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Sample records for oxytocin involves inhibition

  1. Antinociceptive action of oxytocin involves inhibition of potassium channel currents in lamina II neurons of the rat spinal cord

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    Darbon Pascal

    2009-11-01

    Full Text Available Abstract Background Growing evidence in the literature shows that oxytocin (OT has a strong spinal anti-nociceptive action. Oxytocinergic axons originating from a subpopulation of paraventricular hypothalamic neurons establish synaptic contacts with lamina II interneurons but little is known about the functional role of OT with respect to neuronal firing and excitability. Results Using the patch-clamp technique, we have recorded lamina II interneurons in acute transverse lumbar spinal cord slices of rats (15 to 30 days old and analyzed the OT effects on action potential firing ability. In the current clamp mode, we found that bath application of a selective OT-receptor agonist (TGOT reduced firing in the majority of lamina II interneurons exhibiting a bursting firing profile, but never in those exhibiting a single spike discharge upon depolarization. Interestingly, OT-induced reduction in spike frequency and increase of firing threshold were often observed, leading to a conversion of the firing profile from repetitive and delayed profiles into phasic ones and sometimes further into single spike profile. The observed effects following OT-receptor activation were completely abolished when the OT-receptor agonist was co-applied with a selective OT-receptor antagonist. In current and voltage clamp modes, we show that these changes in firing are strongly controlled by voltage-gated potassium currents. More precisely, transient IA currents and delayed-rectifier currents were reduced in amplitude and transient IA current was predominantly inactivated after OT bath application. Conclusion This effect of OT on the firing profile of lamina II neurons is in good agreement with the antinociceptive and analgesic properties of OT described in vivo.

  2. Combined Norepinephrine / Serotonergic Reuptake Inhibition: Effects on Maternal Behavior, Aggression and Oxytocin in the Rat

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    Elizabeth Thomas Cox

    2011-06-01

    Full Text Available BACKGROUND: Few systematic studies exist on the effects of chronic reuptake of monoamine neurotransmitter systems during pregnancy on the regulation of maternal behavior, although many drugs act primarily through one or more of these systems. Previous studies examining fluoxetine and amfonelic acid treatment during gestation on subsequent maternal behavior in rodents indicated significant alterations in postpartum maternal care, aggression and oxytocin levels. In this study, we extended our studies to include chronic gestational treatment with desipramine or amitriptyline to examine differential effects of reuptake inhibition of norepinephrine and combined noradrenergic and serotonergic systems on maternal behavior, aggression, and oxytocin system changes. METHODS: Pregnant Sprague-Dawley rats were treated throughout gestation with saline or one of three doses of either desipramine, which has a high affinity for the norepinephrine monoamine transporter, or amitriptyline, an agent with high affinity for both the norepinephrine and serotonin monoamine transporters. Maternal behavior and postpartum aggression were assessed on postpartum days one and six respectively. Oxytocin levels were measured in relevant brain regions on postpartum day seven. Predictions were that amitriptyline would decrease maternal behavior and increase aggression relative to desipramine, particularly at higher doses. Amygdaloidal oxytocin was expected to decrease with increased aggression. RESULTS: Amitriptyline and desiprimine differentially reduced maternal behavior, and at higher doses reduced aggressive behavior. Hippocampal oxytocin levels were lower after treatment with either drug but were not correlated with specific behavioral effects. These results, in combination with previous findings following gestational treatment with other selective neurotransmitter reuptake inhibitors, highlight the diverse effects of multiple monoamine systems thought to be involved in

  3. Oxytocin is not involved in luteolysis and early maternal recognition of pregnancy (MRP) in alpacas.

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    Ciccarelli, Michela; Waqas, Muhammad Salman; Pru, James K; Tibary, Ahmed

    2017-12-01

    Pregnancy maintenance depends on the maternal recognition of pregnancy (MRP), a physiological process by which the lifespan of the corpus luteum is prolonged. This mechanism is not well characterized in camelids. The objectives of the present research were to determine if exogenous oxytocin prolongs the corpus luteum activity in alpacas and to evaluate expression and localization of oxytocin receptors within the endometrium at 9 and 14days post-mating. In the oxytocin studies, plasma progesterone profiles were determined after ovulation in the same alpacas on 2 cycles: one cycle without oxytocin treatment and one cycle with oxytocin treatment. Oxytocin was administered daily by intramuscular injections (IM) at a dose of 20IU (experiment 1, n=6) or 60IU (experiment 2, n=7 from day 3 through day 10 after induction of ovulation with GnRH IM. There was no significant difference in the length of the luteal phase (i.e. corpus luteum lifespan) between the treated and control cycles using either 20 or 60IU of oxytocin. In the final experiment, uteri from open and pregnant alpacas (n=4 per group) at 9 and 14days post-mating were evaluated for expressions of oxytocin receptors by immunohistochemistry. No significant difference (P≤0.05) in the expression of oxytocin receptors was observed between open and pregnant animals in either staining intensity or tissue localization. We conclude that oxytocin is not involved in luteolysis and early MRP in alpacas. Published by Elsevier B.V.

  4. Serotonergic involvement in stress-induced vasopressin and oxytocin secretion

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    Jørgensen, Henrik; Knigge, Ulrich; Kjaer, Andreas

    2002-01-01

    OBJECTIVE: To investigate the involvement of serotonin (5-hydroxytryptamine - 5-HT) receptors in mediation of stress-induced arginine vasopressin (AVP) and oxytocin (OT) secretion in male rats. DESIGN: Experiments on laboratory rats with control groups. METHODS: Different stress paradigms were...... the swim stress-induced OT response. CONCLUSION: 5-HT(2A), 5-HT(2C) and possibly 5-HT(3) and 5-HT(4) receptors, but not 5-HT(1A) receptors, are involved in the restraint stress-induced AVP secretion. 5-HT does not seem to be involved in the dehydration- or hemorrhage-induced AVP response. The restraint...... stress-induced OT response seems to be mediated via 5-HT(1A), 5-HT(2A) and 5-HT(2C) receptors. The dehydration and hemorrhage-induced OT responses are at least mediated by the 5-HT(2A) and 5-HT(2C) receptors. The 5-HT(3) and 5-HT(4) receptors are not involved in stress-induced OT secretion....

  5. Chronic fluoxetine inhibits sexual behavior in the male rat: reversal with oxytocin.

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    Cantor, J M; Binik, Y M; Pfaus, J G

    1999-06-01

    Selective serotonin reuptake inhibitors, used widely in the treatment of depression, progressively inhibit sexual orgasm in many patients and induce a transient inhibition of sexual desire. We attempted to model the effects of these drugs in sexually experienced male rats during tests of copulation in bilevel chambers. These chambers allow the study of both appetitive and consummatory sexual responses of male rats. Males were treated daily with fluoxetine hydrochloride (0, 1, 5, or 10 mg/kg) and tested for sexual behavior with receptive females at 4-day intervals. Rats were treated with oxytocin (200 ng/kg) or saline after ejaculations had decreased. Fluoxetine decreased ejaculatory responses of male rats in a dose- and time-dependent fashion, but left the copulatory efficiency of the males intact. In contrast, conditioned level changing, a measure of appetitive sexual excitement, was inhibited following acute and chronic treatment with 10 mg/kg, although tolerance may have developed to the effect of 5 mg/kg. Subsequent administration of oxytocin restored the ejaculatory response but not the measure of sexual excitement to baseline levels. The reversal by oxytocin of the fluoxetine-induced deficit in ejaculations is consistent with the hypothesis that serotonin suppresses ejaculatory mechanisms by interrupting the action of oxytocin, which normally accompanies sexual behavior. Co-administration of oxytocin may help to alleviate the predominant sexual side effect of serotonin reuptake blockers.

  6. Methamphetamine Consumption Inhibits Pair Bonding and Hypothalamic Oxytocin in Prairie Voles.

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    Caroline M Hostetler

    Full Text Available Methamphetamine (MA abuse has been linked to violence, risk-taking behaviors, decreased sexual inhibition, and criminal activity. It is important to understand mechanisms underlying these drug effects for prevention and treatment of MA-associated social problems. Previous studies have demonstrated that experimenter-administered amphetamine inhibits pair bonding and increases aggression in monogamous prairie voles. It is not currently known whether similar effects on social behaviors would be obtained under conditions during which the drug is voluntarily (actively administered. The current study investigated whether MA drinking affects pair bonding and what neurocircuits are engaged. In Experiment 1, we exposed male and female voles to 4 days each of 20 and 40 mg/L MA under a continuous 2-bottle choice (2BC procedure. Animals were housed either singly or in mesh-divided cages with a social partner. Voles consumed MA in a drinking solution, but MA drinking was not affected by either sex or housing condition. In Experiment 2, we investigated whether MA drinking disrupts social bonding by measuring aggression and partner preference formation following three consecutive days of 18-hour/day access to 100 mg/L MA in a 2BC procedure. Although aggression toward a novel opposite-sex animal was not affected by MA exposure, partner preference was inhibited in MA drinking animals. Experiment 3 examined whether alterations in hypothalamic neuropeptides provide a potential explanation for the inhibition of partner preference observed in Experiment 2. MA drinking led to significant decreases in oxytocin, but not vasopressin, in the paraventricular nucleus of the hypothalamus. These experiments are the first investigation into how voluntary pre-exposure to MA affects the development of social attachment in a socially monogamous species and identify potential neural circuits involved in these effects.

  7. Maintenance therapy with oxytocin antagonists for inhibiting preterm birth after threatened preterm labour.

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    Papatsonis, Dimitri N M; Flenady, Vicki; Liley, Helen G

    2013-10-13

    In some women, an episode of preterm labour settles and does not result in immediate preterm birth. Subsequent treatment with tocolytic agents such as oxytocin receptor antagonists may then have the potential to prevent the recurrence of preterm labour, prolonging gestation, and preventing the adverse consequences of prematurity for the infant. To assess the effects of maintenance therapy with oxytocin antagonists administered by any route after an episode of preterm labour in order to delay or prevent preterm birth. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2013), sought ongoing and unpublished trials by contacting experts in the field and searched the reference lists of relevant articles. Randomised controlled trials comparing oxytocin antagonists with any alternative tocolytic agent, placebo or no treatment, used for maintenance therapy after an episode of preterm labour. We used the standard methods of The Cochrane Collaboration and the Cochrane Pregnancy and Childbirth Group. Two review authors independently undertook evaluation of methodological quality and extracted trial data. This review includes one trial of 513 women. When compared with placebo, atosiban did not reduce preterm birth before 37 weeks (risk ratio (RR) 0.89; 95% confidence intervals (CI) 0.71 to 1.12), 32 weeks (RR 0.85; 95% CI 0.47 to 1.55), or 28 weeks (RR 0.75; 95% CI 0.28 to 2.01). No difference was shown in neonatal morbidity, or perinatal mortality. There is insufficient evidence to support the use of oxytocin receptor antagonists to inhibit preterm birth after a period of threatened or actual preterm labour. Any future trials using oxytocin antagonists or other drugs as maintenance therapy for preventing preterm birth should examine a variety of important infant outcome measures, including reduction of neonatal morbidity and mortality, and long-term infant follow-up. Future research should also focus on the pathophysiological pathways that

  8. Associative and sensorimotor learning for parenting involves mirror neurons under the influence of oxytocin.

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    Ho, S Shaun; Macdonald, Adam; Swain, James E

    2014-04-01

    Mirror neuron-based associative learning may be understood according to associative learning theories, in addition to sensorimotor learning theories. This is important for a comprehensive understanding of the role of mirror neurons and related hormone modulators, such as oxytocin, in complex social interactions such as among parent-infant dyads and in examples of mirror neuron function that involve abnormal motor systems such as depression.

  9. Associative and sensorimotor learning for parenting involves mirror neurons under the influence of oxytocin

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    Ho, S. Shaun; MacDonald, Adam; Swain, James E.

    2014-01-01

    Mirror neuron–based associative learning may be understood according to associative learning theories, in addition to sensorimotor learning theories. This is important for a comprehensive understanding of the role of mirror neurons and related hormone modulators, such as oxytocin, in complex social interactions such as among parent–infant dyads and in examples of mirror neuron function that involve abnormal motor systems such as depression.

  10. Blocking oxytocin receptors inhibits vaginal marking to male odors in female Syrian hamsters.

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    Martinez, Luis A; Albers, H Elliott; Petrulis, Aras

    2010-12-02

    In Syrian hamsters (Mesocricetus auratus), precopulatory behaviors such as vaginal scent marking are essential for attracting a suitable mate. Vaginal marking is dependent on forebrain areas implicated in the neural regulation of reproductive behaviors in rodents, including the medial preoptic/anterior hypothalamus (MPOA-AH). Within MPOA-AH, the neuropeptide oxytocin (OT) acts to facilitate copulation (lordosis), as well as ultrasonic vocalizations towards males. It is not known, however, if OT in this area also facilitates vaginal marking. In the present study, a specific oxytocin receptor antagonist (OTA) was injected into MPOA-AH of intact female Syrian hamsters to determine if oxytocin receptor-dependent signaling is critical for the normal expression of vaginal marking elicited by male, female, and clean odors. OTA injections significantly inhibited vaginal marking in response to male odors compared with vehicle injections. There was no effect of OTA on marking in response to either female or clean odors. When injected into the bed nucleus of the stria terminalis (BNST), a nearby region to MPOA-AH, OTA was equally effective in decreasing marking. Finally, the effects of OTA appear to be specific to vaginal marking, as OTA injections in MPOA-AH or BNST did not alter general locomotor activity, flank marking, or social odor investigation. Considered together, these results suggest that OT in MPOA-AH and/or BNST normally facilitates male odor-induced vaginal marking, providing further evidence that OT generally supports prosocial interactions among conspecifics. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Oxytocin decreases colonic motility of cold water stressed rats via oxytocin receptors.

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    Yang, Xiao; Xi, Tao-Fang; Li, Yu-Xian; Wang, Hai-Hong; Qin, Ying; Zhang, Jie-Ping; Cai, Wen-Ting; Huang, Meng-Ting; Shen, Ji-Qiao; Fan, Xi-Min; Shi, Xuan-Zheng; Xie, Dong-Ping

    2014-08-21

    To investigate whether cold water intake into the stomach affects colonic motility and the involvement of the oxytocin-oxytocin receptor pathway in rats. Female Sprague Dawley rats were used and some of them were ovariectomized. The rats were subjected to gastric instillation with cold (0-4 °C, cold group) or room temperature (20-25 °C, control group) saline for 14 consecutive days. Colon transit was determined with a bead inserted into the colon. Colonic longitudinal muscle strips were prepared to investigate the response to oxytocin in vitro. Plasma concentration of oxytocin was detected by ELISA. Oxytocin receptor expression was investigated by Western blot analysis. Immunohistochemistry was used to locate oxytocin receptors. Colon transit was slower in the cold group than in the control group (P cold water intake (0.69 ± 0.08 vs 0.88 ± 0.16, P receptors were located in the myenteric plexus, and their expression was up-regulated in the cold group (P Cold water intake increased blood concentration of oxytocin, but this effect was attenuated in ovariectomized rats (286.99 ± 83.72 pg/mL vs 100.56 ± 92.71 pg/mL, P Cold water intake inhibits colonic motility partially through oxytocin-oxytocin receptor signaling in the myenteric nervous system pathway, which is estrogen dependent.

  12. Enkephalin inhibition of angiotensin-stimulated release of oxytocin and vasopressin

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    Keil, L. C.; Chee, O.; Rosella-Dampman, L. M.; Emmert, S.; Summy-Long, J. Y.

    1984-01-01

    The effect of intracerebroventricular (ICV) pretreatment with 100 ng/5 microliter leucine(5)-enkephalin (LE) on the increase in plasma oxytocin (OT) and vasopressin (VP) caused by ICV injection of 10, 50, or 100 ng/5 microliter of angiotensin II (AII) is investigated experimentally in conscious adult male Sprague-Dawley rats; the effects of water-deprivation dehydration and lactation/suckling (in female rats) are also studied. An OT radioimmunoassay (RIA) with a sensitivity of 800 fg/ml (described in detail) and the VP RIA technique of Keil and Severs (1977) are employed. Administration of AII or dehydration for 48 or 72 h cause a significant increase in OT and VP without affecting the ratio, while lactation and suckling increase OT only. LE pretreatment inhibits significantly but does not suppress the AII-stimulated OT-VP response.

  13. Endogenous opioids inhibit oxytocin release during nicotine-stimulated secretion of vasopressin in man.

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    Seckl, J R; Johnson, M; Shakespear, C; Lightman, S L

    1988-05-01

    The effects of the opioid antagonist naloxone on the vasopressin (AVP) and oxytocin (OT) responses to nicotine were studied in male non-smokers (21-30 years old). Either saline (n = 6) or naloxone (4 mg bolus + 6 mg/h, n = 6) was infused i.v. during the study. After 60 min infusion the subjects smoked one high-nicotine content cigarette. Naloxone infusion for 60 min did not alter basal plasma AVP or OT levels. Smoking led to a significant rise in plasma vasopressin in both saline and naloxone-infused subjects (P less than 0.05). There was no significant difference in the plasma AVP response to smoking between the two groups. Saline-infused subjects did not show any change in plasma OT in response to smoking. Naloxone infusion was associated with a significant rise in OT from 1.3 +/- 0.1 pmol/l to 4.3 +/- 2.4 pmol/l 5 min after smoking (P less than 0.05). We conclude that there is endogenous opioid-mediated inhibition of OT which prevents its release when AVP is secreted in response to nicotine in man.

  14. The Involvement of Oxytocin in the Subthalamic Nucleus on Relapse to Methamphetamine-Seeking Behaviour.

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    Sarah Jane Baracz

    Full Text Available The psychostimulant methamphetamine (METH is an addictive drug of abuse. The neuropeptide oxytocin has been shown to modulate METH-related reward and METH-seeking behaviour. Recent findings implicated the subthalamic nucleus (STh as a key brain region in oxytocin modulation of METH-induced reward. However, it is unclear if oxytocin acts in this region to attenuate relapse to METH-seeking behaviour, and if this action is through the oxytocin receptor. We aimed to determine whether oxytocin pretreatment administered into the STh would reduce reinstatement to METH use in rats experienced at METH self-administration, and if this could be reversed by the co-administration of the oxytocin receptor antagonist desGly-NH2,d(CH25[D-Tyr2,Thr4]OVT. Male Sprague Dawley rats underwent surgery to implant an intravenous jugular vein catheter and bilateral microinjection cannulae into the STh under isoflourane anaesthesia. Rats were then trained to self-administer intravenous METH (0.1 mg/kg/infusion by lever press during 2-hour sessions under a fixed ratio 1 schedule for 20 days. Following extinction of lever press activity, the effect of microinjecting saline, oxytocin (0.2 pmol, 0.6 pmol, 1.8 pmol, 3.6 pmol or co-administration of oxytocin (3.6 pmol and desGly-NH2,d(CH25[D-Tyr2,Thr4]OVT (3 nmol into the STh (200 nl/side was examined on METH-primed reinstatement (1 mg/kg; i.p.. We found that local administration of the highest oxytocin dose (3.6 pmol into the STh decreased METH-induced reinstatement and desGly-NH2,d(CH25[D-Tyr2,Thr4]OVT had a non-specific effect on lever press activity. These findings highlight that oxytocin modulation of the STh is an important modulator of relapse to METH abuse.

  15. Brain oxytocin in social fear conditioning and its extinction: involvement of the lateral septum.

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    Zoicas, Iulia; Slattery, David A; Neumann, Inga D

    2014-12-01

    Central oxytocin (OXT) has anxiolytic and pro-social properties both in humans and rodents, and has been proposed as a therapeutic option for anxiety and social dysfunctions. Here, we utilized a mouse model of social fear conditioning (SFC) to study the effects of OXT on social fear, and to determine whether SFC causes alterations in central OXT receptor (OXTR) binding and local OXT release. Central infusion of OXT, but not arginine vasopressin, prior to social fear extinction training completely abolished social fear expression in an OXTR-mediated fashion without affecting general anxiety or locomotion. SFC caused increased OXTR binding in the dorso-lateral septum (DLS), central amygdala, dentate gyrus, and cornu ammunis 1, which normalized after social fear extinction, suggesting that these areas form part of a brain network involved in the development and neural support of social fear. Microdialysis revealed that the increase in OXT release observed in unconditioned mice within the DLS during social fear extinction training was attenuated in conditioned mice. Consequently, increasing the availability of local OXT by infusion of OXT into the DLS reversed social fear. Thus, alterations in the brain OXT system, including altered OXTR binding and OXT release within the DLS, play an important role in SFC and social fear extinction. Thus, we suggest that the OXT system is adversely affected in disorders associated with social fear, such as social anxiety disorder and reinstalling an appropriate balance of the OXT system may alleviate some of the symptoms.

  16. [Oxytocin: the hormone of love, trust and social bond. Clinical use in autism and social phobia].

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    Martin-Du Pan, R C

    2012-03-21

    Oxytocin, an octapeptide synthesized in the hypothalamus, stimulates milk election and uterine contractions. In the brain this hormone acts as a neuropeptide. It could inhibit through the GABAergic system the activity of limbic amygdala, which is involved in the response to fear. Oxytocin could also induce the protective behaviour of the mother towards its offspring through the dopaminergic system. In mankind, oxytocin plays a role in trust, empathy, generosity, stress and sexuality. Clinical studies are testing potential benefits of oxytocin administration in autism, depression and social phobia. Results are still preliminary.

  17. Involvement of the oxytocin system in the nucleus accumbens in the regulation of juvenile social novelty-seeking behavior.

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    Smith, Caroline J W; Mogavero, Jazmin N; Tulimieri, Maxwell T; Veenema, Alexa H

    2017-07-01

    Exploration of novel environments, stimuli, and conspecifics is highly adaptive during the juvenile period, as individuals transition from immaturity to adulthood. We recently showed that juvenile rats prefer to interact with a novel individual over a familiar cage mate. However, the neural mechanisms underlying this juvenile social novelty-seeking behavior remain largely unknown. One potential candidate is the oxytocin (OXT) system, given its involvement in various motivated social behaviors. Here, we show that administration of the specific oxytocin receptor antagonist desGly-NH 2 ,d(CH 2 ) 5 -[Tyr(Me) 2 ,Thr 4 ]OVT reduces social novelty seeking-behavior in juvenile male rats when injected into the nucleus accumbens (10ng/0.5μl/side). The same drug dose was ineffective at altering social novelty-seeking behavior when administered into the lateral septum or basolateral amygdala. These results are the first to suggest the involvement of the OXT system in the nucleus accumbens in the regulation of juvenile social novelty-seeking behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. The ventromedial hypothalamus oxytocin induces locomotor behavior regulated by estrogen.

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    Narita, Kazumi; Murata, Takuya; Matsuoka, Satoshi

    2016-10-01

    Our previous studies demonstrated that excitation of neurons in the rat ventromedial hypothalamus (VMH) induced locomotor activity. An oxytocin receptor (Oxtr) exists in the VMH and plays a role in regulating sexual behavior. However, the role of Oxtr in the VMH in locomotor activity is not clear. In this study we examined the roles of oxytocin in the VMH in running behavior, and also investigated the involvement of estrogen in this behavioral change. Microinjection of oxytocin into the VMH induced a dose-dependent increase in the running behavior in male rats. The oxytocin-induced running activity was inhibited by simultaneous injection of Oxtr-antagonist, (d(CH2)5(1), Try(Me)(2), Orn(8))-oxytocin. Oxytocin injection also induced running behavior in ovariectomized (OVX) female rats. Pretreatment of the OVX rats with estrogen augmented the oxytocin-induced running activity twofold, and increased the Oxtr mRNA in the VMH threefold. During the estrus cycle locomotor activity spontaneously increased in the dark period of proestrus. The Oxtr mRNA was up-regulated in the proestrus afternoon. Blockade of oxytocin neurotransmission by its antagonist before the onset of the dark period of proestrus decreased the following nocturnal locomotor activity. These findings demonstrate that Oxtr in the VMH is involved in the induction of running behavior and that estrogen facilitates this effect by means of Oxtr up-regulation, suggesting the involvement of oxytocin in the locomotor activity of proestrus female rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Radioimmunoassay of oxytocin

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    Dawood, M.Y.; Raghavan, K.S.; Pociask, C.

    1978-01-01

    The evaluation of a radioimmunoassay of oxytocin is described. The method involved careful collection and transportation of blood at 4 0 C, acidification of the plasma, extraction with Fuller's earth and radioimmunoassay using antisera raised in rabbits immunized against oxytocin conjugated to bovine serum albumin and 125 I-labelled oxytocin. The antisera showed insignificant cross-reaction with a variety of small peptides including vasopressin and vasotocin. The limit of detection of the assay was 2.5 pg with intra-assay and interassay coefficients of variation of 7 to 15% and 12 to 18% respectively. Seventy-seven per cent (88 out of 116) of the pregnant women tested had detect-able maternal plasma oxytocin. Serial samples of maternal plasma showed a significant increase in oxytocin from the first to the second stage of labour and a significant decrease in the third stage. Oxytocin concentrations in the umbilical arterial plasma were significantly higher in patients in labour. The significance of these findings is discussed. (author)

  20. DNA methylation of specific CpG sites in the promoter region regulates the transcription of the mouse oxytocin receptor.

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    Shimrat Mamrut

    Full Text Available Oxytocin is a peptide hormone, well known for its role in labor and suckling, and most recently for its involvement in mammalian social behavior. All central and peripheral actions of oxytocin are mediated through the oxytocin receptor, which is the product of a single gene. Transcription of the oxytocin receptor is subject to regulation by gonadal steroid hormones, and is profoundly elevated in the uterus and mammary glands during parturition. DNA methylation is a major epigenetic mechanism that regulates gene transcription, and has been linked to reduced expression of the oxytocin receptor in individuals with autism. Here, we hypothesized that transcription of the mouse oxytocin receptor is regulated by DNA methylation of specific sites in its promoter, in a tissue-specific manner. Hypothalamus-derived GT1-7, and mammary-derived 4T1 murine cell lines displayed negative correlations between oxytocin receptor transcription and methylation of the gene promoter, and demethylation caused a significant enhancement of oxytocin receptor transcription in 4T1 cells. Using a reporter gene assay, we showed that methylation of specific sites in the gene promoter, including an estrogen response element, significantly inhibits transcription. Furthermore, methylation of the oxytocin receptor promoter was found to be differentially correlated with oxytocin receptor expression in mammary glands and the uterus of virgin and post-partum mice, suggesting that it plays a distinct role in oxytocin receptor transcription among tissues and under different physiological conditions. Together, these results support the hypothesis that the expression of the mouse oxytocin receptor gene is epigenetically regulated by DNA methylation of its promoter.

  1. Early involvement in friendships predicts later plasma concentrations of oxytocin and vasopressin in juvenile rhesus macaques (Macaca mulatta

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    Tamara Aliza Rachel Weinstein

    2014-08-01

    Full Text Available The neuropeptides oxytocin (OT and vasopressin (AVP are involved in social bonding in attachment relationships, but their role in friendship is poorly understood. We investigated whether rhesus macaques’ (Macaca mulatta friendships at age one predicted plasma OT and AVP at two later time points. Subjects were 54 rhesus macaques at the California National Primate Research Center. Blood was drawn during a brief capture-and-release in the home cage, and plasma assayed for OT and AVP using an enzyme immunoassay. Separate linear mixed models for each sex tested the effects of dominance rank, age, sampling time point, housing condition, parturition status, two blood draw timing measures, and five friendship types: proximity friendships, play friendships, reciprocal friendships (a preference for a peer that also preferred the subject, multiplex friendships (friendships displayed in more than one behavioral domain, and total number of friendships. Females’ number of reciprocal and play friendships at age one significantly predicted later OT; additionally, these two friendship types interacted with rank, such that high-ranking females with the fewest friendships had the highest OT concentrations. Friendship did not predict later OT levels in males, however proximity, play, reciprocal, and total number of friendships predicted males’ plasma AVP. Play and total number of friendships also tended to predict AVP in females. Our results show that peripheral measures of neuroendocrine functioning in juvenile rhesus monkeys are influenced by early involvement in friendships. Friendships have an especially strong impact on an individual’s psychosocial development, and our data suggest OT and AVP as potential underlying mechanisms. Moreover, sex differences in the functioning of the OT and AVP systems, and their relation to friendship, may have important clinical implications for the use of OT as a therapeutic, as well as informing the social context in

  2. Spasmolytic Mechanism of Aqueous Licorice Extract on Oxytocin-Induced Uterine Contraction through Inhibiting the Phosphorylation of Heat Shock Protein 27

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    Lu Yang

    2017-08-01

    Full Text Available Licorice derived from the roots and rhizomes of Glycyrrhiza uralensis Fisch. (Fabaceae, is one of the most widely-used traditional herbal medicines in China. It has been reported to possess significant analgesic activity for treating spastic pain. The aim of this study is to investigate the spasmolytic molecular mechanism of licorice on oxytocin-induced uterine contractions and predict the relevant bioactive constituents in the aqueous extract. The aqueous extraction from licorice inhibited the amplitude and frequency of uterine contraction in a concentration-dependent manner. A morphological examination showed that myometrial smooth muscle cells of oxytocin-stimulated group were oval-shaped and arranged irregularly, while those with a single centrally located nucleus of control and licorice-treated groups were fusiform and arranged orderly. The percentage of phosphorylation of HSP27 at Ser-15 residue increased up to 50.33% at 60 min after oxytocin stimulation. Furthermore, this increase was significantly suppressed by licorice treatment at the concentration of 0.2 and 0.4 mg/mL. Colocalization between HSP27 and α-SMA was observed in the myometrial tissues, especially along the actin bundles in the oxytocin-stimulated group. On the contrary, the colocalization was no longer shown after treatment with licorice. Additionally, employing ChemGPS-NP provided support for a preliminary assignment of liquiritigenin and isoliquiritigenin as protein kinase C (PKC inhibitors in addition to liquiritigenin, isoliquiritigenin, liquiritin and isoliquiritin as MAPK-activated protein kinase 2 (MK2 inhibitors. These assigned compounds were docked with corresponding crystal structures of respective proteins with negative and low binding energy, which indicated a high affinity and tight binding capacity for the active site of the kinases. These results suggest that licorice exerts its spasmolytic effect through inhibiting the phosphorylation of HSP27 to alter the

  3. Newborn Analgesia Mediated by Oxytocin during Delivery

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    Mazzuca, Michel; Minlebaev, Marat; Shakirzyanova, Anastasia; Tyzio, Roman; Taccola, Giuliano; Janackova, Sona; Gataullina, Svetlana; Ben-Ari, Yehezkel; Giniatullin, Rashid; Khazipov, Rustem

    2011-01-01

    The mechanisms controlling pain in newborns during delivery are poorly understood. We explored the hypothesis that oxytocin, an essential hormone for labor and a powerful neuromodulator, exerts analgesic actions on newborns during delivery. Using a thermal tail-flick assay, we report that pain sensitivity is two-fold lower in rat pups immediately after birth than 2 days later. Oxytocin receptor antagonists strongly enhanced pain sensitivity in newborn, but not in 2-day-old rats, whereas oxytocin reduced pain at both ages suggesting an endogenous analgesia by oxytocin during delivery. Similar analgesic effects of oxytocin, measured as attenuation of pain-vocalization induced by electrical whisker pad stimulation, were also observed in decerebrated newborns. Oxytocin reduced GABA-evoked calcium responses and depolarizing GABA driving force in isolated neonatal trigeminal neurons suggesting that oxytocin effects are mediated by alterations of intracellular chloride. Unlike GABA signaling, oxytocin did not affect responses mediated by P2X3 and TRPV1 receptors. In keeping with a GABAergic mechanism, reduction of intracellular chloride by the diuretic NKCC1 chloride co-transporter antagonist bumetanide mimicked the analgesic actions of oxytocin and its effects on GABA responses in nociceptive neurons. Therefore, endogenous oxytocin exerts an analgesic action in newborn pups that involves a reduction of the depolarizing action of GABA on nociceptive neurons. Therefore, the same hormone that triggers delivery also acts as a natural pain killer revealing a novel facet of the protective actions of oxytocin in the fetus at birth. PMID:21519396

  4. Emergent synchronous bursting of oxytocin neuronal network.

    Directory of Open Access Journals (Sweden)

    Enrico Rossoni

    2008-07-01

    Full Text Available When young suckle, they are rewarded intermittently with a let-down of milk that results from reflex secretion of the hormone oxytocin; without oxytocin, newly born young will die unless they are fostered. Oxytocin is made by magnocellular hypothalamic neurons, and is secreted from their nerve endings in the pituitary in response to action potentials (spikes that are generated in the cell bodies and which are propagated down their axons to the nerve endings. Normally, oxytocin cells discharge asynchronously at 1-3 spikes/s, but during suckling, every 5 min or so, each discharges a brief, intense burst of spikes that release a pulse of oxytocin into the circulation. This reflex was the first, and is perhaps the best, example of a physiological role for peptide-mediated communication within the brain: it is coordinated by the release of oxytocin from the dendrites of oxytocin cells; it can be facilitated by injection of tiny amounts of oxytocin into the hypothalamus, and it can be blocked by injection of tiny amounts of oxytocin antagonist. Here we show how synchronized bursting can arise in a neuronal network model that incorporates basic observations of the physiology of oxytocin cells. In our model, bursting is an emergent behaviour of a complex system, involving both positive and negative feedbacks, between many sparsely connected cells. The oxytocin cells are regulated by independent afferent inputs, but they interact by local release of oxytocin and endocannabinoids. Oxytocin released from the dendrites of these cells has a positive-feedback effect, while endocannabinoids have an inhibitory effect by suppressing the afferent input to the cells.

  5. Oxytocin and potential benefits for obesity treatment.

    Science.gov (United States)

    Olszewski, Pawel K; Klockars, Anica; Levine, Allen S

    2017-10-01

    Laboratory animal experiments have consistently shown that oxytocin causes early termination of food intake, thereby promoting a decrease in body weight in a long term. Recent studies have also assessed some of oxytocin's effects on appetite and energy balance in humans. The present study examines the findings of the key basic research and of the few clinical studies published thus far in the context of potential benefits and challenges stemming from the use of oxytocin in obese patients. Basic research indicates the involvement of oxytocin in satiety, processing, in reducing a drive to eat for pleasure and because of psychosocial factors. Although the results of clinical studies are very scarce, they suggest that oxytocin administered intranasally in humans decreases energy-induced and reward-induced eating, supports cognitive control of food choices, and improves glucose homeostasis, and its effectiveness may be BMI dependent. Despite the wealth of basic research showing broad anorexigenic effects of oxytocin, clinical studies on oxytocin's therapeutic potential in obesity, are still in their infancy. Future implementation of oxytocin-based pharmacological strategies in controlling energy balance will likely depend on our ability to integrate diverse behavioral and metabolic effects of oxytocin in obesity treatment regimens.

  6. Oxytocin determination by radioimmunoassay in cattle. 1

    International Nuclear Information System (INIS)

    Schams, D.; Schmidt-Polex, B.; Kruse, V.

    1979-01-01

    A radioimmunoassay for oxytocin in cow plasma is described. Antisera were raised in rabbits against synthetic oxytocin coupled to bovine thyroglobulin. Iodinated oxytocin free of unlabelled oxytocin and most likely also free of diiodo-oxytocin was used as radioactive tracer. The tracer showed a high degree of purity, and was stable on storage. It could be used in the assay for 2-3 months. The assay showed very little cross-reactivity with vasopressin. Acetone was used for the extraction of oxytocin from plasma as well as from standards made of synthetic exytocin in pooled cow plasma. Inhibition curves obtained with plasma collected from cows at parturition were parallel to those obtained with the oxytocin standard preparation. The mean recovery of oxytocin added to cow plasma was 106% (SD=14). The within-assay coefficient of variation (CV) varied from 5.2 to 10.9%, and the between-assay CV was in the order of 13%. The assay sensitivity was 1 pg (0.5 μU) per tube, corresponding to 3 pg/ml plasma. Around the time of milking the plasma oxytocin profile showed a strong response to the preparation for milking, and a further effect related to the attachment of the teat cups of the milking machine. Peak concentrations were in the range of 15-50 pg/ml. During parturition there was a peak of oxytocin (65 pg/ml) coinciding with the expulsion phase. After this peak levels decreased by remained measurably elevated until the expulsion of the placenta. The plasma disappearance curve for immunoreactive oxutocin after the infusion of 100 IU oxytocin over a period of 1 h showed two components with apparent half-lives of 7-9 and 25 min, respectively. (author)

  7. Testosterone inhibits facilitating effects of parenting experience on parental behavior and the oxytocin neural system in mice.

    Science.gov (United States)

    Okabe, Shota; Kitano, Kanako; Nagasawa, Miho; Mogi, Kazutaka; Kikusui, Takefumi

    2013-06-13

    Parental behavior in mammals is facilitated by sensory experiences from infant, and by endocrine hormones. However, the interactions between these factors in the parental behavior of nonreproductive adults are not understood. We examined the interactive effects of gonadal hormones and the experience of repeated pup exposure on parental behavior in sexually naive mice. We also compared oxytocin (OT) expression levels in the paraventricular nucleus of the hypothalamus to behavioral outcomes. Clear sex differences were observed in retrieving tests; initial retrieving latency was shorter in females than in males, and 5-time pup exposure shortened retrieving latency in females only. Gonadectomy influenced neither initial retrieving latency nor pup sensitization in females. In contrast, gonadectomy shortened initial retrieving latency and caused pup sensitization in males. Estrogen implants given simultaneously with gonadectomy further shortened the initial retrieving latency in males, but pup sensitization was not affected and occurred in both sexes. In contrast, simultaneous testosterone implants impaired pup sensitization in both sexes. Similar to the results for responsiveness to pups, the number of OT neurons was increased by gonadectomy in males only. In comparison to gonadectomy only, OT neurons were decreased by simultaneous testosterone implants, but were not influenced by estrogen in either sex. Considering the parallel inhibitory effects of testosterone on both pup sensitization and number of OT neurons, we postulate that sex differences in parental responsiveness facilitated by repeated pup exposure were caused by an inhibitory effect of testosterone via the OT neural system in mice. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Oxytocin induces penile erection and yawning when injected into the bed nucleus of the stria terminalis: Involvement of glutamic acid, dopamine, and nitric oxide.

    Science.gov (United States)

    Sanna, Fabrizio; Bratzu, Jessica; Argiolas, Antonio; Melis, Maria Rosaria

    2017-11-01

    Oxytocin (5-100ng), but not Arg 8 -vasopressin (100ng), injected unilaterally into the bed nucleus of the stria terminalis (BNST) induces penile erection and yawning in a dose-dependent manner in male rats. The minimal effective dose was 20ng for penile erection and 5ng for yawning. Oxytocin responses were abolished not only by the oxytocin receptor antagonist d(CH 2 ) 5 Tyr(Me) 2 -Orn 8 -vasotocin (1μg), but also by (+) MK-801 (1μg), an excitatory amino acid receptor antagonist of the N-methyl-d-aspartic acid (NMDA) subtype, SCH 23390 (1μg), a D1 receptor antagonist, but not haloperidol (1μg), a D2 receptor antagonist, and SMTC (40μg), an inhibitor of neuronal nitric oxide synthase, injected into the BNST 15min before oxytocin. Oxytocin-induced penile erection, but not yawning, was also abolished by CNQX (1μg), an excitatory amino acid receptor antagonist of the AMPA subtype. In contrast, oxytocin responses were not reduced by bicuculline (20ng), a GABA A receptor antagonist, phaclofen (5μg), a GABA B receptor antagonist, CP 376395, a CRF receptor-1 antagonist (5μg), or astressin 2B, a CRF receptor-2 antagonist (150ng). Considering the ability of NMDA (100ng) to induce penile erection and yawning when injected into the BNST and the available evidence showing possible interaction among oxytocin, glutamic acid, and dopamine in the BNST, oxytocin possibly activates glutamatergic neurotransmission in the BNST. This in turn leads to the activation of neural pathways projecting back to the paraventricular nucleus, medial preoptic area, ventral tegmental area, and/or ventral subiculum/amygdala, thereby inducing penile erection and yawning. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Oxytocin-induced antinociception in the spinal cord is mediated by a subpopulation of glutamatergic neurons in lamina I-II which amplify GABAergic inhibition

    Directory of Open Access Journals (Sweden)

    Schlichter Rémy

    2008-05-01

    Full Text Available Abstract Background Recent evidence suggests that oxytocin (OT, secreted in the superficial spinal cord dorsal horn by descending axons of paraventricular hypothalamic nucleus (PVN neurons, produces antinociception and analgesia. The spinal mechanism of OT is, however, still unclear and requires further investigation. We have used patch clamp recording of lamina II neurons in spinal cord slices and immunocytochemistry in order to identify PVN-activated neurons in the superficial layers of the spinal cord and attempted to determine how this neuronal population may lead to OT-mediated antinociception. Results We show that OT released during PVN stimulation specifically activates a subpopulation of lamina II glutamatergic interneurons which are localized in the most superficial layers of the dorsal horn of the spinal cord (lamina I-II. This OT-specific stimulation of glutamatergic neurons allows the recruitment of all GABAergic interneurons in lamina II which produces a generalized elevation of local inhibition, a phenomenon which might explain the reduction of incoming Aδ and C primary afferent-mediated sensory messages. Conclusion Our results obtained in lamina II of the spinal cord provide the first clear evidence of a specific local neuronal network that is activated by OT release to induce antinociception. This OT-specific pathway might represent a novel and interesting therapeutic target for the management of neuropathic and inflammatory pain.

  10. Oxytocin and Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Gokce Nur Say

    2016-06-01

    Full Text Available Oxytocin is a neuropeptide that plays critical role in mother-infant bonding, pair bonding and prosocial behaviors. Several neuropsychiatric disorders such as autism, schizophrenia, affective disorders, anxiety disorders, attention deficit/hyperactivity disorder, alcohol/substance addiction, aggression, suicide, eating disorders and personality disorders show abnormalities of oxytocin system. These findings have given rise to the studies searching therapeutic use of oxytocin for psychi-atric disorders. The studies of oxytocin interventions in psychiatric disorders yielded potentially promising findings. This paper reviews the role of oxytocin in emotions, behavior and its effects in psychiatric disorders. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(2: 102-113

  11. Oxytocin modulates hemodynamic responses to monetary incentives in humans.

    Science.gov (United States)

    Mickey, Brian J; Heffernan, Joseph; Heisel, Curtis; Peciña, Marta; Hsu, David T; Zubieta, Jon-Kar; Love, Tiffany M

    2016-12-01

    Oxytocin is a neuropeptide widely recognized for its role in regulating social and reproductive behavior. Increasing evidence from animal models suggests that oxytocin also modulates reward circuitry in non-social contexts, but evidence in humans is lacking. We examined the effects of oxytocin administration on reward circuit function in 18 healthy men as they performed a monetary incentive task. The blood oxygenation level-dependent (BOLD) signal was measured using functional magnetic resonance imaging in the context of a randomized, double-blind, placebo-controlled, crossover trial of intranasal oxytocin. We found that oxytocin increases the BOLD signal in the midbrain (substantia nigra and ventral tegmental area) during the late phase of the hemodynamic response to incentive stimuli. Oxytocin's effects on midbrain responses correlated positively with its effects on positive emotional state. We did not detect an effect of oxytocin on responses in the nucleus accumbens. Whole-brain analyses revealed that oxytocin attenuated medial prefrontal cortical deactivation specifically during anticipation of loss. Our findings demonstrate that intranasal administration of oxytocin modulates human midbrain and medial prefrontal function during motivated behavior. These findings suggest that endogenous oxytocin is a neurochemical mediator of reward behaviors in humans-even in a non-social context-and that the oxytocinergic system is a potential target of pharmacotherapy for psychiatric disorders that involve dysfunction of reward circuitry.

  12. Intranasal oxytocin impedes the ability to ignore task-irrelevant facial expressions of sadness in students with depressive symptoms.

    Science.gov (United States)

    Ellenbogen, Mark A; Linnen, Anne-Marie; Cardoso, Christopher; Joober, Ridha

    2013-03-01

    The administration of oxytocin promotes prosocial behavior in humans. The mechanism by which this occurs is unknown, but it likely involves changes in social information processing. In a randomized placebo-controlled study, we examined the influence of intranasal oxytocin and placebo on the interference control component of inhibition (i.e. ability to ignore task-irrelevant information) in 102 participants using a negative affective priming task with sad, angry, and happy faces. In this task, participants are instructed to respond to a facial expression of emotion while simultaneously ignoring another emotional face. On the subsequent trial, the previously-ignored emotional valence may become the emotional valence of the target face. Inhibition is operationalized as the differential delay between responding to a previously-ignored emotional valence and responding to an emotional valence unrelated to the previous one. Although no main effect of drug administration on inhibition was observed, a drug × depressive symptom interaction (β = -0.25; t = -2.6, p < 0.05) predicted the inhibition of sad faces. Relative to placebo, participants with high depression scores who were administered oxytocin were unable to inhibit the processing of sad faces. There was no relationship between drug administration and inhibition among those with low depression scores. These findings are consistent with increasing evidence that oxytocin alters social information processing in ways that have both positive and negative social outcomes. Because elevated depression scores are associated with an increased risk for major depressive disorder, difficulties inhibiting mood-congruent stimuli following oxytocin administration may be associated with risk for depression. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Gender differences in oxytocin-associated disruption of decision bias during emotion perception.

    Science.gov (United States)

    Lynn, Spencer K; Hoge, Elizabeth A; Fischer, Laura E; Barrett, Lisa Feldman; Simon, Naomi M

    2014-09-30

    Oxytocin is associated with differences in the perception of and response to socially mediated information, such as facial expressions. Across studies, however, oxytocin׳s effect on emotion perception has been inconsistent. Outside the laboratory, emotion perception involves interpretation of perceptual uncertainty and assessment of behavioral risk. An account of these factors is largely missing from studies of oxytocin׳s effect on emotion perception and might explain inconsistent results across studies. Of relevance, studies of oxytocin׳s effect on learning and decision-making indicate that oxytocin attenuates risk aversion. We used the probability of encountering angry faces and the cost of misidentifying them as not angry to create a risky environment wherein bias to categorize faces as angry would maximize point earnings. Consistent with an underestimation of the factors creating risk (i.e., encounter rate and cost), men given oxytocin exhibited a worse (i.e., less liberal) response bias than men given placebo. Oxytocin did not influence women׳s performance. These results suggest that oxytocin may impair men׳s ability to adapt to changes in risk and uncertainty when introduced to novel or changing social environments. Because oxytocin also influences behavior in non-social realms, oxytocin pharmacotherapy could have unintended consequences (i.e., risk-prone decision-making) while nonetheless normalizing pathological social interaction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Oxytocin and the Biopsychology of Performance in Team Sports

    NARCIS (Netherlands)

    Pepping, Gert-Jan; Timmermans, Erik J.

