in apparent contrast with the longstanding hypothesis of migraine being a syndrome of chronic low brain 5-HT-levels. We were unable to demonstrate any associations with attack frequency or years with migraine. This suggests that high brain 5-HT-levels may...

  8. Increased plasma serotonin in complex regional pain syndrome type 1

    OpenAIRE

    Wesseldijk, Feikje; Fekkes, Durk; Huygen, Frank; Bogaerts-Taal, Elly; Zijlstra, Freek

    2008-01-01

    textabstractBACKGROUND: In patients with complex regional pain syndrome type 1 (CRPS1), some improvement can be achieved by the administration of ketanserin, a 5-HT2A receptor antagonist. We measured plasma levels of serotonin (5-HT) during CRPS1 and correlated these levels with disease characteristics. METHODS: Plasma 5-HT was measured in 35 patients who had CRPS1 for 3 yr and compared with 35 age-matched healthy controls. RESULTS: The plasma 5-HT levels were 411 ± 263 nmol/L and 29 ± 18 nmo...

  9. [Selective serotonine reuptake inhibitors (SSRI) in the treatment of paraphilia].

    Science.gov (United States)

    Kraus, C; Strohm, K; Hill, A; Habermann, N; Berner, W; Briken, P

    2007-06-01

    For about 15 years selective serotonine reuptake inhibitors (SSRI) have been used in the treatment of paraphilias. In an open, uncontrolled, retrospective study, which was the first in the German speaking countries we investigated 16 male outpatients, who have been treated for different paraphilias with SSRI and psychotherapy. There was a marked reduction in paraphilic symptoms. Despite high rates of sexual side effects most patients reported a high overall treatment satisfaction. SSRI are an important addition in pharmacological treatment of paraphilic patients, especially with a risk of so called "hands-off" delinquency.

  10. Serotonin transporter gene (5-HTT) polymorphisms and compulsive buying.

    Science.gov (United States)

    Devor, E J; Magee, H J; Dill-Devor, R M; Gabel, J; Black, D W

    1999-04-16

    We examined a panel of 21 patients diagnosed with compulsive buying for two DNA sequence polymorphisms found in the gene that encodes the serotonin transport (5-HTT). One polymorphism, found in the promoter region of the 5-HTT gene, involves a 44-base pair (bp) deletion, and the other, found in the second intron, is due to variable numbers of a repeat sequence. We also typed a panel of 38 psychiatrically normal controls for both 5-HH markers. When compared to this control panel, no significant differences were seen for either 5-HTT marker among the compulsive buyers.

  11. Serotonin Syndrome Due to Overdose Intake of SSRI

    Directory of Open Access Journals (Sweden)

    Yavuz Orak

    2015-08-01

    Full Text Available Serotonin syndrome is a drug side effect resulting from serotonergic hyperactivity. The severity of its symptoms can be mild and overlooked and sometimes it may cause life-threatening serious consequences. This syndrome is caused by the administration of one or more drugs having serotonergic activity. This case is a 25-year-old female patient who attempted suicide by ingesting an overdose of her prescription medications: 60 units of 100-mg Faver (Fluvoxamine, 20 units of 50-mg Setral (Setraline, and 10 units of 20-mg Paxil (Paroxetine.

  12. Binding-Induced Fluorescence of Serotonin Transporter Ligands

    DEFF Research Database (Denmark)

    Wilson, James; Ladefoged, Lucy Kate; Babinchak, Michael

    2014-01-01

    The binding-induced fluorescence of 4-(4-(dimethylamino)-phenyl)-1-methylpyridinium (APP(+)) and two new serotonin transporter (SERT)-binding fluorescent analogues, 1-butyl-4-[4-(1-dimethylamino)phenyl]-pyridinium bromide (BPP(+)) and 1-methyl-4-[4-(1-piperidinyl)phenyl]-pyridinium (PPP(+)), has...... calculations reveal that the probes are able to access the nonpolar and conformationally restrictive binding pocket of SERT. As a result, the probes exhibit previously not identified binding-induced turn-on emission that is spectroscopically distinct from dyes that have accumulated intracellularly. Thus......, binding and transport dynamics of SERT ligands can be resolved both spatially and spectroscopically....