    2012-01-01

    Little is known about the biopsychological underpinnings of expert performance in team sports. In this paper we show that there is a vast support for oxytocin as a neuropeptide involved in the encouragement of important processes linked to greater team performance in sport. We argue that oxytocin is

  15. Oxytocin modulates hemodynamic responses to monetary incentives in humans

    Science.gov (United States)

    Mickey, Brian J.; Heffernan, Joseph; Heisel, Curtis; Peciña, Marta; Hsu, David T.; Zubieta, Jon-Kar; Love, Tiffany M.

    2016-01-01

    Oxytocin is a neuropeptide widely recognized for its role in regulating social and reproductive behavior. Increasing evidence from animal models suggests that oxytocin also modulates reward circuitry in non-social contexts, but evidence in humans is lacking. Here we examined the effects of oxytocin administration on reward circuit function in 18 healthy men as they performed a monetary incentive task. The blood oxygenation level dependent (BOLD) signal was measured using functional magnetic resonance imaging in the context of a randomized, double-blind, placebo-controlled, crossover trial of intranasal oxytocin. We found that oxytocin increases the BOLD signal in the midbrain (substantia nigra and ventral tegmental area) during the late phase of the hemodynamic response to incentive stimuli. Oxytocin’s effects on midbrain responses correlated positively with its effects on positive emotional state. We did not detect an effect of oxytocin on responses in the nucleus accumbens. Whole-brain analyses revealed that oxytocin attenuated medial prefrontal cortical deactivation specifically during anticipation of loss. Our findings demonstrate that intranasal administration of oxytocin modulates human midbrain and medial prefrontal function during motivated behavior. These findings suggest that endogenous oxytocin is a neurochemical mediator of reward behaviors in humans – even in a non-social context – and that the oxytocinergic system is a potential target of pharmacotherapy for psychiatric disorders that involve dysfunction of reward circuitry. PMID:27614896

  16. Oxytocin in survivors of childhood-onset craniopharyngioma.

    Science.gov (United States)

    Daubenbüchel, Anna M M; Hoffmann, Anika; Eveslage, Maria; Özyurt, Jale; Lohle, Kristin; Reichel, Julia; Thiel, Christiane M; Martens, Henri; Geenen, Vincent; Müller, Hermann L

    2016-11-01

    Quality of survival of childhood-onset craniopharyngioma patients is frequently impaired by hypothalamic involvement or surgical lesions sequelae such as obesity and neuropsychological deficits. Oxytocin, a peptide hormone produced in the hypothalamus and secreted by posterior pituitary gland, plays a major role in regulation of behavior and body composition. In a cross-sectional study, oxytocin saliva concentrations were analyzed in 34 long-term craniopharyngioma survivors with and without hypothalamic involvement or treatment-related damage, recruited in the German Childhood Craniopharyngioma Registry, and in 73 healthy controls, attending the Craniopharyngioma Support Group Meeting 2014. Oxytocin was measured in saliva of craniopharyngioma patients and controls before and after standardized breakfast and associations with gender, body mass index, hypothalamic involvement, diabetes insipidus, and irradiation were analyzed. Patients with preoperative hypothalamic involvement showed similar oxytocin levels compared to patients without hypothalamic involvement and controls. However, patients with surgical hypothalamic lesions grade 1 (anterior hypothalamic area) presented with lower levels (p = 0.017) of oxytocin under fasting condition compared to patients with surgical lesion of posterior hypothalamic areas (grade 2) and patients without hypothalamic lesions (grade 0). Craniopharyngioma patients' changes in oxytocin levels before and after breakfast correlated (p = 0.02) with their body mass index. Craniopharyngioma patients continue to secrete oxytocin, especially when anterior hypothalamic areas are not involved or damaged, but oxytocin shows less variation due to nutrition. Oxytocin supplementation should be explored as a therapeutic option in craniopharyngioma patients with hypothalamic obesity and/or behavioral pathologies due to lesions of specific anterior hypothalamic areas. Clinical trial number: KRANIOPHARYNGEOM 2000/2007(NCT00258453; NCT01272622).

  17. The role of oxytocin in familiarization-habituation responses to social novelty

    Directory of Open Access Journals (Sweden)

    Mattie eTops

    2013-10-01

    Full Text Available Stress or arousal responses to novel social contexts ease off when individuals get familiar with the social context. In the present study we investigated whether oxytocin is involved in this process of familiarization-habituation, as oxytocin is known to increase trust and decrease anxiety. Fifty-nine healthy female subjects took part in the same experimental procedure in two sessions separated by four weeks. In the first (novelty session state trust scores were significantly positively correlated with salivary oxytocin levels, while in the second (familiarity session state trust scores were significantly negatively correlated with salivary oxytocin levels. In a path model, oxytocin was associated with increased trust in the novelty session and trust was associated with decreased oxytocin levels in the familiarity session. The results are consistent with the idea that oxytocin decreases stress-to-novelty responses by promoting familiarization to novel social contexts.

  18. Oxytocin in survivors of childhood-onset craniopharyngioma

    NARCIS (Netherlands)

    Daubenbuechel, Anna M. M.; Hoffmann, Anika; Eveslage, Maria; Oezyurt, Jale; Lohle, Kristin; Reichel, Julia; Thiel, Christiane M.; Martens, Henri; Geenen, Vincent; Mueller, Hermann L.

    2016-01-01

    Quality of survival of childhood-onset craniopharyngioma patients is frequently impaired by hypothalamic involvement or surgical lesions sequelae such as obesity and neuropsychological deficits. Oxytocin, a peptide hormone produced in the hypothalamus and secreted by posterior pituitary gland, plays

  19. Oxytocin in survivors of childhood-onset craniopharyngioma

    NARCIS (Netherlands)

    Daubenbuechel, Anna M. M.; Hoffmann, Anika; Eveslage, Maria; Oezyurt, Jale; Lohle, Kristin; Reichel, Julia; Thiel, Christiane M.; Martens, Henri; Geenen, Vincent; Mueller, Hermann L.

    Quality of survival of childhood-onset craniopharyngioma patients is frequently impaired by hypothalamic involvement or surgical lesions sequelae such as obesity and neuropsychological deficits. Oxytocin, a peptide hormone produced in the hypothalamus and secreted by posterior pituitary gland, plays

  20. Chloride sensing by WNK1 kinase involves inhibition of autophosphorylation

    Science.gov (United States)

    Piala, Alexander T.; Moon, Thomas M.; Akella, Radha; He, Haixia; Cobb, Melanie H.; Goldsmith, Elizabeth J.

    2014-01-01

    WNK1 [with no lysine (K)] is a serine-threonine kinase associated with a form of familial hypertension. WNK1 is at the top of a kinase cascade leading to phosphorylation of several cotransporters, in particular those transporting sodium, potassium, and chloride (NKCC), sodium and chloride (NCC), and potassium and chloride (KCC). The responsiveness of NKCC, NCC, and KCC to changes in extracellular chloride parallels their phosphorylation state, provoking the proposal that these transporters are controlled by a chloride-sensitive protein kinase. Here, we found that chloride stabilizes the inactive conformation of WNK1, preventing kinase autophosphorylation and activation. Crystallographic studies of inactive WNK1 in the presence of chloride revealed that chloride binds directly to the catalytic site, providing a basis for the unique position of the catalytic lysine. Mutagenesis of the chloride binding site rendered the kinase less sensitive to inhibition of autophosphorylation by chloride, validating the binding site. Thus, these data suggest that WNK1 functions as a chloride sensor through direct binding of a regulatory chloride ion to the active site, which inhibits autophosphorylation. PMID:24803536

  1. Oxytocin and first impressions

    OpenAIRE

    Friberg, Mads

    2012-01-01

    Subtle facial expressions may cause "core impressions" of other people, i.e. a feeling of like or dislike witch is affected by facial cues that is not explicitly and consciously recognized. In the present investigation, we were interested in how the neuropeptide oxytocin affects recognition of these subtle facial expressions. Participants received oxytocin or placebo, and viewed static and dynamic "hybrid" faces that showed a facial expression (happiness, anger, fear, sadness) only in the lo...

  2. Life in groups: the roles of oxytocin in mammalian sociality

    Directory of Open Access Journals (Sweden)

    Allison eAnacker

    2013-12-01

    Full Text Available In recent decades, scientific understanding of the many roles of oxytocin in social behavior has advanced tremendously. The focus of this research has been on maternal attachments and reproductive pair-bonds, and much less is known about the substrates of sociality outside of reproductive contexts. It is now apparent that oxytocin influences many aspects of social behavior including recognition, trust, empathy, and other components of the behavioral repertoire of social species. This review provides a comparative perspective on the contributions of oxytocin to life in mammalian social groups. We provide background on the functions of oxytocin in maternal attachments and the early social environment, and give an overview of the role of oxytocin circuitry in support of different mating systems. We then introduce peer relationships in group-living rodents as a means for studying the importance of oxytocin in non-reproductive affiliative behaviors. We review species differences in oxytocin receptor distributions in solitary and group-living species of South American tuco-tucos and in African mole-rats, as well as singing mice. We discuss variation in oxytocin receptor levels with seasonal changes in social behavior in female meadow voles, and the effects of oxytocin manipulations on peer huddling behavior. Finally, we discuss avenues of promise for future investigation, and relate current findings to research in humans and non-human primates. There is growing evidence that oxytocin is involved in social selectivity, including increases in aggression toward social outgroups and decreased huddling with unfamiliar individuals, which may support existing social structures or relationships at the expense of others. Oxytocin’s effects reach beyond maternal attachment and pair bonds to play a role in affiliative behavior underlying friendships, organization of broad social structures, and maintenance of established social relationships with individuals

  3. Oxytocin and the Biopsychology of Performance in Team Sports

    OpenAIRE

    Pepping, Gert-Jan; Timmermans, Erik J.

    2012-01-01

    Little is known about the biopsychological underpinnings of expert performance in team sports. In this paper we show that there is a vast support for oxytocin as a neuropeptide involved in the encouragement of important processes linked to greater team performance in sport. We argue that oxytocin is related to biopsychological processes aimed at convergence of emotions and moods between people, and in doing so it is a critical neuropeptide involved in the shaping of important team processes i...

  4. Oxytocin modulates human communication by enhancing cognitive exploration.

    Science.gov (United States)

    de Boer, Miriam; Kokal, Idil; Blokpoel, Mark; Liu, Rui; Stolk, Arjen; Roelofs, Karin; van Rooij, Iris; Toni, Ivan

    2017-12-01

    Oxytocin is a neuropeptide known to influence how humans share material resources. Here we explore whether oxytocin influences how we share knowledge. We focus on two distinguishing features of human communication, namely the ability to select communicative signals that disambiguate the many-to-many mappings that exist between a signal's form and meaning, and adjustments of those signals to the presumed cognitive characteristics of the addressee ("audience design"). Fifty-five males participated in a randomized, double-blind, placebo controlled experiment involving the intranasal administration of oxytocin. The participants produced novel non-verbal communicative signals towards two different addressees, an adult or a child, in an experimentally-controlled live interactive setting. We found that oxytocin administration drives participants to generate signals of higher referential quality, i.e. signals that disambiguate more communicative problems; and to rapidly adjust those communicative signals to what the addressee understands. The combined effects of oxytocin on referential quality and audience design fit with the notion that oxytocin administration leads participants to explore more pervasively behaviors that can convey their intention, and diverse models of the addressees. These findings suggest that, besides affecting prosocial drive and salience of social cues, oxytocin influences how we share knowledge by promoting cognitive exploration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Oxytocin and the Biopsychology of Performance in Team Sports

    Science.gov (United States)

    Pepping, Gert-Jan; Timmermans, Erik J.

    2012-01-01

    Little is known about the biopsychological underpinnings of expert performance in team sports. In this paper we show that there is a vast support for oxytocin as a neuropeptide involved in the encouragement of important processes linked to greater team performance in sport. We argue that oxytocin is related to biopsychological processes aimed at convergence of emotions and moods between people, and in doing so it is a critical neuropeptide involved in the shaping of important team processes in sport such as trust, generosity, altruism, cohesion, cooperation, and social motivation, and also envy and gloating. Future research should examine the role of oxytocin in these essential components of sport performance. In particular, the link between oxytocin, emotional contagion and the cultivation of experiences of positive emotions is a worthwhile line of investigation for sport participation and development as well as high performance in sport. PMID:22997498

  6. Oxytocin and the biopsychology of performance in team sports.

    Science.gov (United States)

    Pepping, Gert-Jan; Timmermans, Erik J

    2012-01-01

    Little is known about the biopsychological underpinnings of expert performance in team sports. In this paper we show that there is a vast support for oxytocin as a neuropeptide involved in the encouragement of important processes linked to greater team performance in sport. We argue that oxytocin is related to biopsychological processes aimed at convergence of emotions and moods between people, and in doing so it is a critical neuropeptide involved in the shaping of important team processes in sport such as trust, generosity, altruism, cohesion, cooperation, and social motivation, and also envy and gloating. Future research should examine the role of oxytocin in these essential components of sport performance. In particular, the link between oxytocin, emotional contagion and the cultivation of experiences of positive emotions is a worthwhile line of investigation for sport participation and development as well as high performance in sport.

  7. Oxytocin and the Biopsychology of Performance in Team Sports

    Directory of Open Access Journals (Sweden)

    Gert-Jan Pepping

    2012-01-01

    Full Text Available Little is known about the biopsychological underpinnings of expert performance in team sports. In this paper we show that there is a vast support for oxytocin as a neuropeptide involved in the encouragement of important processes linked to greater team performance in sport. We argue that oxytocin is related to biopsychological processes aimed at convergence of emotions and moods between people, and in doing so it is a critical neuropeptide involved in the shaping of important team processes in sport such as trust, generosity, altruism, cohesion, cooperation, and social motivation, and also envy and gloating. Future research should examine the role of oxytocin in these essential components of sport performance. In particular, the link between oxytocin, emotional contagion and the cultivation of experiences of positive emotions is a worthwhile line of investigation for sport participation and development as well as high performance in sport.

  8. Oxytocin, stress and social behavior: neurogenetics of the human oxytocin system.

    Science.gov (United States)

    Kumsta, Robert; Heinrichs, Markus

    2013-02-01

    The neuropeptide oxytocin has had key roles throughout mammalian evolution in the regulation of complex social cognition and behaviors, such as attachment, parental care, pair-bonding, as well as social exploration and recognition. Recently, studies have begun to provide evidence that the function of this neuropeptide is impaired in mental disorders associated with social deficits. In this review, we focus on the genetic mechanisms of inter-individual variation in the social neuropeptide signaling. We discuss molecular genetic studies which identified variations in specific genes contributing to individual differences in social behavior and cognition, with a focus on the gene coding for the oxytocin receptor (OXTR) emerging as a particularly promising candidate. We conclude that molecular studies are warranted to elucidate functional consequences of variants that have shown stable associations with sociobehavioral phenotypes. With regard to the variability in individual responses to oxytocin administration, we advocate the need for pharmacogenetic approaches in order to test how the efficacy of oxytocin administration is modulated by genetic variation of OXTR or other genes involved in oxytocin signaling. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Oxytocin and eating disorders: a narrative review on emerging findings and perspectives.

    Science.gov (United States)

    Giel, Katrin; Zipfel, Stephan; Hallschmid, Manfred

    2017-11-28

    The hypothalamic neuropeptide oxytocin regulates reproductive behavior and mother-infant interaction, and conclusive studies in humans indicate that oxytocin is also a potent modulator of psychosocial function. Pilot experiments have yielded first evidence that this neuropeptide moreover influences eating behavior. Brain administration of oxytocin in animals with normal weight, but also with diet-induced or genetically induced obesity, attenuates food intake and reduces body weight. In normal-weight and obese individuals, acute intranasal oxytocin delivery curbs calorie intake from main dishes and snacks. Such effects might converge with the poignant social and cognitive impact of oxytocin to also improve dysfunctional eating behavior in the therapeutic context. This assumption has received support in first studies showing that oxytocin might play a role in the disease process of anorexia nervosa. In contrast, respective experiments in patients with bulimia nervosa and binge eating disorder are still scarce. We briefly summarize currently available studies on the involvement of the oxytocin system in the pathophysiology of eating disorders, as well as on the effects of oxytocin administration in patients with these disorders. We propose a framework of oxytocin's role and its therapeutic potential in eating disorders that aims at integrating social and metabolic aspects of its pharmacological profile, and ponder perspectives and limitations of oxytocin use in the clinical setting. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Involvement of the oxytocin system in the bed nucleus of the stria terminalis in the sex-specific regulation of social recognition

    Science.gov (United States)

    Dumais, Kelly M.; Alonso, Andrea G.; Immormino, Marisa A.; Bredewold, Remco; Veenema, Alexa H.

    2015-01-01

    Sex differences in the oxytocin (OT) system in the brain may explain why OT often regulates social behaviors in sex-specific ways. However, a link between sex differences in the OT system and sex-specific regulation of social behavior has not been tested. Here, we determined whether sex differences in the OT receptor (OTR) or in OT release in the posterior bed nucleus of the stria terminalis (pBNST) mediates sex-specific regulation of social recognition in rats. We recently showed that, compared to female rats, male rats have a three-fold higher OTR binding density in the pBNST, a sexually dimorphic area implicated in the regulation of social behaviors. We now demonstrate that OTR antagonist (5 ng/0.5 μl/side) administration into the pBNST impairs social recognition in both sexes, while OT (100 pg/0.5 μl/side) administration into the pBNST prolongs the duration of social recognition in males only. These effects seem specific to social recognition, as neither treatment altered total social investigation time in either sex. Moreover, baseline OT release in the pBNST, as measured with in vivo microdialysis, did not differ between the sexes. However, males showed higher OT release in the pBNST during social recognition compared to females. These findings suggest a sex-specific role of the OT system in the pBNST in the regulation of social recognition. PMID:26630388

  11. Effects of chronic social defeat on social behaviors in adult female mandarin voles (Microtus mandarinus): Involvement of the oxytocin system in the nucleus accumbens.

    Science.gov (United States)

    Wang, Limin; Hou, Wenjuan; He, Zhixiong; Yuan, Wei; Yang, Jinfeng; Yang, Yang; Jia, Rui; Zhu, Zhenxiang; Zhou, Yue; Tai, Fadao

    2018-03-02

    Chronic social defeat affects many aspects of behavior. Most previous studies have focused on effects on males and defeat during adolescence. The extents to which chronic social defeat can impact female social behavior in adulthood and the neural mechanisms of such effects are poorly understood. Using highly social and aggressive female mandarin voles (Microtus mandarinus), the present study found that chronic social defeat reduced social preference in adult females, and that the defeated voles exhibited a high level of freeze, self-grooming and defensive behavior, as well as reduced exploration, intimacy and aggression during social interactions. Furthermore, chronic social defeat reduced levels of oxytocin (OT) and OT receptors (OTR) in the shell region of the nucleus accumbens (NACC). Intra-NACC shell OT microinjections reversed alterations in social behavior induced by chronic social defeat, whereas injections of an OTR antagonist (OTR-A) blocked the effects of OT. Taken together, our data demonstrate that chronic social defeat suppresses measures of sociability, and that these effects are mediated by the action of OT on the OTR in the NACC. NACC OT may be a promising target to treat socio-emotional disorders induced by chronic social stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Oxytocin, testosterone, and human social cognition.

    Science.gov (United States)

    Crespi, Bernard J

    2016-05-01

    I describe an integrative social-evolutionary model for the adaptive significance of the human oxytocinergic system. The model is based on a role for this hormone in the generation and maintenance of social familiarity and affiliation across five homologous, functionally similar, and sequentially co-opted contexts: mothers with offspring, female and male mates, kin groups, individuals with reciprocity partners, and individuals within cooperating and competing social groups defined by culture. In each situation, oxytocin motivates, mediates and rewards the cognitive and behavioural processes that underlie the formation and dynamics of a more or less stable social group, and promotes a relationship between two or more individuals. Such relationships may be positive (eliciting neurological reward, reducing anxiety and thus indicating fitness-enhancing effects), or negative (increasing anxiety and distress, and thus motivating attempts to alleviate a problematic, fitness-reducing social situation). I also present evidence that testosterone exhibits opposite effects from oxytocin on diverse aspects of cognition and behaviour, most generally by favouring self-oriented, asocial and antisocial behaviours. I apply this model for effects of oxytocin and testosterone to understanding human psychological disorders centrally involving social behaviour. Reduced oxytocin and higher testosterone levels have been associated with under-developed social cognition, especially in autism. By contrast, some combination of oxytocin increased above normal levels, and lower testosterone, has been reported in a notable number of studies of schizophrenia, bipolar disorder and depression, and, in some cases, higher oxytocin involves maladaptively 'hyper-developed' social cognition in these conditions. This pattern of findings suggests that human social cognition and behaviour are structured, in part, by joint and opposing effects of oxytocin and testosterone, and that extremes of such joint

  13. An Early Postnatal Oxytocin Treatment Prevents Social and Learning Deficits in Adult Mice Deficient for Magel2, a Gene Involved in Prader-Willi Syndrome and Autism.

    Science.gov (United States)

    Meziane, Hamid; Schaller, Fabienne; Bauer, Sylvian; Villard, Claude; Matarazzo, Valery; Riet, Fabrice; Guillon, Gilles; Lafitte, Daniel; Desarmenien, Michel G; Tauber, Maithé; Muscatelli, Françoise

    2015-07-15

    Mutations of MAGEL2 have been reported in patients presenting with autism, and loss of MAGEL2 is also associated with Prader-Willi syndrome, a neurodevelopmental genetic disorder. This study aimed to determine the behavioral phenotype of Magel2-deficient adult mice, to characterize the central oxytocin (OT) system of these mutant mice, and to test the curative effect of a peripheral OT treatment just after birth. We assessed the social and cognitive behavior of Magel2-deficient mice, analyzed the OT system of mutant mice treated or not by a postnatal administration of OT, and determined the effect of this treatment on the brain. Magel2 inactivation induces a deficit in social recognition and social interaction and a reduced learning ability in adult male mice. In these mice, we reveal anatomical and functional modifications of the OT system and show that these defects change from birth to adulthood. Daily administration of OT in the first postnatal week was sufficient to prevent deficits in social behavior and learning abilities in adult mutant male mice. We show that this OT treatment partly restores a normal OT system. Thus, we report that an alteration of the OT system around birth has long-term consequences on behavior and on cognition. Importantly, an acute OT treatment of Magel2-deficient pups has a curative effect. Our study reveals that OT plays a crucial role in setting social behaviors during a period just after birth. An early OT treatment in this critical period could be a novel therapeutic approach for the treatment of neurodevelopmental disorders such as Prader-Willi syndrome and autism. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. Effects of oxytocin and vasopressin on the neural response to unreciprocated cooperation within brain regions involved in stress and anxiety in men and women.

    Science.gov (United States)

    Chen, Xu; Hackett, Patrick D; DeMarco, Ashley C; Feng, Chunliang; Stair, Sabrina; Haroon, Ebrahim; Ditzen, Beate; Pagnoni, Giuseppe; Rilling, James K

    2016-06-01

    Anxiety disorders are characterized by hyperactivity in both the amygdala and the anterior insula. Interventions that normalize activity in these areas may therefore be effective in treating anxiety disorders. Recently, there has been significant interest in the potential use of oxytocin (OT), as well as vasopressin (AVP) antagonists, as treatments for anxiety disorders. In this double-blind, placebo-controlled, pharmaco- fMRI study, 153 men and 151 women were randomized to treatment with either 24 IU intranasal OT, 20 IU intranasal AVP, or placebo and imaged with fMRI as they played the iterated Prisoner's Dilemma game with same-sex human and computer partners. In men, OT attenuated the fMRI response to unreciprocated cooperation (CD), a negative social interaction, within the amygdala and anterior insula. This effect was specific to interactions with human partners. In contrast, among women, OT unexpectedly attenuated the amygdala and anterior insula response to unreciprocated cooperation from computer but not human partners. Among women, AVP did not significantly modulate the response to unreciprocated cooperation in either the amygdala or the anterior insula. However, among men, AVP attenuated the BOLD response to CD outcomes with human partners across a relatively large cluster including the amygdala and the anterior insula, which was contrary to expectations. Our results suggest that OT may decrease the stress of negative social interactions among men, whereas these effects were not found in women interacting with human partners. These findings support continued investigation into the possible efficacy of OT as a treatment for anxiety disorders.

  15. Social preference and maternal defeat-induced social avoidance in virgin female rats: sex differences in involvement of brain oxytocin and vasopressin.

    Science.gov (United States)

    Lukas, Michael; Neumann, Inga D

    2014-08-30

    Research concerning non-reproductive sociability in rodents is mainly restricted to assessing the effects of oxytocin (OXT) and arginine-vasopressin (AVP) in male rats and mice. Comparable studies on natural social preference and social avoidance in females are substantially lacking. Here, we adapted a behavioral paradigm for monitoring social preference of female rats consisting of two consecutive exposures to either non-social or social stimuli. Further, to induce stimulus-specific social avoidance, female rats were exposed to a single 10-min maternal defeat by a lactating dam. Social preference towards same-sex conspecifics in female rats was shown to be independent of the estrous cycle and even more pronounced than in male rats. Intracerebroventricular (icv) application of OXT, AVP, or their selective receptor antagonists or agonists, did not alter naturally-occurring social preference in female rats. Stimulus-specific social avoidance could be induced by prior exposure to a lactating rat: an effect that could not be reversed/overcome by icv OXT. The female social preference paradigm for rats established in this study detected subtle sex differences in social preference behavior of rats. Further, stimulus-specific social deficits could be induced in female rats using an acute exposure to social defeat - as previously observed in male rodents. Female rats show strong social preference behavior, which can be prevented by social defeat, but does not seem to be regulated by the OXT or AVP systems. Accordingly, icv application of synthetic OXT does not reverse maternal defeat-induced social avoidance in female rats. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Involvement of the oxytocin system in the bed nucleus of the stria terminalis in the sex-specific regulation of social recognition.

    Science.gov (United States)

    Dumais, Kelly M; Alonso, Andrea G; Immormino, Marisa A; Bredewold, Remco; Veenema, Alexa H

    2016-02-01

    Sex differences in the oxytocin (OT) system in the brain may explain why OT often regulates social behaviors in sex-specific ways. However, a link between sex differences in the OT system and sex-specific regulation of social behavior has not been tested. Here, we determined whether sex differences in the OT receptor (OTR) or in OT release in the posterior bed nucleus of the stria terminalis (pBNST) mediates sex-specific regulation of social recognition in rats. We recently showed that, compared to female rats, male rats have a three-fold higher OTR binding density in the pBNST, a sexually dimorphic area implicated in the regulation of social behaviors. We now demonstrate that OTR antagonist (5 ng/0.5 μl/side) administration into the pBNST impairs social recognition in both sexes, while OT (100 pg/0.5 μl/side) administration into the pBNST prolongs the duration of social recognition in males only. These effects seem specific to social recognition, as neither treatment altered total social investigation time in either sex. Moreover, baseline OT release in the pBNST, as measured with in vivo microdialysis, did not differ between the sexes. However, males showed higher OT release in the pBNST during social recognition compared to females. These findings suggest a sex-specific role of the OT system in the pBNST in the regulation of social recognition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Mode of Action of the Natural Insecticide, Decaleside Involves Sodium Pump Inhibition.

    Directory of Open Access Journals (Sweden)

    Yallappa Rajashekar

    Full Text Available Decalesides are a new class of natural insecticides which are toxic to insects by contact via the tarsal gustatory chemosensilla. The symptoms of their toxicity to insects and the rapid knockdown effect suggest neurotoxic action, but the precise mode of action and the molecular targets for decaleside action are not known. We have presented experimental evidence for the involvement of sodium pump inhibition in the insecticidal action of decaleside in the cockroach and housefly. The knockdown effect of decaleside is concomitant with the in vivo inhibition of Na+, K+ -ATPase in the head and thorax. The lack of insecticidal action by experimental ablation of tarsi or blocking the tarsal sites with paraffin correlated with lack of inhibition of Na+- K+ ATPase in vivo. Maltotriose, a trisaccharide, partially rescued the toxic action of decaleside as well as inhibition of the enzyme, suggesting the possible involvement of gustatory sugar receptors. In vitro studies with crude insect enzyme preparation and purified porcine Na+, K+ -ATPase showed that decaleside competitively inhibited the enzyme involving the ATP binding site. Our study shows that the insecticidal action of decaleside via the tarsal gustatory sites is causally linked to the inhibition of sodium pump which represents a unique mode of action. The precise target(s for decaleside in the tarsal chemosensilla and the pathway linked to inhibition of sodium pump and the insecticidal action remain to be understood.

  18. Mode of Action of the Natural Insecticide, Decaleside Involves Sodium Pump Inhibition.

    Science.gov (United States)

    Rajashekar, Yallappa; Shivanandappa, Thimmappa

    2017-01-01

    Decalesides are a new class of natural insecticides which are toxic to insects by contact via the tarsal gustatory chemosensilla. The symptoms of their toxicity to insects and the rapid knockdown effect suggest neurotoxic action, but the precise mode of action and the molecular targets for decaleside action are not known. We have presented experimental evidence for the involvement of sodium pump inhibition in the insecticidal action of decaleside in the cockroach and housefly. The knockdown effect of decaleside is concomitant with the in vivo inhibition of Na+, K+ -ATPase in the head and thorax. The lack of insecticidal action by experimental ablation of tarsi or blocking the tarsal sites with paraffin correlated with lack of inhibition of Na+- K+ ATPase in vivo. Maltotriose, a trisaccharide, partially rescued the toxic action of decaleside as well as inhibition of the enzyme, suggesting the possible involvement of gustatory sugar receptors. In vitro studies with crude insect enzyme preparation and purified porcine Na+, K+ -ATPase showed that decaleside competitively inhibited the enzyme involving the ATP binding site. Our study shows that the insecticidal action of decaleside via the tarsal gustatory sites is causally linked to the inhibition of sodium pump which represents a unique mode of action. The precise target(s) for decaleside in the tarsal chemosensilla and the pathway linked to inhibition of sodium pump and the insecticidal action remain to be understood.

  19. A randomised controlled trial comparing oxytocin and oxytocin + ...

    African Journals Online (AJOL)

    'rule of threes' as a means of administering oxytocin: 3 IU IVI as a slow bolus every 3 minutes depending on the contraction of the uterus.[5] The following guidelines were published in the SAMJ in. April 2015 for primary prophylaxis of PPH at CS:[6] (i) oxytocin. 2.5 IU IVI as a slow bolus (over 30 seconds); (ii) oxytocin 7.5 IU.

  20. Neonatal paternal deprivation impairs social recognition and alters levels of oxytocin and estrogen receptor α mRNA expression in the MeA and NAcc, and serum oxytocin in mandarin voles.

    Science.gov (United States)

    Cao, Yan; Wu, Ruiyong; Tai, Fadao; Zhang, Xia; Yu, Peng; An, Xiaolei; Qiao, Xufeng; Hao, Ping

    2014-01-01

    Paternal care is necessary for the healthy development of social behavior in monogamous rodents and social recognition underpins social behavior in these animals. The effects of paternal care on the development of social recognition and underlying neuroendocrine mechanisms, especially the involvement of oxytocin and estrogen pathways, remain poorly understood. We investigated the effects of paternal deprivation (PD: father was removed from neonatal pups and mother alone raised the offspring) on social recognition in mandarin voles (Microtus mandarinus), a socially monogamous rodent. Paternal deprivation was found to inhibit the development of social recognition in female and male offspring according to a habituation-dishabituation paradigm. Paternal deprivation resulted in increased inactivity and reduced investigation during new encounters with other animals. Paternal deprivation reduced oxytocin receptor (OTR) and estrogen receptor α (ERα) mRNA expression in the medial amygdala and nucleus accumbens. Paternal deprivation reduced serum oxytocin (OT) concentration in females, but had no effect on males. Our results provide substantial evidence that paternal deprivation inhibits the development of social recognition in female and male mandarin voles and alters social behavior later in life. This is possibly the result of altered expression of central OTR and ERα and serum OT levels caused by paternal deprivation. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Hypothalamic oxytocin mediates social buffering of the stress response.

    Science.gov (United States)

    Smith, Adam S; Wang, Zuoxin

    2014-08-15

    While stressful life events can enhance the risk of mental disorders, positive social interactions can propagate good mental health and normal behavioral routines. Still, the neural systems that promote these benefits are undetermined. Oxytocin is a hormone involved in social behavior and stress; thus, we focus on the impact that social buffering has on the stress response and the governing effects of oxytocin. Female prairie voles (Microtus ochrogaster) were exposed to 1 hour immobilization stress and then recovered alone or with their male partner to characterize the effect of social contact on the behavioral, physiological, and neuroendocrine stress response. In addition, we treated immobilized female voles recovering alone with oxytocin or vehicle and female voles recovering with their male partner with a selective oxytocin receptor antagonist or vehicle. Group sizes varied from 6 to 8 voles (N = 98 total). We found that 1 hour immobilization increased anxiety-like behaviors and circulating levels of corticosterone, a stress hormone, in female prairie voles recovering alone but not the female prairie voles recovering with their male partner. This social buffering by the male partner on biobehavioral responses to stress was accompanied by increased oxytocin release in the paraventricular nucleus of the hypothalamus. Intra-paraventricular nucleus oxytocin injections reduced behavioral and corticosterone responses to immobilization, whereas injections of an oxytocin receptor antagonist blocked the effects of the social buffering. Together, our data demonstrate that paraventricular nucleus oxytocin mediates the social buffering effects on the stress response and thus may be a target for treatment of stress-related disorders. Published by Society of Biological Psychiatry on behalf of Society of Biological Psychiatry.

  2. Neonatal oxytocin manipulations have long-lasting, sexually dimorphic effects on vasopressin receptors

    OpenAIRE

    Bales, KL; Plotsky, PM; Young, LJ; Lim, MM; Grotte, N; Ferrer, E; Carter, CS

    2007-01-01

    Developmental exposure to oxytocin (OT) or oxytocin antagonists (OTAs) has been shown to cause long-lasting and often sexually dimorphic effects on social behaviors in prairie voles (Microtus ochrogaster). Because regulation of social behavior in monogamous mammals involves central receptors for OT, arginine vasopressin (AVP), and dopamine, we examined the hypothesis that the lon...

  3. First experiences with neuropsychological effects of oxytocin administration in childhood-onset craniopharyngioma.

    Science.gov (United States)

    Hoffmann, Anika; Özyurt, Jale; Lohle, Kristin; Reichel, Julia; Thiel, Christiane M; Müller, Hermann L

    2017-04-01

    The hypothalamic hormone oxytocin plays a major role in regulation of behavior and body composition. Quality of survival is frequently impaired in childhood craniopharyngioma patients due to sequelae such as behavioral deficits and severe obesity caused by tumor or treatment-related hypothalamic lesions. In our pilot cross-sectional study, we analyzed emotion recognition abilities and oxytocin concentrations in saliva and urine before and after single nasal administration of 24 IU oxytocin in 10 craniopharyngioma patients. Four craniopharyngioma presented with grade I lesions (limited to anterior hypothalamic areas) and 6 craniopharyngioma with grade II lesions (involving mammillary bodies and posterior hypothalamic areas). Emotional tasks were assessed before and after administration of oxytocin using the Geneva multimodal emotion portrayals corpus and the Multidimensional Mood Questionnaire. All patients presented with detectable levels of oxytocin before administration. Nasal administration of oxytocin was well-tolerated and resulted in increased oxytocin concentrations in saliva and urine. After oxytocin administration, craniopharyngioma patients with postsurgical lesions limited to the anterior hypothalamus area showed improvements in emotional identifications compared to craniopharyngioma patients with lesions of anterior and posterior hypothalamic areas. Focusing on correct assignments to positive and negative emotion categories, craniopharyngioma patients improved assignment to negative emotions. Oxytocin might have positive effects on emotion perception in craniopharyngioma patients with specific lesions of the anterior hypothalamic area. Further studies on larger cohorts are warranted.

  4. Oxytocin and social functioning

    OpenAIRE

    Jones, Candace; Barrera, Ingrid; Brothers, Shaun; Ring, Robert; Wahlestedt, Claes

    2017-01-01

    Social anxiety is a form of anxiety characterized by continuous fear of one or more social or performance situations. Although multiple treatment modalities (cognitive behavioral therapy, selective serotonin reuptake inhibitors/selective norepinephrine reuptake inhibitors, benzodiazepines) exist for social anxiety, they are effective for only 60% to 70% of patients. Thus, researchers have looked for other candidates for social anxiety treatment. Our review focuses on the peptide oxytocin as a...

  5. Intrapartum synthetic oxytocin reduce the expression of primitive reflexes associated with breastfeeding.

    Science.gov (United States)

    Marín Gabriel, Miguel A; Olza Fernández, Ibone; Malalana Martínez, Ana M; González Armengod, Carmen; Costarelli, Valeria; Millán Santos, Isabel; Fernández-Cañadas Morillo, Aurora; Pérez Riveiro, Pilar; López Sánchez, Francisco; García Murillo, Lourdes

    2015-05-01

    Several synthetic peptide manipulations during the time surrounding birth can alter the specific neurohormonal status in the newborn brain. This study is aimed at assessing whether intrapartum oxytocin administration has any effect on primitive neonatal reflexes and determining whether such an effect is dose-dependent. A cohort prospective study was conducted at a tertiary hospital. Mother-infant dyads who received intrapartum oxytocin (n=53) were compared with mother-infant dyads who did not receive intrapartum oxytocin (n=45). Primitive neonatal reflexes (endogenous, antigravity, motor, and rhythmic reflexes) were quantified by analyzing videotaped breastfeeding sessions in a biological nurturing position. Two observers blind to the group assignment and the oxytocin dose analyzed the videotapes and assesed the newborn's state of consciousness according to the Brazelton scale. The release of all rhythmic reflexes (p=0.01), the antigravity reflex (p=0.04), and total primitive neonatal reflexes (p=0.02) in the group exposed to oxytocin was lower than in the group not exposed to oxytocin. No correlations were observed between the dose of oxytocin administered and the percentage of primitive neonatal reflexes released (r=0.03; p=0.82). Intrapartum oxytocin administration might inhibit the expression of several primitive neonatal reflexes associated with breastfeeding. This correlation does not seem to be dose-dependent.

  6. Saliva oxytocin measures do not reflect peripheral plasma concentrations after intranasal oxytocin administration in men.

    Science.gov (United States)

    Quintana, Daniel S; Westlye, Lars T; Smerud, Knut T; Mahmoud, Ramy A; Andreassen, Ole A; Djupesland, Per G

    2018-05-16

    Oxytocin plays an important role in social behavior. Thus, there has been significant research interest for the role of the oxytocin system in several psychiatric disorders, and the potential of intranasal oxytocin administration to treat social dysfunction. Measurement of oxytocin concentrations in saliva are sometimes used to approximate peripheral levels of oxytocin; however, the validity of this approach is unclear. In this study, saliva and plasma oxytocin was assessed after two doses of Exhalation Delivery System delivered intranasal oxytocin (8 IU and 24 IU), intravenous oxytocin (1 IU) and placebo in a double-dummy, within-subjects design with men. We found that intranasal oxytocin (8 IU and 24 IU) administration increased saliva oxytocin concentrations in comparison to saliva oxytocin concentration levels after intravenous and placebo administration. Additionally, we found that saliva oxytocin concentrations were not significantly associated with plasma oxytocin concentrations after either intranasal or intravenous oxytocin administration. Altogether, we suggest that saliva oxytocin concentrations do not accurately index peripheral oxytocin after intranasal or intravenous oxytocin administration, at least in men. The data indicates that elevated oxytocin saliva levels after nasal delivery primarily reflect exogenous administered oxytocin that is cleared from the nasal cavity to the oropharynx, and is therefore a weak surrogate for peripheral blood measurements. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. The oxytocin/vasopressin receptor antagonist atosiban delays the gastric emptying of a semisolid meal compared to saline in human

    Directory of Open Access Journals (Sweden)

    Ekberg Olle

    2006-03-01

    Full Text Available Abstract Background Oxytocin is released in response to a meal. Further, mRNA for oxytocin and its receptor have been found throughout the gastrointestinal (GI tract. The aim of this study was therefore to examine whether oxytocin, or the receptor antagonist atosiban, influence the gastric emptying. Methods Ten healthy volunteers (five men were examined regarding gastric emptying at three different occasions: once during oxytocin stimulation using a pharmacological dose; once during blockage of the oxytocin receptors (which also blocks the vasopressin receptors and thereby inhibiting physiological doses of oxytocin; and once during saline infusion. Gastric emptying rate (GER was assessed and expressed as the percentage reduction in antral cross-sectional area from 15 to 90 min after ingestion of rice pudding. The assessment was performed by real-time ultrasonography. At the same time, the feeling of satiety was registered using visual satiety scores. Results Inhibition of the binding of endogenous oxytocin by the receptor antagonist delayed the GER by 37 % compared to saline (p = 0.037. In contrast, infusion of oxytocin in a dosage of 40 mU/min did not affect the GER (p = 0.610. Satiation scores areas in healthy subjects after receiving atosiban or oxytocin did not show any significant differences. Conclusion Oxytocin and/or vasopressin seem to be regulators of gastric emptying during physiological conditions, since the receptor antagonist atosiban delayed the GER. However, the actual pharmacological dose of oxytocin in this study had no effect. The effect of oxytocin and vasopressin on GI motility has to be further evaluated.

  8. Intranasal administration of oxytocin increases envy and schadenfreude (gloating).

    Science.gov (United States)

    Shamay-Tsoory, Simone G; Fischer, Meytal; Dvash, Jonathan; Harari, Hagai; Perach-Bloom, Nufar; Levkovitz, Yechiel

    2009-11-01

    Humans have a strong social tendency to compare themselves with others. We tend to feel envious when we receive less valuable rewards and may rejoice when our payoffs are more advantageous. Envy and schadenfreude (gloating over the other's misfortune) are social emotions widely agreed to be a symptom of the human social tendency to compare one's payoffs with those of others. Given the important social components of envy and gloating, we speculated that oxytocin may have a modulating effect on the intensity of these emotions. Fifty-six participants participated in this double-blind, placebo-controlled, within-subject study. Following the administration of oxytocin or a placebo, participants played a game of chance with another (fake) participant who either won more money (envy manipulation), lost more money (schadenfreude manipulation), or won/lost equal amounts of money. In comparison with the placebo, oxytocin increased the envy ratings during unequal monetary gain conditions involving relative loss (when the participant gained less money than another player). Oxytocin also increased the ratings of gloating during relative gain conditions (when the participant gained more money than the other player). By contrast, oxytocin had no effect on the emotional ratings following equal monetary gains nor did it affect general mood ratings. These results suggest that the oxytocinergic system is involved in modulating envy and gloating. Thus, contrary to the prevailing belief that this system is involved solely in positive prosocial behaviors, it probably plays a key role in a wider range of social emotion-related behaviors.

  9. Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal.

    Science.gov (United States)

    Riem, Madelon M E; van IJzendoorn, Marinus H; Tops, Mattie; Boksem, Maarten A S; Rombouts, Serge A R B; Bakermans-Kranenburg, Marian J

    2013-10-01

    The neuropeptide oxytocin has been implicated in a variety of social processes. However, recent studies indicate that oxytocin does not enhance prosocial behavior in all people in all circumstances. Here, we investigate effects of intranasal oxytocin administration on intrinsic functional brain connectivity with resting state functional magnetic resonance imaging. Participants were 42 women who received a nasal spray containing either 16 IU of oxytocin or a placebo and reported how often their mother used love withdrawal as a disciplinary strategy involving withholding love and affection after a failure or misbehavior. We found that oxytocin changes functional connectivity between the posterior cingulate cortex (PCC) and the brainstem. In the oxytocin group there was a positive connectivity between these regions, whereas the placebo group showed negative connectivity. In addition, oxytocin induced functional connectivity changes between the PCC, the cerebellum and the postcentral gyrus, but only for those participants who experienced low levels of maternal love withdrawal. We speculate that oxytocin enhances prosocial behavior by influencing complex brain networks involved in self-referential processing and affectionate touch, most prominently in individuals with supportive family backgrounds. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

  10. Mechanisms of the anti-obesity effects of oxytocin in diet-induced obese rats.

    Directory of Open Access Journals (Sweden)

    Nicolas Deblon

    Full Text Available Apart from its role during labor and lactation, oxytocin is involved in several other functions. Interestingly, oxytocin- and oxytocin receptor-deficient mice develop late-onset obesity with normal food intake, suggesting that the hormone might exert a series of beneficial metabolic effects. This was recently confirmed by data showing that central oxytocin infusion causes weight loss in diet-induced obese mice. The aim of the present study was to unravel the mechanisms underlying such beneficial effects of oxytocin. Chronic central oxytocin infusion was carried out in high fat diet-induced obese rats. Its impact on body weight, lipid metabolism and insulin sensitivity was determined. We observed a dose-dependent decrease in body weight gain, increased adipose tissue lipolysis and fatty acid β-oxidation, as well as reduced glucose intolerance and insulin resistance. The additional observation that plasma oxytocin levels increased upon central infusion suggested that the hormone might affect adipose tissue metabolism by direct action. This was demonstrated using in vitro, ex vivo, as well as in vivo experiments. With regard to its mechanism of action in adipose tissue, oxytocin increased the expression of stearoyl-coenzyme A desaturase 1, as well as the tissue content of the phospholipid precursor, N-oleoyl-phosphatidylethanolamine, the biosynthetic precursor of the oleic acid-derived PPAR-alpha activator, oleoylethanolamide. Because PPAR-alpha regulates fatty acid β-oxidation, we hypothesized that this transcription factor might mediate the oxytocin effects. This was substantiated by the observation that, in contrast to its effects in wild-type mice, oxytocin infusion failed to induce weight loss and fat oxidation in PPAR-alpha-deficient animals. Altogether, these results suggest that oxytocin administration could represent a promising therapeutic approach for the treatment of human obesity and type 2 diabetes.

  11. Chronic intracerebroventricular morphine and lactation in rats: dependence and tolerance in relation to oxytocin neurones.

    Science.gov (United States)

    Rayner, V C; Robinson, I C; Russell, J A

    1988-02-01

    1. Acutely, opioids inhibit oxytocin secretion. To study the responses of oxytocin neurones during chronic opioid exposure, forty-five lactating rats were infused continuously from a subcutaneous osmotically driven mini-pump via a lateral cerebral ventricle with morphine sulphate solution from day 2 post-partum for 5-7 days; the infusion rate was increased 2- or 2.5-fold each 40 h from 10 micrograms/h initially up to 50 micrograms/h; controls were infused with vehicle (1 microliter/h, twenty-eight rats) or were untreated (eight rats). 2. Maternal behaviour was disrupted in 27% of the morphine-treated rats; in rats that remained maternal morphine did not affect body weight or water intake but increased rectal temperature by 0.82 +/- 0.14 degrees C (mean +/- S.E.M.) across the first 4 days. 3. Weight gain of the litters of maternal morphine-treated rats was reduced by 32% during 7 days, predominantly in the first day of treatment when milk transfer was also reduced. Observation of pup behaviour during suckling showed decreased frequency of milk ejections on only the second day of morphine treatment. Plasma concentration of prolactin after 6 days was similar in maternal morphine-treated and control rats, but reduced by 90% in non-maternal morphine-treated rats, indicating normal control of prolactin secretion by suckling in morphine-treated rats. 4. Oxytocin and vasopressin contents, measured by radioimmunoassay, in the supraoptic and paraventricular nuclei and in the neurohypophysis were similar between fourteen maternal morphine-treated, twelve vehicle-treated and eight untreated lactating rats; thus exposure to morphine did not involve increased production and storage of oxytocin. 5. Distribution of [3H]morphine infused intracerebroventricularly into six virgin female rats for 6 days was measured by scintillation counting of tissue extracts. Morphine concentration in the hypothalamus and neurohypophysis was 2.7 and 12.8 micrograms/g, respectively, and in blood

  12. Streptomyces lunalinharesii Strain 235 Shows the Potential to Inhibit Bacteria Involved in Biocorrosion Processes

    OpenAIRE

    Pacheco da Rosa, Juliana; Korenblum, Elisa; Franco-Cirigliano, Marcella Novaes; Abreu, Fernanda; Lins, Ulysses; Soares, Rosângela M. A.; Macrae, Andrew; Seldin, Lucy; Coelho, Rosalie R. R.

    2013-01-01

    Four actinomycete strains previously isolated from Brazilian soils were tested for their antimicrobial activity against Bacillus pumilus LF-4 and Desulfovibrio alaskensis NCIMB 13491, bacteria that are well known to be involved in biofilm formation and biocorrosion. Strain 235, belonging to the species Streptomyces lunalinharesii, inhibited the growth of both bacteria. The antimicrobial activity was seen over a wide range of pH, and after treatment with several chemicals and heat but not with...

  13. On the role of oxytocin in borderline personality disorder.

    Science.gov (United States)

    Brüne, Martin

    2016-09-01

    Interpersonal dysfunction is central to borderline personality disorder (BPD). Recent research has focused on the role of oxytocin (OT) in BPD, particularly regarding associations of OT activity with symptoms, genetic polymorphisms of the oxytocin receptor coding gene (OXTR) in BPD, and experimental modification of interpersonal core problems of patients with BPD such as hypervigilance towards threat detection, mistrust, and non-verbal behaviour during social interaction by intranasal application of OT. A literature ('medline') review was performed using the keywords 'oxytocin' and 'borderline personality disorder'. Secondary literature on trauma and attachment in relation to OT was also considered relevant. Together, findings suggest that in BPD OT is associated with enhanced defensive mechanisms and avoidance behaviour. Moreover, gene-environment interaction concerning polymorphic variations of the OXTR gene and childhood adversity in BPD suggests that these genes convey developmental flexibility or 'differential susceptibility' to environmental contingencies, whereby BPD resides at the poor outcome end of the spectrum. In view of the conflicting literature, it needs to be studied carefully whether OT can serve as a therapeutic agent given adjunct to psychotherapy in BPD. More research about the role of OT is also required with regard to the prevention of the non-genetic intergenerational transmission of BPD. Clarifying the role of OT in BPD may also benefit from research in non-human animals targeting the interaction between early adversity and OT availability more directly. The study of oxytocin can contribute to the understanding of the neurobiology of borderline personality disorder. Oxytocin is critically involved in attachment security, and methylation of the oxytocin receptor may play a role in the epigenetic modulation of early adversity. The intranasal application of oxytocin may be a useful therapeutic adjunct to psychotherapy. Insecure attachment and

  14. The effects of oxytocin on social cognition in borderline personality disorder.

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    Servan, A; Brunelin, J; Poulet, E

    2018-02-01

    Deficits in social cognition and interpersonal difficulties are key features in borderline personality disorder. Social cognition refers to the function of perceiving and adequately dealing with social signals, leading to the establishment and maintenance of healthy and positive social relationships. Evidence suggests that oxytocin (OT) may improve social cognition and human social behavior. Recently, several studies have highlighted the beneficial effects of oxytocin in several psychiatric conditions involving social cognition deficits such as schizophrenia, autism or social phobia. However, despite growing interest, the effects of oxytocin in patients with borderline personality disorder are far from being clearly demonstrated. The objective of this work was to review and discuss studies investigating the interest of oxytocin in alleviating social cognition deficits in patients with borderline personality disorder (recognition of emotion, trust and cooperation, affective and cognitive empathy, emotional expression and social problem-solving). A systematic review of the literature was conducted up to September 31, 2016 on the Pubmed, Science direct, Medline and Scopus databases using "borderline personality disorder" and "oxytocin" as keywords. To be included, studies were to include patients with borderline personality disorder; to investigate social cognition and to investigate the effect of oxytocin on social cognition in patients with TPB. The initial search yielded 52 articles. Among them, 11 studies were selected according to the PRISMA criteria. The effect of oxytocin on social cognition in patients with borderline personality disorder was mainly investigated in relation to recognition of emotions and trust and cooperation. We did not find any studies investigating the effect of oxytocin on affective and cognitive empathy, emotional expression or social problem-solving abilities. In patients with borderline personality disorder, oxytocin had a beneficial

  15. Involvement of allelopathy in inhibition of understory growth in red pine forests.

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    Kato-Noguchi, Hisashi; Kimura, Fukiko; Ohno, Osamu; Suenaga, Kiyotake

    2017-11-01

    Japanese red pine (Pinus densiflora Sieb. et Zucc.) forests are characterized by sparse understory vegetation although sunlight intensity on the forest floor is sufficient for undergrowth. The possible involvement of pine allelopathy in the establishment of the sparse understory vegetation was investigated. The soil of the red pine forest floor had growth inhibitory activity on six test plant species including Lolium multiflorum, which was observed at the edge of the forest but not in the forest. Two growth inhibitory substances were isolated from the soil and characterized to be 15-hydroxy-7-oxodehydroabietate and 7-oxodehydroabietic acid. Those compounds are probably formed by degradation process of resin acids. Resin acids are produced by pine and delivered into the soil under the pine trees through balsam and defoliation. Threshold concentrations of 15-hydroxy-7-oxodehydroabietate and 7-oxodehydroabietic acid for the growth inhibition of L. multiflorum were 30 and 10μM, respectively. The concentrations of 15-hydroxy-7-oxodehydroabietate and 7-oxodehydroabietic acid in the soil were 312 and 397μM, respectively, which are sufficient concentrations to cause the growth inhibition because of the threshold. These results suggest that those compounds are able to work as allelopathic agents and may prevent from the invasion of herbaceous plants into the forests by inhibiting their growth. Therefore, allelopathy of red pine may be involved in the formation of the sparse understory vegetation. Copyright © 2017 Elsevier GmbH. All rights reserved.

  16. Boosting recovery rather than buffering reactivity: Higher stress-induced oxytocin secretion is associated with increased cortisol reactivity and faster vagal recovery after acute psychosocial stress.

    Science.gov (United States)

    Engert, Veronika; Koester, Anna M; Riepenhausen, Antje; Singer, Tania

    2016-12-01

    Animal models and human studies using paradigms designed to stimulate endogenous oxytocin release suggest a stress-buffering role of oxytocin. We here examined the involvement of stress-induced peripheral oxytocin secretion in reactivity and recovery phases of the human psychosocial stress response. Healthy male and female participants (N=114) were subjected to a standardized laboratory stressor, the Trier Social Stress Test. In addition to plasma oxytocin, cortisol was assessed as a marker of hypothalamic-pituitary-adrenal (HPA-) axis activity, alpha-amylase and heart rate as markers of sympathetic activity, high frequency heart rate variability as a marker of vagal tone and self-rated anxiety as an indicator of subjective stress experience. On average, oxytocin levels increased by 51% following psychosocial stress. The stress-induced oxytocin secretion, however, did not reduce stress reactivity. To the contrary, higher oxytocin secretion was associated with greater cortisol reactivity and peak cortisol levels in both sexes. In the second phase of the stress response the opposite pattern was observed, with higher oxytocin secretion associated with faster vagal recovery. We suggest that after an early stage of oxytocin and HPA-axis co-activation, the stress-reducing action of oxytocin unfolds. Due to the time lag it manifests as a recovery-boosting rather than a reactivity-buffering effect. By reinforcing parasympathetic autonomic activity, specifically during stress recovery, oxytocin may provide an important protective function against the health-compromising effects of sustained stress. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. The Neuropeptide Oxytocin Induces a Social Altruism Bias.

    Science.gov (United States)

    Marsh, Nina; Scheele, Dirk; Gerhardt, Holger; Strang, Sabrina; Enax, Laura; Weber, Bernd; Maier, Wolfgang; Hurlemann, René

    2015-11-25

    Current psychological concepts of social and ecological responsibility emphasize the relevance of altruism, suggesting that more altruistic individuals are more likely to engage in sustainable behaviors. Emerging evidence indicates a central role of the neuropeptide oxytocin in promoting altruism. Whether this influence extends to ecological responsibility or is limited to the social domain remains unknown. In two independent experiments involving 172 human participants, we addressed this question by exposing subjects to a sustainability-related monetary donation task, with the option to support either socially or ecologically framed charities. We found that oxytocin induced a context-dependent change in altruistic behavior away from pro-environmental toward pro-social donations, while keeping constant the overall proportion of donated money. This pro-social bias transcended to the domain of sustainable consumption. Collectively, our findings demonstrate that altruistic priorities vary as a function of oxytocin system activity, which has implications for the promotion of pro-environmental attitudes and eco-friendly behaviors. Individual responses to ecological and social sustainability require a shift in personal priorities away from selfish to more altruistic behaviors. Emerging evidence indicates a central role of the hypothalamic peptide oxytocin in promoting altruism, but whether the influence of oxytocin benefits altruistic decision-making in the context of ecological and social sustainability is unclear. In two independent behavioral experiments involving 172 human subjects, we show that heightened oxytocin system activity induces a social altruism bias at the cost of ecological responsibility. Our results have fundamental implications for policy interventions and business strategies designed to sustain ecological resources by suggesting that a social framing may attract more individuals to engage in pro-environmental and eco-friendly behaviors. Copyright

  18. The Williams syndrome prosociality gene GTF2I mediates oxytocin reactivity and social anxiety in a healthy population.

    Science.gov (United States)

    Procyshyn, Tanya L; Spence, Jason; Read, Silven; Watson, Neil V; Crespi, Bernard J

    2017-04-01

    The neurohormone oxytocin plays a central role in human social behaviour and cognition, and oxytocin dysregulation may contribute to psychiatric disorders. However, genetic factors influencing individual variation in the oxytocinergic system remain poorly understood. We genotyped 169 healthy adults for a functional polymorphism in GTF2I ( general transcription factor II-I ), a gene associated with high prosociality and reduced social anxiety in Williams syndrome, a condition reported to involve high oxytocin levels and reactivity. Participants' salivary oxytocin levels were measured before and after watching a validated empathy-inducing video. Oxytocin reactivity, defined as pre- to post-video percentage change in salivary oxytocin, varied substantially and significantly between individuals with different GTF2I genotypes, with, additionally, a trend towards an interaction between genotype and sex. Individuals with more oxytocin-reactive genotypes also reported significantly lower social anxiety. These findings suggest a model whereby GTF2I has a continuum of effects on human sociality, from the extreme social phenotypes and oxytocin dysregulation associated with gene deletion in Williams syndrome, to individual differences in oxytocin reactivity and sociality associated with common polymorphisms in healthy populations. © 2017 The Author(s).

  19. Oxytocin: Old Hormone, New Drug

    Directory of Open Access Journals (Sweden)

    Jolanta Gutkowska

    2009-12-01

    Full Text Available Oxytocin (OT, traditionally associated with reproductive functions, was revisited recently, and several new functions in cardiovascular regulation were discovered. These functions include stimulation of the cardioprotective mediators nitric oxide (NO and atrial natriuretic peptide. OT’s cardiovascular outcomes comprise: (i natriuresis, (ii blood pressure reduction, (iii negative inotropic and chronotropic effects, (iv parasympathetic neuromodulation, (v NO pathway involvement in vasodilatation and endothelial cell growth, (vi anti-inflammatory and (vii antioxidant activities as well as (viii metabolic effects. In addition, we have reported abundant OT in the early developing heart with its capacity to generate cardiomyocytes (CMs from mouse embryonic stem cells and stem cells residing in the heart. OT increases glucose uptake by cultured CMs, in normal, hypoxic and even in insulin resistance conditions. In experimentally-induced myocardial infarction in rats, continuous in vivo OT delivery improves the cardiac healing process and cardiac work, diminishes inflammation, and stimulates angiogenesis. Therefore, in pathological situations, OT plays an anti-inflammatory and cardioprotective role, enhancing vascular and metabolic functions, with potential therapeutic application(s.

  20. Targeting GLI by GANT61 involves mechanisms dependent on inhibition of both transcription and DNA licensing.

    Science.gov (United States)

    Zhang, Ruowen; Wu, Jiahui; Ferrandon, Sylvain; Glowacki, Katie J; Houghton, Janet A

    2016-12-06

    The GLI genes are transcription factors and in cancers are oncogenes, aberrantly and constitutively activated. GANT61, a specific GLI inhibitor, has induced extensive cytotoxicity in human models of colon cancer. The FOXM1 promoter was determined to be a transcriptional target of GLI1. In HT29 cells, inhibition of GLI1 binding at the GLI consensus sequence by GANT61 led to inhibited binding of Pol II, the pause-release factors DSIF, NELF and p-TEFb. The formation of R-loops (RNA:DNA hybrids, ssDNA), were reduced by GANT61 at the FOXM1 promoter. Pretreatment of HT29 cells with α-amanitin reduced GANT61-induced γH2AX foci. Co-localization of GLI1 and BrdU foci, inhibited by GANT61, indicated GLI1 and DNA replication to be linked. By co-immunoprecipitation and confocal microscopy, GLI1 co-localized with the DNA licensing factors ORC4, CDT1, and MCM2. Significant co-localization of GLI1 and ORC4 was inhibited by GANT61, and enrichment of ORC4 occurred at the GLI binding site in the FOXM1 promoter. CDT1 was found to be a transcription target of GLI1. Overexpression of CDT1 in HT29 and SW480 cells reduced GANT61-induced cell death, gH2AX foci, and cleavage of caspase-3. Data demonstrate involvement of transcription and of DNA replication licensing factors by non-transcriptional and transcriptional mechanisms in the GLI-dependent mechanism of action of GANT61.

  1. Visualization of oxytocin release that mediates paired pulse facilitation in hypothalamic pathways to brainstem autonomic neurons.

    Directory of Open Access Journals (Sweden)

    Ramón A Piñol

    Full Text Available Recent work has shown that oxytocin is involved in more than lactation and uterine contraction. The paraventricular nucleus of the hypothalamus (PVN contains neuroendocrine neurons that control the release of hormones, including vasopressin and oxytocin. Other populations of PVN neurons do not release hormones, but rather project to and release neurotransmitters onto other neurons in the CNS involved in fluid retention, thermoregulation, sexual behavior and responses to stress. Activation of oxytocin receptors can be cardioprotective and reduces the adverse cardiovascular consequences of anxiety and stress, yet how oxytocin can affect heart rate and cardiac function is unknown. While anatomical work has shown the presence of peptides, including oxytocin, in the projections from the PVN to parasympathetic nuclei, electrophysiological studies to date have only demonstrated release of glutamate and activation of fast ligand gated receptors in these pathways. In this study, using rats, we directly show, using sniffer CHO cells that express oxytocin receptors and the Ca2+ indicator R-GECO, that optogenetic activation of channelrhodopsin-2 (ChR2 expressing PVN fibers in the brainstem activates oxytocin receptors in the dorsomotor nucleus of the vagus (DMNV. We also demonstrate that while a single photoactivation of PVN terminals only activates glutamatergic receptors in brainstem cardiac vagal neurons (CVNs, neurons that dominate the neural control of heart rate, both the paired pulse facilitation, and sustained enhancement of glutamate release in this pathway is mediated by activation of oxytocin receptors. Our results provide direct evidence that a pathway from the PVN likely releases oxytocin and enhances short-term plasticity of this critical autonomic connection.

  2. Visualization of Oxytocin Release that Mediates Paired Pulse Facilitation in Hypothalamic Pathways to Brainstem Autonomic Neurons

    Science.gov (United States)

    Piñol, Ramón A.; Jameson, Heather; Popratiloff, Anastas; Lee, Norman H.; Mendelowitz, David

    2014-01-01

    Recent work has shown that oxytocin is involved in more than lactation and uterine contraction. The paraventricular nucleus of the hypothalamus (PVN) contains neuroendocrine neurons that control the release of hormones, including vasopressin and oxytocin. Other populations of PVN neurons do not release hormones, but rather project to and release neurotransmitters onto other neurons in the CNS involved in fluid retention, thermoregulation, sexual behavior and responses to stress. Activation of oxytocin receptors can be cardioprotective and reduces the adverse cardiovascular consequences of anxiety and stress, yet how oxytocin can affect heart rate and cardiac function is unknown. While anatomical work has shown the presence of peptides, including oxytocin, in the projections from the PVN to parasympathetic nuclei, electrophysiological studies to date have only demonstrated release of glutamate and activation of fast ligand gated receptors in these pathways. In this study, using rats, we directly show, using sniffer CHO cells that express oxytocin receptors and the Ca2+ indicator R-GECO, that optogenetic activation of channelrhodopsin-2 (ChR2) expressing PVN fibers in the brainstem activates oxytocin receptors in the dorsomotor nucleus of the vagus (DMNV). We also demonstrate that while a single photoactivation of PVN terminals only activates glutamatergic receptors in brainstem cardiac vagal neurons (CVNs), neurons that dominate the neural control of heart rate, both the paired pulse facilitation, and sustained enhancement of glutamate release in this pathway is mediated by activation of oxytocin receptors. Our results provide direct evidence that a pathway from the PVN likely releases oxytocin and enhances short-term plasticity of this critical autonomic connection. PMID:25379676

  3. Research review: Social motivation and oxytocin in autism--implications for joint attention development and intervention.

    Science.gov (United States)

    Stavropoulos, Katherine K M; Carver, Leslie J

    2013-06-01

    The social motivation hypothesis (SMH) suggests that individuals with autism spectrum disorders (ASD) are less intrinsically rewarded by social stimuli than their neurotypical peers. This difference in social motivation has been posited as a factor contributing to social deficits in ASD. Social motivation is thought to involve the neuropeptide oxytocin. Here, we review the evidence for oxytocin effects in ASD, and discuss its potential role in one important social cognitive behavior. Systematic searches were conducted using the PsychINFO and MEDLINE databases and the search terms 'oxytocin' and 'autism'; the same databases were used for separate searches for 'joint attention', 'intervention', and 'autism', using the same inclusion criteria as an earlier 2011 review but updating it for the period 2010 to October 2012. Several studies suggest that giving oxytocin to both individuals with ASD and neurotypical individuals can enhance performance on social cognitive tasks. Studies that have attempted to intervene in joint attention in ASD suggest that social motivation may be a particular obstacle to lasting effects. The review of the evidence for the SMH suggests a potential role for oxytocin in social motivation deficits in ASD. Because of its importance for later communicative and social development, the focus here is on implications of oxytocin and social motivation in the development of and interventions in joint attention. Joint attention is a central impairment in ASD, and as a result is the focus of several behavioral interventions. In describing this previous research on joint attention interventions in ASD, we pay particular attention to problems encountered in such studies, and propose ways that oxytocin may facilitate behavioral intervention in this area. For future research, integrating behavioral and pharmacological interventions (oxytocin administration) would be a worthwhile experimental direction to improve understanding of the role of oxytocin in ASD

  4. In planta assays involving epigenetically silenced genes reveal inhibition of cytosine methylation by genistein

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    Arase Sachiko

    2012-03-01

    Full Text Available Abstract Background Cytosine methylation is involved in epigenetic control of gene expression in a wide range of organisms. An increasing number of examples indicate that changing the frequency of cytosine methylation in the genome is a feasible tool to engineer novel traits in plants. Although demethylating effects of compounds have been analyzed in human cultured cells in terms of suppressing cancer, their effect in plant cells has not been analyzed extensively. Here, we developed in planta assay systems to detect inhibition of cytosine methylation using plants that contain a transgene transcriptionally silenced by an epigenetic mechanism. Results Seeds of two transgenic plants were used: a petunia line that has been identified as a revertant of the co-suppression of the chalcone synthase-A (CHS-A gene and contains CHS-A transgenes whose transcription is repressed; Nicotiana benthamiana plants that contain the green fluorescent protein (GFP reporter gene whose transcription is repressed through virus-induced transcriptional gene silencing. Seeds of these plants were sown on a medium that contained a demethylating agent, either 5-azacytidine or trichostatin A, and the restoration of the transcriptionally active state of the transgene was detected in seedlings. Using these systems, we found that genistein, a major isoflavonoid compound, inhibits cytosine methylation, thus restoring transgene transcription. Genistein also restored the transcription of an epigenetically silenced endogenous gene in Arabidopsis plants. Conclusions Our assay systems allowed us to assess the inhibition of cytosine methylation, in particular of maintenance of methylation, by compounds in plant cells. These results suggest a novel role of flavonoids in plant cells and that genistein is useful for modifying the epigenetic state of plant genomes.

  5. Atrial natriuretic peptide: a possible mediator involved in dexamethasone's inhibition of cell proliferation in multiple myeloma.

    Science.gov (United States)

    Ding, Jiang-Hua; Chang, Yu-Sui

    2012-08-01

    Atrial natriuretic peptide (ANP) has been recognized for several decades for its role of regulating blood pressure. Recently, cumulating evidences show that ANP plays an anticancer role in various solid tumors via blocking the kinase cascade of Ras-MEK1/2-ERK1/2 with the result of inhibition of DNA synthesis. ANP, as well as its receptors (NPR-A and NPR-C) has been identified present in the embryonic stem cell and a wide range of cancer cells. Various lymphoid organs, such as lymph nodes, have been detected the presence of ANP. Multiple myeloma (MM), though the therapies have evolved significantly, is still an incurable disease as B lymphocyte cell neoplasm. Dexamethasone is the cornerstone in treatment of MM via inactivation of Ras-MEK1/2-ERK1/2 cascade reaction. Coincidently, dexamethasone can increase the expression of ANP markedly. Nevertheless, the role of ANP in MM is unclear. Based on these results above, we raise the hypothesis that ANP is involved in mediating dexamethasone's inhibition of proliferation in MM cells, which suggests that ANP may be a potential agent to treat MM. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  6. Oxytocin and Aggression.

    Science.gov (United States)

    de Jong, Trynke R; Neumann, Inga D

    2017-09-02

    The neuropeptide oxytocin (OT) has a solid reputation as a facilitator of social interactions such as parental and pair bonding, trust, and empathy. The many results supporting a pro-social role of OT have generated the hypothesis that impairments in the endogenous OT system may lead to antisocial behavior, most notably social withdrawal or pathological aggression. If this is indeed the case, administration of exogenous OT could be the "serenic" treatment that psychiatrists have for decades been searching for.In the present review, we list and discuss the evidence for an endogenous "hypo-oxytocinergic state" underlying aggressive and antisocial behavior, derived from both animal and human studies. We furthermore examine the reported effects of synthetic OT administration on aggression in rodents and humans.Although the scientific findings listed in this review support, in broad lines, the link between a down-regulated or impaired OT system activity and increased aggression, the anti-aggressive effects of synthetic OT are less straightforward and require further research. The rather complex picture that emerges adds to the ongoing debate questioning the unidirectional pro-social role of OT, as well as the strength of the effects of intranasal OT administration in humans.

  7. Oxytocin and vasopressin modulation of the neural correlates of motivation and emotion: results from functional MRI studies in awake rats.

    Science.gov (United States)

    Febo, Marcelo; Ferris, Craig F

    2014-09-11

    Oxytocin and vasopressin modulate a range of species typical behavioral functions that include social recognition, maternal-infant attachment, and modulation of memory, offensive aggression, defensive fear reactions, and reward seeking. We have employed novel functional magnetic resonance mapping techniques in awake rats to explore the roles of these neuropeptides in the maternal and non-maternal brain. Results from the functional neuroimaging studies that are summarized here have directly and indirectly confirmed and supported previous findings. Oxytocin is released within the lactating rat brain during suckling stimulation and activates specific subcortical networks in the maternal brain. Both vasopressin and oxytocin modulate brain regions involved unconditioned fear, processing of social stimuli and the expression of agonistic behaviors. Across studies there are relatively consistent brain networks associated with internal motivational drives and emotional states that are modulated by oxytocin and vasopressin. This article is part of a Special Issue entitled Oxytocin and Social Behav. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Streptomyces lunalinharesii Strain 235 Shows the Potential to Inhibit Bacteria Involved in Biocorrosion Processes

    Directory of Open Access Journals (Sweden)

    Juliana Pacheco da Rosa

    2013-01-01

    Full Text Available Four actinomycete strains previously isolated from Brazilian soils were tested for their antimicrobial activity against Bacillus pumilus LF-4 and Desulfovibrio alaskensis NCIMB 13491, bacteria that are well known to be involved in biofilm formation and biocorrosion. Strain 235, belonging to the species Streptomyces lunalinharesii, inhibited the growth of both bacteria. The antimicrobial activity was seen over a wide range of pH, and after treatment with several chemicals and heat but not with proteinase K and trypsin. The antimicrobial substances present in the concentrated supernatant from growth media were partially characterized by SDS-PAGE and extracellular polypeptides were seen. Bands in the size range of 12 to 14.4 kDa caused antimicrobial activity. Transmission electron microscopy of D. alaskensis cells treated with the concentrated supernatant containing the antimicrobial substances revealed the formation of prominent bubbles, the spherical double-layered structures on the cell membrane, and the periplasmic space completely filled with electron-dense material. This is the first report on the production of antimicrobial substances by actinomycetes against bacteria involved in biocorrosion processes, and these findings may be of great relevance as an alternative source of biocides to those currently employed in the petroleum industry.

  9. Involvement of CNOT3 in mitotic progression through inhibition of MAD1 expression

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Akinori [Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639 (Japan); Kikuguchi, Chisato [Cell Signal Unit, Okinawa Institute of Science and Technology, Kunigami, Okinawa 904-0412 (Japan); Morita, Masahiro; Shimodaira, Tetsuhiro; Tokai-Nishizumi, Noriko; Yokoyama, Kazumasa; Ohsugi, Miho; Suzuki, Toru [Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639 (Japan); Yamamoto, Tadashi, E-mail: tyamamot@ims.u-tokyo.ac.jp [Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639 (Japan); Cell Signal Unit, Okinawa Institute of Science and Technology, Kunigami, Okinawa 904-0412 (Japan)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer CNOT3 depletion increases the mitotic index. Black-Right-Pointing-Pointer CNOT3 inhibits the expression of MAD1. Black-Right-Pointing-Pointer CNOT3 destabilizes the MAD1 mRNA. Black-Right-Pointing-Pointer MAD1 knockdown attenuates the CNOT3 depletion-induced mitotic arrest. -- Abstract: The stability of mRNA influences the dynamics of gene expression. The CCR4-NOT complex, the major deadenylase in mammalian cells, shortens the mRNA poly(A) tail and contributes to the destabilization of mRNAs. The CCR4-NOT complex plays pivotal roles in various physiological functions, including cell proliferation, apoptosis, and metabolism. Here, we show that CNOT3, a subunit of the CCR4-NOT complex, is involved in the regulation of the spindle assembly checkpoint, suggesting that the CCR4-NOT complex also plays a part in the regulation of mitosis. CNOT3 depletion increases the population of mitotic-arrested cells and specifically increases the expression of MAD1 mRNA and its protein product that plays a part in the spindle assembly checkpoint. We showed that CNOT3 depletion stabilizes the MAD1 mRNA, and that MAD1 knockdown attenuates the CNOT3 depletion-induced increase of the mitotic index. Basing on these observations, we propose that CNOT3 is involved in the regulation of the spindle assembly checkpoint through its ability to regulate the stability of MAD1 mRNA.

  10. Involvement of CNOT3 in mitotic progression through inhibition of MAD1 expression

    International Nuclear Information System (INIS)

    Takahashi, Akinori; Kikuguchi, Chisato; Morita, Masahiro; Shimodaira, Tetsuhiro; Tokai-Nishizumi, Noriko; Yokoyama, Kazumasa; Ohsugi, Miho; Suzuki, Toru; Yamamoto, Tadashi

    2012-01-01

    Highlights: ► CNOT3 depletion increases the mitotic index. ► CNOT3 inhibits the expression of MAD1. ► CNOT3 destabilizes the MAD1 mRNA. ► MAD1 knockdown attenuates the CNOT3 depletion-induced mitotic arrest. -- Abstract: The stability of mRNA influences the dynamics of gene expression. The CCR4–NOT complex, the major deadenylase in mammalian cells, shortens the mRNA poly(A) tail and contributes to the destabilization of mRNAs. The CCR4–NOT complex plays pivotal roles in various physiological functions, including cell proliferation, apoptosis, and metabolism. Here, we show that CNOT3, a subunit of the CCR4–NOT complex, is involved in the regulation of the spindle assembly checkpoint, suggesting that the CCR4–NOT complex also plays a part in the regulation of mitosis. CNOT3 depletion increases the population of mitotic-arrested cells and specifically increases the expression of MAD1 mRNA and its protein product that plays a part in the spindle assembly checkpoint. We showed that CNOT3 depletion stabilizes the MAD1 mRNA, and that MAD1 knockdown attenuates the CNOT3 depletion-induced increase of the mitotic index. Basing on these observations, we propose that CNOT3 is involved in the regulation of the spindle assembly checkpoint through its ability to regulate the stability of MAD1 mRNA.

  11. Streptomyces lunalinharesii strain 235 shows the potential to inhibit bacteria involved in biocorrosion processes.

    Science.gov (United States)

    Pacheco da Rosa, Juliana; Korenblum, Elisa; Franco-Cirigliano, Marcella Novaes; Abreu, Fernanda; Lins, Ulysses; Soares, Rosângela M A; Macrae, Andrew; Seldin, Lucy; Coelho, Rosalie R R

    2013-01-01

    Four actinomycete strains previously isolated from Brazilian soils were tested for their antimicrobial activity against Bacillus pumilus LF-4 and Desulfovibrio alaskensis NCIMB 13491, bacteria that are well known to be involved in biofilm formation and biocorrosion. Strain 235, belonging to the species Streptomyces lunalinharesii, inhibited the growth of both bacteria. The antimicrobial activity was seen over a wide range of pH, and after treatment with several chemicals and heat but not with proteinase K and trypsin. The antimicrobial substances present in the concentrated supernatant from growth media were partially characterized by SDS-PAGE and extracellular polypeptides were seen. Bands in the size range of 12 to 14.4 kDa caused antimicrobial activity. Transmission electron microscopy of D. alaskensis cells treated with the concentrated supernatant containing the antimicrobial substances revealed the formation of prominent bubbles, the spherical double-layered structures on the cell membrane, and the periplasmic space completely filled with electron-dense material. This is the first report on the production of antimicrobial substances by actinomycetes against bacteria involved in biocorrosion processes, and these findings may be of great relevance as an alternative source of biocides to those currently employed in the petroleum industry.

  12. Oxytocin enhances the appropriate use of human social cues by the domestic dog (Canis familiaris) in an object choice task.

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    Oliva, J L; Rault, J-L; Appleton, B; Lill, A

    2015-05-01

    It has been postulated that the neuropeptide, oxytocin, is involved in human-dog bonding. This may explain why dogs, compared to wolves, are such good performers on object choice tasks, which test their ability to attend to, and use, human social cues in order to find hidden food treats. The objective of this study was to investigate the effect of intranasal oxytocin administration, which is known to increase social cognition in humans, on domestic dogs' ability to perform such a task. We hypothesised that dogs would perform better on the task after an intranasal treatment of oxytocin. Sixty-two (31 males and 31 females) pet dogs completed the experiment over two different testing sessions, 5-15 days apart. Intranasal oxytocin or a saline control was administered 45 min before each session. All dogs received both treatments in a pseudo-randomised, counterbalanced order. Data were collected as scores out of ten for each of the four blocks of trials in each session. Two blocks of trials were conducted using a momentary distal pointing cue and two using a gazing cue, given by the experimenter. Oxytocin enhanced performance using momentary distal pointing cues, and this enhanced level of performance was maintained over 5-15 days time in the absence of oxytocin. Oxytocin also decreased aversion to gazing cues, in that performance was below chance levels after saline administration but at chance levels after oxytocin administration.

  13. Perception of social interaction compresses subjective duration in an oxytocin-dependent manner.

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    Liu, Rui; Yuan, Xiangyong; Chen, Kepu; Jiang, Yi; Zhou, Wen

    2018-05-22

    Communication through body gestures permeates our daily life. Efficient perception of the message therein reflects one's social cognitive competency. Here we report that such competency is manifested temporally as shortened subjective duration of social interactions: motion sequences showing agents acting communicatively are perceived to be significantly shorter in duration as compared with those acting noncommunicatively. The strength of this effect is negatively correlated with one's autistic-like tendency. Critically, intranasal oxytocin administration restores the temporal compression effect in socially less proficient individuals, whereas the administration of atosiban, a competitive antagonist of oxytocin, diminishes the effect in socially proficient individuals. These findings indicate that perceived time, rather than being a faithful representation of physical time, is highly idiosyncratic and ingrained with one's personality trait. Moreover, they suggest that oxytocin is involved in mediating time perception of social interaction, further supporting the role of oxytocin in human social cognition. © 2018, Liu et al.

  14. Oxytocin augmentation during labor: how to implement medical guidelines into clinical practice.

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    Holmgren, Stina; Silfver, Kristina Gren; Lind, Cecilia; Nordström, Lennart

    2011-11-01

    To describe an extensive process to implement guidelines for oxytocin use during labor and to report its effects on compliance to clinical practice guidelines after 1 year. A multifaceted strategy was developed to involve all obstetric staff and identify possible local barriers to change in advance. The process lasted for more than 1 year. To describe the implementation of oxytocin use according to the new guidelines, and to compare management in clinical practice with guideline recommendations from audits performed before and after the project. Identification of possible barriers to change, academic detailing, audits with feedback, and local opinion leaders were important factors for a successful process. Documentation of the indication for oxytocin use increased from 54% before, to 86% after the completion of the project (Pcheck list to monitor oxytocin use. However, audits with feedback need to continue for medical safety, and have been planned to take place every 6 months. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Oxytocin receptor antagonist atosiban impairs consolidation, but not reconsolidation of contextual fear memory in rats.

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    Abdullahi, Payman Rasise; Eskandarian, Sharaf; Ghanbari, Ali; Rashidy-Pour, Ali

    2018-05-23

    There is increasing evidence that oxytocin is involved in learning and memory process. This study investigated the effects of blockade of oxytocin receptors using the selective oxytocin receptor antagonist atosiban (ATO) on contextual fear memory consolidation and reconsolidation in male rats. Post-training injections of different doses of ATO (1, 10, 100 or 1000 µg/kg) impaired the 48 h retention performance in a dose-dependent manner. The same doses of ATO following memory reactivation did not impair subsequent expression of contextual fear memories which formed under low or high shock intensities and tested 24 h or one week following memory reactivation. Also, no effect was found when ATO was administrated in the absence of memory reactivation. Our finding is the first report that indicates endogenous oxytocin released during training play an important role in the consolidation, but not reconsolidation of contextual fear memory in rats. Copyright © 2018. Published by Elsevier B.V.

  16. No laughing matter: intranasal oxytocin administration changes functional brain connectivity during exposure to infant laughter.

    Science.gov (United States)

    Riem, Madelon M E; van IJzendoorn, Marinus H; Tops, Mattie; Boksem, Maarten A S; Rombouts, Serge A R B; Bakermans-Kranenburg, Marian J

    2012-04-01

    Infant laughter is a rewarding experience. It activates neural reward circuits and promotes parental proximity and care, thus facilitating parent-infant attachment. The neuropeptide oxytocin might enhance the incentive salience of infant laughter by modulating neural circuits related to the perception of infant cues. In a randomized controlled trial with functional magnetic resonance imaging we investigated the influence of intranasally administered oxytocin on functional brain connectivity in response to infant laughter. Blood oxygenation level-dependent responses to infant laughter were measured in 22 nulliparous women who were administered oxytocin and 20 nulliparous women who were administered a placebo. Elevated oxytocin levels reduced activation in the amygdala during infant laughter and enhanced functional connectivity between the amygdala and the orbitofrontal cortex, the anterior cingulate, the hippocampus, the precuneus, the supramarginal gyri, and the middle temporal gyrus. Increased functional connectivity between the amygdala and regions involved in emotion regulation may reduce negative emotional arousal while enhancing the incentive salience of the infant laughter.

  17. Oxytocin administration suppresses hypothalamic activation in response to visual food cues.

    Science.gov (United States)

    van der Klaauw, Agatha A; Ziauddeen, Hisham; Keogh, Julia M; Henning, Elana; Dachi, Sekesai; Fletcher, Paul C; Farooqi, I Sadaf

    2017-06-27

    The aim of this study was to use functional neuroimaging to investigate whether oxytocin modulates the neural response to visual food cues in brain regions involved in the control of food intake. Twenty-four normal weight volunteers received intranasal oxytocin (24 IU) or placebo in a double-blind, randomized crossover study. Measurements were made forty-five minutes after dosing. On two occasions, functional MRI (fMRI) scans were performed in the fasted state; the blood oxygen level-dependent (BOLD) response to images of high-calorie foods versus low-calorie foods was measured. Given its critical role in eating behaviour, the primary region of interest was the hypothalamus. Secondary analyses examined the parabrachial nuclei and other brain regions involved in food intake and food reward. Intranasal oxytocin administration suppressed hypothalamic activation to images of high-calorie compared to low-calorie food (P = 0.0125). There was also a trend towards suppression of activation in the parabrachial nucleus (P = 0.0683). No effects of intranasal oxytocin were seen in reward circuits or on ad libitum food intake. Further characterization of the effects of oxytocin on neural circuits in the hypothalamus is needed to establish the utility of targeting oxytocin signalling in obesity.

  18. Exercise Inhibits the Effects of Smoke-Induced COPD Involving Modulation of STAT3

    Directory of Open Access Journals (Sweden)

    Maysa Alves Rodrigues Brandao-Rangel

    2017-01-01

    Full Text Available Purpose. Evaluate the participation of STAT3 in the effects of aerobic exercise (AE in a model of smoke-induced COPD. Methods. C57Bl/6 male mice were divided into control, Exe, COPD, and COPD+Exe groups. Smoke were administered during 90 days. Treadmill aerobic training begun on day 61 until day 90. Pulmonary inflammation, systemic inflammation, the level of lung emphysema, and the airway remodeling were evaluated. Analysis of integral and phosphorylated expression of STAT3 by airway epithelial cells, peribronchial leukocytes, and parenchymal leukocytes was performed. Results. AE inhibited smoke-induced accumulation of total cells (p<0.001, lymphocytes (p<0.001, and neutrophils (p<0.001 in BAL, as well as BAL levels of IL-1β (p<0.001, CXCL1 (p<0.001, IL-17 (p<0.001, and TNF-α (p<0.05, while increased the levels of IL-10 (p<0.001. AE also inhibited smoke-induced increases in total leukocytes (p<0.001, neutrophils (p<0.05, lymphocytes (p<0.001, and monocytes (p<0.01 in blood, as well as serum levels of IL-1β (p<0.01, CXCL1 (p<0.01, IL-17 (p<0.05, and TNF-α (p<0.01, while increased the levels of IL-10 (p<0.001. AE reduced smoke-induced emphysema (p<0.001 and collagen fiber accumulation in the airways (p<0.001. AE reduced smoke-induced STAT3 and phospho-STAT3 expression in airway epithelial cells (p<0.001, peribronchial leukocytes (p<0.001, and parenchymal leukocytes (p<0.001. Conclusions. AE reduces smoke-induced COPD phenotype involving STAT3.

  19. [Oxytocin, a mediator of anti-stress, well-being, social interaction, growth and healing].

    Science.gov (United States)

    Uvnas-Moberg, Kerstin; Petersson, Maria

    2005-01-01

    The neuroendocrine and physiological systems related to pain and stress have long been subjected to study. More recently, the corresponding systems promoting anti-stress and restoration have also come into focus. It is not only important to investigate the mechanisms underlying disease but also to examine the physiological and psychological mechanisms which protect and heal the body and soul. The nonapeptide oxytocin, originally known to stimulate labour and milk ejection, appears to play an important role in this regard. Oxytocin can induce anti-stress-like effects such as reduction of blood pressure and cortisol levels. It increases pain thresholds, exerts an anxiolytic-like effect and stimulates various types of positive social interaction. In addition, it promotes growth and healing. Repeated exposure to oxytocin causes long-lasting effects by influencing the activity of other transmitter systems, a pattern which makes oxytocin potentially clinically relevant. Oxytocin can be released by various types of non-noxious sensory stimulation, for example by touch and warmth. Ingestion of food triggers oxytocin release by activation of vagal afferents. Most likely, oxytocin can also be released by stimulation of other senses such as olfaction, as well as by certain types of sound and light. In addition, purely psychological mechanisms may trigger the release of oxytocin. This means that positive interaction involving touch and psychological support may be health-promoting. The social interaction of daily life, as well as a positive environment, continuously activate this system. In addition, various types of psychotherapy involving transfer of support, warmth and empathy are likely to induce similar effects, which thus contribute to the positive effects of these kinds of therapies.

  20. Social support, oxytocin, and PTSD

    NARCIS (Netherlands)

    Olff, Miranda; Koch, Saskia B. J.; Nawijn, Laura; Frijling, Jessie L.; van Zuiden, Mirjam; Veltman, Dick J.

    2014-01-01

    A lack of social support and recognition by the environment is one of the most consistent risk factors for posttraumatic stress disorder (PTSD), and PTSD patients will recover faster with proper social support. The oxytocin system has been proposed to underlie beneficial effects of social support as

  1. A Modified Glycosaminoglycan, GM-0111, Inhibits Molecular Signaling Involved in Periodontitis.

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    Justin R Savage

    Full Text Available Periodontitis is characterized by microbial infection, inflammation, tissue breakdown, and accelerated loss of alveolar bone matrix. Treatment targeting these multiple stages of the disease provides ways to treat or prevent periodontitis. Certain glycosaminoglycans (GAGs block multiple inflammatory mediators as well as suppress bacterial growth, suggesting that these GAGs may be exploited as a therapeutic for periodontitis.We investigated the effects of a synthetic GAG, GM-0111, on various molecular events associated with periodontitis: growth of Porphyromonas gingivalis (P. gingivalis and Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans pathogenic bacteria associated with periodontitis; activation of pro-inflammatory signaling through TLR2 and TLR4 in mouse macrophage RAW 264.7 cells and heterologously expressed HEK 293 cells; osteoclast formation and bone matrix resorption in cultured mouse pre-osteoclasts.(1 GM-0111 suppressed the growth of P. gingivalis and A. actinomycetemcomitans even at 1% (w/v solution. The antibacterial effects of GM-0111 were stronger than hyaluronic acid (HA or xylitol in P. gingivalis at all concentrations and comparable to xylitol in A. actinomycetemcomitans at ≥2% (w/v solution. We also observed that GM-0111 suppressed biofilm formation of P. gingivalis and these effects were much stronger than HA. (2 GM-0111 inhibited TLR-mediated pro-inflammatory cellular signaling both in macrophage and HEK 293 cells with higher selectivity for TLR2 than TLR4 (IC50 of 1-10 ng/mL vs. > 100 μg/mL, respectively. (3 GM-0111 blocked RANKL-induced osteoclast formation (as low as 300 ng/mL and bone matrix resorption. While GM-0111 showed high affinity binding to RANKL, it did not interfere with RANKL/RANK/NF-κB signaling, suggesting that GM-0111 inhibits osteoclast formation by a RANKL-RANK-independent mechanism.We report that GM-0111 inhibits multiple molecular events involved in periodontitis, spanning from the

  2. Caffeine inhibits STAT1 signaling and downregulates inflammatory pathways involved in autoimmunity.

    Science.gov (United States)

    Iris, Merve; Tsou, Pei-Suen; Sawalha, Amr H

    2018-04-18

    Caffeine is a widely consumed pharmacologically active product. We focused on characterizing immunomodulatory effects of caffeine on peripheral blood mononuclear cells. Caffeine at high doses showed a robust downregulatory effect on cytokine activity and genes related to several autoimmune diseases including lupus and rheumatoid arthritis. Dose-dependent validation experiments showed downregulation at the mRNA levels of key inflammation-related genes including STAT1, TNF, IFNG, and PPARG. TNF and PPARG were suppressed even with the lowest caffeine dose tested, which corresponds to the serum concentration of caffeine after administration of one cup of coffee. Cytokine levels of IL-8, MIP-1β, IL-6, IFN-γ, GM-CSF, TNF, IL-2, IL-4, MCP-1, and IL-10 were decreased significantly with caffeine treatment. Upstream regulator analysis suggests that caffeine inhibits STAT1 signaling, which was confirmed by showing reduced phosphorylated STAT1 after caffeine treatment. Further studies exploring disease-modulating potential of caffeine in autoimmune diseases and further exploring the mechanisms involved are warranted. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. The association between oxytocin and social capital.