  13. Effects of early serotonin programming on behavior and central monoamine concentrations in an avian model

    Science.gov (United States)

    Serotonin (5-HT) acts as a neurogenic compound in the developing brain; however serotonin altering drugs such as SSRIs are often prescribed to pregnant and lactating mothers. Early agonism of 5-HT receptors could alter the development of serotonergic circuitry, altering neurotransmission and behavio...

  14. Blood levels of serotonin are differentially affected by romantic love in men and women

    NARCIS (Netherlands)

    S.J.E. Langeslag (Sandra); F.M. van der Veen (Frederik); D. Fekkes (Durk)

    2012-01-01

    textabstractPeople who are in love think about their beloved the whole day, which is supposed to be associated with serotonin. The research questions were how peripheral serotonin levels differ between individuals that are in love compared to individuals that are not in love, and how these levels

  15. Loss of serotonin 2A receptors exceeds loss of serotonergic projections in early Alzheimer's disease

    DEFF Research Database (Denmark)

    Marner, Lisbeth; Frøkjær, Vibe; Kalbitzer, Jan

    2012-01-01

    In patients with Alzheimer's disease (AD), postmortem and imaging studies have revealed early and prominent reductions in cerebral serotonin 2A (5-HT(2A)) receptors. To establish if this was due to a selective disease process of the serotonin system, we investigated the cerebral 5-HT(2A) receptor...

  16. Serotonin markers show altered transcription levels in an experimental pig model of mitral regurgitation

    DEFF Research Database (Denmark)

    Cremer, Signe Emilie; Zois, Nora Elisabeth; Moesgaard, S. G.

    2015-01-01

    Serotonin (5-hydroxytryptamine, 5-HT) signalling is implicated in the pathogenesis of myxomatous mitral valve disease (MMVD) through 5-HT1B receptor (R), 5-HT2AR and 5-HT2BR-induced myxomatous pathology. Based on increased tryptophan hydroxylase-1 (TPH-1) and decreased serotonin re-uptake transpo...

  17. Ligand induced conformational changes of the human serotonin transporter revealed by molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Heidi Koldsø

    Full Text Available The competitive inhibitor cocaine and the non-competitive inhibitor ibogaine induce different conformational states of the human serotonin transporter. It has been shown from accessibility experiments that cocaine mainly induces an outward-facing conformation, while the non-competitive inhibitor ibogaine, and its active metabolite noribogaine, have been proposed to induce an inward-facing conformation of the human serotonin transporter similar to what has been observed for the endogenous substrate, serotonin. The ligand induced conformational changes within the human serotonin transporter caused by these three different types of ligands, substrate, non-competitive and competitive inhibitors, are studied from multiple atomistic molecular dynamics simulations initiated from a homology model of the human serotonin transporter. The results reveal that diverse conformations of the human serotonin transporter are captured from the molecular dynamics simulations depending on the type of the ligand bound. The inward-facing conformation of the human serotonin transporter is reached with noribogaine bound, and this state resembles a previously identified inward-facing conformation of the human serotonin transporter obtained from molecular dynamics simulation with bound substrate, but also a recently published inward-facing conformation of a bacterial homolog, the leucine transporter from Aquifex Aoelicus. The differences observed in ligand induced behavior are found to originate from different interaction patterns between the ligands and the protein. Such atomic-level understanding of how an inhibitor can dictate the conformational response of a transporter by ligand binding may be of great importance for future drug design.

  18. Serotonin transporter gene polymorphisms in Southwestern Iranian patients with irritable bowel syndrome.

    Science.gov (United States)

    Farjadian, Shirin; Fakhraei, Bahareh; Moeini, Maryam; Nasiri, Mahboubeh; Fattahi, Mohammad Reza