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    Takeo Fujiwara

    Full Text Available BACKGROUND: Oxytocin is known to be related to social behaviors, including trust. However, few studies have investigated the association between oxytocin levels and social capital. Thus, we tested the hypothesis that endogenous oxytocin levels are positively associated with social capital. We also considered whether the association differed across gender because previous studies have shown differential effects of OT on social behaviors depending on gender. METHODS: We recruited a convenience sample of 50 women and 31 men in Japan via community sampling from whom we obtained urine sample with which to measure oxytocin levels. Individual-level cognitive social capital (social trust and mutual aid and structural social capital (community participation were assessed using a questionnaire. We used multivariate regression, adjusted for covariates (age, number of children, self-rated health, and education, and stratified by gender to consider associations between oxytocin and social capital. RESULTS: Among women, oxytocin was inversely associated with social trust and mutual aid (p<0.05. However, women participating in only 1 organization in the community showed higher oxytocin than women who participated in either no organizations (p<0.05 or 2 or more organization (i.e. inverse-U shape association. Among men, no association was observed between oxytocin and either form of cognitive and structural social capital. CONCLUSION: Women who perceived low cognitive social capital showed higher oxytocin levels, while structural social capital showed inverse-U shape association with oxytocin. No association between oxytocin and social capital was found among men. Further study is needed to elucidate why oxytocin was inversely associated with cognitive social capital only among women.

  4. Research Review: Social motivation and oxytocin in autism – implications for joint attention development and intervention

    Science.gov (United States)

    Stavropoulos, Katherine K. M.; Carver, Leslie J.

    2013-01-01

    Background and Scope The social motivation hypothesis (SMH) suggests that individuals with autism spectrum disorders (ASD) are less intrinsically rewarded by social stimuli than their neurotypical peers. This difference in social motivation has been posited as a factor contributing to social deficits in ASD. Social motivation is thought to involve the neuropeptide oxytocin. Here, we review the evidence for oxytocin effects in ASD, and discuss its potential role in one important social cognitive behavior. Methods Systematic searches were conducted using the PsychINFO and MEDLINE databases and the search terms “oxytocin”, and “autism”; the same databases were used for separate searches for “joint attention”, “intervention”, and “autism”, using the same inclusion criteria as an earlier 2011 review but updating it for the period 2010 to October 2012. Findings Several studies suggest that giving oxytocin to both individuals with ASD and typically developing individuals can enhance performance on social cognitive tasks. Studies that have attempted to intervene in joint attention in ASD suggest that social motivation may be a particular obstacle to lasting effects. Conclusions The review of the evidence for the SMH suggests a potential role for oxytocin in social motivation deficits in ASD. Because of its importance for later communicative and social development, the focus here is on implications of oxytocin and social motivation in the development of and interventions in joint attention. Joint attention is a central impairment in ASD, and as a result is the focus of several behavioral interventions. In describing this previous research on joint attention interventions in ASD, we pay particular attention to problems encountered in such studies, and propose ways that oxytocin may facilitate behavioral intervention in this area. For future research, integrating behavioral and pharmacological interventions (oxytocin administration) would be a worthwhile

  5. As time goes by: Oxytocin influences the subjective perception of time in a social context.

    Science.gov (United States)

    Colonnello, Valentina; Domes, Gregor; Heinrichs, Markus

    2016-06-01

    Time perception depends on an event's emotional relevance to the beholder; a subjective time dilation effect is associated with self-relevant, emotionally salient stimuli. Previous studies have revealed that oxytocin modulates the salience of social stimuli and attention to social cues. However, whether the oxytocin system is involved in human subjective time perception is unknown. The aim of the present study was to investigate whether increased oxytocin levels would induce a time dilation effect for self-relevant, positive social cues. In a double-blind, placebo-controlled, between-subject design, heterosexual men were administered intranasal oxytocin or placebo. After about 50min, participants completed a time-bisection task in which they estimated lengths of exposure to happy female faces (self-relevant positive stimuli, based on sexual orientation), emotionally neutral and negative female faces (control), and happy, neutral, and negative male faces (control). Oxytocin induced a subjective time dilation effect for happy female faces and a time compression effect for happy male faces. Our results provide evidence that oxytocin influences time perception, a primary form of human subjectivity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Effects of Intranasal Oxytocin on the Blood Oxygenation Level-Dependent Signal in Food Motivation and Cognitive Control Pathways in Overweight and Obese Men.

    Science.gov (United States)

    Plessow, Franziska; Marengi, Dean A; Perry, Sylvia K; Felicione, Julia M; Franklin, Rachel; Holmes, Tara M; Holsen, Laura M; Makris, Nikolaos; Deckersbach, Thilo; Lawson, Elizabeth A

    2018-02-01

    Recent research indicates that the hypothalamic neuropeptide hormone oxytocin is a key central nervous system factor in the regulation of food intake and weight. However, the mechanisms underlying the anorexigenic effects of oxytocin in humans are unknown and critical to study to consider oxytocin as a neurohormonal weight loss treatment. We performed a randomized, double-blind, placebo-controlled crossover study with single-dose intranasal oxytocin (24 IU) in ten overweight or obese, otherwise healthy men. Following oxytocin/placebo administration, participants completed an established functional magnetic resonance imaging food motivation paradigm. We hypothesized that oxytocin would reduce the blood oxygenation level-dependent (BOLD) signal to high-calorie food vs non-food visual stimuli in the ventral tegmental area (VTA), the origin of the mesolimbic dopaminergic reward system. Following oxytocin administration, compared to placebo, participants showed bilateral VTA hypoactivation to high-calorie food stimuli. A secondary exploratory whole-brain analysis revealed hypoactivation in additional hedonic (orbitofrontal cortex, insula, globus pallidus, putamen, hippocampus, and amygdala) and homeostatic (hypothalamus) food motivation and hyperactivation in cognitive control (anterior cingulate and frontopolar cortex) brain regions following oxytocin administration vs placebo. Oxytocin administration reduces the BOLD signal in reward-related food motivation brain regions, providing a potential neurobiological mechanism for the anorexigenic oxytocin effects in humans. Furthermore, our data indicate that oxytocin administration reduces activation in homeostatic and increases activation in cognitive control brain regions critically involved in regulating food intake and resolving affective conflict, respectively. Future studies are required to link these changes in brain activation to oxytocin effects on food intake and weight.

  7. Oxytocin is a cardiovascular hormone

    Directory of Open Access Journals (Sweden)

    Gutkowska J.

    2000-01-01

    Full Text Available Oxytocin (OT, a nonapeptide, was the first hormone to have its biological activities established and chemical structure determined. It was believed that OT is released from hypothalamic nerve terminals of the posterior hypophysis into the circulation where it stimulates uterine contractions during parturition, and milk ejection during lactation. However, equivalent concentrations of OT were found in the male hypophysis, and similar stimuli of OT release were determined for both sexes, suggesting other physiological functions. Indeed, recent studies indicate that OT is involved in cognition, tolerance, adaptation and complex sexual and maternal behaviour, as well as in the regulation of cardiovascular functions. It has long been known that OT induces natriuresis and causes a fall in mean arterial pressure, both after acute and chronic treatment, but the mechanism was not clear. The discovery of the natriuretic family shed new light on this matter. Atrial natriuretic peptide (ANP, a potent natriuretic and vasorelaxant hormone, originally isolated from rat atria, has been found at other sites, including the brain. Blood volume expansion causes ANP release that is believed to be important in the induction of natriuresis and diuresis, which in turn act to reduce the increase in blood volume. Neurohypophysectomy totally abolishes the ANP response to volume expansion. This indicates that one of the major hypophyseal peptides is responsible for ANP release. The role of ANP in OT-induced natriuresis was evaluated, and we hypothesized that the cardio-renal effects of OT are mediated by the release of ANP from the heart. To support this hypothesis, we have demonstrated the presence and synthesis of OT receptors in all heart compartments and the vasculature. The functionality of these receptors has been established by the ability of OT to induce ANP release from perfused heart or atrial slices. Furthermore, we have shown that the heart and large vessels

  8. Fluorescent visualization of oxytocin in the hypothalamo-neurohypophysial system

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    Hirofumi eHashimoto

    2014-07-01

    Full Text Available Oxytocin (OXT is well known for its ability to the milk ejection reflex and uterine contraction. It is also involved in several other behaviors, such as anti-nociception, anxiety, feeding, social recognition and stress responses. OXT is synthesized in the magnocellular neurosecretory cells (MNCs in the hypothalamic paraventricular (PVN and the supraoptic nuclei (SON that terminate their axons in the posterior pituitary (PP. We generated transgenic rats that express the OXT and fluorescent protein fusion gene in order to visualize oxytocin in the hypothalamo-neurohypophysial system. In these transgenic rats, fluorescent proteins were observed in the MNCs and axon terminals in the PP. This transgenic rat is a new tool to study the physiological role of OXT in the hypothalamo-neurohypophysial system.

  9. Oxytocin biotransformation in the rat limbic brain

    NARCIS (Netherlands)

    Burbach, J.P.H.; Schotman, P.; Kloet, E.R. de

    2006-01-01

    Two peptide fragments of oxytocin were isolated by high-pressure liquid chromatography from digests of oxytocin obtained after exposure to a SPM preparation of the rat limbic brain. The structures of these peptides, being Gln-Asn-Cys(O)x-Pro-Leu-GlyNH2 and Gln-Asn-Cys(-S-S-Cys)-Pro-Leu-GlyNH2, were

  10. Oxytocin receptor (OXTR) does not play a major role in the aetiology of autism: genetic and molecular studies.

    Science.gov (United States)

    Tansey, Katherine E; Brookes, Keeley J; Hill, Matthew J; Cochrane, Lynne E; Gill, Michael; Skuse, David; Correia, Catarina; Vicente, Astrid; Kent, Lindsey; Gallagher, Louise; Anney, Richard J L

    2010-05-03

    Oxytocin (OXT) has been hypothesized to play a role in aetiology of autism based on a demonstrated involvement in the regulation of social behaviours. It is postulated that OXT reduces activation of the amygdala, inhibiting social anxiety, indicating a neural mechanism for the effects of OXT in social cognition. Genetic variation at the oxytocin receptor gene (OXTR) has been reported to be associated with autism. We examined 18 SNPs at the OXTR gene for association in three independent autism samples from Ireland, Portugal and the United Kingdom. We investigated cis-acting genetic effects on OXTR expression in lymphocytes and amygdala region of the brain using an allelic expression imbalance (AEI) assay and by investigating the correlation between RNA levels and genotype in the amygdala region. No marker survived multiple correction for association with autism in any sample or in a combined sample (n=436). Results from the AEI assay performed in the lymphoblast cell lines highlighted two SNPs associated with relative allelic abundance in OXTR (rs237897 and rs237895). Two SNPs were found to be effecting cis-acting variation through AEI in the amygdala. One was weakly correlated with total gene expression (rs13316193) and the other was highlighted in the lymphoblast cell lines (rs237895). Data presented here does not support the role of common genetic variation in OXTR in the aetiology of autism spectrum disorders in Caucasian samples. 2010 Elsevier Ireland Ltd. All rights reserved.

  11. Intranasal oxytocin reduces social perception in women: Neural activation and individual variation.

    Science.gov (United States)

    Hecht, Erin E; Robins, Diana L; Gautam, Pritam; King, Tricia Z

    2017-02-15

    Most intranasal oxytocin research to date has been carried out in men, but recent studies indicate that females' responses can differ substantially from males'. This randomized, double-blind, placebo-controlled study involved an all-female sample of 28 women not using hormonal contraception. Participants viewed animations of geometric shapes depicting either random movement or social interactions such as playing, chasing, or fighting. Probe questions asked whether any shapes were "friends" or "not friends." Social videos were preceded by cues to attend to either social relationships or physical size changes. All subjects received intranasal placebo spray at scan 1. While the experimenter was not blinded to nasal spray contents at Scan 1, the participants were. Scan 2 followed a randomized, double-blind design. At scan 2, half received a second placebo dose while the other half received 24 IU of intranasal oxytocin. We measured neural responses to these animations at baseline, as well as the change in neural activity induced by oxytocin. Oxytocin reduced activation in early visual cortex and dorsal-stream motion processing regions for the social > size contrast, indicating reduced activity related to social attention. Oxytocin also reduced endorsements that shapes were "friends" or "not friends," and this significantly correlated with reduction in neural activation. Furthermore, participants who perceived fewer social relationships at baseline were more likely to show oxytocin-induced increases in a broad network of regions involved in social perception and social cognition, suggesting that lower social processing at baseline may predict more positive neural responses to oxytocin. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Oxytocin and Estrogen Receptor β in the Brain: An Overview

    OpenAIRE

    Acevedo-Rodriguez, Alexandra; Mani, Shaila K.; Handa, Robert J.

    2015-01-01

    Oxytocin is a neuropeptide synthesized primarily by neurons of the paraventricular and supraoptic nuclei of the hypothalamus. These neurons have axons that project into the posterior pituitary and release oxytocin into the bloodstream to promote labor and lactation; however, oxytocin neurons also project to other brain areas where it plays a role in numerous brain functions. Oxytocin binds to the widely expressed oxytocin receptor, and, in doing so, it regulates homeostatic processes, social ...

  13. High-dose alcohol intoxication differentially modulates cognitive subprocesses involved in response inhibition.

    Science.gov (United States)

    Stock, Ann-Kathrin; Schulz, Tom; Lenhardt, Martin; Blaszkewicz, Meinolf; Beste, Christian

    2016-01-01

    Aside from well-known physiological effects, high-dose alcohol intoxication (a.k.a. binge drinking) can lead to aversive social and legal consequences because response inhibition is usually compromised under the influence of alcohol. Although the behavioral aspects of this phenomenon were reported on extensively, the underlying neurophysiological mechanisms mediating this disinhibition are unclear. To close this gap, we used both behavioral and neurophysiological measures (event-related potentials, ERPs) to investigate which subprocesses of response inhibition are altered under the influence of high-dose alcohol intoxication. Using a within-subject design, we asked young healthy participants (n = 27) to complete a GO/NOGO task once sober and once intoxicated (approximately 1.2‰). During intoxication, high-dose alcohol effects were highest in a condition where the participants could not rely on automated stimulus-response mapping processes during response inhibition. In this context, the NOGO-P3 (ERP), that likely depends on dopaminergic signaling within mesocorticolimbic pathways and is thought to reflect motor inhibition and/or the evaluation of inhibitory processes, was altered in the intoxicated state. In contrast to this, the N2 component, which largely depends on nigrostriatal dopamine pathways and is thought to reflect inhibition on a pre-motor level, was not altered. Based on these results, we demonstrate that alcohol-induced changes of dopaminergic neurotransmission do not exert a global effect on response inhibition. Instead, changes are highly subprocess-specific and seem to mainly target mesocorticolimbic pathways that contribute to motor inhibition and the evaluation of such. © 2014 Society for the Study of Addiction.

  14. Different mechanisms are involved in the antibody mediated inhibition of ligand binding to the urokinase receptor

    DEFF Research Database (Denmark)

    List, K; Høyer-Hansen, G; Rønne, E

    1999-01-01

    Certain monoclonal antibodies are capable of inhibiting the biological binding reactions of their target proteins. At the molecular level, this type of effect may be brought about by completely different mechanisms, such as competition for common binding determinants, steric hindrance or interfer......Certain monoclonal antibodies are capable of inhibiting the biological binding reactions of their target proteins. At the molecular level, this type of effect may be brought about by completely different mechanisms, such as competition for common binding determinants, steric hindrance......) can be employed as a highly useful tool to characterize the inhibitory mechanism of specific antagonist antibodies. Two inhibitory antibodies against uPAR, mAb R3 and mAb R5, were shown to exhibit competitive and non-competitive inhibition, respectively, of ligand binding to the receptor. The former...

  15. Interactions between dopamine and oxytocin in the control of sexual behaviour.

    Science.gov (United States)

    Baskerville, Tracey A; Douglas, Alison J

    2008-01-01

    Dopamine and oxytocin are two key neuromodulators involved in reproductive behaviours, such as mating and maternal care. Much evidence underlies their separate roles in such behaviours, but particularly in sexual behaviour. It is generally believed that central dopaminergic and oxytocinergic systems work together to regulate the expression of penile erection, but relatively little is known regarding how they interact. Thus, this review aims to discuss neuroanatomical proof, neuromodulator secretory profiles in the hypothalamus and behavioural pharmacological evidence which support a dopamine-oxytocin link in three hypothalamic nuclei that have been implicated in sexual behaviour, namely the medial preoptic nucleus, supraoptic nucleus and paraventricular nucleus (PVN). We also aim to provide an overview of potential dopamine-mediated transduction pathways that occur within these nuclei and are correlated with the exhibition of penile erection. The PVN provides the most convincing evidence for a dopamine-oxytocin link and it is becoming increasingly apparent that parvocellular oxytocinergic neurons in the PVN, in part, mediate the effects of dopamine to elicit penile erection. However, while we show that oxytocin neurons express dopamine receptors, other evidence on whether dopaminergic activation of PVN oxytocin cells involves a direct and/or indirect mechanism is inconclusive and further evidence is required to establish whether the two systems interact synergistically or sequentially in the regulation of penile erection.

  16. The orgasmic history of oxytocin: Love, lust, and labor

    Directory of Open Access Journals (Sweden)

    Navneet Magon

    2011-01-01

    Full Text Available Oxytocin has been best known for its roles in female reproduction. It is released in large amounts during labor, and after stimulation of the nipples. It is a facilitator for childbirth and breastfeeding. However, recent studies have begun to investigate oxytocin′s role in various behaviors, including orgasm, social recognition, bonding, and maternal behaviors. This small nine amino acid peptide is now believed to be involved in a wide variety of physiological and pathological functions such as sexual activity, penile erection, ejaculation, pregnancy, uterine contraction, milk ejection, maternal behavior, social bonding, stress and probably many more, which makes oxytocin and its receptor potential candidates as targets for drug therapy. From an innocuous agent as an aid in labor and delivery, oxytocin has come a long way in being touted as the latest party drug. The hormone of labor during the course of the last 100 years has had multiple orgasms to be the hormone of love. Many more shall be seen in the times to come!

  17. Oxytocin mediates copulation-induced hypoalgesia of male rats.

    Science.gov (United States)

    Futagami, Hiroko; Sakuma, Yasuo; Kondo, Yasuhiko

    2016-04-08

    Copulatory behavior has been reported to raise the pain threshold in male rats. In this study, we examined the effect of copulatory behavior with or without ejaculation on pain threshold measured by electrical shock via an electrode attached to the tail. It was demonstrated that ejaculation is not necessary to raise the pain threshold in male rats. In addition, we examined whether oxytocin, a hypothalamic neuropeptide, was involved in copulation-induced hypoalgesia. Sexually experienced males were subjected to stereotaxic implantation of a guide cannula targeting the lateral ventricle. After the recovery period, half of the males were intracerebroventricularly treated with an oxytocin antagonist (OTA, 100ng d(CH2)51,Tyr(Me)2,Thr4, Orn8,Tyr-NH29]-vasotocin/1μL saline) and the remaining half were administered saline without anesthesia. Fifteen minutes later, half of each group were given sexual behavior with receptive females. We found no effect of OTA on sexual activity. Immediately after ejaculation, pain threshold was measured. While raised pain threshold was observed after sexual behavior in saline-treated males, no change in pain threshold was found in OTA-treated males even after copulation. The results suggest that central oxytocin mediates copulation-induced hypoalgesia in male rats. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Inhibition of potassium currents is involved in antiarrhythmic effect of moderate ethanol on atrial fibrillation

    International Nuclear Information System (INIS)

    Yang, Baode; Li, Chenxing; Sun, Junyi; Wang, Xinghui; Liu, Xinling; Yang, Chun; Chen, Lina; Zhou, Jun; Hu, Hao

    2017-01-01

    Excessive consumption of alcohol is a well-established risk factor of atrial fibrillation (AF). However, the effects of moderate alcohol drinking remain to be elucidated. This study was designed to determine the effects of moderate ethanol ingestion on atrial fibrillation and the electrophysiological mechanisms. In acetylcholine-induced canine and mouse AF models, the moderate ethanol prevented the generation and persistence of AF through prolonging the latent period of AF and shortening the duration of AF. The action potential duration (APD) was remarkably prolonged under the concentration range of 12.5–50.0 mM ethanol in guinea pig atrial myocytes. Ultra-rapid delayed rectified potassium currents (I Kv1.5 ) were markedly inhibited by 12.5–50.0 mM ethanol in a concentration-dependent manner. Ethanol with 50.0 mM could inhibit rapid delayed rectifier potassium currents (I hERG ). Ethanol under 6.25–50.0 mM did not affect on inward rectifier potassium currents (I Kir2.1 ). Collectively, the present study provided an evidence that moderate ethanol intake can prolong the APD of atrial myocytes by inhibition of I Kv1.5 and I hERG , which contributed to preventing the development and duration of AF. - Highlights: • Moderate ethanol prevented the development of AF in animal models. • Moderate ethanol prolonged APD in guinea pig atrial myocytes. • Moderate ethanol inhibited Kv1.5 currents.

  19. Involvement of reactive oxygen species in the electrochemical inhibition of barnacle (Amphibalanus amphitrite) settlement

    Science.gov (United States)

    Rodolfo E. Perez-Roa; Marc A. Anderson; Dan Rittschof; Christopher G. Hunt; Daniel R. Noguera

    2009-01-01

    The role of reactive oxygen species (ROS) in electrochemical biofouling inhibition was investigated using a series of abiotic tests and settlement experiments with larvae of the barnacle Amphibalanus amphitrite, a cosmopolitan fouler. Larval settlement, a measure of biofouling potential, was reduced from 43% ± 14% to 5% ± 6% upon the application of...

  20. Effects of neonatal oxytocin manipulation on development of social behaviors in mice.

    Science.gov (United States)

    Mogi, Kazutaka; Ooyama, Rumi; Nagasawa, Miho; Kikusui, Takefumi

    2014-06-22

    The oxytocin (OT) neural system is thought to be involved in the underlying mechanisms that guide the development of social behaviors. In the present study, we examined the effects of neonatal oxytocin manipulation in mice. Within 24 hours after birth, pups in the treatment group randomly received an intraperitoneal injection of OT or OT antagonist (OTA), and those in the control group received a saline injection or handling only. Some of these mice underwent a test that counted the number of isolation-induced ultrasound vocalizations they made on postnatal day 6, and they were further tested for sociability at 8-9 weeks of age and for neuroendocrine stress response to novel environments at 19-20 weeks of age. Another group of mice was tested for alloparental responsiveness at 13-15 weeks of age. The OT injection affected sociability and alloparental responsiveness. In an approach/avoidance test, most of the mice made a social approach to an unfamiliar conspecific of the same sex, but females that had received a neonatal injection of 3 μg of OTA did not show this response. The neonatal OTA treatment appeared to inhibit females' sociability in a dose-dependent fashion. In a retrieving test, females that had received a neonatal injection of 3 μg of OT retrieved significantly more pups than did those that had received 3 μg of OTA, although neither of the treatments caused the females to behave significantly differently from control group females. Meanwhile, a neonatal injection of 3 μg of OTA increased the latency to retrieve pups in males. These results suggested that neonatal OT action may positively regulate alloparental responsiveness in adulthood. Considering that the organizational effects of OT have also been shown in voles and rats, the mechanism by which neonatal OT modifies the development of social behaviors appears to be common to all rodents. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. The effect of oxytocin on biological motion perception in dogs (Canis familiaris).

    Science.gov (United States)

    Kovács, Krisztina; Kis, Anna; Kanizsár, Orsolya; Hernádi, Anna; Gácsi, Márta; Topál, József

    2016-05-01

    Recent studies have shown that the neuropeptide oxytocin is involved in the regulation of several complex human social behaviours. There is, however, little research on the effect of oxytocin on basic mechanisms underlying human sociality, such as the perception of biological motion. In the present study, we investigated the effect of oxytocin on biological motion perception in dogs (Canis familiaris), a species adapted to the human social environment and thus widely used to model many aspects of human social behaviour. In a within-subjects design, dogs (N = 39), after having received either oxytocin or placebo treatment, were presented with 2D projection of a moving point-light human figure and the inverted and scrambled version of the same movie. Heart rate (HR) and heart rate variability (HRV) were measured as physiological responses, and behavioural response was evaluated by observing dogs' looking time. Subjects were also rated on the personality traits of Neuroticism and Agreeableness by their owners. As expected, placebo-pretreated (control) dogs showed a spontaneous preference for the biological motion pattern; however, there was no such preference after oxytocin pretreatment. Furthermore, following the oxytocin pretreatment female subjects looked more at the moving point-light figure than males. The individual variations along the dimensions of Agreeableness and Neuroticism also modulated dogs' behaviour. Furthermore, HR and HRV measures were affected by oxytocin treatment and in turn played a role in subjects' looking behaviour. We discuss how these findings contribute to our understanding of the neurohormonal regulatory mechanisms of human (and non-human) social skills.

  2. Administration of an oxytocin receptor antagonist attenuates sexual motivation in male rats.

    Science.gov (United States)

    Blitzer, D S; Wells, T E; Hawley, W R

    2017-08-01

    In male rats, oxytocin impacts both sexual arousal and certain types of consummatory sexual behaviors. However, the role of oxytocin in the motivational aspects of sexual behavior has received limited attention. Given the role that oxytocin signaling plays in consummatory sexual behaviors, it was hypothesized that pharmacological attenuation of oxytocin signaling would reduce sexual motivation in male rats. Sexually experienced Long-Evans male rats were administered either an oxytocin receptor antagonist (L368,899 hydrochloride; 1mg/kg) or vehicle control into the intraperitoneal cavity 40min prior to placement into the center chamber of a three-chambered arena designed to assess sexual motivation. During the 20-minute test, a sexually experienced stimulus male rat and a sexually receptive stimulus female rat were separately confined to smaller chambers that were attached to the larger end chambers of the arena. However, physical contact between test and stimulus rats was prevented by perforated dividers. Immediately following the sexual motivation test, test male rats were placed with a sexually receptive female to examine consummatory sexual behaviors. Although both drug and vehicle treated rats exhibited a preference for the female, treatment with an oxytocin receptor antagonist decreased the amount of time spent with the female. There were no differences between drug and vehicle treated rats in either general activity, exploratory behaviors, the amount of time spent near the stimulus male rat, or consummatory sexual behaviors. Extending previous findings, these results indicate that oxytocin receptors are involved in sexual motivation in male rats. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Molecular mechanisms involved in the inhibition of tumor cells proliferation exposed to elevated concentrations of the epidermal growth factor

    International Nuclear Information System (INIS)

    Guillen, Isabel A; Berlanga, Jorge; Camacho, Hanlet

    2013-01-01

    The EGF promotes inhibition of cell proliferation in vitro and in vivo models depending on its concentration, application schema and the type of tumor cells on which it acts. Our research hypothesis was based on the fact that the EGF varies the expression of genes involved in a negative regulation of tumor cell lines proliferation carrying high levels of its receptor (EGFR). Our objectives were, to obtain information about the effect of EGF on tumor cell proliferation in vitro and in vivo models and, know the gene expression patterns of a group of genes involved in cancer signaling pathways and EGFR. The results showed that EGF at nanomolar concentrations inhibits the tumor cells proliferation bearing high levels of EGFR and, promotes the survival of treated animals, establishing a direct relationship between the inhibition of cell proliferation, high concentrations of EGF and, high amount of EGFR in the cells. The differential gene expression profile showed a variation in a group of genes which exert a powerful control over the cell cycle progression, gene transcription and apoptosis. It was concluded that the inhibition of tumor cell proliferation by the action of EGF is due to activation of molecular mechanisms controlling cell cycle progression. This work won the Annual Award of the Cuban Academy of Sciences in 2012

  4. Oxytocin determination by radioimmunoassay in cattle. 2

    International Nuclear Information System (INIS)

    Schams, D.; Baumann, G.; Leidl, W.

    1982-01-01

    Oxytocin concentration in jugular vein blood was measured radioimmunologically with a detection limit of 3 pg/ml plasma in male and female cattle. Five bulls were tested; during mating a cow in oestrus with intromission and ejaculation, during mounting a dummy or another bull with ejaculation into an artificial vagina or during false mounts. No increase in oxytocin concentrations could be observed, but stimulation with an electro-ejaculator caused an increase ranging from 5-84 pg/ml after a latent period of 3-5 min. A similar response was observed in two cows following the same procedure. The contact with a bull, false mount or mating with intromission and ejaculation was not followed by a measurable oxytocin release in 5 test cows. The following stimulation techniques, massage of vulva and clitoris, massage of cervix and uterus per rectum, artificial insemination, introduction of a speculum into the vagina or insufflation of air into the vagina were performed with 5 cows and 5 heifers. Insufflation of air into the vagina was the most effective stimulus, eleciting an oxytocin release up to 588 pg/ml. All 5 heiers responded positively, as well as 4 cows in oestrus. The other manipulations cuased an oxytocin response mainly in heifers (whether in oestrus or dioestrus), whereas only one cow in oestrus responded with an oxytocin release. In general, oxytocin concentrations increase about 30-90 s after the start of the stimulus. (author)

  5. Oxytocin improves emotion recognition for older males.

    Science.gov (United States)

    Campbell, Anna; Ruffman, Ted; Murray, Janice E; Glue, Paul

    2014-10-01

    Older adults (≥60 years) perform worse than young adults (18-30 years) when recognizing facial expressions of emotion. The hypothesized cause of these changes might be declines in neurotransmitters that could affect information processing within the brain. In the present study, we examined the neuropeptide oxytocin that functions to increase neurotransmission. Research suggests that oxytocin benefits the emotion recognition of less socially able individuals. Men tend to have lower levels of oxytocin and older men tend to have worse emotion recognition than older women; therefore, there is reason to think that older men will be particularly likely to benefit from oxytocin. We examined this idea using a double-blind design, testing 68 older and 68 young adults randomly allocated to receive oxytocin nasal spray (20 international units) or placebo. Forty-five minutes afterward they completed an emotion recognition task assessing labeling accuracy for angry, disgusted, fearful, happy, neutral, and sad faces. Older males receiving oxytocin showed improved emotion recognition relative to those taking placebo. No differences were found for older females or young adults. We hypothesize that oxytocin facilitates emotion recognition by improving neurotransmission in the group with the worst emotion recognition. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Mechanisms involved in growth inhibition induced by clofibrate in hepatoma cells

    International Nuclear Information System (INIS)

    Muzio, Giuliana; Maggiora, Marina; Trombetta, Antonella; Martinasso, Germana; Reffo, Patrizia; Colombatto, Sebastiano; Canuto, Rosa Angela

    2003-01-01

    Low concentrations of some peroxisome proliferators have been found to decrease apoptosis in rat liver cells, whereas higher but pharmacological concentrations have been found to inhibit cell proliferation or to induce apoptosis in human and rat hepatoma cells. The highly deviated JM2 rat hepatoma cell line was used to examine the mechanisms underlying the inhibitory effect on cell proliferation. Clofibrate chiefly inhibited cell proliferation in these cells. Parallel to the decrease in cell proliferation there was an increase of peroxisome proliferator activated receptor (PPAR) gamma and of protein phosphatase 2A, whose importance was confirmed, respectively, by using antisense oliginucleotides (AS-ODN) or okadaic acid. The increase of protein phosphatase 2A induced by PPARgamma caused a decrease of MAPK, an intracellular signaling transduction pathway, as shown by evaluation of Erk1,2 and c-myc. In light of these results, clofibrate, like conventional synthetic ligands of PPARgamma, may be regarded as a possible prototype anti-tumour drug

  7. Inhibition of potassium currents is involved in antiarrhythmic effect of moderate ethanol on atrial fibrillation

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Baode; Li, Chenxing [Department of Pharmacology, Health Science Center, Xi' an Jiaotong University, Xi' an (China); Sun, Junyi [Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi' an Jiaotong University, Xi' an (China); Department of Periodontology, College of Stomatology, Xi' an Jiaotong University, Xi' an (China); Wang, Xinghui; Liu, Xinling [Basic Medical Experiment Teaching Center, Health Science Center, Xi' an Jiaotong University, Xi' an (China); Yang, Chun [Department of Cardiology, The First Affiliated Hospital, Xi' an Jiaotong University, Xi' an (China); Chen, Lina; Zhou, Jun [Department of Pharmacology, Health Science Center, Xi' an Jiaotong University, Xi' an (China); Key Laboratory of Environment and Genes Related to Diseases, Xi' an Jiaotong University, Ministry of Education of China, Xi' an (China); Hu, Hao, E-mail: huhao@mail.xjtu.edu.cn [Department of Pharmacology, Health Science Center, Xi' an Jiaotong University, Xi' an (China); Key Laboratory of Environment and Genes Related to Diseases, Xi' an Jiaotong University, Ministry of Education of China, Xi' an (China)

    2017-05-01

    Excessive consumption of alcohol is a well-established risk factor of atrial fibrillation (AF). However, the effects of moderate alcohol drinking remain to be elucidated. This study was designed to determine the effects of moderate ethanol ingestion on atrial fibrillation and the electrophysiological mechanisms. In acetylcholine-induced canine and mouse AF models, the moderate ethanol prevented the generation and persistence of AF through prolonging the latent period of AF and shortening the duration of AF. The action potential duration (APD) was remarkably prolonged under the concentration range of 12.5–50.0 mM ethanol in guinea pig atrial myocytes. Ultra-rapid delayed rectified potassium currents (I{sub Kv1.5}) were markedly inhibited by 12.5–50.0 mM ethanol in a concentration-dependent manner. Ethanol with 50.0 mM could inhibit rapid delayed rectifier potassium currents (I{sub hERG}). Ethanol under 6.25–50.0 mM did not affect on inward rectifier potassium currents (I{sub Kir2.1}). Collectively, the present study provided an evidence that moderate ethanol intake can prolong the APD of atrial myocytes by inhibition of I{sub Kv1.5} and I{sub hERG}, which contributed to preventing the development and duration of AF. - Highlights: • Moderate ethanol prevented the development of AF in animal models. • Moderate ethanol prolonged APD in guinea pig atrial myocytes. • Moderate ethanol inhibited Kv1.5 currents.

  8. Food sharing is linked to urinary oxytocin levels and bonding in related and unrelated wild chimpanzees

    Science.gov (United States)

    Wittig, Roman M.; Crockford, Catherine; Deschner, Tobias; Langergraber, Kevin E.; Ziegler, Toni E.; Zuberbühler, Klaus

    2014-01-01

    Humans excel in cooperative exchanges between unrelated individuals. Although this trait is fundamental to the success of our species, its evolution and mechanisms are poorly understood. Other social mammals also build long-term cooperative relationships between non-kin, and recent evidence shows that oxytocin, a hormone involved in parent–offspring bonding, is likely to facilitate non-kin as well as kin bonds. In a population of wild chimpanzees, we measured urinary oxytocin levels following a rare cooperative event—food sharing. Subjects showed higher urinary oxytocin levels after single food-sharing events compared with other types of social feeding, irrespective of previous social bond levels. Also, urinary oxytocin levels following food sharing were higher than following grooming, another cooperative behaviour. Therefore, food sharing in chimpanzees may play a key role in social bonding under the influence of oxytocin. We propose that food-sharing events co-opt neurobiological mechanisms evolved to support mother–infant bonding during lactation bouts, and may act as facilitators of bonding and cooperation between unrelated individuals via the oxytocinergic system across social mammals. PMID:24430853

  9. Exposure to synthetic oxytocin during delivery and its effect on psychomotor development.

    Science.gov (United States)

    González-Valenzuela, María-José; López-Montiel, Dolores; González-Mesa, Ernesto Santiago

    2015-12-01

    The main objective is to examine the influence of oxytocin administration during delivery on psychomotor development at age five years. This was a retrospective cohort study involving two groups: children of mothers exposed vs. not exposed to oxytocin during labor. Of the 7,465 newborns registered in our maternity service during 2006 we randomly selected an initial sample of 400 children. Of these, 146 children were assessed using the motor scale of the Battelle Developmental Inventory. Other predictor variables that could potentially act as confounders and/or interact with the main relationship were also examined. The data were subjected to bivariate analysis, estimates of measures of strength of association, stratified analysis and multivariate binary logistic regression. The results indicate that exposure to synthetic oxytocin during delivery is an independent risk factor for a delay in gross and fine motor development. This was the case after controlling for the variables duration of labor and sex of the newborn, none of which modified the effect of oxytocin on gross and fine motor development. However, sex of the newborn were shown to be confounding gross motor development. In light of these results, and with the aim of preventing possible psychomotor alterations, further studies are now needed to analyze the effect that the oxytocin dose and the duration of perfusion may have on children's subsequent development. © 2015 Wiley Periodicals, Inc.

  10. Oxytocin modulates third-party sanctioning of selfish and generous behavior within and between groups.

    Science.gov (United States)

    Daughters, Katie; Manstead, Antony S R; Ten Velden, Femke S; De Dreu, Carsten K W

    2017-03-01

    Human groups function because members trust each other and reciprocate cooperative contributions, and reward others' cooperation and punish their non-cooperation. Here we examined the possibility that such third-party punishment and reward of others' trust and reciprocation is modulated by oxytocin, a neuropeptide generally involved in social bonding and in-group (but not out-group) serving behavior. Healthy males and females (N=100) self-administered a placebo or 24 IU of oxytocin in a randomized, double-blind, between-subjects design. Participants were asked to indicate (incentivized, costly) their level of reward or punishment for in-group (outgroup) investors donating generously or fairly to in-group (outgroup) trustees, who back-transferred generously, fairly or selfishly. Punishment (reward) was higher for selfish (generous) investments and back-transfers when (i) investors were in-group rather than outgroup, and (ii) trustees were in-group rather than outgroup, especially when (iii) participants received oxytocin rather than placebo. It follows, first, that oxytocin leads individuals to ignore out-groups as long as out-group behavior is not relevant to the in-group and, second, that oxytocin contributes to creating and enforcing in-group norms of cooperation and trust. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Oxytocin Promotes Facial Emotion Recognition and Amygdala Reactivity in Adults with Asperger Syndrome

    Science.gov (United States)

    Domes, Gregor; Kumbier, Ekkehardt; Heinrichs, Markus; Herpertz, Sabine C

    2014-01-01

    The neuropeptide oxytocin has recently been shown to enhance eye gaze and emotion recognition in healthy men. Here, we report a randomized double-blind, placebo-controlled trial that examined the neural and behavioral effects of a single dose of intranasal oxytocin on emotion recognition in individuals with Asperger syndrome (AS), a clinical condition characterized by impaired eye gaze and facial emotion recognition. Using functional magnetic resonance imaging, we examined whether oxytocin would enhance emotion recognition from facial sections of the eye vs the mouth region and modulate regional activity in brain areas associated with face perception in both adults with AS, and a neurotypical control group. Intranasal administration of the neuropeptide oxytocin improved performance in a facial emotion recognition task in individuals with AS. This was linked to increased left amygdala reactivity in response to facial stimuli and increased activity in the neural network involved in social cognition. Our data suggest that the amygdala, together with functionally associated cortical areas mediate the positive effect of oxytocin on social cognitive functioning in AS. PMID:24067301

  12. Neural circuits containing olfactory neurons are involved in prepulse inhibition of the startle reflex in rats

    Directory of Open Access Journals (Sweden)

    Haichen eNiu

    2015-03-01

    Full Text Available Many neuropsychiatric disorders, such as schizophrenia, have been associated with abnormalities in the function of the olfactory system and prepulse inhibition (PPI of the startle reflex. However, whether these two abnormalities are related is unclear. The present study was designed to determine whether inhibiting olfactory sensory input via the infusion of zinc sulfate (ZnE, 0.17 M, 0.5 ml into the olfactory naris disrupts PPI. Furthermore, lidocaine/MK801 was bilaterally microinjected into the olfactory bulb (OB to examine whether the blockade of olfactory sensory input impairs PPI. To identify the neural projections that connect the olfaction- and PPI-related areas of the CNS, trans-synaptic retrograde tracing using a recombinant pseudorabies virus (PRV was performed. Our results demonstrated that blocking olfactory sensory input altered olfaction-related behavior. At the functional level, we demonstrated that the inhibition of olfactory sensory input impaired PPI of the startle response subsequent to a decrease in c-fos expression in relevant brain regions. Furthermore, the results of a similar and more robust experiment indicated that blocking olfactory sensory input via the microinjection of lidocaine/MK801 into the OB impaired PPI. At the circuit level, based on trans-synaptic retrograde tracing using PRV, we demonstrated that a large portion of the labeled neurons in several regions of the olfactory cortices connected to the pedunculopontine tegmental nucleus (PPTg. Thus, these data suggest that the olfactory system participates in the regulation of PPI and plays a role in the effect of PPI on the startle response in rats.

  13. Antidepressants inhibit P2X4 receptor function: a possible involvement in neuropathic pain relief

    Directory of Open Access Journals (Sweden)

    Tozaki-Saitoh Hidetoshi

    2009-04-01

    Full Text Available Abstract Background Neuropathic pain is characterized by pain hypersensitivity to innocuous stimuli (tactile allodynia that is nearly always resistant to known treatments such as non-steroidal anti-inflammatory drugs or even opioids. It has been reported that some antidepressants are effective for treating neuropathic pain. However, the underlying molecular mechanisms are not well understood. We have recently demonstrated that blocking P2X4 receptors in the spinal cord reverses tactile allodynia after peripheral nerve injury in rats, implying that P2X4 receptors are a key molecule in neuropathic pain. We investigated a possible role of antidepressants as inhibitors of P2X4 receptors and analysed their analgesic mechanism using an animal model of neuropathic pain. Results Antidepressants strongly inhibited ATP-mediated Ca2+ responses in P2X4 receptor-expressing 1321N1 cells, which are known to have no endogenous ATP receptors. Paroxetine exhibited the most powerful inhibition of calcium influx via rat and human P2X4 receptors, with IC50 values of 2.45 μM and 1.87 μM, respectively. Intrathecal administration of paroxetine produced a striking antiallodynic effect in an animal model of neuropathic pain. Co-administration of WAY100635, ketanserin or ondansetron with paroxetine induced no significant change in the antiallodynic effect of paroxetine. Furthermore, the antiallodynic effect of paroxetine was observed even in rats that had received intrathecal pretreatment with 5,7-dihydroxytryptamine, which dramatically depletes spinal 5-hydroxytryptamine. Conclusion These results suggest that paroxetine acts as a potent analgesic in the spinal cord via a mechanism independent of its inhibitory effect on serotonin transporters. Powerful inhibition on P2X4 receptors may underlie the analgesic effect of paroxetine, and it is possible that some antidepressants clinically used in patients with neuropathic pain show antiallodynic effects, at least in part

  14. Tetrahydroxystilbene glucoside improves TNF-α-induced endothelial dysfunction: involvement of TGFβ/Smad pathway and inhibition of vimentin expression.

    Science.gov (United States)

    Yao, Wenjuan; Gu, Chengjing; Shao, Haoran; Meng, Guoliang; Wang, Huiming; Jing, Xiang; Zhang, Wei

    2015-01-01

    Endothelial dysfunction plays an important role in the pathogenesis of atherogenesis. 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), an active component of the rhizome extract from Polygonum multiflorum (PM), exhibits significant anti-atherosclerotic activity. Here, we used human umbilical vein endothelial cells (HUVECs) induced by tumor necrosis factor-α (TNF-α) in vitro to investigate the cytoprotective effects of TSG on TNF-α-induced endothelial injury and the related mechanisms. Pretreatment with 50 and 100 μM TSG markedly attenuated TNF-α-induced loss of cell viability and release of lactate dehydrogenase (LDH) and inhibited TNF-α-induced cell apoptosis. The inhibition of vimentin expression was involved in the cytoprotection afforded by TSG. Using inhibitors for PI3K and TGFβ or siRNA for Akt and Smad2, we found that vimentin production in HUVECs is regulated by TGFβ/Smad signaling, but not by PI3K-Akt-mTOR signaling. Meanwhile, TSG inhibited both the expression of TGFβ1 and the phosphorylation of Smad2 and Smad3, and TSG suppressed the nuclear translocation of Smad4 induced by TNF-α. These results suggest that TSG protects HUVECs against TNF-α-induced cell damage by inhibiting vimentin expression via the interruption of the TGFβ/Smad signaling pathway.

  15. NO involvement in the inhibition of ghrelin on voltage-dependent potassium currents in rat hippocampal cells.

    Science.gov (United States)

    Lu, Yong; Dang, Shaokang; Wang, Xu; Zhang, Junli; Zhang, Lin; Su, Qian; Zhang, Huiping; Lin, Tianwei; Zhang, Xiaoxiao; Zhang, Yurong; Sun, Hongli; Zhu, Zhongliang; Li, Hui

    2018-01-01

    Ghrelin is a peptide hormone that plays an important role in promoting appetite, regulating distribution and rate of use of energy, cognition, and mood disorders, but the relevant neural mechanisms of these function are still not clear. In this study, we examined the effect of ghrelin on voltage-dependent potassium (K + ) currents in hippocampal cells of 1-3 days SD rats by whole-cell patch-clamp technique, and discussed whether NO was involved in this process. The results showed that ghrelin significantly inhibited the voltage-dependent K + currents in hippocampal cells, and the inhibitory effect was more significant when l-arginine was co-administered. In contrast, N-nitro- l-arginine methyl ester increased the ghrelin inhibited K + currents and attenuated the inhibitory effect of ghrelin. While d-arginine (D-AA) showed no significant impact on the ghrelin-induced decrease in K + current. These results show that ghrelin may play a physiological role by inhibiting hippocampal voltage dependent K + currents, and the NO pathway may be involved in this process. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Activation of Supraoptic Oxytocin Neurons by Secretin Facilitates Social Recognition.

    Science.gov (United States)

    Takayanagi, Yuki; Yoshida, Masahide; Takashima, Akihide; Takanami, Keiko; Yoshida, Shoma; Nishimori, Katsuhiko; Nishijima, Ichiko; Sakamoto, Hirotaka; Yamagata, Takanori; Onaka, Tatsushi

    2017-02-01

    Social recognition underlies social behavior in animals, and patients with psychiatric disorders associated with social deficits show abnormalities in social recognition. Oxytocin is implicated in social behavior and has received attention as an effective treatment for sociobehavioral deficits. Secretin receptor-deficient mice show deficits in social behavior. The relationship between oxytocin and secretin concerning social behavior remains to be determined. Expression of c-Fos in oxytocin neurons and release of oxytocin from their dendrites after secretin application were investigated. Social recognition was examined after intracerebroventricular or local injection of secretin, oxytocin, or an oxytocin receptor antagonist in rats, oxytocin receptor-deficient mice, and secretin receptor-deficient mice. Electron and light microscopic immunohistochemical analysis was also performed to determine whether oxytocin neurons extend their dendrites into the medial amygdala. Supraoptic oxytocin neurons expressed the secretin receptor. Secretin activated supraoptic oxytocin neurons and facilitated oxytocin release from dendrites. Secretin increased acquisition of social recognition in an oxytocin receptor-dependent manner. Local application of secretin into the supraoptic nucleus facilitated social recognition, and this facilitation was blocked by an oxytocin receptor antagonist injected into, but not outside of, the medial amygdala. In the medial amygdala, dendrite-like thick oxytocin processes were found to extend from the supraoptic nucleus. Furthermore, oxytocin treatment restored deficits of social recognition in secretin receptor-deficient mice. The results of our study demonstrate that secretin-induced dendritic oxytocin release from supraoptic neurons enhances social recognition. The newly defined secretin-oxytocin system may lead to a possible treatment for social deficits. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights

  17. Oxytocin reduces alcohol consumption in prairie voles.

    Science.gov (United States)

    Stevenson, J R; Wenner, S M; Freestone, D M; Romaine, C C; Parian, M C; Christian, S M; Bohidar, A E; Ndem, J R; Vogel, I R; O'Kane, C M

    2017-10-01

    Alcohol use disorder (AUD) negatively affects millions of people every year in the United States, and effective treatments for AUD are still needed. The neuropeptide oxytocin has shown promise for reducing alcohol drinking in mice and rats. Because oxytocin also plays a key role in complex prosocial behaviors like bonding and attachment, we tested the effect of oxytocin on alcohol drinking in prairie voles, a species that both consumes high amounts of alcohol and forms oxytocin dependent social bonds in a manner similar to humans. Oxytocin treatment (1.0, 3.0, and 10.0mg/kg, i.p.) reduced alcohol consumption in male and female prairie voles in animals that had access to 15% ethanol vs water every other day for 12 alcohol drinking sessions. In animals with continuous access to 15% alcohol and water, oxytocin (3.0mg/kg) reduced alcohol consumption only in the first hour of access after treatment, with no significant effects on consumption over the 24-hr period. In an open field locomotor test, oxytocin (1.0, 3.0, and 10.0mg/kg, i.p.) did not affect overall locomotor activity; however, ethanol (2g/kg, i.p.) increased locomotor activity in males and females, and produced anxiolytic effects (increased time in the center of an open field) in females only. Because prairie voles have been shown to match the alcohol consumption of their cage mate, we evaluated the relationship between cage mates' alcohol drinking. There was an overall pattern of social facilitation (consumption by one cage mate predicted consumption by the other cage mate); however, we found significant individual differences across cages in which many cages did not show significant matching, and, in some cases one cage mate's consumption negatively predicted the other cage mate's consumption. Overall, our data provide support for the potential of oxytocin as a treatment to reduce alcohol consumption. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Aminopeptidase N inhibition could be involved in the anti-angiogenic effect of dobesilates

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    Farsa Oldřich

    2015-01-01

    Full Text Available Calcium, magnesium and zinc 2,5-dihydroxybenzenesulfonates (dobesilates were synthesized by sulfonation of hydroquinone with sulfuric acid under mild conditions. To form the salts, neutralization with calcium carbonate followed by cation exchange by means of magnesium or zinc sulfates was performed. The dobesilates were characterized by standard spectral methods and by AAS for metal content and then tested for inhibitory activity against aminopeptidase N. Calcium and magnesium 2,5-dihydroxybenzene sulfonates exhibited rather weak inhibitory activity to aminopeptidase N as demonstrated by IC50 values of 978.0 and 832.1 mmol l-1 respectively while zinc 2,5-dihydroxybenzene sulfonate reached the more significant inhibitory activity characterized by IC50 77.4 mmol l-1. The inhibitory activity results suggest that the inhibition of aminopeptidase N could play a role in the anti-angiogenic activity of 2,5-dihydroxybenzenesulfonates.

  19. Nitric oxide signaling pathways involved in the inhibition of spontaneous activity in the guinea pig prostate.

    Science.gov (United States)

    Dey, Anupa; Lang, Richard J; Exintaris, Betty

    2012-06-01

    We investigated nitric oxide mediated inhibition of spontaneous activity recorded in young and aging guinea pig prostates. Conventional intracellular microelectrode and tension recording techniques were used. The nitric oxide donor sodium nitroprusside (10 μM) abolished spontaneous contractions and slow wave activity in 5 young and 5 aging prostates. Upon adding the nitric oxide synthase inhibitor L-NAME (10 μM) the frequency of spontaneous contractile and electrical activity was significantly increased in each age group. This increase was significantly larger in 4 to 8 preparations of younger vs aging prostates (about 40% to 50% vs about 10% to 20%, 2-way ANOVA pguinea pig prostates (Student paired t test pproduction. This may further explain the increase in prostatic smooth muscle tone observed in age related prostate specific conditions, such as benign prostatic hyperplasia. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  20. Epigenetic Regulation of the Oxytocin Receptor Gene: Implications for Behavioral Neuroscience

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    Robert eKumsta

    2013-05-01

    Full Text Available Genetic approaches have improved our understanding of the neurobiological basis of social behavior and cognition. For instance, common polymorphisms of genes involved in oxytocin signaling have been associated with sociobehavioral phenotypes in healthy samples as well as in subjects with mental disorders. More recently, attention has been drawn to epigenetic mechanisms, which regulate genetic function and expression without changes to the underlying DNA sequence. We provide an overview of the functional importance of oxytocin receptor gene (OXTR promoter methylation and summarize studies that have investigated the role of OXTR methylation in behavioral phenotypes. There is first evidence that OXTR methylation is associated with autism, high callous-unemotional traits, and differential activation of brain regions involved in social perception. Furthermore, psychosocial stress exposure might dynamically regulate OXTR. Given evidence that epigenetic states of genes can be modified by experiences, especially those occurring in sensitive periods early in development, we conclude with a discussion on the effects of traumatic experience on the developing oxytocin system. Epigenetic modification of genes involved in oxytocin signaling might be involved in the mechanisms mediating the long-term influence of early adverse experiences on socio-behavioral outcomes.

  1. Oxytocin promotes group-serving dishonesty.

    Science.gov (United States)

    Shalvi, Shaul; De Dreu, Carsten K W

    2014-04-15

    To protect and promote the well-being of others, humans may bend the truth and behave unethically. Here we link such tendencies to oxytocin, a neuropeptide known to promote affiliation and cooperation with others. Using a simple coin-toss prediction task in which participants could dishonestly report their performance levels to benefit their group's outcome, we tested the prediction that oxytocin increases group-serving dishonesty. A double-blind, placebo-controlled experiment allowing individuals to lie privately and anonymously to benefit themselves and fellow group members showed that healthy males (n = 60) receiving intranasal oxytocin, rather than placebo, lied more to benefit their group, and did so faster, yet did not necessarily do so because they expected reciprocal dishonesty from fellow group members. Treatment effects emerged when lying had financial consequences and money could be gained; when losses were at stake, individuals in placebo and oxytocin conditions lied to similar degrees. In a control condition (n = 60) in which dishonesty only benefited participants themselves, but not fellow group members, oxytocin did not influence lying. Together, these findings fit a functional perspective on morality revealing dishonesty to be plastic and rooted in evolved neurobiological circuitries, and align with work showing that oxytocin shifts the decision-maker's focus from self to group interests. These findings highlight the role of bonding and cooperation in shaping dishonesty, providing insight into when and why collaboration turns into corruption.

  2. Belinostat-induced apoptosis and growth inhibition in pancreatic cancer cells involve activation of TAK1-AMPK signaling axis

    International Nuclear Information System (INIS)

    Wang, Bing; Wang, Xin-bao; Chen, Li-yu; Huang, Ling; Dong, Rui-zen

    2013-01-01

    Highlights: •Belinostat activates AMPK in cultured pancreatic cancer cells. •Activation of AMPK is important for belinostat-induced cytotoxic effects. •ROS and TAK1 are involved in belinostat-induced AMPK activation. •AMPK activation mediates mTOR inhibition by belinostat. -- Abstract: Pancreatic cancer accounts for more than 250,000 deaths worldwide each year. Recent studies have shown that belinostat, a novel pan histone deacetylases inhibitor (HDACi) induces apoptosis and growth inhibition in pancreatic cancer cells. However, the underlying mechanisms are not fully understood. In the current study, we found that AMP-activated protein kinase (AMPK) activation was required for belinostat-induced apoptosis and anti-proliferation in PANC-1 pancreatic cancer cells. A significant AMPK activation was induced by belinostat in PANC-1 cells. Inhibition of AMPK by RNAi knockdown or dominant negative (DN) mutation significantly inhibited belinostat-induced apoptosis in PANC-1 cells. Reversely, AMPK activator AICAR and A-769662 exerted strong cytotoxicity in PANC-1 cells. Belinostat promoted reactive oxygen species (ROS) production in PANC-1 cells, increased ROS induced transforming growth factor-β-activating kinase 1 (TAK1)/AMPK association to activate AMPK. Meanwhile, anti-oxidants N-Acetyl-Cysteine (NAC) and MnTBAP as well as TAK1 shRNA knockdown suppressed belinostat-induced AMPK activation and PANC-1 cell apoptosis. In conclusion, we propose that belinostat-induced apoptosis and growth inhibition require the activation of ROS-TAK1-AMPK signaling axis in cultured pancreatic cancer cells

  3. Belinostat-induced apoptosis and growth inhibition in pancreatic cancer cells involve activation of TAK1-AMPK signaling axis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Bing, E-mail: wangbin69@yahoo.com; Wang, Xin-bao; Chen, Li-yu; Huang, Ling; Dong, Rui-zen

    2013-07-19

    Highlights: •Belinostat activates AMPK in cultured pancreatic cancer cells. •Activation of AMPK is important for belinostat-induced cytotoxic effects. •ROS and TAK1 are involved in belinostat-induced AMPK activation. •AMPK activation mediates mTOR inhibition by belinostat. -- Abstract: Pancreatic cancer accounts for more than 250,000 deaths worldwide each year. Recent studies have shown that belinostat, a novel pan histone deacetylases inhibitor (HDACi) induces apoptosis and growth inhibition in pancreatic cancer cells. However, the underlying mechanisms are not fully understood. In the current study, we found that AMP-activated protein kinase (AMPK) activation was required for belinostat-induced apoptosis and anti-proliferation in PANC-1 pancreatic cancer cells. A significant AMPK activation was induced by belinostat in PANC-1 cells. Inhibition of AMPK by RNAi knockdown or dominant negative (DN) mutation significantly inhibited belinostat-induced apoptosis in PANC-1 cells. Reversely, AMPK activator AICAR and A-769662 exerted strong cytotoxicity in PANC-1 cells. Belinostat promoted reactive oxygen species (ROS) production in PANC-1 cells, increased ROS induced transforming growth factor-β-activating kinase 1 (TAK1)/AMPK association to activate AMPK. Meanwhile, anti-oxidants N-Acetyl-Cysteine (NAC) and MnTBAP as well as TAK1 shRNA knockdown suppressed belinostat-induced AMPK activation and PANC-1 cell apoptosis. In conclusion, we propose that belinostat-induced apoptosis and growth inhibition require the activation of ROS-TAK1-AMPK signaling axis in cultured pancreatic cancer cells.

  4. The effects of oxytocine in autism : De werking van oxytocine bij autisme

    NARCIS (Netherlands)

    Groen, Yvonne; Althaus, Monika; Oosterhoff, Menno; van Balkom, Ingrid; Hoekstra, Pieter J.

    2017-01-01

    Oxytocin is viewed as the hormone of calm, healing and love, and plays an important role in establishing and maintaining social relationships. As autism is characterized by difficulties in social relationships, a dysregulated oxytocin system could possibly be an underlying factor. Our recently

  5. Revisiting the wandering womb: Oxytocin in endometriosis and bipolar disorder.

    Science.gov (United States)

    Dinsdale, Natalie L; Crespi, Bernard J

    2017-11-01

    Hippocrates attributed women's high emotionality - hysteria - to a 'wandering womb'. Although hysteria diagnoses were abandoned along with the notion that displaced wombs cause emotional disturbance, recent research suggests that elevated levels of oxytocin occur in both bipolar disorder and endometriosis, a gynecological condition involving migration of endometrial tissue beyond the uterus. We propose and evaluate the hypothesis that elevated oxytocinergic system activity jointly contributes to bipolar disorder and endometriosis. First, we provide relevant background on endometriosis and bipolar disorder, and then we examine evidence for comorbidity between these conditions. We next: (1) review oxytocin's associations with personality traits, especially extraversion and openness, and how they overlap with bipolar spectrum traits; (2) describe evidence for higher oxytocinergic activity in both endometriosis and bipolar disorder; (3) examine altered hypothalamic-pituitary-gonadal axis functioning in both conditions; (4) describe data showing that medications that treat one condition can improve symptoms of the other; (5) discuss fitness-related impacts of endometriosis and bipolar disorder; and (6) review a pair of conditions, polycystic ovary syndrome and autism, that show evidence of involving reduced oxytocinergic activity, in direct contrast to endometriosis and bipolar disorder. Considered together, the bipolar spectrum and endometriosis appear to involve dysregulated high extremes of normally adaptive pleiotropy in the female oxytocin system, whereby elevated levels of oxytocinergic activity coordinate outgoing sociality with heightened fertility, apparently characterizing, overall, a faster life history. These findings should prompt a re-examination of how mind-body interactions, and the pleiotropic endocrine systems that underlie them, contribute to health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Salinity-induced inhibition of growth in the aquatic pteridophyte Azolla microphylla primarily involves inhibition of photosynthetic components and signaling molecules as revealed by proteome analysis.

    Science.gov (United States)

    Thagela, Preeti; Yadav, Ravindra Kumar; Mishra, Vagish; Dahuja, Anil; Ahmad, Altaf; Singh, Pawan Kumar; Tiwari, Budhi Sagar; Abraham, Gerard

    2017-01-01

    Salinity stress causes adverse physiological and biochemical changes in the growth and productivity of a plant. Azolla, a symbiotic pteridophyte and potent candidate for biofertilizer due to its nitrogen fixation ability, shows reduced growth and nitrogen fixation during saline stress. To better understand regulatory components involved in salinity-induced physiological changes, in the present study, Azolla microphylla plants were exposed to NaCl (6.74 and 8.61 ds/m) and growth, photochemical reactions of photosynthesis, ion accumulation, and changes in cellular proteome were studied. Maximum dry weight was accumulated in control and untreated plant while a substantial decrease in dry weight was observed in the plants exposed to salinity. Exposure of the organism to different concentrations of salt in hydroponic conditions resulted in differential level of Na + and K + ion accumulation. Comparative analysis of salinity-induced proteome changes in A. microphylla revealed 58 salt responsive proteins which were differentially expressed during the salt exposure. Moreover, 42 % spots among differentially expressed proteins were involved in different signaling events. The identified proteins are involved in photosynthesis, energy metabolism, amino acid biosynthesis, protein synthesis, and defense. Downregulation of these key metabolic proteins appears to inhibit the growth of A. microphylla in response to salinity. Altogether, the study revealed that in Azolla, increased salinity primarily affected signaling and photosynthesis that in turn leads to reduced biomass.

  7. The impact of oxytocin administration on charitable donating is moderated by experiences of parental love-withdrawal

    Directory of Open Access Journals (Sweden)

    Marinus H. Van Ijzendoorn

    2011-10-01

    Full Text Available Oxytocin has been implicated in a variety of prosocial processes but most of this work has used laboratory tasks (such as the ultimatum game or the dictator game to evaluate oxytocin’s prosocial effects. In a double blind randomized trial we examined the influence of intranasal administration of oxytocin on real, high-cost donating money to a charity without any expectation for reciprocation. Participants in the current study were 57 female undergraduate students, aged 18-30 years, who received a nasal spray containing either 24 IU of oxytocin or a placebo, and were then given the opportunity to make a charitable donation. The participants reported how often their parents used love-withdrawal as a disciplinary strategy involving withholding love and affection after a failure or misbehavior. Oxytocin appeared to increase the participants’ willingness to donate money to a charity but only in participants who experienced low levels of parental love-withdrawal. In contrast, oxytocin administration was ineffective in enhancing donating behavior in individuals who experienced high levels of parental love-withdrawal. We conclude that the positive effect of oxytocin administration on prosocial behavior may be limited to individuals with supportive backgrounds.

  8. p8 inhibits the growth of human pancreatic cancer cells and its expression is induced through pathways involved in growth inhibition and repressed by factors promoting cell growth

    Directory of Open Access Journals (Sweden)

    Vasseur Sophie

    2003-11-01

    Full Text Available Abstract Background p8 is a stress-induced protein with multiple functions and biochemically related to the architectural factor HMG-I/Y. We analyzed the expression and function of p8 in pancreatic cancer-derived cells. Methods Expression of p8 was silenced in the human pancreatic cancer cell lines Panc-1 and BxPc-3 by infection with a retrovirus expressing p8 RNA in the antisense orientation. Cell growth was measured in control and p8-silenced cells. Influence on p8 expression of the induction of intracellular pathways promoting cellular growth or growth arrest was monitored. Results p8-silenced cells grew more rapidly than control cells transfected with the empty retrovirus. Activation of the Ras→Raf→MEK→ERK and JNK intracellular pathways down-regulated p8 expression. In addition, the MEK1/2 inhibitor U0126 and the JNK inhibitor SP600125 up-regulates expression of p8. Conversely, p38 or TGFβ-1 induced p8 expression whereas the specific p38 inhibitor SB203580 down-regulated p8 expression. Finally, TGFβ-1 induction was in part mediated through p38. Conclusions p8 inhibits the growth of human pancreatic cancer cells. p8 expression is induced through pathways involved in growth inhibition and repressed by factors that promote cell growth. These results suggest that p8 belongs to a pathway regulating the growth of pancreatic cancer cells.

  9. Oxytocin and the oxytocin receptor underlie intrastrain, but not interstrain, social recognition.

    Science.gov (United States)

    Macbeth, A H; Lee, H-J; Edds, J; Young, W S

    2009-07-01

    We studied three lines of oxytocin (Oxt) and oxytocin receptor (Oxtr) knockout (KO) male mice [Oxt(-/-), total Oxtr(-/-) and partial forebrain Oxtr (Oxtr(FB/FB))] with established deficits in social recognition to further refine our understanding of their deficits with regard to stimulus female's strain. We used a modified social discrimination paradigm in which subjects are singly housed only for the duration of the test. Additionally, stimulus females are singly housed throughout testing and are presented within corrals for rapid comparison of investigation by subject males. Wild-type (WT) males from all three lines discriminated between familiar and novel females of three different strains (C57BL/6, BALB/c and Swiss-Webster). No KO males discriminated between familiar and novel BALB/c or C57BL/6 females. Male Oxt(-/-) and Oxtr(-/-) mice, but not Oxtr(FB/FB) mice, discriminated between familiar and novel Swiss-Webster females. As this might indicate a global deficit in individual recognition for Oxtr(FB/FB) males, we examined their ability to discriminate between females from different strains and compared performance with Oxtr(-/-) males. WT and KO males from both lines were able to distinguish between familiar and novel females from different strains, indicating the social recognition deficit is not universal. Instead, we hypothesize that the Oxtr is involved in 'fine' intrastrain recognition, but is less important in 'broad' interstrain recognition. We also present the novel finding of decreased investigation across tests, which is likely an artifact of repeated testing and not because of stimulus female's strain or age of subject males.

  10. Pineal-mediated inhibition of prolactin cell activity: Investigation of dopaminergic involvement

    International Nuclear Information System (INIS)

    Burns, D.M.

    1989-01-01

    The present studies in the male Syrian hamster addressed two issues. First, it was of interest to determine if anterior pituitaries of long photoperiod-exposed male hamsters possess dopamine receptors, which are presumably necessary for responsiveness to dopamine. This was accomplished by analysis of 3 H-spiperone binding to anterior pituitary membranes. Second, possible changes in pituitary sensitivity to dopamine were assessed by comparison of dose response curves for the inhibition by dopamine of prolactin release from hemipituitaries incubated in vitro from both long and short photoperiod-exposed animals over a series of time points from three to fifteen weeks. In the second series of experiments, adult female F344 rats received daily injection of melatonin or saline vehicle. After two weeks, half of the animals were sacrificed for analysis of 3 H-spiperone binding to anterior pituitary membranes, measurement of hypothalamic dopamine turnover and analysis of in vitro pituitary sensitivity to dopamine. The remaining animals received subcutaneous implants containing DES and injections were continued on the same schedule until sacrifice four weeks later for measurement of the same parameters

  11. Direct evidence that FK506 inhibition of FcepsilonRI-mediated exocytosis from RBL mast cells involves calcineurin.

    Science.gov (United States)

    Hultsch, T; Brand, P; Lohmann, S; Saloga, J; Kincaid, R L; Knop, J

    1998-05-01

    FcepsilonRI-mediated exocytosis of preformed mediators from mast cells and basophils (e.g. histamine, serotonin, beta-hexosaminidase) is sensitive to the immunosuppressants cyclosporin A and FK506 (IC50 200 and 4 nM, respectively) but not rapamycin. The mechanism of inhibition does not appear to involve tyrosine phosphorylation, hydrolysis of inositol phosphates or calcium flux. Here we report experiments using a molecular approach to assess the role of calcineurin, a serine/threonine phosphatase thought to be the primary pharmacological target of these drugs. Calcineurin's activity requires association of its catalytic (A) subunit with an intrinsic regulatory (B) subunit. We hypothesized that calcineurin-sensitive signalling events should be affected by the depletion of calcineurin B subunits, thereby reducing the number of active A:B complexes. We therefore transfected rat basophilic leukemia (RBL) cells with an inhibitory (dominant negative) form of the calcineurin A subunit, which binds the calcineurin B subunit with high affinity but does not possess catalytic activity (B subunit knock-out, BKO). In these transfected cells, the dose-response curve for the inhibition of FcepsilonRI-mediated exocytosis by FK506 was shifted to the left, indicating an increased drug sensitivity of BKO-transfected cells. We conclude that FK506 inhibition of FcepsilonRI-mediated exocytosis in mast cells specifically targets calcineurin activity.

  12. Acropetal Auxin Transport Inhibition Is Involved in Indeterminate But Not Determinate Nodule Formation

    Directory of Open Access Journals (Sweden)

    Jason L. P. Ng

    2018-02-01

    Full Text Available Legumes enter into a symbiotic relationship with nitrogen-fixing rhizobia, leading to nodule development. Two main types of nodules have been widely studied, indeterminate and determinate, which differ in the location of the first cell division in the root cortex, and persistency of the nodule meristem. Here, we compared the control of auxin transport, content, and response during the early stages of indeterminate and determinate nodule development in the model legumes Medicago truncatula and Lotus japonicus, respectively, to investigate whether differences in auxin transport control could explain the differences in the location of cortical cell divisions. While auxin responses were activated in dividing cortical cells during nodulation of both nodule types, auxin (indole-3-acetic acid content at the nodule initiation site was transiently increased in M. truncatula, but transiently reduced in L. japonicus. Root acropetal auxin transport was reduced in M. truncatula at the very start of nodule initiation, in contrast to a prolonged increase in acropetal auxin transport in L. japonicus. The auxin transport inhibitors 2,3,5-triiodobenzoic acid and 1-N-naphthylphthalamic acid (NPA only induced pseudonodules in legume species forming indeterminate nodules, but failed to elicit such structures in a range of species forming determinate nodules. The development of these pseudonodules in M. truncatula exhibited increased auxin responses in a small primordium formed from the pericycle, endodermis, and inner cortex, similar to rhizobia-induced nodule primordia. In contrast, a diffuse cortical auxin response and no associated cortical cell divisions were found in L. japonicus. Collectively, we hypothesize that a step of acropetal auxin transport inhibition is unique to the process of indeterminate nodule development, leading to auxin responses in pericycle, endodermis, and inner cortex cells, while increased auxin responses in outer cortex cells likely

  13. Mechanisms involved in the chemical inhibition of the Eosin-sensitized photooxidation of trypsin

    Energy Technology Data Exchange (ETDEWEB)

    Rizzuto, F.; Spikes, J.D.

    1975-01-01

    A large series of compounds was screened for ability to protect trypsin from eosin-sensitized photodynamic inactivation. Eosin-sensitized photooxidation reactions of this type typically proceed via the triplet state of the dye and often involve singlet state oxygen as the oxidizing entity. In order to determine the mechanisms by which trypsin is protected from photoinactivation, a number of good protective agents (inhibitors) and some non-protective agents were selected for more detailed flash photolysis studies. Good inhibitors such as p-phenylenediamine, n-propyl gallate, serotonin creatinine sulfate and p-toluenediamine competed efficiently with oxygen and with trypsin for reaction with the triplet state of eosin. The inhibitors were shown to quench triplet eosin to the ground state and/or reduce triplet eosin to form the semireduced eosin radical and an oxidized form of the inhibitor. In the latter case, oxidized inhibitor could react by a reverse electron transfer reaction with the semireduced eosin radical to regenerate ground state eosin and the inhibitor. The good inhibitors also competed effectively with trypsin for oxidation by semioxidized eosin, thus giving another possible protective mechanism. Non-inhibitors such as halogen ions and the paramagnetic ions Co/sup + +/, Cu/sup + +/ and Mn/sup + +/ reacted only slowly with triplet and with semioxidized eosin. The primary pathway for the eosin-sensitized photooxidation of trypsin at pH 8.0 involved singlet oxygen, although semioxidized eosin may also participate.

  14. Oxytocin promotes social bonding in dogs.

    Science.gov (United States)

    Romero, Teresa; Nagasawa, Miho; Mogi, Kazutaka; Hasegawa, Toshikazu; Kikusui, Takefumi

    2014-06-24

    Recent evidence suggests that enduring social bonds have fitness benefits. However, very little is known about the neural circuitry and neurochemistry underlying the formation and maintenance of stable social bonds outside reproductive contexts. Oxytocin (OT), a neuropeptide synthetized by the hypothalamus in mammals, regulates many complex forms of social behavior and cognition in both human and nonhuman animals. Animal research, however, has concentrated on monogamous mammals, and it remains unknown whether OT also modulates social bonds in nonreproductive contexts. In this study we provide behavioral evidence that exogenous OT promotes positive social behaviors in the domestic dog toward not only conspecifics but also human partners. Specifically, when sprayed with OT, dogs showed higher social orientation and affiliation toward their owners and higher affiliation and approach behaviors toward dog partners than when sprayed with placebo. Additionally, the exchange of socio-positive behaviors with dog partners triggered the release of endogenous OT, highlighting the involvement of OT in the development of social relationships in the domestic dog. These data provide new insight into the mechanisms that facilitate the maintenance of close social bonds beyond immediate reproductive interest or genetic ties and complement a growing body of evidence that identifies OT as one of the neurochemical foundations of sociality in mammalian species.

  15. A general approach-avoidance hypothesis of oxytocin: accounting for social and non-social effects of oxytocin.

    Science.gov (United States)

    Harari-Dahan, Osnat; Bernstein, Amit

    2014-11-01

    We critically reexamine extant theory and empirical study of Oxytocin. We question whether OT is, in fact, a "social neuropeptide" as argued in dominant theories of OT. We critically review human and animal research on the social and non-social effects of Oxytocin, including behavioral, psychophysiological, neurobiological, and neuroimaging studies. We find that extant (social) theories of Oxytocin do not account for well-documented non-social effects of Oxytocin. Furthermore, we find a range of evidence that social and non-social effects of Oxytocin may be mediated by core approach-avoidance motivational processes. We propose a General Approach-avoidance Hypothesis of Oxytocin (GAAO). We argue that the GAAO may provide a parsimonious account of established social and non-social effects of Oxytocin. We thus re-conceptualize the basic function(s) and mechanism(s) of action of Oxytocin. Finally, we highlight implications of the GAAO for basic and clinical research in humans

  16. Oxytocin in the Treatment of Dystocia in Mice

    Science.gov (United States)

    Narver, Heather L

    2012-01-01

    Physicians and veterinarians often prescribe oxytocin to treat dystocia. However, oxytocin administration to pregnant women or animals is not without risk. In the venue of laboratory animal medicine, the use of oxytocin may present confounding variables to research. Although oxytocin has been studied extensively, many of its physiologic effects and interactions with other hormones remain unclear. Investigator concerns about adverse and confounding effects of oxytocin in their research mice prompted the current review of oxytocin and its use to treat murine dystocia. Well-controlled studies of oxytocin in dystocic mice have not been conducted. However, in humans and other animals, inconsistent and adverse effects are well-documented. Limited knowledge of the complex physiologic and molecular mechanisms of action of oxytocin and scant support for the efficacy of oxytocin in dystocic mice fail to meet the standards of evidence-based veterinary medical practice. The administration of oxytocin is contraindicated in many cases of dystocia in research mice, and its use in dystocic mice may be unfounded. A brief review of oxytocin and the physiologic mechanisms of parturition are provided to support this conclusion. Alternative treatments for murine dystocia are discussed, and a holistic approach is advocated to better serve animal welfare and to safeguard the integrity of valuable research. Laboratory animal veterinarians overseeing the development of guidelines or standard operating procedures for technician or investigator treatment of dystocic mice should understand the effects of oxytocin administration in light of relevant research. PMID:22330862

  17. ERK1/2 pathway is involved in renal gluconeogenesis inhibition under conditions of lowered NADPH oxidase activity.

    Science.gov (United States)

    Winiarska, Katarzyna; Jarzyna, Robert; Dzik, Jolanta M; Jagielski, Adam K; Grabowski, Michal; Nowosielska, Agata; Focht, Dorota; Sierakowski, Bartosz

    2015-04-01

    The aim of this study was to elucidate the mechanisms involved in the inhibition of renal gluconeogenesis occurring under conditions of lowered activity of NADPH oxidase (Nox), the enzyme considered to be one of the main sources of reactive oxygen species in kidneys. The in vitro experiments were performed on primary cultures of rat renal proximal tubules, with the use of apocynin, a selective Nox inhibitor, and TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a potent superoxide radical scavenger. In the in vivo experiments, Zucker diabetic fatty (ZDF) rats, a well established model of diabetes type 2, were treated with apocynin solution in drinking water. The main in vitro findings are the following: (1) both apocynin and TEMPOL attenuate the rate of gluconeogenesis, inhibiting the step catalyzed by phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme of the process; (2) in the presence of the above-noted compounds the expression of PEPCK and the phosphorylation of transcription factor CREB and ERK1/2 kinases are lowered; (3) both U0126 (MEK inhibitor) and 3-(2-aminoethyl)-5-((4-ethoxyphenyl)methylene)-2,4-thiazolidinedione (ERK inhibitor) diminish the rate of glucose synthesis via mechanisms similar to those of apocynin and TEMPOL. The observed apocynin in vivo effects include: (1) slight attenuation of hyperglycemia; (2) inhibition of renal gluconeogenesis; (3) a decrease in renal PEPCK activity and content. In view of the results summarized above, it can be concluded that: (1) the lowered activity of the ERK1/2 pathway is of importance for the inhibition of renal gluconeogenesis found under conditions of lowered superoxide radical production by Nox; (2) the mechanism of this phenomenon includes decreased PEPCK expression, resulting from diminished activity of transcription factor CREB; (3) apocynin-evoked inhibition of renal gluconeogenesis contributes to the hypoglycemic action of this compound observed in diabetic animals. Thus, the study has

  18. Oxytocin influences avoidant reactions to social threat in adults with borderline personality disorder.

    Science.gov (United States)

    Brüne, Martin; Ebert, Andreas; Kolb, Meike; Tas, Cumhur; Edel, Marc-Andreas; Roser, Patrik

    2013-11-01

    Borderline personality disorder (BPD) is characterized by interpersonal dysfunction, emotional instability, impulsivity, and risk-taking behavior. Recent research has focused on the role of oxytocin in BPD, with mixed results as regards the processing of social stimuli. In a double-blind randomized placebo-controlled study, 13 BPD patients and 13 controls performed a dot probe task to examine attentional biases to happy and angry faces after intranasal application of oxytocin or placebo. Childhood trauma was examined using the childhood trauma questionnaire. In the placebo condition, patients with BPD (but not controls) showed an avoidant reaction to angry faces (but not happy faces). The strength of the avoidant reaction correlated with the severity of childhood trauma. This behavioral response (as well as the correlation) was abolished in the oxytocin condition. Adult patients with BPD show an avoidant response to social threat, a reaction that is linked with traumatic experiences during childhood. This response pattern is altered by oxytocin, possibly by reducing stress and inhibiting social withdrawal from distressing social stimuli. Copyright © 2013 John Wiley & Sons, Ltd.

  19. eIF4A inhibition allows translational regulation of mRNAs encoding proteins involved in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Andrew Bottley

    2010-09-01

    Full Text Available Alzheimer's disease (AD is the main cause of dementia in our increasingly aging population. The debilitating cognitive and behavioral symptoms characteristic of AD make it an extremely distressing illness for patients and carers. Although drugs have been developed to treat AD symptoms and to slow disease progression, there is currently no cure. The incidence of AD is predicted to increase to over one hundred million by 2050, placing a heavy burden on communities and economies, and making the development of effective therapies an urgent priority. Two proteins are thought to have major contributory roles in AD: the microtubule associated protein tau, also known as MAPT; and the amyloid-beta peptide (A-beta, a cleavage product of amyloid precursor protein (APP. Oxidative stress is also implicated in AD pathology from an early stage. By targeting eIF4A, an RNA helicase involved in translation initiation, the synthesis of APP and tau, but not neuroprotective proteins, can be simultaneously and specifically reduced, representing a novel avenue for AD intervention. We also show that protection from oxidative stress is increased upon eIF4A inhibition. We demonstrate that the reduction of these proteins is not due to changes in mRNA levels or increased protein degradation, but is a consequence of translational repression conferred by inhibition of the helicase activity of eIF4A. Inhibition of eIF4A selectively and simultaneously modulates the synthesis of proteins involved in Alzheimer's disease: reducing A-beta and tau synthesis, while increasing proteins predicted to be neuroprotective.

  20. Determination of plasma oxytocin by radioimmunoassay

    International Nuclear Information System (INIS)

    Ogawa, Satsuki; Fukuchi, Soitsu; Miura, Tadashi

    1978-01-01

    A simple radioimmunoassay was applied to the measurement of oxytocin in human plasma. A high specificity of immunoassay was demonstrated by the fact that large excess of angiotensin I and II, and ACTH did not displace labelled oxytocin from the antibody. Lysine-8-vasopressin and arginine-8-vasopressin showed very little cross-reaction in the assay, possessing only 0.002% of the immunological potency of oxytocin. The specific activity of 125 I-oxytocin was 166 μCi/μg. Adsorption and extraction capacities of Florisil were 96.6 +- 2.1% and 85.7 +- 2.5%, respectively. Intra- and inter-assay variability were 7.2 +- 4.9% and 4.3 +- 2.2%, respectively. The sensitivity of the assay was below 1 pg/tube. Normal levels of plasma oxytocin were 0 - 2.2 pg/ml (n=13) in males and 0 - 10.4 pg/ml (n=10) in females. Plasma oxytocin levels in the 39th and 40th weeks of pregnancy were 27.9 +- 4.14 pg/ml (n=4) and 29.8 +- 17.1 pg/ml (n=13), respectively. The levels increased to 33.1 +- 12.1 pg/ml (n=7) and 37.1 +- 17.5 pg/ml (n=7) in the first and third stages of labor, and decreased to 13.6 +- 5.25 pg/ml (n=6) on the 2nd to 8th day after labor. The radioimmunoassay for oxytocin in plasma is considered to be sufficiently applicable for clinical use. (auth.)

  1. A randomised controlled trial comparing oxytocin and oxytocin + ergometrine for prevention of postpartum haemorrhage at caesarean section.

    Science.gov (United States)

    Koen, Sandy; Snyman, Leon Cornelius; Pattinson, Robert C; Makin, Jennifer A

    2016-03-07

    Globally 166 000 women die annually as a result of obstetric haemorrhage. More than 50% of these deaths occur in sub-Saharan Africa. Uterine atony is the commonest cause of severe postpartum haemorrhage (PPH). Bleeding at or after caesarean section (CS) is responsible for >30% of maternal deaths due to obstetric haemorrhage in South Africa (SA). To compare oxytocin alone with oxytocin + ergometrine in terms of primary prophylaxis for PPH at the time of CS. This was a double-blind randomised controlled interventional study comparing oxytocin with oxytocin + ergometrine administered during CS. Patients were randomised to receive oxytocin alone intravenously as a bolus or oxytocin + ergometrine intramuscularly, with the placebo being an injection of sterile water. The study population consisted of women undergoing CS at Kalafong Provincial Tertiary Hospital in Atteridgeville, Gauteng, SA. Five hundred and forty women were randomised and data for 416 women, of whom 214 received oxytocin and 202 oxytocin + ergometrine, were available for analysis. In the oxytocin group 19 women (8.9%) required blood transfusion, compared with seven (3.5%) in the oxytocin + ergometrine group (p=0.01; relative risk = 2.78; 95% confidence interval 1.21 - 6.4). There were no statistically significant differences in the mean estimated visual and mean calculated blood loss. The overall need for blood transfusion was significantly reduced by about two-thirds in women receiving the oxytocin + ergometrine combination. Consideration should be given to using oxytocin + ergometrine for prophylaxis of PPH at CS.

  2. Decreased activity of neutrophils in the presence of diferuloylmethane (curcumin) involves protein kinase C inhibition.

    Science.gov (United States)

    Jancinová, Viera; Perecko, Tomás; Nosál, Radomír; Kostálová, Daniela; Bauerová, Katarína; Drábiková, Katarína

    2009-06-10

    Diferuloylmethane (curcumin) has been shown to act beneficially in arthritis, particularly through downregulated expression of proinflammatory cytokines and collagenase as well as through the modulated activities of T lymphocytes and macrophages. In this study its impact on activated neutrophils was investigated both in vitro and in experimental arthritis. Formation of reactive oxygen species in neutrophils was recorded on the basis of luminol- or isoluminol-enhanced chemiluminescence. Phosphorylation of neutrophil protein kinases C alpha and beta II was assessed by Western blotting, using phosphospecific antibodies. Adjuvant arthritis was induced in Lewis rats by heat-killed Mycobacterium butyricum. Diferuloylmethane or methotrexate was administered over a period of 28 days after arthritis induction. Under in vitro conditions, diferuloylmethane (1-100 microM) reduced dose-dependently oxidant formation both at extra- and intracellular level and it effectively reduced protein kinase C activation. Adjuvant arthritis was accompanied by an increased number of neutrophils in blood and by a more pronounced spontaneous as well as PMA (phorbol myristate acetate) stimulated chemiluminescence. Whereas the arthritis-related alterations in neutrophil count and in spontaneous chemiluminescence were not modified by diferuloylmethane, the increased reactivity of neutrophils to PMA was less evident in diferuloylmethane-treated animals. The effects of diferuloylmethane were comparable with those of methotrexate. Diferuloylmethane was found to be a potent inhibitor of neutrophil functions both in vitro and in experimental arthritis. As neutrophils are considered to be cells with the greatest capacity to inflict damage within diseased joints, the observed effects could represent a further mechanism involved in the antirheumatic activity of diferuloylmethane.

  3. Fto colocalizes with a satiety mediator oxytocin in the brain and upregulates oxytocin gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Olszewski, Pawel K., E-mail: olsze005@umn.edu [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Minnesota Obesity Center, Saint Paul, MN 55108 (United States); Fredriksson, Robert; Eriksson, Jenny D. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Mitra, Anaya [Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Radomska, Katarzyna J. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Gosnell, Blake A. [Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Solvang, Maria N. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Levine, Allen S. [Minnesota Obesity Center, Saint Paul, MN 55108 (United States); Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Schioeth, Helgi B. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden)

    2011-05-13

    Highlights: {yields} The majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto. {yields} The level of colocalization is similar in the male and female brain. {yields} Fto overexpression in hypothalamic neurons increases oxytocin mRNA levels by 50%. {yields} Oxytocin does not affect Fto expression through negative feedback mechanisms. -- Abstract: Single nucleotide polymorphisms in the fat mass and obesity-associated (FTO) gene have been associated with obesity in humans. Alterations in Fto expression in transgenic animals affect body weight, energy expenditure and food intake. Fto, a nuclear protein and proposed transcription co-factor, has been speculated to affect energy balance through a functional relationship with specific genes encoding feeding-related peptides. Herein, we employed double immunohistochemistry and showed that the majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto in the brain of male and female mice. We then overexpressed Fto in a murine hypothalamic cell line and, using qPCR, detected a 50% increase in the level of oxytocin mRNA. Expression levels of several other feeding-related genes, including neuropeptide Y (NPY) and Agouti-related protein (AgRP), were unaffected by the FTO transfection. Addition of 10 and 100 nmol oxytocin to the cell culture medium did not affect Fto expression in hypothalamic cells. We conclude that Fto, a proposed transcription co-factor, influences expression of the gene encoding a satiety mediator, oxytocin.

  4. Fto colocalizes with a satiety mediator oxytocin in the brain and upregulates oxytocin gene expression

    International Nuclear Information System (INIS)

    Olszewski, Pawel K.; Fredriksson, Robert; Eriksson, Jenny D.; Mitra, Anaya; Radomska, Katarzyna J.; Gosnell, Blake A.; Solvang, Maria N.; Levine, Allen S.; Schioeth, Helgi B.

    2011-01-01

    Highlights: → The majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto. → The level of colocalization is similar in the male and female brain. → Fto overexpression in hypothalamic neurons increases oxytocin mRNA levels by 50%. → Oxytocin does not affect Fto expression through negative feedback mechanisms. -- Abstract: Single nucleotide polymorphisms in the fat mass and obesity-associated (FTO) gene have been associated with obesity in humans. Alterations in Fto expression in transgenic animals affect body weight, energy expenditure and food intake. Fto, a nuclear protein and proposed transcription co-factor, has been speculated to affect energy balance through a functional relationship with specific genes encoding feeding-related peptides. Herein, we employed double immunohistochemistry and showed that the majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto in the brain of male and female mice. We then overexpressed Fto in a murine hypothalamic cell line and, using qPCR, detected a 50% increase in the level of oxytocin mRNA. Expression levels of several other feeding-related genes, including neuropeptide Y (NPY) and Agouti-related protein (AgRP), were unaffected by the FTO transfection. Addition of 10 and 100 nmol oxytocin to the cell culture medium did not affect Fto expression in hypothalamic cells. We conclude that Fto, a proposed transcription co-factor, influences expression of the gene encoding a satiety mediator, oxytocin.

  5. Oxytocin attenuates social and non-social avoidance: Re-thinking the social specificity of Oxytocin.

    Science.gov (United States)

    Harari-Dahan, Osnat; Bernstein, Amit

    2017-07-01

    Re-examining decades of the social construal of Oxytocin, the General Approach-Avoidance Hypothesis of Oxytocin (GAAO) predicts that Oxytocin will modulate responding to emotionally-evocative and personally-relevant social and non-social stimuli due to its action on the neural substrate of approach and avoidance motivation. We report the first critical experimental test of GAAO predictions by means of a double-blind intra-nasal administration of Oxytocin vs. placebo in 90 healthy adults (N=90, 50% women). As predicted, we found that among men and women for whom negative emotion (anxious arousal) is motivationally-relevant, intra-nasal administration of Oxytocin reduced behavioral avoidance of emotionally-evocative negatively-valenced social and non-social stimuli, but not closely matched emotionally-neutral stimuli. Findings cannot be explained by extant social theories of Oxytocin. We discuss the implications of the present findings for basic and translational clinical Oxytocin research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Intramuscular oxytocin versus intravenous oxytocin to prevent postpartum haemorrhage at vaginal delivery (LabOR trial): study protocol for a randomised controlled trial.

    Science.gov (United States)

    Adnan, Nita; Boland, Fiona; Murphy, Deirdre J

    2017-11-15

    Primary postpartum haemorrhage (PPH) is one of the leading causes of maternal morbidity and mortality worldwide. The most common cause of primary PPH is uterine atony. Atonic PPH rates are increasing in developed countries despite routine active management of the third stage of labour. In less-developed countries, primary PPH remains the leading cause of maternal death. Although the value of routine oxytocics in the third stage of labour has been well established, there is inconsistent practice in the choice of agent and route of administration. Oxytocin is the preferred agent because it has fewer side effects than other uterotonics with similar efficacy. It can be given intravenously or intramuscularly; however, to date, the most effective route of administering oxytocin has not been established. A double-blind randomised controlled trial is planned. The aim of the study is to compare the effects of an intramuscular bolus of oxytocin (10 IU in 1 mL) and placebo intravenous injection (1 mL 0.9% saline given slowly) with an intravenous bolus of oxytocin (10 IU in 1 mL given slowly over 1 min) and placebo intramuscular injection (1 mL 0.9% saline) at vaginal delivery. The study will recruit 1000 women at term (>36 weeks) with singleton pregnancies who are aiming for a vaginal delivery. The primary outcome will be PPH (measured blood loss ≥ 500 mL). A study involving 1000 women will have 80% power at the 5% two-sided alpha level, to detect differences in the proportion of patients with measured blood loss > 500 ml of 10% vs 5%. Given the increasing trends of atonic PPH it is both important and timely that we evaluate the most effective route of oxytocin administration for the management of the third stage of labour. To date, there has been limited research comparing the efficacy of intramuscular oxytocin vs intravenous oxytocin for the third stage of labour. ISRCTN Registry, ISRCTN14718882 . Registered on 4 January 2016. Pilot commenced 12

  7. Long-term social recognition memory is mediated by oxytocin-dependent synaptic plasticity in the medial amygdala.

    Science.gov (United States)

    Gur, Rotem; Tendler, Alex; Wagner, Shlomo

    2014-09-01

    Recognition of specific individuals is fundamental to mammalian social behavior and is mediated in most mammals by the main and accessory olfactory systems. Both these systems innervate the medial amygdala (MeA), where activity of the neuropeptide oxytocin is thought to mediate social recognition memory (SRM). The specific contribution of the MeA to SRM formation and the specific actions of oxytocin in the MeA are unknown. We used the social discrimination test to evaluate short-term and long-term SRM in adult Sprague-Dawley male rats (n = 38). The role of protein synthesis in the MeA was investigated by local application of the protein synthesis blocker anisomycin (n = 11). Synaptic plasticity was assessed in vivo by recording the MeA evoked field potential responses to stimulation of the main (n = 21) and accessory (n = 56) olfactory bulbs before and after theta burst stimulation. Intracerebroventricular administration of saline, oxytocin, or oxytocin receptor antagonist was used to measure the effect of oxytocin on synaptic plasticity. Anisomycin application to the MeA prevented the formation of long-term SRM. In addition, the responses of MeA neurons underwent long-term depression (LTD) after theta burst stimulation of the accessory olfactory bulb, but not the main accessory bulb, in an oxytocin-dependent manner. No LTD was found in socially isolated rats, which are known to lack long-term SRM. Finally, accessory olfactory bulb stimulation before SRM acquisition blocked long-term SRM, supporting the involvement of LTD in the MeA in formation of long-term SRM. Our results indicate that long-term SRM in rats involves protein synthesis and oxytocin-dependent LTD in the MeA. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  8. Neurofunctional maps of the 'maternal brain' and the effects of oxytocin: a multimodal voxel-based meta-analysis.