    2013-06-01

    Irritable bowel syndrome is a common chronic functional gastrointestinal disorder of unknown etiology. Serotonin is an important factor in sensory signaling in the brain-gut axis, which plays a key role in intestinal motility and secretion. Serotonin clearance is mediated by a specific protein called the serotonin reuptake transporter. Transcription activity of the serotonin transporter gene is affected by some polymorphisms in this gene. The aim of this study was to investigate the relationship between serotonin transporter gene polymorphisms and irritable bowel syndrome. The 5-HTTLPR, rs25531 and STin2VNTR polymorphisms of the serotonin transporter gene were analyzed by PCR-based methods in 50 patients with irritable bowel syndrome and 100 healthy controls. Serotonin transporter polymorphisms were similar in patients and healthy controls. There were no significant differences in allele or genotype frequencies between the two groups. Our findings suggest that polymorphisms in the gene encoding for the serotonin transporter are not associated with irritable bowel syndrome. Interactions between environmental factors and predisposing genetic factors are important in the pathophysiology of irritable bowel syndrome, and further genetic and epigenetic research may provide novel insights into the mechanisms contributing to this disease. Copyright © 2013 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All rights reserved.

  19. Prenatal exposure to selective serotonin reuptake inhibitors and childhood overweight at 7 years of age

    DEFF Research Database (Denmark)

    Grzeskowiak, Luke E; Gilbert, Andrew L; Sørensen, Thorkild

    2013-01-01

    To investigate a possible association between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and childhood overweight at 7 years of age.......To investigate a possible association between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and childhood overweight at 7 years of age....

  20. Common variants in the gene for the serotonin receptor 6 (HTR6) do ...

    Indian Academy of Sciences (India)

    We selected HTR6 (serotonin receptor 6) as a candidate gene to test for associations with obesity since earlier studies have shown that mice with a disrupted serotonin receptor are less prone to become obese on a high-fat diet. We genotyped three tagSNPs (rs6658108, rs6699866 and rs9659997) and included one ...

  1. Nutrient-induced glucagon like peptide-1 release is modulated by serotonin

    NARCIS (Netherlands)

    Ripken, Dina; Wielen, van der Nikkie; Wortelboer, Heleen M.; Meijerink, Jocelijn; Witkamp, Renger F.; Hendriks, Henk F.J.

    2016-01-01

    Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis

  2. FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin

    Science.gov (United States)

    Kode, Aruna; Mosialou, Ioanna; Silva, Barbara C.; Rached, Marie-Therese; Zhou, Bin; Wang, Ji; Townes, Tim M.; Hen, Rene; DePinho, Ronald A.; Guo, X. Edward; Kousteni, Stavroula

    2012-01-01

    Serotonin is a critical regulator of bone mass, fulfilling different functions depending on its site of synthesis. Brain-derived serotonin promotes osteoblast proliferation, whereas duodenal-derived serotonin suppresses it. To understand the molecular mechanisms of duodenal-derived serotonin action on osteoblasts, we explored its transcriptional mediation in mice. We found that the transcription factor FOXO1 is a crucial determinant of the effects of duodenum-derived serotonin on bone formation We identified two key FOXO1 complexes in osteoblasts, one with the transcription factor cAMP-responsive element–binding protein 1 (CREB) and another with activating transcription factor 4 (ATF4). Under normal levels of circulating serotonin, the proliferative activity of FOXO1 was promoted by a balance between its interaction with CREB and ATF4. However, high circulating serotonin levels prevented the association of FOXO1 with CREB, resulting in suppressed osteoblast proliferation. These observations identify FOXO1 as the molecular node of an intricate transcriptional machinery that confers the signal of duodenal-derived serotonin to inhibit bone formation. PMID:22945629

  3. Nutrient-induced glucagon like peptide-1 release is modulated by serotonin

    NARCIS (Netherlands)

    Ripken, D.; Wielen, N. van der; Wortelboer, H.M.; Meijerink, J.; Witkamp, R.F.; Hendriks, H.F.J.

    2016-01-01

    Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis

  4. Activation of serotonin receptors promotes microglial injury-induced motility but attenuates phagocytic activity

    NARCIS (Netherlands)

    Krabbe, Grietje; Matyash, Vitali; Pannasch, Ulrike; Mamer, Lauren; Boddeke, Hendrikus W. G. M.; Kettenmann, Helmut

    Microglia, the brain immune cell, express several neurotransmitter receptors which modulate microglial functions. In this project we studied the impact of serotonin receptor activation on distinct microglial properties as serotonin deficiency not only has been linked to a number of psychiatric

  5. Differences in sexual behaviour in male and female rodents: role of serotonin

    NARCIS (Netherlands)

    Olivier, B.; Chan, J.S.; Snoeren, E.M.; Olivier, J.D.A.; Veening, J.G.; Vinkers, C.H.; Waldinger, M.D.; Oosting, R.S.