    Science.gov (United States)

    Rocchetti, Matteo; Radua, Joaquim; Paloyelis, Yannis; Xenaki, Lida-Alkisti; Frascarelli, Marianna; Caverzasi, Edgardo; Politi, Pierluigi; Fusar-Poli, Paolo

    2014-10-01

    Several studies have tried to understand the possible neurobiological basis of mothering. The putative involvement of oxytocin, in this regard, has been deeply investigated. Performing a voxel-based meta-analysis, we aimed at testing the hypothesis of overlapping brain activation in functional magnetic resonance imaging (fMRI) studies investigating the mother-infant interaction and the oxytocin modulation of emotional stimuli in humans. We performed two systematic literature searches: fMRI studies investigating the neurofunctional correlates of the 'maternal brain' by employing mother-infant paradigms; and fMRI studies employing oxytocin during emotional tasks. A unimodal voxel-based meta-analysis was performed on each database, whereas a multimodal voxel-based meta-analytical tool was adopted to assess the hypothesis that the neurofunctional effects of oxytocin are detected in brain areas implicated in the 'maternal brain.' We found greater activation in the bilateral insula extending to the inferior frontal gyrus, basal ganglia and thalamus during mother-infant interaction and greater left insular activation associated with oxytocin administration versus placebo. Left insula extending to basal ganglia and frontotemporal gyri as well as bilateral thalamus and amygdala showed consistent activation across the two paradigms. Right insula also showed activation across the two paradigms, and dorsomedial frontal cortex activation in mothers but deactivation with oxytocin. Significant activation in areas involved in empathy, emotion regulation, motivation, social cognition and theory of mind emerged from our multimodal meta-analysis, supporting the need for further studies directly investigating the neurobiology of oxytocin in the mother-infant relationship. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

  9. Oxytocin, Motivation and the Role of Dopamine

    Science.gov (United States)

    Love, Tiffany M.

    2013-01-01

    The hypothalamic neuropeptide oxytocin has drawn the attention of scientists for more than a century. The understanding of the function of oxytocin has expanded dramatically over the years from a simple peptide adept at inducing uterine contractions and milk ejection to a complex neuromodulator with a capacity to shape human social behavior. Decades of research have outlined oxytocin’s ability to enhance intricate social activities ranging from pair bonding, sexual activity, affiliative preferences, and parental behaviors. The precise neural mechanisms underlying oxytocin’s influence on such behaviors have just begun to be understood. Research suggests that oxytocin interacts closely with the neural pathways responsible for processing motivationally relevant stimuli. In particular, oxytocin appears to impact dopaminergic activity within the mesocorticolimbic dopamine system, which is crucial not only for reward and motivated behavior but also for the expression of affiliative behaviors. Though most of the work performed in this area has been done using animal models, several neuroimaging studies suggest similar relationships may be observed in humans. In order to introduce this topic further, this paper will review the recent evidence that oxytocin may exert some of its social-behavioral effects through its impact on motivational networks. PMID:23850525

  10. Oxytocin and Socioemotional Aging─Current Knowledge and Future Trends

    Directory of Open Access Journals (Sweden)

    Natalie C. Ebner

    2013-08-01

    Full Text Available The oxytocin (OT system is involved in various aspects of social cognition and prosocial behavior. Specifically, OT has been examined in the context of social memory, emotion recognition, cooperation, trust, empathy, and bonding, and─though evidence is somewhat mixed─intranasal OT appears to benefit aspects of socioemotional functioning. However, most of the extant data on aging and OT is from animal research and human OT research has focused largely on young adults. As such, though we know that various socioemotional capacities change with age, we know little about whether age-related changes in the OT system may underlie age-related differences in socioemotional functioning. In this review, we take a genetic-neuro-behavioral approach and evaluate current evidence on age-related changes in the OT system as well as the putative effects of these alterations on age-related socioemotional functioning. Looking forward, we identify informational gaps and propose an Age-Related Genetic, Neurobiological, Sociobehavioral Model of Oxytocin (AGeNeS-OT model which may structure and inform investigations into aging-related genetic, neural, and sociocognitive processes related to OT. As an exemplar of the use of the model, we report exploratory data suggesting differences in socioemotional processing associated with genetic variation in the oxytocin receptor gene (OXTR in samples of young and older adults. Information gained from this arena has translational potential in depression, social stress, and anxiety─all of which have high relevance in aging─and may contribute to reducing social isolation and improving well-being of individuals across the lifespan.

  11. Involvement of activation of PKR in HBx-siRNA-mediated innate immune effects on HBV inhibition.

    Directory of Open Access Journals (Sweden)

    Qiuju Han

    Full Text Available RNA interference (RNAi of virus-specific genes offers the possibility of developing a new anti-hepatitis B virus (anti-HBV therapy. Recent studies have revealed that siRNAs can induce an innate immune response in vitro and in vivo. Here, HBVx (HBx mRNA expression and HBV replication were significantly inhibited, followed by the enhancement of expression of type I interferons (IFNs, IFN-stimulated genes (ISG15 and ISG56 and proinflammatory cytokines after HepG2.2.15 cells were transfected with chemically synthesized HBx-siRNAs. Transfection with HBx-siRNAs also significantly increased expression of dsRNA-dependent protein kinase R (PKR in HepG2.2.15 cells, followed by activation of downstream signaling events such as eukaryotic initiation factor 2α (eIF2-α. In PKR-over-expressing HepG2.2.15 cells, HBx-siRNAs exerted more potent inhibitory effects on HBV replication and greater production of type I IFNs. By contrast, the inhibitory effect of HBx-siRNAs on HBV replication was attenuated when PKR was inhibited or silenced, demonstrating that HBx-siRNAs greatly promoted PKR activation, leading to the higher production of type I IFN. Therefore, we concluded that PKR is involved in the innate immune effects mediated by HBx-siRNAs and further contributes to HBV inhibition. The bifunctional siRNAs with both gene silencing and innate immune activation properties may represent a new potential strategy for treatment of HBV.

  12. Imagining is Not Doing but Involves Specific Motor Commands: A Review of Experimental Data Related to Motor Inhibition.

    Science.gov (United States)

    Guillot, Aymeric; Di Rienzo, Franck; Macintyre, Tadhg; Moran, Aidan; Collet, Christian

    2012-01-01

    There is now compelling evidence that motor imagery (MI) and actual movement share common neural substrate. However, the question of how MI inhibits the transmission of motor commands into the efferent pathways in order to prevent any movement is largely unresolved. Similarly, little is known about the nature of the electromyographic activity that is apparent during MI. In addressing these gaps in the literature, the present paper argues that MI includes motor execution commands for muscle contractions which are blocked at some level of the motor system by inhibitory mechanisms. We first assemble data from neuroimaging studies that demonstrate that the neural networks mediating MI and motor performance are not totally overlapping, thereby highlighting potential differences between MI and actual motor execution. We then review MI data indicating the presence of subliminal muscular activity reflecting the intrinsic characteristics of the motor command as well as increased corticomotor excitability. The third section not only considers the inhibitory mechanisms involved during MI but also examines how the brain resolves the problem of issuing the motor command for action while supervising motor inhibition when people engage in voluntary movement during MI. The last part of the paper draws on imagery research in clinical contexts to suggest that some patients move while imagining an action, although they are not aware of such movements. In particular, experimental data from amputees as well as from patients with Parkinson's disease are discussed. We also review recent studies based on comparing brain activity in tetraplegic patients with that from healthy matched controls that provide insights into inhibitory processes during MI. We conclude by arguing that based on available evidence, a multifactorial explanation of motor inhibition during MI is warranted.

  13. Imagining is not doing but involves specific motor commands: a review of experimental data related to motor inhibition

    Directory of Open Access Journals (Sweden)

    Aymeric eGuillot

    2012-09-01

    Full Text Available There is now compelling evidence that motor imagery (MI and actual movement share common neural substrate. However, the question of how MI inhibits the transmission of motor commands into the efferent pathways in order to prevent any movement is largely unresolved. Similarly, little is known about the nature of the electromyographic activity that is apparent during MI. In addressing these gaps in the literature, the present paper argues that MI includes motor execution commands for muscle contractions which are blocked at some level of the motor system by inhibitory mechanisms. We first assemble data from neuroimaging studies that demonstrate that the neural networks mediating MI and motor performance are not totally overlapping, thereby highlighting potential differences between MI and actual motor execution. We then review MI data indicating the presence of subliminal muscular activity reflecting the intrinsic characteristics of the motor command as well as increased corticomotor excitability. The third section not only considers the inhibitory mechanisms involved during MI but also examines how the brain resolves the problem of issuing the motor command for action while supervising motor inhibition when people engage in voluntary movement during MI. The last part of the paper draws on imagery research in clinical contexts to suggest that some patients move while imagining an action, although they are not aware of such movements. In particular, experimental data from amputees as well as from patients with Parkinson’s disease are discussed. We also review recent studies based on comparing brain activity in tetraplegic patients with that from healthy matched controls that provide insights into inhibitory processes during MI. We conclude by arguing that based on available evidence, a multifactorial explanation of motor inhibition during MI is warranted.

  14. Oxytocin and Estrogen Receptor β in the Brain: An Overview

    Directory of Open Access Journals (Sweden)

    Alexandra eAcevedo-Rodriguez

    2015-10-01

    Full Text Available Oxytocin is a neuropeptide synthesized primarily by neurons of the paraventricular and supraoptic nuclei of the hypothalamus. These neurons have axons that project into the posterior pituitary and release oxytocin into the bloodstream to promote labor and lactation; however, oxytocin neurons also project to other brain areas where it plays a role in numerous brain functions. Oxytocin binds to the widely expressed oxytocin receptor, and, in doing so, it regulates homeostatic processes, social recognition and fear conditioning. In addition to these functions, oxytocin decreases neuroendocrine stress signaling and anxiety-related and depression-like behaviors. Steroid hormones differentially modulate stress responses and alter oxytocin receptor expression. In particular, estrogen receptor β activation has been found to both reduce anxiety-related behaviors and increase oxytocin peptide transcription, suggesting a role for oxytocin in this estrogen receptor β mediated anxiolytic effect. Further research is needed to identify modulators of oxytocin signaling and the pathways utilized and to elucidate molecular mechanisms controlling oxytocin expression to allow better therapeutic manipulations of this system in patient populations.

  15. The Cytotoxicity of Benzaldehyde Nitrogen Mustard-2-Pyridine Carboxylic Acid Hydrazone Being Involved in Topoisomerase IIα Inhibition

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    Yun Fu

    2014-01-01

    Full Text Available The antitumor property of iron chelators and aromatic nitrogen mustard derivatives has been well documented. Combination of the two pharmacophores in one molecule in drug designation is worth to be explored. We reported previously the syntheses and preliminary cytotoxicity evaluation of benzaldehyde nitrogen mustard pyridine carboxyl acid hydrazones (BNMPH as extended study, more tumor cell lines (IC50 for HepG2: 26.1 ± 3.5 μM , HCT-116: 57.5 ± 5.3 μM, K562: 48.2 ± 4.0 μM, and PC-12: 19.4 ± 2.2 μM were used to investigate its cytotoxicity and potential mechanism. In vitro experimental data showed that the BNMPH chelating Fe2+ caused a large number of ROS formations which led to DNA cleavage, and this was further supported by comet assay, implying that ROS might be involved in the cytotoxicity of BNMPH. The ROS induced changes of apoptosis related genes, but the TFR1 and NDRG1 metastatic genes were not obviously regulated, prompting that BNMPH might not be able to deprive Fe2+ of ribonucleotide reductase. The BNMPH induced S phase arrest was different from that of iron chelators (G1 and alkylating agents (G2. BNMPH also exhibited its inhibition of human topoisomerase IIα. Those revealed that the cytotoxic mechanism of the BNMPH could stem from both the topoisomerase II inhibition, ROS generation and DNA alkylation.

  16. Inhibition of beta-amino acid transport by diamide does not involve the brush border membrane surface

    International Nuclear Information System (INIS)

    Chesney, R.W.; Gusowski, N.; Albright, P.

    1985-01-01

    Diamide (dicarboxylic acid bis-(N,N-dimethylamide) has been shown in previous studies to block the uptake of the beta-amino acid taurine at its high affinity transport site in rat renal cortex slices. Diamide may act by increasing the efflux of taurine from the slice. Studies performed in rat slices again indicate enhanced efflux over 8-12 minutes. The time course of reduced glutathione (GSH) depletion from renal cortex is similar, indicating a potential interaction between GSH depletion and inhibition of taurine accumulation. The effect of 9 mM diamide on the Na+ -dependent accumulation of taurine (10 and 250 microM) by brush border membrane vesicles was examined, and the taurine uptake value both initially and at equilibrium was the same in the presence and absence of diamide. Isolation of the brush border surface and subsequent transport studies of taurine are not influenced by diamide. Thus, diamide inhibition of taurine uptake does not involve physiochemical alteration of the membrane surface where active amino acid transport occurs, despite the thiol-oxidizing properties of this agent. Further, these studies suggest that diamide either acts at the basolateral surface, rather than the brush border surface of rat renal cortex or requires the presence of an intact tubule, capable of metabolism, prior to its inhibitory action

  17. Melatonin inhibits the migration of human lung adenocarcinoma A549 cell lines involving JNK/MAPK pathway.

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    Qiaoyun Zhou

    Full Text Available OBJECTIVE: Melatonin, an indolamine produced and secreted predominately by the pineal gland, exhibits a variety of physiological functions, possesses antioxidant and antitumor properties. But, the mechanisms for the anti-cancer effects are unknown. The present study explored the effects of melatonin on the migration of human lung adenocarcinoma A549 cells and its mechanism. METHODS: MTT assay was employed to measure the viability of A549 cells treated with different concentrations of melatonin. The effect of melatonin on the migration of A549 cells was analyzed by wound healing assay. Occludin location was observed by immunofluorescence. The expression of occludin, osteopontin (OPN, myosin light chain kinase (MLCK and phosphorylation of myosin light chain (MLC, JNK were detected by western blots. RESULTS: After A549 cells were treated with melatonin, the viability and migration of the cells were inhibited significantly. The relative migration rate of A549 cells treated with melatonin was only about 20% at 24 h. The expression level of OPN, MLCK and phosphorylation of MLC of A549 cells were reduced, while the expression of occludin was conversely elevated, and occludin located on the cell surface was obviously increased. The phosphorylation status of JNK in A549 cells was also reduced when cells were treated by melatonin. CONCLUSIONS: Melatonin significantly inhibits the migration of A549 cells, and this may be associated with the down-regulation of the expression of OPN, MLCK, phosphorylation of MLC, and up-regulation of the expression of occludin involving JNK/MAPK pathway.

  18. Initiator of carcinogenesis selectively and stably inhibits stem cell differentiation: a concept that initiation of carcinogenesis involves multiple phases

    International Nuclear Information System (INIS)

    Scott, R.E.; Maercklein, P.B.

    1985-01-01

    A concept of carcinogenesis was recently devised in our laboratory that suggests the development of defects in the control of cell differentiation is associated with an early phase of carcinogenesis. To test this proposal directly, the effects of an initiator of carcinogenesis (i.e., UV irradiation) on proadipocyte stem cell differentiation and proliferation was assayed. In this regard, 3T3 T proadipocytes represent a nontransformed mesenchymal stem cell line that possesses the ability to regulate its differentiation at a distinct state in the G 1 phase of the cell cycle as well as the ability to regulate its proliferation at two additional G 1 states. The results establish that a slow dosage of 254 nm UV irradiation selectivity and stably inhibits the differentiation of a high percentage of proadipocyte stem cells without significantly altering their ability to regulate cellular proliferation in growth factor-deficient or nutrient-deficient culture conditions. Differentiation-defect proadipocyte stem cells are demonstrated not to be completely transformed but to show an increased spontaneous transformation rate, as evidenced by the formation of type III foci in high density cell cultures. These data support the role of defects in the control of differentiation in the inhibition of carcinogenesis. These observations support a concept that the initiation of carcinogenesis involves multiple phases

  19. T Lymphocyte Inhibition by Tumor-Infiltrating Dendritic Cells Involves Ectonucleotidase CD39 but Not Arginase-1

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    Malika Trad

    2015-01-01

    Full Text Available T lymphocytes activated by dendritic cells (DC which present tumor antigens play a key role in the antitumor immune response. However, in patients suffering from active cancer, DC are not efficient at initiating and supporting immune responses as they participate to T lymphocyte inhibition. DC in the tumor environment are functionally defective and exhibit a characteristic of immature phenotype, different to that of DC present in nonpathological conditions. The mechanistic bases underlying DC dysfunction in cancer responsible for the modulation of T-cell responses and tumor immune escape are still being investigated. Using two different mouse tumor models, we showed that tumor-infiltrating DC (TIDC are constitutively immunosuppressive, exhibit a semimature phenotype, and impair responder T lymphocyte proliferation and activation by a mechanism involving CD39 ectoenzyme.

  20. The Way Dogs (Canis familiaris Look at Human Emotional Faces Is Modulated by Oxytocin. An Eye-Tracking Study

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    Anna Kis

    2017-10-01

    Full Text Available Dogs have been shown to excel in reading human social cues, including facial cues. In the present study we used eye-tracking technology to further study dogs’ face processing abilities. It was found that dogs discriminated between human facial regions in their spontaneous viewing pattern and looked most to the eye region independently of facial expression. Furthermore dogs played most attention to the first two images presented, afterwards their attention dramatically decreases; a finding that has methodological implications. Increasing evidence indicates that the oxytocin system is involved in dogs’ human-directed social competence, thus as a next step we investigated the effects of oxytocin on processing of human facial emotions. It was found that oxytocin decreases dogs’ looking to the human faces expressing angry emotional expression. More interestingly, however, after oxytocin pre-treatment dogs’ preferential gaze toward the eye region when processing happy human facial expressions disappears. These results provide the first evidence that oxytocin is involved in the regulation of human face processing in dogs. The present study is one of the few empirical investigations that explore eye gaze patterns in naïve and untrained pet dogs using a non-invasive eye-tracking technique and thus offers unique but largely untapped method for studying social cognition in dogs.

  1. Human ovolution and plasma oxytocin

    International Nuclear Information System (INIS)

    Kumaresan, Perianna; Kumaresan, Malathi; Hossini, Mahmood; Arellano, Carolina; Vasicka, Alois

    1983-01-01

    Plasma oxytocin (OT) concentrations were measured by radioimmunoassay (RIA) method without extracting plasma in 11 normal menstruating women. Mean plasma OT level began to increase steadily from the 7th day of the menstrual cycle and this level rose up to 20+-5 μU/ml (Mean+-S.E.) on the 10th day of the cycle. OT level declined to 13+-6 μU/ml on the day of the LH peak and continuously declined for another 2 days - then rose. The OT level was higher during the follicular phase than during the luteal phase. In 1 individual OT measured in 2 cycles a year apart showed the highest level of OT coincided with LH and FSH peak and abruptly declined. When there was the highest level of progesterone, the OT level was measurable 1 out of 11 cycles. From this study, we conclude that OT may have a role in human ovulation either synergistically or alone with other ovulatory mechanisms and ovarian estradiol and progesterone control the secretion of OT and also suggests that OT may play some role in the regulation of the luteolysis and the menstrual cycle in women. (author)

  2. Oxytocin signaling in mouse taste buds.

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    Michael S Sinclair

    2010-08-01

    Full Text Available The neuropeptide, oxytocin (OXT, acts on brain circuits to inhibit food intake. Mutant mice lacking OXT (OXT knockout overconsume salty and sweet (i.e. sucrose, saccharin solutions. We asked if OXT might also act on taste buds via its receptor, OXTR.Using RT-PCR, we detected the expression of OXTR in taste buds throughout the oral cavity, but not in adjacent non-taste lingual epithelium. By immunostaining tissues from OXTR-YFP knock-in mice, we found that OXTR is expressed in a subset of Glial-like (Type I taste cells, and also in cells on the periphery of taste buds. Single-cell RT-PCR confirmed this cell-type assignment. Using Ca2+ imaging, we observed that physiologically appropriate concentrations of OXT evoked [Ca2+]i mobilization in a subset of taste cells (EC50 approximately 33 nM. OXT-evoked responses were significantly inhibited by the OXTR antagonist, L-371,257. Isolated OXT-responsive taste cells were neither Receptor (Type II nor Presynaptic (Type III cells, consistent with our immunofluorescence observations. We also investigated the source of OXT peptide that may act on taste cells. Both RT-PCR and immunostaining suggest that the OXT peptide is not produced in taste buds or in their associated nerves. Finally, we also examined the morphology of taste buds from mice that lack OXTR. Taste buds and their constituent cell types appeared very similar in mice with two, one or no copies of the OXTR gene.We conclude that OXT elicits Ca2+ signals via OXTR in murine taste buds. OXT-responsive cells are most likely a subset of Glial-like (Type I taste cells. OXT itself is not produced locally in taste tissue and is likely delivered through the circulation. Loss of OXTR does not grossly alter the morphology of any of the cell types contained in taste buds. Instead, we speculate that OXT-responsive Glial-like (Type I taste bud cells modulate taste signaling and afferent sensory output. Such modulation would complement central pathways of

  3. Oxytocin signaling in mouse taste buds.

    Science.gov (United States)

    Sinclair, Michael S; Perea-Martinez, Isabel; Dvoryanchikov, Gennady; Yoshida, Masahide; Nishimori, Katsuhiko; Roper, Stephen D; Chaudhari, Nirupa

    2010-08-05

    The neuropeptide, oxytocin (OXT), acts on brain circuits to inhibit food intake. Mutant mice lacking OXT (OXT knockout) overconsume salty and sweet (i.e. sucrose, saccharin) solutions. We asked if OXT might also act on taste buds via its receptor, OXTR. Using RT-PCR, we detected the expression of OXTR in taste buds throughout the oral cavity, but not in adjacent non-taste lingual epithelium. By immunostaining tissues from OXTR-YFP knock-in mice, we found that OXTR is expressed in a subset of Glial-like (Type I) taste cells, and also in cells on the periphery of taste buds. Single-cell RT-PCR confirmed this cell-type assignment. Using Ca2+ imaging, we observed that physiologically appropriate concentrations of OXT evoked [Ca2+]i mobilization in a subset of taste cells (EC50 approximately 33 nM). OXT-evoked responses were significantly inhibited by the OXTR antagonist, L-371,257. Isolated OXT-responsive taste cells were neither Receptor (Type II) nor Presynaptic (Type III) cells, consistent with our immunofluorescence observations. We also investigated the source of OXT peptide that may act on taste cells. Both RT-PCR and immunostaining suggest that the OXT peptide is not produced in taste buds or in their associated nerves. Finally, we also examined the morphology of taste buds from mice that lack OXTR. Taste buds and their constituent cell types appeared very similar in mice with two, one or no copies of the OXTR gene. We conclude that OXT elicits Ca2+ signals via OXTR in murine taste buds. OXT-responsive cells are most likely a subset of Glial-like (Type I) taste cells. OXT itself is not produced locally in taste tissue and is likely delivered through the circulation. Loss of OXTR does not grossly alter the morphology of any of the cell types contained in taste buds. Instead, we speculate that OXT-responsive Glial-like (Type I) taste bud cells modulate taste signaling and afferent sensory output. Such modulation would complement central pathways of appetite

  4. Common polymorphism in the oxytocin receptor gene (OXTR) is associated with human social recognition skills.

    Science.gov (United States)

    Skuse, David H; Lori, Adriana; Cubells, Joseph F; Lee, Irene; Conneely, Karen N; Puura, Kaija; Lehtimäki, Terho; Binder, Elisabeth B; Young, Larry J

    2014-02-04

    The neuropeptides oxytocin and vasopressin are evolutionarily conserved regulators of social perception and behavior. Evidence is building that they are critically involved in the development of social recognition skills within rodent species, primates, and humans. We investigated whether common polymorphisms in the genes encoding the oxytocin and vasopressin 1a receptors influence social memory for faces. Our sample comprised 198 families, from the United Kingdom and Finland, in whom a single child had been diagnosed with high-functioning autism. Previous research has shown that impaired social perception, characteristic of autism, extends to the first-degree relatives of autistic individuals, implying heritable risk. Assessments of face recognition memory, discrimination of facial emotions, and direction of gaze detection were standardized for age (7-60 y) and sex. A common SNP in the oxytocin receptor (rs237887) was strongly associated with recognition memory in combined probands, parents, and siblings after correction for multiple comparisons. Homozygotes for the ancestral A allele had impairments in the range -0.6 to -1.15 SD scores, irrespective of their diagnostic status. Our findings imply that a critical role for the oxytocin system in social recognition has been conserved across perceptual boundaries through evolution, from olfaction in rodents to visual memory in humans.

  5. Prophylactic oxytocin for the third stage of labour to prevent postpartum haemorrhage.

    Science.gov (United States)

    Westhoff, Gina; Cotter, Amanda M; Tolosa, Jorge E

    2013-10-30

    Active management of the third stage of labour has been shown to reduce the risk of postpartum haemorrhage (PPH) greater than 1000 mL. One aspect of the active management protocol is the administration of prophylactic uterotonics, however, the type of uterotonic, dose, and route of administration vary across the globe and may have an impact on maternal outcomes. To determine the effectiveness of prophylactic oxytocin at any dose to prevent PPH and other adverse maternal outcomes related to the third stage of labour. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013). Randomised or quasi-randomised controlled trials including pregnant women anticipating a vaginal delivery where prophylactic oxytocin was given during management of the third stage of labour. The primary outcomes were blood loss > 500 mL and the use of therapeutic uterotonics. Two review authors independently assessed trials for inclusion, assessed trial quality and extracted data. Data were checked for accuracy. This updated review included 20 trials (involving 10,806 women). Prophylactic oxytocin versus placebo Prophylactic oxytocin compared with placebo reduced the risk of PPH greater than 500 mL, (risk ratio (RR) 0.53; 95% confidence interval (CI) 0.38 to 0.74; six trials, 4203 women; T² = 0.11, I² = 78%) and the need for therapeutic uterotonics (RR 0.56; 95% CI 0.36 to 0.87, four trials, 3174 women; T² = 0.10, I² = 58%). The benefit of prophylactic oxytocin to prevent PPH greater than 500 mL was seen in all subgroups. Decreased use of therapeutic uterotonics was only seen in the following subgroups: randomised trials with low risk of bias (RR 0.58; 95% CI 0.36 to 0.92; three trials, 3122 women; T² = 0.11, I² = 69%); trials that performed active management of the third stage (RR 0.39; 95% CI 0.26 to 0.58; one trial, 1901 women; heterogeneity not applicable); trials that delivered oxytocin as an IV bolus (RR 0.57; 95% CI 0.39 to 0.82; one trial, 1000 women

  6. Intranasal oxytocin modulates neural functional connectivity during human social interaction.

    Science.gov (United States)

    Rilling, James K; Chen, Xiangchuan; Chen, Xu; Haroon, Ebrahim

    2018-02-10

    Oxytocin (OT) modulates social behavior in primates and many other vertebrate species. Studies in non-primate animals have demonstrated that, in addition to influencing activity within individual brain areas, OT influences functional connectivity across networks of areas involved in social behavior. Previously, we used fMRI to image brain function in human subjects during a dyadic social interaction task following administration of either intranasal oxytocin (INOT) or placebo, and analyzed the data with a standard general linear model. Here, we conduct an extensive re-analysis of these data to explore how OT modulates functional connectivity across a neural network that animal studies implicate in social behavior. OT induced widespread increases in functional connectivity in response to positive social interactions among men and widespread decreases in functional connectivity in response to negative social interactions among women. Nucleus basalis of Meynert, an important regulator of selective attention and motivation with a particularly high density of OT receptors, had the largest number of OT-modulated connections. Regions known to receive mesolimbic dopamine projections such as the nucleus accumbens and lateral septum were also hubs for OT effects on functional connectivity. Our results suggest that the neural mechanism by which OT influences primate social cognition may include changes in patterns of activity across neural networks that regulate social behavior in other animals. © 2018 Wiley Periodicals, Inc.

  7. Plasma oxytocin and personality traits in psychiatric outpatients.

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    Bendix, Marie; Uvnäs-Moberg, Kerstin; Petersson, Maria; Gustavsson, Petter; Svanborg, Pär; Åsberg, Marie; Jokinen, Jussi

    2015-07-01

    The oxytocin system is regarded as being of relevance for social interaction. In spite of this, very few studies have investigated the relationship between oxytocin and personality traits in clinical psychiatric populations. We assessed the relationship between personality traits and plasma oxytocin levels in a population of 101 medication-free psychiatric outpatients (men = 37, women = 64). We used the Karolinska Scale of Personality (KSP) and diagnostic and symptomatic testing. Plasma oxytocin levels were analysed with a specific radioimmunoassay at inclusion and after one month for testing of stability. Plasma oxytocin levels were stable over time and did not differ between patients with or without personality disorders, nor were they related to severity of depressive or anxiety symptoms. The KSP factors Impulsiveness and Negative Emotionality were significant independent predictors of plasma oxytocin. A subscale analysis of these personality factors showed significant positive correlations between baseline plasma oxytocin and the KSP subscales monotony avoidance and psychic anxiety. The significant association between the KSP factor Impulsiveness and oxytocin levels observed at baseline was observed also one month later in men. These findings suggest that personality traits such as Impulsiveness and Negative emotionality which are linked to social functioning in several psychiatric disorders seem to be associated with endogenous plasma oxytocin levels. These variations in oxytocin levels might have an impact on social sensitivity or social motivation with possible gender differences. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Dyrk1A-ASF-CaMKIIδ Signaling Is Involved in Valsartan Inhibition of Cardiac Hypertrophy in Renovascular Hypertensive Rats.

    Science.gov (United States)

    Yao, Jian; Qin, Xiaotong; Zhu, Jianhua; Sheng, Hongzhuan

    2016-01-01

    It is known that the expression, activity and alternative splicing of Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ) are dysregulated in the cardiac remodeling process. Recently, we found a further signaling pathway, by which dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) regulates the alternative splicing of CaMKIIδ via the alternative splicing factor (ASF), i.e., Dyrk1A-ASF-CaMKIIδ. In this study, we aimed to investigate whether Dyrk1A-ASF-CaMKIIδ signaling was involved in valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats. Rats were subjected to two kidney-one clip (2K1C) surgery and then treated with valsartan (30 mg/kg/day) for 8 weeks. Hypertrophic parameter analysis was then performed. Western blot analysis was used to determine the protein expression of Dyrk1A and ASF and RT-PCR was used to analyze the alternative splicing of CaMKIIδ in the left ventricular (LV) sample. Valsartan attenuated cardiac hypertrophy in 2K1C rats but without impairment of cardiac systolic function. Increased protein expression of Dyrk1A and decreased protein expression of ASF were observed in the LV sample of 2K1C rats. Treatment of 2K1C rats with valsartan reversed the changes in Dyrk1A and ASF expression in the LV sample. Valsartan adjusted the 2K1C-induced imbalance in alternative splicing of CaMKIIδ by upregulating the mRNA expression of CaMKIIδC and downregulating the mRNA expression of CaMKIIδA and CaMKIIδB. Valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats was mediated, at least partly, by Dyrk1A-ASF-CaMKIIδ signaling. © 2015 S. Karger AG, Basel.

  9. A network approach to response inhibition: dissociating functional connectivity of neural components involved in action restraint and action cancellation

    NARCIS (Netherlands)

    Dambacher, F.; Sack, A.T.; Lobbestael, J.; Arntz, A.; Brugman, S.; Schuhmann, T.

    2014-01-01

    The ability to inhibit action tendencies is vital for adaptive human behaviour. Various paradigms are supposed to assess action inhibition and are often used interchangeably. However, these paradigms are based on different conceptualizations (action restraint vs. action cancellation) and the

  10. Ovarian hormone deprivation reduces oxytocin expression in Paraventricular Nucleus preautonomic neurons and correlates with baroreflex impairment in rats

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    Vitor Ulisses De Melo

    2016-10-01

    Full Text Available The prevalence of cardiovascular diseases including hypertension increases dramatically in women after menopause, however the mechanisms involved remain incompletely understood. Oxytocinergic (OTergic neurons are largely present within the paraventricular nucleus of the hypothalamus (PVN. Several studies have shown that OTergic drive from PVN to brainstem increases baroreflex sensitivity and improves autonomic control of the circulation. Since preautonomic PVN neurons express different types of estrogen receptors, we hypothesize that ovarian hormone deprivation causes baroreflex impairment, autonomic imbalance and hypertension by negatively impacting OTergic drive and oxytocin levels in pre-autonomic neurons. Here, we assessed oxytocin gene and protein expression (qPCR and immunohistochemistry within PVN subnuclei in sham-operated and ovariectomized Wistar rats. Conscious hemodynamic recordings were used to assess resting blood pressure and heart rate and the autonomic modulation of heart and vessels was estimated by power spectral analysis. We observed that the ovarian hormone deprivation in ovariectomized rats decreased baroreflex sensitivity, increased sympathetic and reduced vagal outflows to the heart and augmented the resting blood pressure. Of note, ovariectomized rats had reduced PVN oxytocin mRNA and protein expression in all pre-autonomic PVN subnuclei. Furthermore, reduced PVN oxytocin protein levels were positively correlated with decreased baroreflex sensitivity and negatively correlated with increased LF/HF ratio. These findings suggest that reduced oxytocin expression in OTergic neurons of the PVN contributes to the baroreflex dysfunction and autonomic dysregulation observed with ovarian hormone deprivation.

  11. Sniffing and Oxytocin: Effects on Olfactory Memories.

    Science.gov (United States)

    Stoop, Ron

    2016-05-04

    In this issue of Neuron, Oettl et al. (2016) show how oxytocin can boost processing of olfactory information in female rats by a top-downregulation from the anterior olfactory nucleus onto the main olfactory bulb. As a result, interactions with juvenile conspecifics receive more attention and are longer memorized. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Labor Augmentation with Oxytocin Decreases Glutathione Level

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    Naomi Schneid-Kofman

    2009-01-01

    Full Text Available Objective. To compare oxidative stress following spontaneous vaginal delivery with that induced by Oxytocin augmented delivery. Methods. 98 women recruited prior to labor. 57 delivered spontaneously, while 41 received Oxytocin for augmentation of labor. Complicated deliveries and high-risk pregnancies were excluded. Informed consent was documented. Arterial cord blood gases, levels of Hematocrit, Hemoglobin, and Bilirubin were studied. Glutathione (GSH concentration was measured by a spectroscopic method. Plasma and red blood cell (RBC levels of Malondialdehyde indicated lipid peroxidation. RBC uptake of phenol red denoted cell penetrability. SPSS data analysis was used. Results. Cord blood GSH was significantly lower in the Oxytocin group (2.3±0.55 mM versus 2.55±0.55 mM, =.01. No differences were found in plasma or RBC levels of MDA or in uptake of Phenol red between the groups. Conclusion. Lower GSH levels following Oxytocin augmentation indicate an oxidative stress, though selected measures of oxidative stress demonstrate no cell damage.

  13. Postnatal depression, oxytocin and maternal sensitivity

    NARCIS (Netherlands)

    Mah, Beth Lynette

    2015-01-01

    Intra nasal oxytocin administered to a population of mothers with a diagnosis of postnatal depression: -lowers their current mood -causes mothers to report that their infants are more difficult but their relationship with them is more positive -increases their protective response towards them in the

  14. A common oxytocin receptor gene (OXTR) polymorphism modulates intranasal oxytocin effects on the neural response to social cooperation in humans.

    Science.gov (United States)

    Feng, C; Lori, A; Waldman, I D; Binder, E B; Haroon, E; Rilling, J K

    2015-09-01

    Intranasal oxytocin (OT) can modulate social-emotional functioning and related brain activity in humans. Consequently, OT has been discussed as a potential treatment for psychiatric disorders involving social behavioral deficits. However, OT effects are often heterogeneous across individuals. Here we explore individual differences in OT effects on the neural response to social cooperation as a function of the rs53576 polymorphism of the oxytocin receptor gene (OXTR). Previously, we conducted a double-blind, placebo-controlled study in which healthy men and women were randomized to treatment with intranasal OT or placebo. Afterwards, they were imaged with functional magnetic resonance imaging while playing an iterated Prisoner's Dilemma Game with same-sex partners. Within the left ventral caudate nucleus, intranasal OT treatment increased activation to reciprocated cooperation in men, but tended to decrease activation in women. Here, we show that these sex differences in OT effects are specific to individuals with the rs53576 GG genotype, and are not found for other genotypes (rs53576 AA/AG). Thus, OT may increase the reward or salience of positive social interactions for male GG homozygotes, while decreasing those processes for female GG homozygotes. These results suggest that rs53576 genotype is an important variable to consider in future investigations of the clinical efficacy of intranasal OT treatment. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  15. Thinking and doing: the effects of dopamine and oxytocin genes and executive function on mothering behaviours.

    Science.gov (United States)

    Tombeau Cost, K; Unternaehrer, E; Plamondon, A; Steiner, M; Meaney, M; Atkinson, L; Kennedy, J L; Fleming, A S

    2017-02-01

    Animal and human studies suggest that initial expression of maternal behaviour depends on oxytocin and dopamine systems. However, the mechanism by which these systems affect parenting behaviours and the timing of these effects are not well understood. This article explores the role of mothers' executive function in mediating the relation between oxytocin and dopamine gene variants and maternal responsiveness at 48 months post-partum. Participants (n = 157) were mothers recruited in the Maternal Adversity, Vulnerability and Neurodevelopment Study, which assesses longitudinally two cohorts of mothers and children in Canada. We examined single nucleotide polymorphisms (SNPs) related to the dopamine and oxytocin systems (DRD1 rs686, DRD1 rs265976, OXTR rs237885 and OXTR rs2254298), assessed mothers' decision-making at 48 months using the Cambridge Neurological Automated Testing Battery (CANTAB) and evaluated maternal responsiveness from videotaped interactions during the Etch-A-Sketch co-operation task. Mediation analyses showed that OXTR rs2254298 A-carriers had an indirect effect on positive parenting which was mediated by mothers' performance on decision-making task (estimate = 0.115, P Dopamine SNPs were not associated with any measure of executive function or parenting (all P > 0.05). While oxytocin has previously been associated with only the early onset of maternal behaviour, we show that an OXTR polymorphism is involved in maternal behaviour at 48 months post-partum through mothers' executive function. This research highlights the importance of the oxytocin system to maternal parenting beyond infancy. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  16. The effect of resveratrol on beta amyloid-induced memory impairment involves inhibition of phosphodiesterase-4 related signaling.

    Science.gov (United States)

    Wang, Gang; Chen, Ling; Pan, Xiaoyu; Chen, Jiechun; Wang, Liqun; Wang, Weijie; Cheng, Ruochuan; Wu, Fan; Feng, Xiaoqing; Yu, Yingcong; Zhang, Han-Ting; O'Donnell, James M; Xu, Ying

    2016-04-05

    Resveratrol, a natural polyphenol found in red wine, has wide spectrum of pharmacological properties including antioxidative and antiaging activities. Beta amyloid peptides (Aβ) are known to involve cognitive impairment, neuroinflammatory and apoptotic processes in Alzheimer's disease (AD). Activation of cAMP and/or cGMP activities can improve memory performance and decrease the neuroinflammation and apoptosis. However, it remains unknown whether the memory enhancing effect of resveratrol on AD associated cognitive disorders is related to the inhibition of phosphodiesterase 4 (PDE4) subtypes and subsequent increases in intracellular cAMP and/or cGMP activities. This study investigated the effect of resveratrol on Aβ1-42-induced cognitive impairment and the participation of PDE4 subtypes related cAMP or cGMP signaling. Mice microinfused with Aβ1-42 into bilateral CA1 subregions displayed learning and memory impairment, as evidenced by reduced memory acquisition and retrieval in the water maze and retention in the passive avoidance tasks; it was also significant that neuroinflammatory and pro-apoptotic factors were increased in Aβ1-42-treated mice. Aβ1-42-treated mice also increased in PDE4A, 4B and 4D expression, and decreased in PKA level. However, PKA inhibitor H89, but not PKG inhibitor KT5823, prevented resveratrol's effects on these parameters. Resveratrol also reversed Aβ1-42-induced decreases in phosphorylated cAMP response-element binding protein (pCREB), brain derived neurotrophic factor (BDNF) and anti-apoptotic factor BCl-2 expression, which were reversed by H89. These findings suggest that resveratrol reversing Aβ-induced learning and memory disorder may involve the regulation of neuronal inflammation and apoptosis via PDE4 subtypes related cAMP-CREB-BDNF signaling.

  17. Oxytocin mediated behavior in invertebrates: An evolutionary perspective.

    Science.gov (United States)

    Lockard, Meghan A; Ebert, Margaret S; Bargmann, Cornelia I

    2017-02-01

    The molecular and functional conservation of oxytocin-related neuropeptides in behavior is striking. In animals separated by at least 600 million years of evolution, from roundworms to humans, oxytocin homologs play critical roles in the modulation of reproductive behavior and other biological functions. Here, we review the roles of oxytocin in invertebrate behavior from an evolutionary perspective. We begin by tracing the evolution of oxytocin through the invertebrate animal lineages, and then describe common themes in invertebrate behaviors that are mediated by oxytocin-related peptides, including reproductive behavior, learning and memory, food arousal, and predator/prey relationships. Finally, we discuss interesting future directions that have recently become experimentally tractable. Studying oxytocin in invertebrates offers precise insights into the activity of neuropeptides on well-defined neural circuits; the principles that emerge may also be represented in the more complex vertebrate brain. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 128-142, 2017. © 2016 Wiley Periodicals, Inc.

  18. Ceramide-mediated macroautophagy involves inhibition of protein kinase B and up-regulation of beclin 1.

    Science.gov (United States)

    Scarlatti, Francesca; Bauvy, Chantal; Ventruti, Annamaria; Sala, Giusy; Cluzeaud, Françoise; Vandewalle, Alain; Ghidoni, Riccardo; Codogno, Patrice

    2004-04-30

    The sphingolipid ceramide is involved in the cellular stress response. Here we demonstrate that ceramide controls macroautophagy, a major lysosomal catabolic pathway. Exogenous C(2)-ceramide stimulates macroautophagy (proteolysis and accumulation of autophagic vacuoles) in the human colon cancer HT-29 cells by increasing the endogenous pool of long chain ceramides as demonstrated by the use of the ceramide synthase inhibitor fumonisin B(1). Ceramide reverted the interleukin 13-dependent inhibition of macroautophagy by interfering with the activation of protein kinase B. In addition, C(2)-ceramide stimulated the expression of the autophagy gene product beclin 1. Ceramide is also the mediator of the tamoxifen-dependent accumulation of autophagic vacuoles in the human breast cancer MCF-7 cells. Monodansylcadaverine staining and electron microscopy showed that this accumulation was abrogated by myriocin, an inhibitor of de novo synthesis ceramide. The tamoxifen-dependent accumulation of vacuoles was mimicked by 1-phenyl-2-decanoylamino-3-morpholino-1-propanol, an inhibitor of glucosylceramide synthase. 1-Phenyl-2-decanoylamino-3-morpholino-1-propanol, tamoxifen, and C(2)-ceramide stimulated the expression of beclin 1, whereas myriocin antagonized the tamoxifen-dependent up-regulation. Tamoxifen and C(2)-ceramide interfere with the activation of protein kinase B, whereas myriocin relieved the inhibitory effect of tamoxifen. In conclusion, the control of macroautophagy by ceramide provides a novel function for this lipid mediator in a cell process with major biological outcomes.

  19. Electroacupuncture Inhibition of Hyperalgesia in Rats with Adjuvant Arthritis: Involvement of Cannabinoid Receptor 1 and Dopamine Receptor Subtypes in Striatum

    Directory of Open Access Journals (Sweden)

    Yin Shou

    2013-01-01

    Full Text Available Electroacupuncture (EA has been regarded as an alternative treatment for inflammatory pain for several decades. However, the molecular mechanisms underlying the antinociceptive effect of EA have not been thoroughly clarified. Previous studies have shown that cannabinoid CB1 receptors are related to pain relief. Accumulating evidence has shown that the CB1 and dopamine systems sometimes interact and may operate synergistically in rat striatum. To our knowledge, dopamine D1/D2 receptors are involved in EA analgesia. In this study, we found that repeated EA at Zusanli (ST36 and Kunlun (BL60 acupoints resulted in marked improvements in thermal hyperalgesia. Both western blot assays and FQ-PCR analysis results showed that the levels of CB1 expression in the repeated-EA group were much higher than those in any other group (P=0.001. The CB1-selective antagonist AM251 inhibited the effects of repeated EA by attenuating the increases in CB1 expression. The two kinds of dopamine receptors imparted different actions on the EA-induced CB1 upregulation in AA rat model. These results suggested that the strong activation of the CB1 receptor after repeated EA resulted in the concomitant phenomenon of the upregulation of D1 and D2 levels of gene expression.