    2011-01-01

    Serotonin plays an important role in both male and female sexual behaviour. In general, reduction of 5-HT function facilitates, whereas enhancement inhibits sexual behaviour. Most fundamental research on the involvement of 5-HT in sex has been performed in rats. Selective serotonin reuptake

  6. Augmentation of SSRI effects on serotonin by 5-HT2C antagonists : Mechanistic studies

    NARCIS (Netherlands)

    Cremers, Thomas I. F. H.; Rea, Kieran; Bosker, Fokko J.; Wikstrom, Hakan V.; Hogg, Sandra; Mork, Arne; Westerink, Ben H. C.

    The treatment of depression may be improved by using an augmentation approach involving selective serotonin reuptake inhibitors (SSRIs) in combination with compounds that focus on antagonism of inhibitory serotonin receptors. Using microdialysis coupled to HPLC, it has recently been shown that the

  7. Serotonin is critical for rewarded olfactory short-term memory in Drosophila.

    Science.gov (United States)

    Sitaraman, Divya; LaFerriere, Holly; Birman, Serge; Zars, Troy

    2012-06-01

    The biogenic amines dopamine, octopamine, and serotonin are critical in establishing normal memories. A common view for the amines in insect memory performance has emerged in which dopamine and octopamine are largely responsible for aversive and appetitive memories. Examination of the function of serotonin begins to challenge the notion of one amine type per memory because altering serotonin function also reduces aversive olfactory memory and place memory levels. Could the function of serotonin be restricted to the aversive domain, suggesting a more specific dopamine/serotonin system interaction? The function of the serotonergic system in appetitive olfactory memory was examined. By targeting the tetanus toxin light chain (TNT) and the human inwardly rectifying potassium channel (Kir2.1) to the serotonin neurons with two different GAL4 driver combinations, the serotonergic system was inhibited. Additional use of the GAL80(ts1) system to control expression of transgenes to the adult stage of the life cycle addressed a potential developmental role of serotonin in appetitive memory. Reduction in appetitive olfactory memory performance in flies with these transgenic manipulations, without altering control behaviors, showed that the serotonergic system is also required for normal appetitive memory. Thus, serotonin appears to have a more general role in Drosophila memory, and implies an interaction with both the dopaminergic and octopaminergic systems.

  8. Association of central serotonin transporter availability and body mass index in healthy Europeans

    DEFF Research Database (Denmark)

    Hesse, Swen; van de Giessen, Elsmarieke; Zientek, Franziska

    2014-01-01

    UNLABELLED: Serotonin-mediated mechanisms, in particular via the serotonin transporter (SERT), are thought to have an effect on food intake and play an important role in the pathophysiology of obesity. However, imaging studies that examined the correlation between body mass index (BMI) and SERT a...

  9. Niacin (Vitamin B-3) Supplementation in Patients with Serotonin-Producing Neuroendocrine Tumor

    NARCIS (Netherlands)

    Bouma, Grietje; van Faassen, Martijn; Kats-Ugurlu, Gursah; Vries, de Elisabeth G. E.; Kema, Ido P.; Walenkamp, Annemiek M. E.

    2016-01-01

    BACKGROUND/AIMS: Tryptophan is the precursor of serotonin and niacin (vitamin B3). The latter is critical for normal cellular metabolism. Tryptophan and niacin can be deficient in patients with serotonin producing neuroendocrine tumors (NETs). Niacin deficiency can lead to severe symptoms including

  10. Brain Serotonin Transporter Binding In a Minipig Model of Parkinson's Disease

    DEFF Research Database (Denmark)

    Lillethorup, Thea Pinholt; Glud, Andreas Nørgaard; Sørensen, Jens Christian Hedemann

    Objectives: Some of the debilitating non-motor aspects of Parkinson’s disease (PD) are related to the serotonin system1. To investigate the involvement of the brain serotonergic system in a PD animal model, we measured the in vivo binding of [11C]-DASB to the serotonin transporter (SERT...

  11. Brief Report: Whole Blood Serotonin Levels and Gastrointestinal Symptoms in Autism Spectrum Disorder

    Science.gov (United States)

    Marler, Sarah; Ferguson, Bradley J.; Lee, Evon Batey; Peters, Brittany; Williams, Kent C.; McDonnell, Erin; Macklin, Eric A.; Levitt, Pat; Gillespie, Catherine Hagan; Anderson, George M.; Margolis, Kara Gross; Beversdorf, David Q.; Veenstra-VanderWeele, Jeremy

    2016-01-01

    Elevated whole blood serotonin levels are observed in more than 25% of children with autism spectrum disorder (ASD). Co-occurring gastrointestinal (GI) symptoms are also common in ASD but have not previously been examined in relationship with hyperserotonemia, despite the synthesis of serotonin in the gut. In 82 children and adolescents with ASD,…

  12. A new balancing act: The many roles of melatonin and serotonin in plant growth and development

    Science.gov (United States)

    Erland, Lauren A E; Murch, Susan J; Reiter, Russel J; Saxena, Praveen K

    2015-01-01

    Melatonin and serotonin are indoleamines first identified as neurotransmitters in vertebrates; they have now been found to be ubiquitously present across all forms of life. Both melatonin and serotonin were discovered in plants several years after their discovery in mammals, but their presence has now been confirmed in almost all plant families. The mechanisms of action of melatonin and serotonin are still poorly defined. Melatonin and serotonin possess important roles in plant growth and development, including functions in chronoregulation and modulation of reproductive development, control of root and shoot organogenesis, maintenance of plant tissues, delay of senescence, and responses to biotic and abiotic stresses. This review focuses on the roles of melatonin and serotonin as a novel class of plant growth regulators. Their roles in reproductive and vegetative plant growth will be examined including an overview of current hypotheses and knowledge regarding their mechanisms of action in specific responses. PMID:26418957

  13. A new balancing act: The many roles of melatonin and serotonin in plant growth and development.

    Science.gov (United States)

    Erland, Lauren A E; Murch, Susan J; Reiter, Russel J; Saxena, Praveen K

    2015-01-01

    Melatonin and serotonin are indoleamines first identified as neurotransmitters in vertebrates; they have now been found to be ubiquitously present across all forms of life. Both melatonin and serotonin were discovered in plants several years after their discovery in mammals, but their presence has now been confirmed in almost all plant families. The mechanisms of action of melatonin and serotonin are still poorly defined. Melatonin and serotonin possess important roles in plant growth and development, including functions in chronoregulation and modulation of reproductive development, control of root and shoot organogenesis, maintenance of plant tissues, delay of senescence, and responses to biotic and abiotic stresses. This review focuses on the roles of melatonin and serotonin as a novel class of plant growth regulators. Their roles in reproductive and vegetative plant growth will be examined including an overview of current hypotheses and knowledge regarding their mechanisms of action in specific responses.

  14. Human Beta Cells Produce and Release Serotonin to Inhibit Glucagon Secretion from Alpha Cells.

    Science.gov (United States)

    Almaça, Joana; Molina, Judith; Menegaz, Danusa; Pronin, Alexey N; Tamayo, Alejandro; Slepak, Vladlen; Berggren, Per-Olof; Caicedo, Alejandro

    2016-12-20

    In the pancreatic islet, serotonin is an autocrine signal increasing beta cell mass during metabolic challenges such as those associated with pregnancy or high-fat diet. It is still unclear whether serotonin is relevant for regular islet physiology and hormone secretion. Here, we show that human beta cells produce and secrete serotonin when stimulated with increases in glucose concentration. Serotonin secretion from beta cells decreases cyclic AMP (cAMP) levels in neighboring alpha cells via 5-HT1F receptors and inhibits glucagon secretion. Without serotonergic input, alpha cells lose their ability to regulate glucagon secretion in response to changes in glucose concentration, suggesting that diminished serotonergic control of alpha cells can cause glucose blindness and the uncontrolled glucagon secretion associated with diabetes. Supporting this model, pharmacological activation of 5-HT1F receptors reduces glucagon secretion and has hypoglycemic effects in diabetic mice. Thus, modulation of serotonin signaling in the islet represents a drug intervention opportunity. Published by Elsevier Inc.