  20. Oxytocin versus no treatment or delayed treatment for slow progress in the first stage of spontaneous labour.

    Science.gov (United States)

    Bugg, George J; Siddiqui, Farah; Thornton, Jim G

    2013-06-23

    Slow progress in the first stage of spontaneous labour is associated with an increased caesarean section rate and fetal and maternal morbidity. Oxytocin has long been advocated as a treatment for slow progress in labour but it is unclear to what extent it improves the outcomes for that labour and whether it actually reduces the caesarean section rate or maternal and fetal morbidity. This review will address the use of oxytocin and whether it improves the outcomes for women who are progressing slowly in labour compared to situations where it is not used or where its administration is delayed. To determine if the use of oxytocin for the treatment of slow progress in the first stage of spontaneous labour is associated with a reduction in the incidence of caesarean sections, or maternal and fetal morbidity compared to situations where it is not used or where its administration is delayed. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (23 February 2013) and bibliographies of relevant papers. Randomised controlled trials which compared oxytocin with either placebo, no treatment or delayed oxytocin in the active stage of spontaneous labour in low-risk women at term. Two authors independently assessed studies for inclusion, assessed risk of bias and extracted data. We sought additional information from trial authors. We included eight studies in the review involving a total of 1338 low-risk women in the first stage of spontaneous labour at term. Two comparisons were made; 1) the use of oxytocin versus placebo or no treatment (three trials); 2) the early use of oxytocin versus its delayed use (five trials). There were no significant differences in the rates of caesarean section or instrumental vaginal delivery in either comparison. Early use of oxytocin resulted in an increase in uterine hyperstimulation associated with fetal heart changes. However, the early use of oxytocin versus its delayed use resulted in no significant differences in a range

  1. Sex differences in methamphetamine seeking in rats: Impact of oxytocin

    OpenAIRE

    Cox, Brittney M.; Young, Amy B.; See, Ronald E.; Reichel, Carmela M.

    2013-01-01

    Previous evidence in an animal model of drug self-administration and drug seeking showed that acute oxytocin decreased methamphetamine (meth) seeking in male rats, suggesting potential clinical efficacy for the treatment of psychostimulant addiction. However, based on the well-established role of oxytocin in reproduction and pair bond formation, it is important to know how this effect extrapolates to females. Here, we tested whether oxytocin (1 mg/kg, IP) would decrease meth seeking in female...

  2. Oxytocin and the neural mechanisms regulating social cognition and affiliative behavior.

    Science.gov (United States)

    Ross, Heather E; Young, Larry J

    2009-10-01

    Oxytocin is produced in the hypothalamus and released into the circulation through the neurohypophyseal system. Peripherally released oxytocin facilitates parturition and milk ejection during nursing. Centrally released oxytocin coordinates the onset of maternal nurturing behavior at parturition and plays a role in mother-infant bonding. More recent studies have revealed a more general role for oxytocin in modulating affiliative behavior in both sexes. Oxytocin regulates alloparental care and pair bonding in female monogamous prairie voles. Social recognition in male and female mice is also modulated by oxytocin. In humans, oxytocin increases gaze to the eye region of human faces and enhances interpersonal trust and the ability to infer the emotions of others from facial cues. While the neurohypopheseal oxytocin system has been well characterized, less is known regarding the nature of oxytocin release within the brain. Here we review the role of oxytocin in the regulation of prosocial interactions, and discuss the neuroanatomy of the central oxytocin system.

  3. Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1

    Directory of Open Access Journals (Sweden)

    Yelena Nersesyan

    2017-11-01

    Full Text Available Oxytocin is a hormone with various actions. Oxytocin-containing parvocellular neurons project to the brainstem and spinal cord. Oxytocin release from these neurons suppresses nociception of inflammatory pain, the molecular mechanism of which remains unclear. Here, we report that the noxious stimulus receptor TRPV1 is an ionotropic oxytocin receptor. Oxytocin elicits TRPV1 activity in native and heterologous expression systems, regardless of the presence of the classical oxytocin receptor. In TRPV1 knockout mice, DRG neurons exhibit reduced oxytocin sensitivity relative to controls, and oxytocin injections significantly attenuate capsaicin-induced nociception in in vivo experiments. Furthermore, oxytocin potentiates TRPV1 in planar lipid bilayers, supporting a direct agonistic action. Molecular modeling and simulation experiments provide insight into oxytocin-TRPV1 interactions, which resemble DkTx. Together, our findings suggest the existence of endogenous regulatory pathways that modulate nociception via direct action of oxytocin on TRPV1, implying its analgesic effect via channel desensitization.

  4. Metformin-mediated growth inhibition involves suppression of the IGF-I receptor signalling pathway in human pancreatic cancer cells

    International Nuclear Information System (INIS)

    Karnevi, Emelie; Said, Katarzyna; Andersson, Roland; Rosendahl, Ann H

    2013-01-01

    Epidemiological studies have shown direct associations between type 2 diabetes and obesity, both conditions associated with hyperglycaemia and hyperinsulinemia, and the risk of pancreatic cancer. Up to 80% of pancreatic cancer patients present with either new-onset type 2 diabetes or impaired glucose tolerance at the time of diagnosis. Recent population studies indicate that the incidence of pancreatic cancer is reduced among diabetics taking metformin. In this study, the effects of exposure of pancreatic cancer cells to high glucose levels on their growth and response to metformin were investigated. The human pancreatic cancer cell lines AsPC-1, BxPC-3, PANC-1 and MIAPaCa-2 were grown in normal (5 mM) or high (25 mM) glucose conditions, with or without metformin. The influence by metformin on proliferation, apoptosis and the AMPK and IGF-IR signalling pathways were evaluated in vitro. Metformin significantly reduced the proliferation of pancreatic cancer cells under normal glucose conditions. Hyperglycaemia however, protected against the metformin-induced growth inhibition. The anti-proliferative actions of metformin were associated with an activation of AMP-activated protein kinase AMPK Thr172 together with an inhibition of the insulin/insulin-like growth factor-I (IGF-I) receptor activation and downstream signalling mediators IRS-1 and phosphorylated Akt. Furthermore, exposure to metformin during normal glucose conditions led to increased apoptosis as measured by poly(ADP-ribose) polymerase (PARP) cleavage. In contrast, exposure to high glucose levels promoted a more robust IGF-I response and Akt activation which correlated to stimulated AMPK Ser485 phosphorylation and impaired AMPK Thr172 phosphorylation, resulting in reduced anti-proliferative and apoptotic effects by metformin. Our results indicate that metformin has direct anti-tumour activities in pancreatic cancer cells involving AMPK Thr172 activation and suppression of the insulin/IGF signalling pathways

  5. Gibberellin Is Involved in Inhibition of Cucumber Growth and Nitrogen Uptake at Suboptimal Root-Zone Temperatures.

    Directory of Open Access Journals (Sweden)

    Longqiang Bai

    Full Text Available Suboptimal temperature stress often causes heavy yield losses of vegetables by suppressing plant growth during winter and early spring. Gibberellin acid (GA has been reported to be involved in plant growth and acquisition of mineral nutrients. However, no studies have evaluated the role of GA in the regulation of growth and nutrient acquisition by vegetables under conditions of suboptimal temperatures in greenhouse. Here, we investigated the roles of GA in the regulation of growth and nitrate acquisition of cucumber (Cucumis sativus L. plants under conditions of short-term suboptimal root-zone temperatures (Tr. Exposure of cucumber seedlings to a Tr of 16°C led to a significant reduction in root growth, and this inhibitory effect was reversed by exogenous application of GA. Expression patterns of several genes encoding key enzymes in GA metabolism were altered by suboptimal Tr treatment, and endogenous GA concentrations in cucumber roots were significantly reduced by exposure of cucumber plants to 16°C Tr, suggesting that inhibition of root growth by suboptimal Tr may result from disruption of endogenous GA homeostasis. To further explore the mechanism underlying the GA-dependent cucumber growth under suboptimal Tr, we studied the effect of suboptimal Tr and GA on nitrate uptake, and found that exposure of cucumber seedlings to 16°C Tr led to a significant reduction in nitrate uptake rate, and exogenous application GA can alleviate the down-regulation by up regulating the expression of genes associated with nitrate uptake. Finally, we demonstrated that N accumulation in cucumber seedlings under suboptimal Tr conditions was improved by exogenous application of GA due probably to both enhanced root growth and nitrate absorption activity. These results indicate that a reduction in endogenous GA concentrations in roots due to down-regulation of GA biosynthesis at transcriptional level may be a key event to underpin the suboptimal Tr

  6. The impact of intranasal oxytocin on attention to social emotional stimuli in patients with anorexia nervosa: a double blind within-subject cross-over experiment.

    Directory of Open Access Journals (Sweden)

    Youl-Ri Kim

    Full Text Available BACKGROUND AND AIM: Social factors may be of importance causally and act as maintenance factors in patients with anorexia nervosa. Oxytocin is a neuromodulatory hormone involved in social emotional processing associated with attentional processes. This study aimed to examine the impact of oxytocin on attentional processes to social faces representing anger, disgust, and happiness in patients with anorexia nervosa. METHOD: A double-blind, placebo-controlled within-subject crossover design was used. Intranasal oxytocin or placebo followed by a visual probe detection task with faces depicting anger, disgust, and happiness was administered to 64 female subjects: 31 patients with anorexia nervosa and 33 control students. RESULTS: Attentional bias to the disgust stimuli was observed in both groups under the placebo condition. The attentional bias to disgust was reduced under the oxytocin condition (a moderate effect in the patient group. Avoidance of angry faces was observed in the patient group under the placebo condition and vigilance was observed in the healthy comparison group; both of these information processing responses were moderated by oxytocin producing an increase in vigilance in the patients. Happy/smiling faces did not elicit an attentional response in controls or the patients under either the placebo or oxytocin conditions. CONCLUSION: Oxytocin attenuated attentional vigilance to disgust in patients with anorexia nervosa and healthy controls. On the other hand, oxytocin changed the response to angry faces from avoidance to vigilance in patients but reduced vigilance to anger in healthy controls. We conclude that patients with anorexia nervosa appear to use different strategies/circuits to emotionally process anger from their healthy counterparts.

  7. Increase in salivary oxytocin and decrease in salivary cortisol after listening to relaxing slow-tempo and exciting fast-tempo music.

    Directory of Open Access Journals (Sweden)

    Yuuki Ooishi

    Full Text Available Relaxation and excitation are components of the effects of music listening. The tempo of music is often considered a critical factor when determining these effects: listening to slow-tempo and fast-tempo music elicits relaxation and excitation, respectively. However, the chemical bases that underlie these relaxation and excitation effects remain unclear. Since parasympathetic and sympathetic nerve activities are facilitated by oxytocin and glucocorticoid, respectively, we hypothesized that listening to relaxing slow-tempo and exciting fast-tempo music is accompanied by increases in the oxytocin and cortisol levels, respectively. We evaluated the change in the salivary oxytocin and cortisol levels of participants listening to slow-tempo and fast-tempo music sequences. We measured the heart rate (HR and calculated the heart rate variability (HRV to evaluate the strength of autonomic nerve activity. After listening to a music sequence, the participants rated their arousal and valence levels. We found that both the salivary oxytocin concentration and the high frequency component of the HRV (HF increased and the HR decreased when a slow-tempo music sequence was presented. The salivary cortisol level decreased and the low frequency of the HRV (LF to HF ratio (LF/HF increased when a fast-tempo music sequence was presented. The ratio of the change in the oxytocin level was correlated with the change in HF, LF/HF and HR, whereas that in the cortisol level did not show any correlation with indices of autonomic nerve activity. There was no correlation between the change in oxytocin level and self-reported emotions, while the change in cortisol level correlated with the arousal level. These findings suggest that listening to slow-tempo and fast-tempo music is accompanied by an increase in the oxytocin level and a decrease in the cortisol level, respectively, and imply that such music listening-related changes in oxytocin and cortisol are involved in

  8. Increase in salivary oxytocin and decrease in salivary cortisol after listening to relaxing slow-tempo and exciting fast-tempo music

    Science.gov (United States)

    Watanabe, Ken; Kawato, Suguru; Kashino, Makio

    2017-01-01

    Relaxation and excitation are components of the effects of music listening. The tempo of music is often considered a critical factor when determining these effects: listening to slow-tempo and fast-tempo music elicits relaxation and excitation, respectively. However, the chemical bases that underlie these relaxation and excitation effects remain unclear. Since parasympathetic and sympathetic nerve activities are facilitated by oxytocin and glucocorticoid, respectively, we hypothesized that listening to relaxing slow-tempo and exciting fast-tempo music is accompanied by increases in the oxytocin and cortisol levels, respectively. We evaluated the change in the salivary oxytocin and cortisol levels of participants listening to slow-tempo and fast-tempo music sequences. We measured the heart rate (HR) and calculated the heart rate variability (HRV) to evaluate the strength of autonomic nerve activity. After listening to a music sequence, the participants rated their arousal and valence levels. We found that both the salivary oxytocin concentration and the high frequency component of the HRV (HF) increased and the HR decreased when a slow-tempo music sequence was presented. The salivary cortisol level decreased and the low frequency of the HRV (LF) to HF ratio (LF/HF) increased when a fast-tempo music sequence was presented. The ratio of the change in the oxytocin level was correlated with the change in HF, LF/HF and HR, whereas that in the cortisol level did not show any correlation with indices of autonomic nerve activity. There was no correlation between the change in oxytocin level and self-reported emotions, while the change in cortisol level correlated with the arousal level. These findings suggest that listening to slow-tempo and fast-tempo music is accompanied by an increase in the oxytocin level and a decrease in the cortisol level, respectively, and imply that such music listening-related changes in oxytocin and cortisol are involved in physiological

  9. Increase in salivary oxytocin and decrease in salivary cortisol after listening to relaxing slow-tempo and exciting fast-tempo music.

    Science.gov (United States)

    Ooishi, Yuuki; Mukai, Hideo; Watanabe, Ken; Kawato, Suguru; Kashino, Makio

    2017-01-01

    Relaxation and excitation are components of the effects of music listening. The tempo of music is often considered a critical factor when determining these effects: listening to slow-tempo and fast-tempo music elicits relaxation and excitation, respectively. However, the chemical bases that underlie these relaxation and excitation effects remain unclear. Since parasympathetic and sympathetic nerve activities are facilitated by oxytocin and glucocorticoid, respectively, we hypothesized that listening to relaxing slow-tempo and exciting fast-tempo music is accompanied by increases in the oxytocin and cortisol levels, respectively. We evaluated the change in the salivary oxytocin and cortisol levels of participants listening to slow-tempo and fast-tempo music sequences. We measured the heart rate (HR) and calculated the heart rate variability (HRV) to evaluate the strength of autonomic nerve activity. After listening to a music sequence, the participants rated their arousal and valence levels. We found that both the salivary oxytocin concentration and the high frequency component of the HRV (HF) increased and the HR decreased when a slow-tempo music sequence was presented. The salivary cortisol level decreased and the low frequency of the HRV (LF) to HF ratio (LF/HF) increased when a fast-tempo music sequence was presented. The ratio of the change in the oxytocin level was correlated with the change in HF, LF/HF and HR, whereas that in the cortisol level did not show any correlation with indices of autonomic nerve activity. There was no correlation between the change in oxytocin level and self-reported emotions, while the change in cortisol level correlated with the arousal level. These findings suggest that listening to slow-tempo and fast-tempo music is accompanied by an increase in the oxytocin level and a decrease in the cortisol level, respectively, and imply that such music listening-related changes in oxytocin and cortisol are involved in physiological

  10. Involvement of lymphocyte function-associated antigen-1 (LFA-1) in HIV infection: inhibition by monoclonal antibody

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C; Mathiesen, Lars Reinhardt

    1991-01-01

    Monoclonal antibodies (MAbs) against the alpha- and beta-chain of lymphocyte-associated antigen-1 (LFA-1) were examined for inhibition of HIV-1 infection in vitro. Infection of the T cell line MT4 and the monocytic cell line U937 by isolates HTLVIIIB and SSI-002, respectively was inhibited...

  11. Oxytocin: parallel processing in the social brain?

    Science.gov (United States)

    Dölen, Gül

    2015-06-01

    Early studies attempting to disentangle the network complexity of the brain exploited the accessibility of sensory receptive fields to reveal circuits made up of synapses connected both in series and in parallel. More recently, extension of this organisational principle beyond the sensory systems has been made possible by the advent of modern molecular, viral and optogenetic approaches. Here, evidence supporting parallel processing of social behaviours mediated by oxytocin is reviewed. Understanding oxytocinergic signalling from this perspective has significant implications for the design of oxytocin-based therapeutic interventions aimed at disorders such as autism, where disrupted social function is a core clinical feature. Moreover, identification of opportunities for novel technology development will require a better appreciation of the complexity of the circuit-level organisation of the social brain. © 2015 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.

  12. Involvement of lymphocyte function-associated antigen-1 (LFA-1) in HIV infection: inhibition by monoclonal antibody

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C; Mathiesen, Lars Reinhardt

    1991-01-01

    Monoclonal antibodies (MAbs) against the alpha- and beta-chain of lymphocyte-associated antigen-1 (LFA-1) were examined for inhibition of HIV-1 infection in vitro. Infection of the T cell line MT4 and the monocytic cell line U937 by isolates HTLVIIIB and SSI-002, respectively was inhibited...... in a concentration dependent manner by MAb against the beta-chain but not against the alpha-chain. No cross-reactivity was found between MAb against LFA-1 and against the CD4 receptor (MAb Leu3a). MAbs against the beta-chain and the CD4 receptor were found to act synergistically in inhibiting HIV infection...

  13. Modulation of α-synuclein fibrillization by ring-fused 2-pyridones: templation and inhibition involve oligomers with different structure.

    Science.gov (United States)

    Horvath, Istvan; Sellstedt, Magnus; Weise, Christoph; Nordvall, Lina-Maria; Krishna Prasad, G; Olofsson, Anders; Larsson, Göran; Almqvist, Fredrik; Wittung-Stafshede, Pernilla

    2013-04-15

    In a recent study we discovered that a ring-fused 2-pyridone compound triggered fibrillization of a key protein in Parkinson's disease, α-synuclein. To reveal how variations in compound structure affect protein aggregation, we now prepared a number of strategic analogs and tested their effects on α-synuclein amyloid fiber formation in vitro. We find that, in contrast to the earlier templating effect, some analogs inhibit α-synuclein fibrillization. For both templating and inhibiting compounds, the key species formed in the reactions are α-synuclein oligomers that contain compound. Despite similar macroscopic appearance, the templating and inhibiting oligomers are distinctly different in secondary structure content. When the inhibitory oligomers are added in seed amounts, they inhibit fresh α-synuclein aggregation reactions. Our study demonstrates that small chemical changes to the same central fragment can result in opposite effects on protein aggregation. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. No association between oxytocin receptor (OXTR gene polymorphisms and experimentally elicited social preferences.

    Directory of Open Access Journals (Sweden)

    Coren L Apicella

    Full Text Available BACKGROUND: Oxytocin (OXT has been implicated in a suite of complex social behaviors including observed choices in economic laboratory experiments. However, actual studies of associations between oxytocin receptor (OXTR gene variants and experimentally elicited social preferences are rare. METHODOLOGY/PRINCIPAL FINDINGS: We test hypotheses of associations between social preferences, as measured by behavior in two economic games, and 9 single nucleotide polymorphisms (SNPs of the OXTR gene in a sample of Swedish twins (n = 684. Two standard economic games, the dictator game and the trust game, both involving real monetary consequences, were used to elicit such preferences. After correction for multiple hypothesis testing, we found no significant associations between any of the 9 single nucleotide polymorphisms (SNPs and behavior in either of the games. CONCLUSION: We were unable to replicate the most significant association reported in previous research between the amount donated in a dictator game and an OXTR genetic variant.

  15. Oxytocin improves synchronisation in leader-follower interaction

    DEFF Research Database (Denmark)

    Gebauer, L.; Witek, M. A. G.; Hansen, N. C.

    2016-01-01

    , there was no effect when following a regular metronome or when both tappers were mutually adapting to each other. Furthermore, relative to their self-paced tapping partners, oxytocin followers were less variable than placebo followers. Our data suggests that oxytocin improves synchronisation to an unresponsive...

  16. Oxytocin: the neuropeptide of love reveals some of its secrets.

    Science.gov (United States)

    Neumann, Inga D

    2007-04-01

    The neuropeptide oxytocin is synthesized in the brain and released from neurohypophyseal terminals into the blood and within defined brain regions that regulate emotional, cognitive, and social behaviors. A recent study of CD38-/- mice (Jin et al., 2007) has demonstrated an essential role for the transmembrane receptor CD38 in secretion of oxytocin into the blood.

  17. Intranasal Oxytocin Failed to Affect Chimpanzee (Pan troglodytes) Social Behavior

    Science.gov (United States)

    Calcutt, Sarah E.; Burke, Kimberly; de Waal, Frans B. M.

    2017-01-01

    Oxytocin has been suggested as a treatment to promote positive social interactions in people with Autism Spectrum Disorders (ASD). However, it is difficult to test this effect outside of the laboratory in realistic social situations. One way to resolve this issue is to study behavioral changes in closely related species with complex social relationships, such as chimpanzees. Here, we use captive, socially housed chimpanzees to evaluate the effects of oxytocin in a socially complex environment. After administering intranasal oxytocin or a placebo to an individual chimpanzee (total n = 8), she was returned to her social group. An experimenter blind to the condition measured the subject's social behavior. We failed to find a behavioral difference between conditions. As one of the goals for oxytocin administration as a treatment for ASD is increasing prosocial behaviors during ‘real world’ encounters, it is problematic that we failed to detect behavioral changes in our closest living relatives. However, our null findings may be related to methodological challenges such as determining an effective dose of oxytocin for chimpanzees and how long oxytocin takes to cross the blood-brain barrier. Thus, more research on intranasal oxytocin dosing and uptake are needed to continue exploring whether oxytocin changes social behavior in naturalistic settings and as a treatment for ASD. PMID:28845444

  18. Evolution of oxytocin pathways in the brain of vertebrates

    Directory of Open Access Journals (Sweden)

    H. Sophie Knobloch

    2014-02-01

    Full Text Available The central oxytocin system transformed tremendously during the evolution, thereby adapting to the expanding properties of species. In more basal vertebrates (paraphyletic taxon Anamnia, which includes agnathans, fish and amphibians, magnocellular neurosecretory neurons producing oxytocin, vasopressin and their homologs reside in the wall of the third ventricle of the hypothalamus composing a single hypothalamic structure, the preoptic nucleus. This nucleus further diverged in advanced vertebrates (monophyletic taxon Amniota, which includes reptiles, birds and mammals into the paraventricular and supraoptic nuclei with accessory nuclei between them. The individual magnocellular neurons underwent a process of transformation from primitive uni- or bipolar neurons into highly differentiated neurons. Due to these microanatomical and cytological changes, the ancient release modes of oxytocin into the cerebrospinal fluid were largely replaced by vascular release. However, the most fascinating feature of the progressive transformations of the oxytocin system has been the expansion of oxytocin axonal projections to forebrain regions. In the present review we provide a background on these evolutionary advancements. Furthermore, we draw attention to the non-synaptic axonal release in small and defined brain regions with the aim to clearly distinguish this way of oxytocin action from the classical synaptic transmission on one side and from dendritic release followed by a global diffusion on the other side. Finally, we will summarize the effects of oxytocin and its homologs on pro-social reproductive behaviors in representatives of the phylogenetic tree and will propose anatomically plausible pathways of oxytocin release contributing to these behaviors in basal vertebrates and amniots.

  19. Oxytocin augmentation: Poison or potion in the multipara? | Cluver ...

    African Journals Online (AJOL)

    Oxytocin is one of the most commonly used drugs in obstetric practice but it is also the drug associated with the most preventable adverse events in childbirth. In this review we look at the use of oxytocin augmentation in the multigravida. We look at the concept of whether the multigravida is different to the primigravida.

  20. Sex differences in methamphetamine seeking in rats: impact of oxytocin.

    Science.gov (United States)

    Cox, Brittney M; Young, Amy B; See, Ronald E; Reichel, Carmela M

    2013-10-01

    Previous evidence in an animal model of drug self-administration and drug seeking showed that acute oxytocin decreased methamphetamine (meth) seeking in male rats, suggesting potential clinical efficacy for the treatment of psychostimulant addiction. However, based on the well-established role of oxytocin in reproduction and pair bond formation, it is important to know how this effect extrapolates to females. Here, we tested whether oxytocin (1mg/kg, IP) would decrease meth seeking in female rats across various stages of the estrous cycle (Experiment 1). Freely cycling Long Evans female rats self-administered meth (IV) in 2-h daily sessions, followed by daily extinction sessions. Following extinction, rats received oxytocin (0, 0.3, or 1mg/kg, IP) 30min before a meth priming injection (1mg/kg, IP) to assess reinstatement of meth seeking. Next, we examined the effects of oxytocin on motivated meth- and sucrose-taking and seeking in male and female rats. In separate experiments, males and females self-administered meth (Experiment 2) or sucrose (Experiment 3) until responding was stabilized along a fixed ratio (FR) 5 schedule of reinforcement. Subsequently, rats received either oxytocin or vehicle prior to self-administration along a progressive ratio (PR) schedule of reinforcement. Rats were subsequently tested for cue-, meth-, and stress-induced reinstatement after pretreatment with oxytocin or vehicle. While oxytocin reduced meth seeking in females, we found that estrous cycle stage (as determined from vaginal cytology) did not influence meth-primed reinstatement or the ability of oxytocin to decrease reinstatement of meth seeking. Oxytocin reduced PR responding for meth only in females. Females responded more than males during cue-induced reinstatement of meth and sucrose seeking, and oxytocin reduced this responding only in meth females. In both sexes, oxytocin attenuated meth seeking in response to a meth prime and yohimbine (a pharmacological stressor). The

  1. Oxytocin and Social Cognition in Affective and Psychotic Disorders

    Science.gov (United States)

    Perez-Rodriguez, M. Mercedes; Mahon, Katie; Russo, Manuela; Ungar, Allison K.; Burdick, Katherine E.

    2014-01-01

    Impairments in social cognition are now recognized as core illness features in psychotic and affective disorders. Despite the significant disability caused by social cognitive abnormalities, treatments for this symptom dimension are lacking. Here, we describe the evidence demonstrating abnormalities in social cognition in schizophrenia, major depressive disorder, and bipolar disorder, as well as the neurobiology of social cognition including the role of oxytocin. We then review clinical trials of oxytocin administration in psychotic and affective disorders and the impact of this agent on social cognition. To date, several studies have demonstrated that oxytocin may improve social cognition in schizophrenia; too few studies have been conducted in affective disorders to determine the effect of oxytocin on social cognition in these disorders. Future work is needed to clarify which aspects of social cognition may be improved with oxytocin treatment in psychotic and affective disorders. PMID:25153535

  2. Enteric serotonin and oxytocin: endogenous regulation of severity in a murine model of necrotizing enterocolitis.

    Science.gov (United States)

    Gross Margolis, Kara; Vittorio, Jennifer; Talavera, Maria; Gluck, Karen; Li, Zhishan; Iuga, Alina; Stevanovic, Korey; Saurman, Virginia; Israelyan, Narek; Welch, Martha G; Gershon, Michael D

    2017-11-01

    Necrotizing enterocolitis (NEC), a gastrointestinal inflammatory disease of unknown etiology that may also affect the liver, causes a great deal of morbidity and mortality in premature infants. We tested the hypothesis that signaling molecules, which are endogenous to the bowel, regulate the severity of intestinal and hepatic damage in an established murine NEC model. Specifically, we postulated that mucosal serotonin (5-HT), which is proinflammatory, would exacerbate experimental NEC and that oxytocin (OT), which is present in enteric neurons and is anti-inflammatory, would oppose it. Genetic deletion of the 5-HT transporter (SERT), which increases and prolongs effects of 5-HT, was found to increase the severity of systemic manifestations, intestinal inflammation, and associated hepatotoxicity of experimental NEC. In contrast, genetic deletion of tryptophan hydroxylase 1 (TPH1), which is responsible for 5-HT biosynthesis in enterochromaffin (EC) cells of the intestinal mucosa, and TPH inhibition with LP-920540 both decrease the severity of experimental NEC in the small intestine and liver. These observations suggest that 5-HT from EC cells helps to drive the inflammatory damage to the gut and liver that occurs in the murine NEC model. Administration of OT decreased, while the OT receptor antagonist atosiban exacerbated, the intestinal inflammation of experimental NEC. Data from the current investigation are consistent with the tested hypotheses-that the enteric signaling molecules, 5-HT (positively) and OT (negatively) regulate severity of inflammation in a mouse model of NEC. Moreover, we suggest that mucosally restricted inhibition of 5-HT biosynthesis and/or administration of OT may be useful in the treatment of NEC. NEW & NOTEWORTHY Serotonin (5-HT) and oxytocin reciprocally regulate the severity of intestinal inflammation and hepatotoxicity in a murine model of necrotizing enterocolitis (NEC). Selective depletion of mucosal 5-HT through genetic deletion or

  3. Growth inhibition induced by antiprogestins RU-38486, ORG-31710, and CDB-2914 in ovarian cancer cells involves inhibition of cyclin dependent kinase 2.

    Science.gov (United States)

    Goyeneche, Alicia A; Seidel, Erin E; Telleria, Carlos M

    2012-06-01

    Antiprogestins have been largely utilized in reproductive medicine, yet their repositioning for oncologic use is rapidly emerging. In this study we investigated the molecular mediators of the anti-ovarian cancer activity of the structurally related antiprogestins RU-38486, ORG-31710 and CDB-2914. We studied the responses of wt p53 OV2008 and p53 null SK-OV-3 cells to varying doses of RU-38486, ORG-31710 and CDB-2914. The steroids inhibited the growth of both cell lines with a potency of RU-38486 > ORG-31710 > CDB-2914, and were cytostatic at lower doses but lethal at higher concentrations. Antiprogestin-induced lethality associated with morphological features of apoptosis, hypodiploid DNA content, DNA fragmentation, and cleavage of executer caspase substrate PARP. Cell death ensued despite RU-38486 caused transient up-regulation of anti-apoptotic Bcl-2, ORG-31710 induced transient up-regulation of inhibitor of apoptosis XIAP, and CDB-2914 up-regulated both XIAP and Bcl-2. The antiprogestins induced accumulation of Cdk inhibitors p21(cip1) and p27(kip1) and increased association of p21(cip1) and p27(kip1) with Cdk-2. They also promoted nuclear localization of p21(cip1) and p27(kip1), reduced the nuclear abundances of Cdk-2 and cyclin E, and blocked the activity of Cdk-2 in both nucleus and cytoplasm. The cytotoxic potency of the antiprogestins correlated with the magnitude of the inhibition of Cdk-2 activity, ranging from G1 cell cycle arrest towards cell death. Our results suggest that, as a consequence of their cytostatic and lethal effects, antiprogestin steroids of well-known contraceptive properties emerge as attractive new agents to be repositioned for ovarian cancer therapeutics.

  4. Autophagy and gap junctional intercellular communication inhibition are involved in cadmium-induced apoptosis in rat liver cells

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Hui [College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009 (China); Zhuo, Liling [College of Life Science, Zaozhuang University, Zaozhuang, Shandong, 277160 (China); Han, Tao; Hu, Di; Yang, Xiaokang; Wang, Yi; Yuan, Yan; Gu, Jianhong; Bian, Jianchun; Liu, Xuezhong [College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009 (China); Liu, Zongping, E-mail: liuzongping@yzu.edu.cn [College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009 (China)

    2015-04-17

    Cadmium (Cd) is known to induce hepatotoxicity, yet the underlying mechanism of how this occurs is not fully understood. In this study, Cd-induced apoptosis was demonstrated in rat liver cells (BRL 3A) with apoptotic nuclear morphological changes and a decrease in cell index (CI) in a time- and concentration-dependent manner. The role of gap junctional intercellular communication (GJIC) and autophagy in Cd-induced apoptosis was investigated. Cd significantly induced GJIC inhibition as well as downregulation of connexin 43 (Cx43). The prototypical gap junction blocker carbenoxolone disodium (CBX) exacerbated the Cd-induced decrease in CI. Cd treatment was also found to cause autophagy, with an increase in mRNA expression of autophagy-related genes Atg-5, Atg-7, Beclin-1, and microtubule-associated protein light chain 3 (LC3) conversion from cytosolic LC3-I to membrane-bound LC3-II. The autophagic inducer rapamycin (RAP) prevented the Cd-induced CI decrease, while the autophagic inhibitor chloroquine (CQ) caused a further reduction in CI. In addition, CBX promoted Cd-induced autophagy, as well as changes in expression of Atg-5, Atg-7, Beclin-1 and LC3. CQ was found to block the Cd-induced decrease in Cx43 and GJIC inhibition, whereas RAP had opposite effect. These results demonstrate that autophagy plays a protective role during Cd-induced apoptosis in BRL 3A cells during 6 h of experiment, while autophagy exacerbates Cd-induced GJIC inhibition which has a negative effect on cellular fate. - Highlights: • GJIC and autophagy is crucial for biological processes. • Cd exposure causes GJIC inhibition and autophagy increase in BRL 3A cells. • Autophagy protects Cd induced BRL 3A cells apoptosis at an early stage. • Autophagy exacerbates Cd-induced GJIC inhibition. • GJIC plays an important role in autophagy induced cell death or survival.

  5. Gamma-hydroxybutyrate enhances mood and prosocial behavior without affecting plasma oxytocin and testosterone.

    Science.gov (United States)

    Bosch, Oliver G; Eisenegger, Christoph; Gertsch, Jürg; von Rotz, Robin; Dornbierer, Dario; Gachet, M Salomé; Heinrichs, Markus; Wetter, Thomas C; Seifritz, Erich; Quednow, Boris B

    2015-12-01

    Gamma-hydroxybutyrate (GHB) is a GHB-/GABAB-receptor agonist. Reports from GHB abusers indicate euphoric, prosocial, and empathogenic effects of the drug. We measured the effects of GHB on mood, prosocial behavior, social and non-social cognition and assessed potential underlying neuroendocrine mechanisms. GHB (20mg/kg) was tested in 16 healthy males, using a randomized, placebo-controlled, cross-over design. Subjective effects on mood were assessed by visual-analogue-scales and the GHB-Specific-Questionnaire. Prosocial behavior was examined by the Charity Donation Task, the Social Value Orientation test, and the Reciprocity Task. Reaction time, memory, empathy, and theory-of-mind were also tested. Blood plasma levels of GHB, oxytocin, testosterone, progesterone, dehydroepiandrosterone (DHEA), cortisol, aldosterone, and adrenocorticotropic-hormone (ACTH) were determined. GHB showed stimulating and sedating effects, and elicited euphoria, disinhibition, and enhanced vitality. In participants with low prosociality, the drug increased donations and prosocial money distributions. In contrast, social cognitive abilities such as emotion recognition, empathy, and theory-of-mind, and basal cognitive functions were not affected. GHB increased plasma progesterone, while oxytocin and testosterone, cortisol, aldosterone, DHEA, and ACTH levels remained unaffected. GHB has mood-enhancing and prosocial effects without affecting social hormones such as oxytocin and testosterone. These data suggest a potential involvement of GHB-/GABAB-receptors and progesterone in mood and prosocial behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. NEUROANATOMICAL ASSOCIATION OF HYPOTHALAMIC HSD2-CONTAINING NEURONS WITH ERα, CATECHOLAMINES, OR OXYTOCIN: IMPLICATIONS FOR FEEDING?

    Directory of Open Access Journals (Sweden)

    Maegan L. Askew

    2015-06-01

    Full Text Available This study used immunohistochemical methods to investigate the possibility that hypothalamic neurons that contain 11-β-hydroxysteroid dehydrogenase type 2 (HSD2 are involved in the control of feeding by rats via neuroanatomical associations with the α subtype of estrogen receptor (ERα, catecholamines, and/or oxytocin. An aggregate of HSD2-containing neurons is located laterally in the hypothalamus, and the numbers of these neurons were greatly increased by estradiol treatment in ovariectomized rats compared to numbers in male rats and in ovariectomized rats that were not given estradiol. However, HSD2-containing neurons were anatomically segregated from ERα-containing neurons in the Ventromedial Hypothalamus and the Arcuate Nucleus. There was an absence of oxytocin-immunolabeled fibers in the area of HSD2-labeled neurons. Taken together, these findings provide no support for direct associations between hypothalamic HSD2 and ERα or oxytocin neurons in the control of feeding. In contrast, there was catecholamine-fiber labeling in the area of HSD2-labeled neurons, and these fibers occasionally were in close apposition to HSD2-labeled neurons. Therefore, we cannot rule out interactions between HSD2 and catecholamines in the control of feeding; however, given the relative sparseness of the appositions, any such interaction would appear to be modest. Thus, these studies do not conclusively identify a neuroanatomical substrate by which HSD2-containing neurons in the hypothalamus may alter feeding, and leave the functional role of hypothalamic HSD2-containing neurons subject to further investigation.

  7. Oxytocin gene polymorphisms influence human dopaminergic function in a sex-dependent manner.

    Science.gov (United States)

    Love, Tiffany M; Enoch, Mary-Anne; Hodgkinson, Colin A; Peciña, Marta; Mickey, Brian; Koeppe, Robert A; Stohler, Christian S; Goldman, David; Zubieta, Jon-Kar

    2012-08-01

    Oxytocin, classically involved in social and reproductive activities, is increasingly recognized as an antinociceptive and anxiolytic agent, effects which may be mediated via oxytocin's interactions with the dopamine system. Thus, genetic variation within the oxytocin gene (OXT) is likely to explain variability in dopamine-related stress responses. As such, we examined how OXT variation is associated with stress-induced dopaminergic neurotransmission in a healthy human sample. Fifty-five young healthy volunteers were scanned using [¹¹C]raclopride positron emission tomography while they underwent a standardized physical and emotional stressor that consisted of moderate levels of experimental sustained deep muscle pain, and a baseline, control state. Four haplotype tagging single nucleotide polymorphisms located in regions near OXT were genotyped. Measures of pain, affect, anxiety, well-being and interpersonal attachment were also assessed. Female rs4813625 C allele carriers demonstrated greater stress-induced dopamine release, measured as reductions in receptor availability from baseline to the pain-stress condition relative to female GG homozygotes. No significant differences were detected among males. We also observed that female rs4813625 C allele carriers exhibited higher attachment anxiety, higher trait anxiety and lower emotional well-being scores. In addition, greater stress-induced dopamine release was associated with lower emotional well-being scores in female rs4813625 C allele carriers. Our results suggest that variability within the oxytocin gene appear to explain interindividual differences in dopaminergic responses to stress, which are shown to be associated with anxiety traits, including those linked to attachment style, as well as emotional well-being in women. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  8. Oxytocin's role on the cardiorespiratory activity of endotoxemic rats.

    Science.gov (United States)

    Elorza-Ávila, Ana Rosa; Reyes-Lagos, José Javier; Hadamitzky, Martin; Peña-Castillo, Miguel Ángel; Echeverría, Juan Carlos; Ortiz-Pedroza, María Del Rocío; Lückemann, Laura; Schedlowski, Manfred; Pacheco-López, Gustavo

    2017-02-01

    Recent findings concerning oxytocin indicate its anti-inflammatory, cardioprotective and parasympathetic modulating properties. In this study, we investigated the effects of systemically applied oxytocin on the cardiorespiratory activity in a rodent model of moderate endotoxemia. Telemetrically recorded electrocardiogram (ECGs) from animals which received lipopolysaccharide (LPS); oxytocin (Ox); lipopolysaccharide+oxytocin (LPS+Ox), or vehicle (V) were analyzed using the ECG-derived respiration (EDR) technique to estimate the respiratory rate. The mean R-R interval and the spectral parameters of heart rate variability (HRV), such as the natural logarithm of the high frequency (lnHF) and low frequency (lnLF) components were also estimated up to 24h after treatment. The endotoxemic animals (LPS) showed an elevated respiratory rate as well as a reduced mean R-R interval, lnHF and lnLF components compared to controls (V) from +5 to +12h after the treatment. The administration of oxytocin significantly attenuated the hyperventilation produced by the LPS-induced endotoxemia (LPS+Ox) and restored the values of the mean R-R interval and such spectral parameters at different time points. Our results support the existence of a link among the respiratory, cardiovascular, and immune systems in which oxytocin seems to act as a potential cardioprotective peptide by favoring cardiac cholinergic autonomic coupling. As a result, oxytocin diminished animal's endotoxemic tachypnea and restored the cardiorespiratory interactions, which was indicated by the spectral components of HRV. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Factors associated with higher oxytocin requirements in labor.

    Science.gov (United States)

    Frey, Heather A; Tuuli, Methodius G; England, Sarah K; Roehl, Kimberly A; Odibo, Anthony O; Macones, George A; Cahill, Alison G

    2015-09-01

    To identify clinical characteristics associated with high maximum oxytocin doses in women who achieve complete cervical dilation. A retrospective nested case-control study was performed within a cohort of all term women at a single center between 2004 and 2008 who reached the second stage of labor. Cases were defined as women who had a maximum oxytocin dose during labor >20 mu/min, while women in the control group had a maximum oxytocin dose during labor of ≤20 mu/min. Exclusion criteria included no oxytocin administration during labor, multiple gestations, major fetal anomalies, nonvertex presentation, and prior cesarean delivery. Multiple maternal, fetal, and labor factors were evaluated with univariable analysis and multivariable logistic regression. Maximum oxytocin doses >20 mu/min were administered to 108 women (3.6%), while 2864 women received doses ≤20 mu/min. Factors associated with higher maximum oxytocin dose after adjusting for relevant confounders included maternal diabetes, birthweight >4000 g, intrapartum fever, administration of magnesium, and induction of labor. Few women who achieve complete cervical dilation require high doses of oxytocin. We identified maternal, fetal and labor factors that characterize this group of parturients.

  10. An Impermeant Ganetespib Analog Inhibits Extracellular Hsp90-Mediated Cancer Cell Migration that Involves Lysyl Oxidase 2-like Protein

    Energy Technology Data Exchange (ETDEWEB)

    McCready, Jessica [Department of Natural Sciences, Assumption College, Worcester, MA 01609 (United States); Wong, Daniel S. [Department of Developmental Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States); Cell and Molecular Physiology Program, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111 (United States); Burlison, Joseph A.; Ying, Weiwen [Synta Pharmaceuticals, Lexington, MA 02421 (United States); Jay, Daniel G., E-mail: daniel.jay@tufts.edu [Department of Developmental Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States); Cell and Molecular Physiology Program, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111 (United States)

    2014-04-30

    Extracellular Hsp90 (eHsp90) activates a number of client proteins outside of cancer cells required for migration and invasion. Therefore, eHsp90 may serve as a novel target for anti-metastatic drugs as its inhibition using impermeant Hsp90 inhibitors would not affect the numerous vital intracellular Hsp90 functions in normal cells. While some eHsp90 clients are known, it is important to establish other proteins that act outside the cell to validate eHsp90 as a drug target to limit cancer spread. Using mass spectrometry we identified two precursor proteins Galectin 3 binding protein (G3BP) and Lysyl oxidase 2-like protein (LOXL2) that associate with eHsp90 in MDA-MB231 breast cancer cell conditioned media and confirmed that LOXL2 binds to eHsp90 in immunoprecipitates. We introduce a novel impermeant Hsp90 inhibitor STA-12-7191 derived from ganetespib and show that it is markedly less toxic to cells and can inhibit cancer cell migration in a dose dependent manner. We used STA-12-7191 to test if LOXL2 and G3BP are potential eHsp90 clients. We showed that while LOXL2 can increase wound healing and compensate for STA-12-7191-mediated inhibition of wound closure, addition of G3BP had no affect on this assay. These findings support of role for LOXL2 in eHsp90 stimulated cancer cell migration and provide preliminary evidence for the use of STA-12-7191 to inhibit eHsp90 to limit cancer invasion.

  11. An Impermeant Ganetespib Analog Inhibits Extracellular Hsp90-Mediated Cancer Cell Migration that Involves Lysyl Oxidase 2-like Protein

    International Nuclear Information System (INIS)

    McCready, Jessica; Wong, Daniel S.; Burlison, Joseph A.; Ying, Weiwen; Jay, Daniel G.

    2014-01-01

    Extracellular Hsp90 (eHsp90) activates a number of client proteins outside of cancer cells required for migration and invasion. Therefore, eHsp90 may serve as a novel target for anti-metastatic drugs as its inhibition using impermeant Hsp90 inhibitors would not affect the numerous vital intracellular Hsp90 functions in normal cells. While some eHsp90 clients are known, it is important to establish other proteins that act outside the cell to validate eHsp90 as a drug target to limit cancer spread. Using mass spectrometry we identified two precursor proteins Galectin 3 binding protein (G3BP) and Lysyl oxidase 2-like protein (LOXL2) that associate with eHsp90 in MDA-MB231 breast cancer cell conditioned media and confirmed that LOXL2 binds to eHsp90 in immunoprecipitates. We introduce a novel impermeant Hsp90 inhibitor STA-12-7191 derived from ganetespib and show that it is markedly less toxic to cells and can inhibit cancer cell migration in a dose dependent manner. We used STA-12-7191 to test if LOXL2 and G3BP are potential eHsp90 clients. We showed that while LOXL2 can increase wound healing and compensate for STA-12-7191-mediated inhibition of wound closure, addition of G3BP had no affect on this assay. These findings support of role for LOXL2 in eHsp90 stimulated cancer cell migration and provide preliminary evidence for the use of STA-12-7191 to inhibit eHsp90 to limit cancer invasion

  12. Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Tianqing; Teng, Jiajun; Jiang, Liyan; Zhong, Hua; Han, Baohui, E-mail: baohuihan1@163.com

    2014-01-17

    Highlights: •DKK1 level was associated with NSCLC bone metastases. •Lung tumor cells derived DKK1 inhibited osteoblast differentiation. •Lung tumor cells derived DKK1 modulates β-catenin and RUNX2. -- Abstract: Wnt/β-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferably metastasizes to skeleton. But the role of them in bone dissemination is poorly understood. This study aims to define the role of DKK1 in lung cancer bone metastases and investigate the underlying mechanism. Our results demonstrated that DKK1 over-expression was a frequent event in non-small-cell lung cancer (NSCLC) blood samples, and serous DKK1 level was much higher in bone metastatic NSCLC compared to non-bone metastatic NSCLC. We also found that conditioned medium from DKK1 over-expressing lung cancer cells inhibited the differentiation of osteoblast, determined by alkaline phosphatase activity and osteocalcin secretion, whereas the conditioned medium from DKK1 silencing lung cancer cells exhibited the opposite effects. Mechanistically, DKK1 reduced the level of β-catenin and RUNX2, as well as inhibiting the nuclear translocation of β-catenin. Taken together, these results suggested that lung cancer-produced DKK1 may be an important mechanistic link between NSCLC and bone metastases, and targeting DKK1 may be an effective method to treat bone metastase of NSCLC.