  15. Intact coding region of the serotonin transporter gene in obsessive-compulsive disorder

    Energy Technology Data Exchange (ETDEWEB)

    Altemus, M.; Murphy, D.L.; Greenberg, B. [NIMH, NIH, Bethesda, MD (United States); Lesch, K.P. [Univ. of Wuerzburg (Germany)

    1996-07-26

    Epidemiologic studies indicate that obsessive-compulsive disorder is genetically transmitted in some families, although no genetic abnormalities have been identified in individuals with this disorder. The selective response of obsessive-compulsive disorder to treatment with agents which block serotonin reuptake suggests the gene coding for the serotonin transporter as a candidate gene. The primary structure of the serotonin-transporter coding region was sequenced in 22 patients with obsessive-compulsive disorder, using direct PCR sequencing of cDNA synthesized from platelet serotonin-transporter mRNA. No variations in amino acid sequence were found among the obsessive-compulsive disorder patients or healthy controls. These results do not support a role for alteration in the primary structure of the coding region of the serotonin-transporter gene in the pathogenesis of obsessive-compulsive disorder. 27 refs.

  16. Molecular modeling of the human serotonin(1A) receptor : role of membrane cholesterol in ligand binding of the receptor

    NARCIS (Netherlands)

    Paila, Yamuna Devi; Tiwari, Shrish; Sengupta, Durba; Chattopadhyay, Amitabha

    2011-01-01

    Serotonin(1A) receptors are important neurotransmitter receptors and belong to the superfamily of G-protein coupled receptors (GPCRs). Although it is an important drug target, the crystal structure of the serotonin(1A) receptor has not been solved yet. Earlier homology models of the serotonin(1A)

  17. Serotonin transporter is not required for the development of severe pulmonary hypertension in the Sugen hypoxia rat model

    NARCIS (Netherlands)

    de Raaf, Michiel Alexander; Kroeze, Yvet; Middelman, Anthonieke; de Man, Frances S.; de Jong, Helma; Vonk-Noordegraaf, Anton; de Korte, Chris; Voelkel, Norbert F.; Homberg, Judith; Bogaard, Harm Jan

    2015-01-01

    Increased serotonin serum levels have been proposed to play a key role in pulmonary arterial hypertension (PAH) by regulating vessel tone and vascular smooth muscle cell proliferation. An intact serotonin system, which critically depends on a normal function of the serotonin transporter (SERT), is

  18. Interaction between serotonin transporter and serotonin receptor 1 B genes polymorphisms may be associated with antisocial alcoholism.

    Science.gov (United States)

    Wang, Tzu-Yun; Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chen, Shih-Heng; Chu, Chun-Hsien; Huang, San-Yuan; Tzeng, Nian-Sheng; Wang, Chen-Lin; Lee, I Hui; Yeh, Tzung Lieh; Yang, Yen Kuang; Lu, Ru-Band

    2012-07-11

    Several studies have hypothesized that genes regulating the components of the serotonin system, including serotonin transporter (5-HTTLPR) and serotonin 1 B receptor (5-HT1B), may be associated with alcoholism, but their results are contradictory because of alcoholism's heterogeneity. Therefore, we examined whether the 5-HTTLPR gene and 5-HT1B gene G861C polymorphism are susceptibility factors for a specific subtype of alcoholism, antisocial alcoholism in Han Chinese in Taiwan. We recruited 273 Han Chinese male inmates with antisocial personality disorder (ASPD) [antisocial alcoholism (AS-ALC) group (n=120) and antisocial non-alcoholism (AS-N-ALC) group (n=153)] and 191 healthy male controls from the community. Genotyping was done using PCR-RFLP. There were no significant differences in the genotypic frequency of the 5-HT1B G861C polymorphism between the 3 groups. Although AS-ALC group members more frequently carried the 5-HTTLPR S/S, S/LG, and LG/LG genotypes than controls, the difference became non-significant after controlling for the covarying effects of age. However, the 5-HTTLPR S/S, S/LG, and LG/LG genotypes may have interacted with the 5-HT1B G861C C/C polymorphism and increased the risk of becoming antisocial alcoholism. Our study suggests that neither the 5-HTTLPR gene nor the 5-HT1B G861C polymorphism alone is a risk factor for antisocial alcoholism in Taiwan's Han Chinese population, but that the interaction between both genes may increase susceptibility to antisocial alcoholism.

  19. Interaction between Serotonin Transporter and Serotonin Receptor 1 B genes polymorphisms may be associated with antisocial alcoholism

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    Wang Tzu-Yun

    2012-07-01

    Full Text Available Abstract Background Several studies have hypothesized that genes regulating the components of the serotonin system, including serotonin transporter (5-HTTLPR and serotonin 1 B receptor (5-HT1B, may be associated with alcoholism, but their results are contradictory because of alcoholism’s heterogeneity. Therefore, we examined whether the 5-HTTLPR gene and 5-HT1B gene G861C polymorphism are susceptibility factors for a specific subtype of alcoholism, antisocial alcoholism in Han Chinese in Taiwan. Methods We recruited 273 Han Chinese male inmates with antisocial personality disorder (ASPD [antisocial alcoholism (AS-ALC group (n = 120 and antisocial non-alcoholism (AS-N-ALC group (n = 153] and 191 healthy male controls from the community. Genotyping was done using PCR-RFLP. Results There were no significant differences in the genotypic frequency of the 5-HT1B G861C polymorphism between the 3 groups. Although AS-ALC group members more frequently carried the 5-HTTLPR S/S, S/LG, and LG/LG genotypes than controls, the difference became non-significant after controlling for the covarying effects of age. However, the 5-HTTLPR S/S, S/LG, and LG/LG genotypes may have interacted with the 5-HT1B G861C C/C polymorphism and increased the risk of becoming antisocial alcoholism. Conclusion Our study suggests that neither the 5-HTTLPR gene nor the 5-HT1B G861C polymorphism alone is a risk factor for antisocial alcoholism in Taiwan’s Han Chinese population, but that the interaction between both genes may increase susceptibility to antisocial alcoholism.

  20. Moderate prenatal alcohol exposure and serotonin genotype interact to alter CNS serotonin function in rhesus monkey offspring.

    Science.gov (United States)

    Schneider, Mary L; Moore, Colleen F; Barr, Christina S; Larson, Julie A; Kraemer, Gary W

    2011-05-01

    Moderate prenatal alcohol exposure can contribute to neurodevelopmental impairments and disrupt several neurotransmitter systems. We examined the timing of moderate level alcohol exposure, serotonin transporter gene polymorphic region variation (rh5-HTTLPR), and levels of primary serotonin and dopamine (DA) metabolites in cerebrospinal fluid (CSF) in rhesus monkeys. Thirty-two 30-month old rhesus monkeys (Macaca mulatta) from 4 groups of females were assessed: (i) early alcohol-exposed group (n = 9), in which mothers voluntarily consumed 0.6 g/kg/d alcohol solution on gestational days 0 to 50; (ii) middle-to-late gestation alcohol-exposed group (n = 6), mothers consumed 0.6 g/kg/d alcohol solution on gestational days 50 to 135; (iii) a continuous-exposure group (n = 8), mothers consumed 0.6 g/kg/d alcohol solution on gestational days 0 to 135; and (iv) controls (n = 9), mothers consumed an isocaloric control solution on gestational days 0 to 50, 50 to 135, or 0 to 135. Serotonin transporter promoter region allelic variants (homozygous s/s or heterozygous s/l vs. homozygous l/l) were determined. We examined CSF concentrations of the 5-HT and DA metabolites, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), respectively, at baseline and 50 hours after separation from cage-mates, when the monkeys were 30 months old. Early- and middle-to-late gestation-alcohol exposed monkeys carrying the short allele had lower concentrations of 5-HIAA in CSF relative to other groups. Concentrations of 5-HIAA in CSF were lower for s allele carriers and increased from baseline relative to pre-separation values, whereas 5-HIAA levels in l/l allele carriers were not affected by separation. Monkeys carrying the short allele had lower basal concentrations of HVA in CSF compared with monkeys homozygous for the long allele. Carrying the s allele of the 5-HT transporter increased the probability of reduced 5-HIAA in early- and middle-to-late gestation alcohol-exposed monkeys and