  13. Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation

    International Nuclear Information System (INIS)

    Chu, Tianqing; Teng, Jiajun; Jiang, Liyan; Zhong, Hua; Han, Baohui

    2014-01-01

    Highlights: •DKK1 level was associated with NSCLC bone metastases. •Lung tumor cells derived DKK1 inhibited osteoblast differentiation. •Lung tumor cells derived DKK1 modulates β-catenin and RUNX2. -- Abstract: Wnt/β-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferably metastasizes to skeleton. But the role of them in bone dissemination is poorly understood. This study aims to define the role of DKK1 in lung cancer bone metastases and investigate the underlying mechanism. Our results demonstrated that DKK1 over-expression was a frequent event in non-small-cell lung cancer (NSCLC) blood samples, and serous DKK1 level was much higher in bone metastatic NSCLC compared to non-bone metastatic NSCLC. We also found that conditioned medium from DKK1 over-expressing lung cancer cells inhibited the differentiation of osteoblast, determined by alkaline phosphatase activity and osteocalcin secretion, whereas the conditioned medium from DKK1 silencing lung cancer cells exhibited the opposite effects. Mechanistically, DKK1 reduced the level of β-catenin and RUNX2, as well as inhibiting the nuclear translocation of β-catenin. Taken together, these results suggested that lung cancer-produced DKK1 may be an important mechanistic link between NSCLC and bone metastases, and targeting DKK1 may be an effective method to treat bone metastase of NSCLC

  14. Brief Report: Oxytocin Enhances Paternal Sensitivity to a Child with Autism--A Double-Blind Within-Subject Experiment with Intranasally Administered Oxytocin

    Science.gov (United States)

    Naber, Fabienne B. A.; Poslawsky, Irina E.; van Ijzendoorn, Marinus H.; van Engeland, Herman; Bakermans-Kranenburg, Marian J.

    2013-01-01

    Oxytocin seems associated with parenting style, and experimental work showed positive effects of intranasally administered oxytocin on parenting style of fathers. Here, the first double-blind, placebo-controlled, within-subject experiment with intranasal oxytocin administration to fathers of children with autism spectrum disorder (ASD) is…

  15. Inhibition of phosphatidylinositol 3-kinase promotes tumor cell resistance to chemotherapeutic agents via a mechanism involving delay in cell cycle progression

    International Nuclear Information System (INIS)

    McDonald, Gail T.; Sullivan, Richard; Pare, Genevieve C.; Graham, Charles H.

    2010-01-01

    Approaches to overcome chemoresistance in cancer cells have involved targeting specific signaling pathways such as the phosphatidylinositol 3-kinase (PI3K) pathway, a stress response pathway known to be involved in the regulation of cell survival, apoptosis and growth. The present study determined the effect of PI3K inhibition on the clonogenic survival of human cancer cells following exposure to various chemotherapeutic agents. Treatment with the PI3K inhibitors LY294002 or Compound 15e resulted in increased survival of MDA-MB-231 breast carcinoma cells after exposure to doxorubicin, etoposide, 5-fluorouracil, and vincristine. Increased survival following PI3K inhibition was also observed in DU-145 prostate, HCT-116 colon and A-549 lung carcinoma cell lines exposed to doxorubicin. Increased cell survival mediated by LY294002 was correlated with a decrease in cell proliferation, which was linked to an increase in the proportion of cells in the G 1 phase of the cell cycle. Inhibition of PI3K signaling also resulted in higher levels of the cyclin-dependent kinase inhibitors p21 Waf1/Cip1 and p27 Kip1 ; and knockdown of p27 kip1 with siRNA attenuated resistance to doxorubicin in cells treated with LY294002. Incubation in the presence of LY294002 after exposure to doxorubicin resulted in decreased cell survival. These findings provide evidence that PI3K inhibition leads to chemoresistance in human cancer cells by causing a delay in cell cycle; however, the timing of PI3K inhibition (either before or after exposure to anti-cancer agents) may be a critical determinant of chemosensitivity.

  16. The Antiproliferative Effect of Cyclodipeptides from Pseudomonas aeruginosa PAO1 on HeLa Cells Involves Inhibition of Phosphorylation of Akt and S6k Kinases.

    Science.gov (United States)

    Hernández-Padilla, Laura; Vázquez-Rivera, Dolores; Sánchez-Briones, Luis A; Díaz-Pérez, Alma L; Moreno-Rodríguez, José; Moreno-Eutimio, Mario A; Meza-Carmen, Victor; Cruz, Homero Reyes-De la; Campos-García, Jesús

    2017-06-20

    Pseudomonas aeruginosa PAO1, a potential pathogen of plants and animals, produces the cyclodipeptides cyclo(l-Pro-l-Tyr), cyclo(l-Pro-l-Phe), and cyclo(l-Pro-l-Val) (PAO1-CDPs), whose effects have been implicated in inhibition of human tumor cell line proliferation. Our purpose was to investigate in depth in the mechanisms of HeLa cell proliferation inhibition by the PAO1-CDPs. The results indicate that PAO1-CDPs, both purified individually and in mixtures, inhibited HeLa cell proliferation by arresting the cell cycle at the G0-G1 transition. The crude PAO1-CDPs mixture promoted cell death in HeLa cells in a dose-dependent manner, showing efficacy similar to that of isolated PAO1-CDPs (LD 50 of 60-250 µM) and inducing apoptosis with EC 50 between 0.6 and 3.0 µM. Moreover, PAO1-CDPs showed a higher proapoptotic activity (~10³-10⁵ fold) than their synthetic analogs did. Subsequently, the PAO1-CDPs affected mitochondrial membrane potential and induced apoptosis by caspase-9-dependent pathway. The mechanism of inhibition of cells proliferation in HeLa cells involves inhibition of phosphorylation of both Akt-S473 and S6k-T389 protein kinases, showing a cyclic behavior of their expression and phosphorylation in a time and concentration-dependent fashion. Taken together our findings indicate that PI3K-Akt-mTOR-S6k signaling pathway blockage is involved in the antiproliferative effect of the PAO1-CDPs.

  17. Piperine Inhibits the Activities of Platelet Cytosolic Phospholipase A2 and Thromboxane A2 Synthase without Affecting Cyclooxygenase-1 Activity: Different Mechanisms of Action Are Involved in the Inhibition of Platelet Aggregation and Macrophage Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Dong Ju Son

    2014-08-01

    Full Text Available PURPOSE: Piperine, a major alkaloid of black pepper (Piper nigrum and long pepper (Piper longum, was shown to have anti-inflammatory activity through the suppression of cyclooxygenase (COX-2 gene expression and enzyme activity. It is also reported to exhibit anti-platelet activity, but the mechanism underlying this action remains unknown. In this study, we investigated a putative anti-platelet aggregation mechanism involving arachidonic acid (AA metabolism and how this compares with the mechanism by which it inhibits macrophage inflammatory responses; METHODS: Rabbit platelets and murine macrophage RAW264.7 cells were treated with piperine, and the effect of piperine on the activity of AA-metabolizing enzymes, including cytosolic phospholipase A2 (cPLA2, COX-1, COX-2, and thromboxane A2 (TXA2 synthase, as well as its effect on AA liberation from the plasma membrane components, were assessed using isotopic labeling methods and enzyme immunoassay kit; RESULTS: Piperine significantly suppressed AA liberation by attenuating cPLA2 activity in collagen-stimulated platelets. It also significantly inhibited the activity of TXA2 synthase, but not of COX-1, in platelets. These results suggest that piperine inhibits platelet aggregation by attenuating cPLA2 and TXA2 synthase activities, rather than through the inhibition of COX-1 activity. On the other hand, piperine significantly inhibited lipopolysaccharide-induced generation of prostaglandin (PGE2 and PGD2 in RAW264.7 cells by suppressing the activity of COX-2, without effect on cPLA2; CONCLUSION: Our findings indicate that piperine inhibits platelet aggregation and macrophage inflammatory response by different mechanisms.

  18. Inhibition of MHC-I by Brucella abortus is an early event during infection and involves EGFR pathway.

    Science.gov (United States)

    Velásquez, Lis N; Milillo, M Ayelén; Delpino, M Victoria; Trotta, Aldana; Mercogliano, M Florencia; Pozner, Roberto G; Schillaci, Roxana; Elizalde, Patricia V; Giambartolomei, Guillermo H; Barrionuevo, Paula

    2017-04-01

    Brucella abortus is able to persist inside the host despite the development of potent CD8 + T-cell responses. We have recently reported the ability of B. abortus to inhibit the interferon-γ-induced major histocompatibility complex (MHC)-I cell surface expression on human monocytes. This phenomenon was due to the B. abortus-mediated retention of MHC-I molecules within the Golgi apparatus and was dependent on bacterial viability. However, the implications of bacterial virulence or replicative capacity and the signaling pathways remained unknown. Here we demonstrated that the B. abortus mutant strains RB51 and virB10 - are able to inhibit MHC-I expression in the same manner as wild-type B. abortus, even though they are unable to persist inside human monocytes for a long period of time. Consistent with this, the phenomenon was triggered early in time and could be observed at 8 h postinfection. At 24 and 48 h, it was even stronger. Regarding the signaling pathway, targeting epidermal growth factor (EGF) receptor (EGFR), ErbB2 (HER2) or inhibition of tumor necrosis factor-α-converting enzyme, one of the enzymes which generates soluble EGF-like ligands, resulted in partial recovery of MHC-I surface expression. Moreover, recombinant EGF and transforming growth factor-α as well as the combination of both were also able to reproduce the B. abortus-induced MHC-I downmodulation. Finally, when infection was performed in the presence of an extracellular signal-regulated kinase 1/2 (Erk1/2) inhibitor, MHC-I surface expression was significantly recovered. Overall, these results describe how B. abortus evades CD8 + T-cell responses early during infection and exploits the EGFR-ERK signaling pathway to escape from the immune system and favor chronicity.

  19. Effects of Oxytocin Administration on Receiving Help.

    Science.gov (United States)

    Human, Lauren J; Woolley, Joshua D; Mendes, Wendy Berry

    2017-11-27

    Receiving help can be a "mixed blessing." Despite the many psychosocial benefits it can carry, it sometimes has negative psychological consequences, such as loss in self-esteem or enhanced guilt. It is, therefore, important to understand the factors that modify responses to receiving help from others. We explored the role of the hormone oxytocin (OT) on affective and social responses to receiving help, given the putative role of OT in social bonding and attunement. To this end, we manipulated whether help was received from a same-sex interaction partner (confederate) versus a control condition, crossed with a double-blind administration of intranasal OT (vs. placebo), and examined subjective and observer-rated participant responses to help. We observed significant interactions between OT and the help manipulation. In the placebo condition, receiving help from the interaction partner compared with the control condition had negative consequences, such that participants reported greater negative affect and came to view themselves and their interaction partners more negatively after interacting together on several tasks. What is important, however, is that OT administration buffered against these negative subjective responses to receiving help. Further, outside observers rated participants who received OT administration as expressing greater happiness and gratitude in response to help, relative to those who received placebo. In sum, in the context of receiving help from a stranger, oxytocin administration fostered more positive affective and social responses. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  20. Human cytosolic glutathione-S-transferases: quantitative analysis of expression, comparative analysis of structures and inhibition strategies of isozymes involved in drug resistance.

    Science.gov (United States)

    Mohana, Krishnamoorthy; Achary, Anant

    2017-08-01

    Glutathione-S-transferase (GST) inhibition is a strategy to overcome drug resistance. Several isoforms of human GSTs are present and they are expressed in almost all the organs. Specific expression levels of GSTs in various organs are collected from the human transcriptome data and analysis of the organ-specific expression of GST isoforms is carried out. The variations in the level of expressions of GST isoforms are statistically significant. The GST expression differs in diseased conditions as reported by many investigators and some of the isoforms of GSTs are disease markers or drug targets. Structure analysis of various isoforms is carried out and literature mining has been performed to identify the differences in the active sites of the GSTs. The xenobiotic binding H site is classified into H1, H2, and H3 and the differences in the amino acid composition, the hydrophobicity and other structural features of H site of GSTs are discussed. The existing inhibition strategies are compared. The advent of rational drug design, mechanism-based inhibition strategies, availability of high-throughput screening, target specific, and selective inhibition of GST isoforms involved in drug resistance could be achieved for the reversal of drug resistance and aid in the treatment of diseases.

  1. Empathy toward strangers triggers oxytocin release and subsequent generosity.

    Science.gov (United States)

    Barraza, Jorge A; Zak, Paul J

    2009-06-01

    Empathy is related to a variety of prosocial behaviors, but the brain mechanisms producing the experience of empathy have not been fully characterized. This study investigated whether the experience of empathy raises oxytocin levels and affects subsequent generosity toward strangers. Short video clips of an emotional scene and an unemotional scene were used as stimuli. Participants rated the emotions they experienced and then played a $40 ultimatum game to gauge their generosity. We found that empathy was associated with a 47% increase in oxytocin from baseline. We also found the empathy-oxytocin response was stronger in women than in men. Higher levels of empathy were also associated with more generous monetary offers toward strangers in the ultimatum game. Our findings provide the first evidence that oxytocin is a physiologic signature for empathy and that empathy mediates generosity.

  2. Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder

    NARCIS (Netherlands)

    Koch, Saskia B. J.; van Zuiden, Mirjam; Nawijn, Laura; Frijling, Jessie L.; Veltman, Dick J.; Olff, Miranda

    2016-01-01

    The neuropeptide oxytocin (OT) has been suggested as a promising pharmacological agent for medication-enhanced psychotherapy in posttraumatic stress disorder (PTSD) because of its anxiolytic and prosocial properties. We therefore investigated the behavioral and neurobiological effects of a single

  3. Oxytocin use in South Africa — a review

    African Journals Online (AJOL)

    Nicky

    2005-06-28

    Jun 28, 2005 ... The aim of this study was to examine the use of oxytocin by obstetricians ... Use with grand multipara ... Labour is induced when delivery will benefit the health of ..... intensive nursing. ... No one used auscultation exclusively in.

  4. Functional characterisation of eel dopamine D2 receptors and involvement in the direct inhibition of pituitary gonadotrophins

    DEFF Research Database (Denmark)

    Jolly, C.; Rousseau, K.; Prézeau, L.

    2016-01-01

    and antagonists, supporting subtle structure/activity differences. Furthermore, using eel pituitary cell primary cultures, the expression by gonadotroph cells of both native eel D2‐R paralogues was examined by in situ hybridisation of D2A‐R or D2B‐R transcripts, coupled with immunofluorescence of luteinising...... hormone (LH)β or follicle‐stimulating (FSH)β. LH and to a lesser extent, FSH cells expressed both D2‐R transcripts but with a clear predominance of D2B‐R. Notably, D2B‐R transcripts were detected for the majority of LH cells. Accordingly, using these cultures, we showed that DA potently inhibited basal...

  5. Inhibition of hydrogen sulfide on the proliferation of vascular smooth muscle cells involved in the modulation of calcium sensing receptor in high homocysteine

    International Nuclear Information System (INIS)

    Wang, Yuwen; Wang, Xiyao; Liang, Xiaohui; Wu, Jichao; Dong, Shiyun; Li, Hongzhu; Jin, Meili; Sun, Dianjun; Zhang, Weihua; Zhong, Xin

    2016-01-01

    Hyperhomocysteinemia induces the proliferation of vascular smooth muscle cells (VSMCs). Hydrogen sulfide (H 2 S) inhibits the phenotype switch of VSMCs and calcium-sensing receptor (CaSR) regulated the production of endogenous H 2 S. However, whether CaSR inhibits the proliferation of VSMCs by regulating the endogenous cystathionine-gamma-lyase (CSE, a major enzyme that produces H 2 S) pathway in high homocysteine (HHcy) has not been previously investigated. The intracellular calcium concentration, the concentration of H 2 S, the cell viability, the proliferation and the expression of proteins of cultured VSMCs from rat thoracic aortas were measured, respectively. The results showed that the [Ca 2+ ] i and the expression of p-CaMK and CSE increased upon treatment with CaSR agonist. In HHcy, the H 2 S concentration decrease, the proliferation and migration rate increased, the expression of Cyclin D1, PCNA, Osteopontin and p-Erk1/2 increased while the α-SM actin, P21 Cip/WAK−1 and Calponin decreased. The CaSR agonist or exogenous H 2 S significantly reversed the changes of VSMCs caused by HHcy. In conclusion, our results demonstrated that CaSR regulate the endogenous CSE/H 2 S is related to the PLC-IP 3 receptor and CaM signal pathways which inhibit the proliferation of VSMCs, and the latter is involved in the Erk1/2 dependent signal pathway in high homocysteine. - Highlights: • CaSR activation increased the production of endogenous H 2 S in high homocysteine VSMCs. • CaSR modulated the CSE/H 2 S are related to the PLC-IP 3 R and Ca 2+ -CaM signal pathways. • Inhibition of H 2 S on the proliferation of VSMCs is involved in the Erk1/2 pathway. • Explore the potential roles of CaSR in regulating VSMCs proliferation in high homocysteine.

  6. Maternal and Paternal Plasma, Salivary, and Urinary Oxytocin and Parent-Infant Synchrony: Considering Stress and Affiliation Components of Human Bonding

    Science.gov (United States)

    Feldman, Ruth; Gordon, Ilanit; Zagoory-Sharon, Orna

    2011-01-01

    Studies in mammals have implicated the neuropeptide oxytocin (OT) in processes of bond formation and stress modulation, yet the involvement of OT in human bonding throughout life remains poorly understood. We assessed OT in the plasma, saliva, and urine of 112 mothers and fathers interacting with their 4-6-month-old infants. Parent-infant…

  7. Labor stimulation with oxytocin: effects on obstetrical and neonatal outcomes

    Directory of Open Access Journals (Sweden)

    Pedro Hidalgo-Lopezosa

    Full Text Available Abstract Objective: to evaluate the effects of labor stimulation with oxytocin on maternal and neonatal outcomes. Method: descriptive and analytical study with 338 women who gave birth at a tertiary hospital. Obstetric and neonatal variables were measured and compared in women submitted and non-submitted to stimulation with oxytocin. Statistics were performed using Chi-square test, Fisher exact test, Student t-test; and crude Odds Ratio with 95% confidence interval were calculated. A p < 0.05 was considered statistically significant. Results: stimulation with oxytocin increases the rates of cesarean sections, epidural anesthesia and intrapartum maternal fever in primiparous and multiparous women. It has also been associated with low pH values of umbilical cord blood and with a shorter duration of the first stage of labor in primiparous women. However, it did not affect the rates of 3rd and 4th degree perineal lacerations, episiotomies, advanced neonatal resuscitation, 5-minute Apgar scores and meconium. Conclusion: stimulation with oxytocin should not be used systematically, but only in specific cases. These findings provide further evidence to health professionals and midwives on the use of oxytocin during labor. Under normal conditions, women should be informed of the possible effects of labor stimulation with oxytocin.

  8. "Lie to me"-Oxytocin impairs lie detection between sexes.

    Science.gov (United States)

    Pfundmair, Michaela; Erk, Wiebke; Reinelt, Annika

    2017-10-01

    The hormone oxytocin modulates various aspects of social behaviors and even seems to lead to a tendency for gullibility. The aim of the current study was to investigate the effect of oxytocin on lie detection. We hypothesized that people under oxytocin would be particularly susceptible to lies told by people of the opposite sex. After administration of oxytocin or a placebo, male and female participants were asked to judge the veracity of statements from same- vs. other-sex actors who either lied or told the truth. Results showed that oxytocin decreased the ability of both male and female participants to correctly classify other-sex statements as truths or lies compared to placebo. This effect was based on a lower ability to detect lies and not a stronger bias to regard truth statements as false. Revealing a new effect of oxytocin, the findings may support assumptions about the hormone working as a catalyst for social adaption. Copyright © 2017. Published by Elsevier Ltd.

  9. Effects of Exogenous Oxytocin on Embryonic Survival in Cows

    Directory of Open Access Journals (Sweden)

    A. Yildiz

    2006-01-01

    Full Text Available The aim of this study was to evaluate the effect of oxytocin on embryonic survival in dairy cows. Pregnancy was verified using the early pregnancy factor (EPF activity on Day 4 after artificial insemination (AI. Pregnant cows were randomly allotted to two groups: treated (n = 8 and control (n = 8. Oxytocin (100 IU, 5 ml, DIF Turkey was administered twice daily by intravenous injections to treated cows and sterile saline (5 ml to control cows immediately before milking on days 4 to 7 after AI. Blood samples were taken via jugular vein every day from day 4 to 8 and every other day until Day 20 following insemination to evaluate the effect of oxytocin on embryonic survival. The embryonic loss was diagnosed in 3 of the 8 cows treated with oxytocin, and embryonic survival rate was 62.5% in this group versus 87.5% in controls. Short cycles occurred in 37.5% of oxytocin-treated cows. At the same time their serum progesterone concentrations rose more slowly than in controls. It was concluded that cows administered oxytocin on days 4 to 7 after insemination are at a higher risk of pregnancy loss.

  10. Metformin inhibits epithelial–mesenchymal transition in prostate cancer cells: Involvement of the tumor suppressor miR30a and its target gene SOX4

    International Nuclear Information System (INIS)

    Zhang, Jing; Shen, Chengwu; Wang, Lin; Ma, Quanping; Xia, Pingtian; Qi, Mei; Yang, Muyi; Han, Bo

    2014-01-01

    Highlights: • Metformin inhibits TGF-β-induced EMT in prostate cancer (PCa) cells. • Metformin upregulates tumor suppressor miR30a and downregulates SOX4 in PCa cells. • SOX4 is a target gene of miR30a. - Abstract: Tumor metastasis is the leading cause of mortality and morbidity of prostate cancer (PCa) patients. Epithelial–mesenchymal transition (EMT) plays a critical role in cancer progression and metastasis. Recent evidence suggested that diabetic patients treated with metformin have lower PCa risk and better prognosis. This study was aimed to investigate the effects of metformin on EMT in PCa cells and the possible microRNA (miRNA)-based mechanisms. MiRNAs have been shown to regulate various processes of cancer metastasis. We herein showed that metformin significantly inhibits proliferation of Vcap and PC-3 cells, induces G0/G1 cell cycle arrest and inhibits invasiveness and motility capacity of Vcap cells. Metformin could inhibit TGF-β-induced EMT in Vcap cells, as manifested by inhibition of the increase of N-cadherin (p = 0.013), Vimentin (p = 0.002) and the decrease of E-cadherin (p = 0.0023) and β-catenin (p = 0.034) at mRNA and protein levels. Notably, we demonstrated significant upregulation of miR30a levels by metformin (P < 0.05) and further experiments indicated that miR30a significantly inhibits proliferation and EMT process of Vcap cells. Interestingly, we identified that SOX4, a previously reported oncogenic transcriptional factor and modulator of EMT, is a direct target gene of miR30a. Finally, we screened the expression of miR30a and SOX4 in 84 PCa cases with radical prostatectomy. Of note, SOX4 overexpression is significantly associated with decreased levels of miR30a in PCa cases. In all, our study suggested that inhibition of EMT by metformin in PCa cells may involve upregulation of miR30a and downregulation of SOX4

  11. Puerarin exerts antipyretic effect on lipopolysaccharide-induced fever in rats involving inhibition of pyrogen production from macrophages.

    Science.gov (United States)

    Yao, Xiu-Juan; Yin, Ji-Ai; Xia, Yu-Feng; Wei, Zhi-Feng; Luo, Yu-Bin; Liu, Mei; Feleder, Carlos; Dai, Yue

    2012-05-07

    Puerarin is the most abundant isoflavonoid in Radix Puerariae (Gegen), which has been prescribed as a medicinal herb for treating fever in China for a long history. The present study aimed at evaluating the antipyretic effect of puerarin and revealing the related mechanisms. Lipopolysaccharide (LPS)-induced fever in rats was used to assess the antipyretic effect of puerarin. After an intraperitoneal injection of LPS (100μg/kg), body temperature was tested every 30min up to 8h. Different doses of puerarin (25, 50, 100mg/kg) were intraperitoneally administered 30min before LPS injection. In vitro, LPS-stimulated RAW 264.7 cells were treated with various concentrations of puerarin (25-200μM). The pyrogenic mediators, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandin E(2) (PGE(2)) and nitric oxide (NO), were examined on both transcription and expression levels. Furthermore, the influences of the activation of nuclear factor-kappa B (NF-κB) and the phosphorylation of mitogen-activated protein kinases (MAPKs) by puerarin were assayed by western blot. The intraperitoneal administration of puerarin at test doses clearly demonstrated apparent antipyretic effect through the declines in body temperature elevated by LPS in rats. The in vitro data showed that puerarin inhibited the production of IL-1β, TNF-α, IL-6, PGE(2) and NO; moreover, the RT-PCR analysis and the western blot analysis indicated that puerarin regulated the transcriptional level via suppression of NF-κB activation and blockade of MAPK signal pathway. In summary, the antipyretic property of puerarin might result, at least in part, from an inhibition of endogenous pyrogen production and expression. Taken in this sense, our findings provide an explanation for puerarin acting as an important constituent in Gegen, thus, provide scientific basis for the wide use of Radix Puerariae in China as a traditional antipyretic. Copyright © 2012 Elsevier Ireland

  12. Sex differences in the neural and behavioral response to intranasal oxytocin and vasopressin during human social interaction

    OpenAIRE

    Rilling James K.; DeMarco Ashley C.; Hackett Patrick D.; Chen Xu; Gautam Pritam; Stair Sabrina; Haroon Ebrahim; Thompson Richmond; Ditzen Beate; Patel Rajan; Pagnoni Giuseppe

    2014-01-01

    Both oxytocin (OT) and vasopressin (AVP) are known to modulate social behavior, and dysfunction in both systems has been postulated as a potential cause of certain psychiatric disorders that involve social behavioral deficits. In particular, there is growing interest in intranasal OT as a potential treatment for certain psychiatric disorders, and preliminary preclinical and clinical studies suggest efficacy in alleviating some of the associated symptoms. However, the vast majority of research...

  13. Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.

    Science.gov (United States)

    Kosaka, H; Okamoto, Y; Munesue, T; Yamasue, H; Inohara, K; Fujioka, T; Anme, T; Orisaka, M; Ishitobi, M; Jung, M; Fujisawa, T X; Tanaka, S; Arai, S; Asano, M; Saito, D N; Sadato, N; Tomoda, A; Omori, M; Sato, M; Okazawa, H; Higashida, H; Wada, Y

    2016-08-23

    Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD.

  14. Randomised controlled trial of oxytocin alone versus oxytocin and ergometrine in active management of third stage of labour.

    OpenAIRE

    McDonald, S J; Prendiville, W J; Blair, E

    1993-01-01

    OBJECTIVE--To compare intramuscular oxytocin alone and intramuscular oxytocin with ergometrine (Syntometrine) for their effect in reducing the risk of postpartum haemorrhage when both are used as part of the active management of the third stage of labour. DESIGN--Double blind, randomised controlled trial. SETTING--Two metropolitan teaching hospitals in Perth, Western Australia. SUBJECTS--All women who expected a vaginal birth during the period of the trial. Informed consent was obtained. MAIN...

  15. NF-κB inhibition is involved in tobacco smoke-induced apoptosis in the lungs of rats

    International Nuclear Information System (INIS)

    Zhong Caiyun; Zhou Yamei; Pinkerton, Kent E.

    2008-01-01

    Apoptosis is a vital mechanism for the regulation of cell turnover and plays a critical role in tissue homeostasis and development of many disease processes. Previous studies have demonstrated the apoptotic effect of tobacco smoke; however, the molecular mechanisms by which tobacco smoke triggers apoptosis remain unclear. In the present study we investigated the effects of tobacco smoke on the induction of apoptosis in the lungs of rats and modulation of nuclear factor-kappa B (NF-κB) in this process. Exposure of rats to 80 mg/m 3 tobacco smoke significantly induced apoptosis in the lungs. Tobacco smoke resulted in inhibition of NF-κB activity, noted by suppression of inhibitor of κB (IκB) kinase (IKK), accumulation of IκBα, decrease of NF-κB DNA binding activity, and downregulation of NF-κB-dependent anti-apoptotic proteins, including Bcl-2, Bcl-xl, and inhibitors of apoptosis. Initiator caspases for the death receptor pathway (caspase 8) and the mitochondrial pathway (caspase 9) as well as effector caspase 3 were activated following tobacco smoke exposure. Tobacco smoke exposure did not alter the levels of p53 and Bax proteins. These findings suggest the role of NF-κB pathway in tobacco smoke-induced apoptosis

  16. Systematic screen for mutants resistant to TORC1 inhibition in fission yeast reveals genes involved in cellular ageing and growth

    Directory of Open Access Journals (Sweden)

    Charalampos Rallis

    2014-01-01

    Target of rapamycin complex 1 (TORC1, which controls growth in response to nutrients, promotes ageing in multiple organisms. The fission yeast Schizosaccharomyces pombe emerges as a valuable genetic model system to study TORC1 function and cellular ageing. Here we exploited the combinatorial action of rapamycin and caffeine, which inhibit fission yeast growth in a TORC1-dependent manner. We screened a deletion library, comprising ∼84% of all non-essential fission yeast genes, for drug-resistant mutants. This screen identified 33 genes encoding functions such as transcription, kinases, mitochondrial respiration, biosynthesis, intra-cellular trafficking, and stress response. Among the corresponding mutants, 5 showed shortened and 21 showed increased maximal chronological lifespans; 15 of the latter mutants showed no further lifespan increase with rapamycin and might thus represent key targets downstream of TORC1. We pursued the long-lived sck2 mutant with additional functional analyses, revealing that the Sck2p kinase functions within the TORC1 network and is required for normal cell growth, global protein translation, and ribosomal S6 protein phosphorylation in a nutrient-dependent manner. Notably, slow cell growth was associated with all long-lived mutants while oxidative-stress resistance was not.

  17. Correlation between oxytocin neuronal sensitivity and oxytocin receptor binding: An electrophysiological and autoradiographical study comparing rat and guinea pig hippocampus

    International Nuclear Information System (INIS)

    Raggenbass, M.; Tribollet, E.; Dubois-Dauphin, M.; Dreifuss, J.J.

    1989-01-01

    In transverse hippocampal slices from rat and guinea pig brains, the authors obtained unitary extracellular recordings from nonpyramidal neurones located in or near the stratum pyramidale in the CA1 field and in the transition region between the CA1 and the subiculum. In rats, these neurones responded to oxytocin at 50-1,000 nM by a reversible increase in firing rate. The oxytocin-induced excitation was suppressed by a synthetic structural analogue that acts as a potent, selective antioxytocic on peripheral receptors. Nonpyramidal neurones were also excited by carbachol at 0.5-10 μM. The effect of this compound was postsynaptic and was blocked by the muscarinic antagonist atropine. In guinea pigs, by contrast, nonpyramidal neurones were unaffected by oxytocin, although they were excited by carbachol. Light microscopic autoradiography, carried out using a radioiodinated selective antioxytocic as a ligand, revealed labeling in the subiculum and in the CA1 area of the hippocampus of rats, whereas no oxytocin-binding sites were detected in the hippocampus of guinea pigs. The results indicate (i) that a hippocampal action of oxytocin is species-dependent and (ii) that a positive correlation exists between neuronal responsiveness to oxytocin and the presence in the hippocampus of high-affinity binding sites for this peptide

  18. Physicians' subjectivity in evaluating oxytocin challenge tests.

    Science.gov (United States)

    Peck, T M

    1980-07-01

    Five physicians subspecializing in maternal-fetal medicine individually evaluated 50 oxytocin challenge tests (OCTs), of which 33 were originally read as positive. There was considerable disagreement among the study physicians (SPs) such that 2 SPs would agree, on the average, only 52% of the time on any one OCT. The SPs were also asked to evaluate fetal heart rate (FHR) reactivity patterns, if present. Again, there was great disagreement. When the majority (3 of 5 or more) of SPs agreed on the OCT result and/or reactivity, there was reasonable correlation with neonatal outcome, indicating the validity of the physiologic premise of the test. In particular, the presence or absence of FHR accelerations with fetal motion, regardless of the OCT reading, correlated extremely well with eventual neonatal outcome. This indicates that the most significant variable in antepartum FHR monitoring is the FHR acceleration pattern.

  19. Radioimmunoassay of urine oxytocin in man

    International Nuclear Information System (INIS)

    Zebidi, A.; Geelen, G.; Allevard, A.M.; Sempore, B.; Jarsaillon, E.; Meunier, C.; Gharib, C.

    1978-01-01

    A radioimmunoassay (RIA) for oxytocin (OT) in urine is described. 125 I-OT was prepared, and antibodies were raised in rabbits against OT coupled to bovine serumalbumine. This allowed us to set up a RIA for OT which limit of detection is 1.25 pg/tube (0.6 μU). The use of an extraction procedure using CG 50 Amberlite is essential. The recovery after extraction reaches 70.5 %. pH 5 is the optimum pH were urine samples must be stored. The superposition of the elution peak of endogenous OT on that of exogenous hormone is an argument in favour of the validity of such an extraction procedure. Daily urinary excretion of OT reaches 9.58 mU +- 3.48 in 18 healthy young men [fr

  20. Nanoparticle-Encapsulated Curcumin Inhibits Diabetic Neuropathic Pain Involving the P2Y12 Receptor in the Dorsal Root Ganglia

    Directory of Open Access Journals (Sweden)

    Tianyu Jia

    2018-01-01

    Full Text Available Diabetic peripheral neuropathy results in diabetic neuropathic pain (DNP. Satellite glial cells (SGCs enwrap the neuronal soma in the dorsal root ganglia (DRG. The purinergic 2 (P2 Y12 receptor is expressed on SGCs in the DRG. SGC activation plays an important role in the pathogenesis of DNP. Curcumin has anti-inflammatory and antioxidant properties. Because curcumin has poor metabolic stability in vivo and low bioavailability, nanoparticle-encapsulated curcumin was used to improve its targeting and bioavailability. In the present study, our aim was to investigate the effects of nanoparticle-encapsulated curcumin on DNP mediated by the P2Y12 receptor on SGCs in the rat DRG. Diabetic peripheral neuropathy increased the expression levels of the P2Y12 receptor on SGCs in the DRG and enhanced mechanical and thermal hyperalgesia in rats with diabetes mellitus (DM. Up-regulation of the P2Y12 receptor in SGCs in the DRG increased the production of pro-inflammatory cytokines. Up-regulation of interleukin-1β (IL-1β and connexin43 (Cx43 resulted in mechanical and thermal hyperalgesia in rats with DM. The nanoparticle-encapsulated curcumin decreased up-regulated IL-1β and Cx43 expression and reduced levels of phosphorylated-Akt (p-Akt in the DRG of rats with DM. The up-regulation of P2Y12 on SGCs and the up-regulation of the IL-1β and Cx43 in the DRG indicated the activation of SGCs in the DRG. The nano-curcumin treatment inhibited the activation of SGCs accompanied by its anti-inflammatory effect to decrease the up-regulated CGRP expression in the DRG neurons. Therefore, the nanoparticle-encapsulated curcumin treatment decreased the up-regulation of the P2Y12 receptor on SGCs in the DRG and decreased mechanical and thermal hyperalgesia in rats with DM.

  1. Novel Antiplatelet Activity of Minocycline Involves Inhibition of MLK3-p38 Mitogen Activated Protein Kinase Axis.

    Science.gov (United States)

    Jackson, Joseph W; Singh, Meera V; Singh, Vir B; Jones, Letitia D; Davidson, Gregory A; Ture, Sara; Morrell, Craig N; Schifitto, Giovanni; Maggirwar, Sanjay B

    2016-01-01

    Platelets play an essential role in hemostasis and wound healing by facilitating thrombus formation at sites of injury. Platelets also mediate inflammation and contain several pro-inflammatory molecules including cytokines and chemokines that mediate leukocyte recruitment and activation. Not surprisingly, platelet dysfunction is known to contribute to several inflammatory disorders. Antiplatelet therapies, such as aspirin, adenosine diphosphate (ADP) antagonists, glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors, and anticoagulants such as warfarin, dampen platelet activity at the risk of unwarranted bleeding. Thus, the development of drugs that reduce platelet-mediated inflammation without interfering with thrombus formation is of importance to combat platelet-associated disorders. We have shown here for the first time that the tetracycline antibiotic, minocycline, administered to HIV-infected individuals reduces plasma levels of soluble CD40L and platelet factor 4 levels, host molecules predominately released by platelets. Minocycline reduced the activation of isolated platelets in the presence of the potent platelet activator, thrombin, as measured by ELISA and flow cytometry. Platelet degranulation was reduced upon exposure to minocycline as shown by mepacrine retention and flow cytometry. However, minocycline had no effect on spreading, aggregation, GPIIb/IIIa activation, or in vivo thrombus formation. Lastly, immunoblot analysis suggests that the antiplatelet activity of minocycline is likely mediated by inhibition of mixed lineage kinase 3 (MLK3)-p38 MAPK signaling axis and loss of p38 activity. Our findings provide a better understanding of platelet biology and a novel repurposing of an established antibiotic, minocycline, to specifically reduce platelet granule release without affecting thrombosis, which may yield insights in generating novel, specific antiplatelet therapies.

  2. The radioimmunoassay of plasma oxytocin in pregnancy and at parturition

    International Nuclear Information System (INIS)

    Kogure, Satohisa

    1976-01-01

    The titer of the antiserum obtained by inoculating oxytocin-bovine serum albumin antigen into mature male rabbits was 1:64,000 in the final dilution, and the rate of conjugation with labeled-oxytocin was 34%. The cross reaction rate of the antiserum was 0.01% or below, both for lysine vasopressin and arginine vasopressin. The sensitivity of the radioimmunoassay using this antiserum was 5μIU. When a known quantity of oxytocin was added to plasma for measurement, the mean recovery rate was about 93%. The blood oxytocin concentration was 6.1+-2.5μIU/ml (ml omitted hereafter) in the early stage of pregnancy, 12.5+-6.0μIU in the middle stage, and 27.0+-7.5μIU in the terminal stage. The oxytocin concentration in the maternal blood was 34.1+-4.9μIU in the second stage, the concentration in the umbilical arterial blood immediately after delivery 3.5+-5.3μIU, and that in the umbilical venous blood 30.0+-4.2μIU. In cases of caesarean section not in labor, the oxytocin concentration in the maternal blood was 27.1+-6.6μIU, that in the umbilical arterial blood 25.1+-5.4μIU, and that in the umbilical venous blood 25.4+-5.4μIU. In cases of caesarean section in labor, the oxytocin concentration in the maternal blood was 37.1+-7.1μIU, that in the umbilical arterial blood 31.4+-6.7μIU, and that in the umbilical venous blood 27.0+-7.8μIU. The half-life of the oxytocin in the peripheral blood in cases injected with oxytocin was 5-10 minutes. When prostaglandin F2α was administered intravenously, the oxytocin concentration in the peripheral blood was increased in cases in labor. (Chiba, N.)

  3. Plasma oxytocin during third stage of labour: comparison of natural and active management.

    OpenAIRE

    Thornton, S.; Davison, J. M.; Baylis, P. H.

    1988-01-01

    The incidences of postpartum haemorrhage and retained placenta have decreased with the use of synthetic oxytocin and controlled cord traction. Whether such treatment is valuable is open to question because of the lack of clinical and physiological studies. The physiological effects of synthetic oxytocin on plasma concentrations of oxytocin and events during delivery were assessed. Plasma oxytocin concentration was determined in serial samples during the late second stage and throughout the th...

  4. Oxytocin signaling in the medial amygdala is required for sex discrimination of social cues

    OpenAIRE

    Yao, Shenqin; Bergan, Joseph; Lanjuin, Anne; Dulac, Catherine

    2017-01-01

    eLife digest Oxytocin is a hormone that promotes milk production, contractions during childbirth, and many social interactions in humans and other creatures. It has also been implicated in conditions like autism or schizophrenia, which show altered social interactions. Oxytocin is made and released by cells in the brain called neurons. The oxytocin-producing neurons are clustered in a brain region called the hypothalamus, and oxytocin can act over a long distance in the brain or in the body. ...

  5. Oxytocin Differentially Affects Sucrose Taking and Seeking in Male and Female Rats

    OpenAIRE

    Zhou, Luyi; Ghee, Shannon M.; See, Ronald E.; Reichel, Carmela M.

    2015-01-01

    Oxytocin has a modulatory role in natural and drug reward processes. While the role of oxytocin in pair bonding and reproduction has been extensively studied, sex differences in conditioned and unconditioned behavioral responses to oxytocin treatment have not been fully characterized. Here, we determined whether male and female rats would show similar dose response curves in response to acute oxytocin on measures of locomotor activity, sucrose seeking, and sucrose intake. Male and freely cycl...

  6. Oxytocin is required for nursing but is not essential for parturition or reproductive behavior.

    OpenAIRE

    Nishimori, K; Young, L J; Guo, Q; Wang, Z; Insel, T R; Matzuk, M M

    1996-01-01

    Oxytocin, a neurohypophyseal hormone, has been traditionally considered essential for mammalian reproduction. In addition to uterine contractions during labor and milk ejection during nursing, oxytocin has been implicated in anterior pituitary function, paracrine effects in the testis and ovary and the neural control of maternal and sexual behaviors. To determine the essential role(s) of oxytocin in mammalian reproductive function, mice deficient in oxytocin have been generated using embryoni...

  7. Rosmarinic acid counteracts activation of hepatic stellate cells via inhibiting the ROS-dependent MMP-2 activity: Involvement of Nrf2 antioxidant system

    International Nuclear Information System (INIS)

    Lu, Changfang; Zou, Yu; Liu, Yuzhang; Niu, Yingcai

    2017-01-01

    Recently, oxidative stress is involved in hepatofibrogenesis. Matrix metalloproteinase-2 (MMP-2) is required for activation of hepatic stellate cells (HSCs) in response to reactive oxygen species (ROS). This study was designed to explore the hypothesis that the inhibitory effect of rosmarinic acid (RA) on HSCs activation might mainly result from its antioxidant capability by increasing the synthesis of glutathione (GSH) involved in nuclear factor kappa B (NF-κB)-dependent inhibition of MMP-2 activity. Here, we demonstrate that RA reverses activated HSCs to quiescent cells. Concomitantly, RA inhibits MMP-2 activity. RNA interference-imposed knockdown of NF-κB abolished down-regulation of MMP-2 by RA. RA-mediated inactivation of NF-κB could be blocked by the diphenyleneiodonium chloride (DPI; a ROS inhibitor). Conversely, transfection of dominant-negative (DN) mutant of extracellular signal-regulated kinases 2 (ERK2), c-Jun N-terminal kinase 1 (JNK1), or p38α kinase had no such effect. Simultaneously, RA suppresses ROS generation and lipid peroxidation (LPO) whereas increases cellular GSH in HSC-T6 cells. Furthermore, RA significantly increased antioxidant response element (ARE)-mediated luciferase activity, nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and catalytic subunits from glutamate cysteine ligase (GCLc) expression, but not modulatory subunits from GCL (GCLm). RA-mediated up-regulation of GClc is inhibited by the shRNA-induced Nrf2 knockdown. The knocking down of Nrf2 or buthionine sulfoximine (a GCL inhibitor) abolished RA-mediated inhibition of ROS. Collectively, these results provide novel insights into the mechanisms of RA as an antifibrogenic candidate in the prevention and treatment of liver fibrosis. - Highlights: • RA reverses activated HSCs to quiescent cells. • RA suppresses MMP-2 activity through a NF-κB-dependent pathway. • Inhibition of oxidative stress by RA is dependent on nuclear translocation of Nrf2

  8. Rosmarinic acid counteracts activation of hepatic stellate cells via inhibiting the ROS-dependent MMP-2 activity: Involvement of Nrf2 antioxidant system

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Changfang; Zou, Yu; Liu, Yuzhang; Niu, Yingcai, E-mail: nyc1968@126.com

    2017-03-01

    Recently, oxidative stress is involved in hepatofibrogenesis. Matrix metalloproteinase-2 (MMP-2) is required for activation of hepatic stellate cells (HSCs) in response to reactive oxygen species (ROS). This study was designed to explore the hypothesis that the inhibitory effect of rosmarinic acid (RA) on HSCs activation might mainly result from its antioxidant capability by increasing the synthesis of glutathione (GSH) involved in nuclear factor kappa B (NF-κB)-dependent inhibition of MMP-2 activity. Here, we demonstrate that RA reverses activated HSCs to quiescent cells. Concomitantly, RA inhibits MMP-2 activity. RNA interference-imposed knockdown of NF-κB abolished down-regulation of MMP-2 by RA. RA-mediated inactivation of NF-κB could be blocked by the diphenyleneiodonium chloride (DPI; a ROS inhibitor). Conversely, transfection of dominant-negative (DN) mutant of extracellular signal-regulated kinases 2 (ERK2), c-Jun N-terminal kinase 1 (JNK1), or p38α kinase had no such effect. Simultaneously, RA suppresses ROS generation and lipid peroxidation (LPO) whereas increases cellular GSH in HSC-T6 cells. Furthermore, RA significantly increased antioxidant response element (ARE)-mediated luciferase activity, nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and catalytic subunits from glutamate cysteine ligase (GCLc) expression, but not modulatory subunits from GCL (GCLm). RA-mediated up-regulation of GClc is inhibited by the shRNA-induced Nrf2 knockdown. The knocking down of Nrf2 or buthionine sulfoximine (a GCL inhibitor) abolished RA-mediated inhibition of ROS. Collectively, these results provide novel insights into the mechanisms of RA as an antifibrogenic candidate in the prevention and treatment of liver fibrosis. - Highlights: • RA reverses activated HSCs to quiescent cells. • RA suppresses MMP-2 activity through a NF-κB-dependent pathway. • Inhibition of oxidative stress by RA is dependent on nuclear translocation of Nrf2

  9. Oxytocin decreases sweet taste sensitivity in mice.

    Science.gov (United States)

    Sinclair, Michael S; Perea-Martinez, Isabel; Abouyared, Marianne; St John, Steven J; Chaudhari, Nirupa

    2015-03-15

    Oxytocin (OXT) suppresses food intake and lack of OXT leads to overconsumption of sucrose. Taste bud cells were recently discovered to express OXT-receptor. In the present study we tested whether administering OXT to wild-type mice affects their licking behavior for tastants in a paradigm designed to be sensitive to taste perception. We injected C57BL/6J mice intraperitoneally (i.p.) with 10mg/kg OXT and assayed their brief-access lick responses, motivated by water deprivation, to NaCl (300mM), citric acid (20mM), quinine (0.3mM), saccharin (10mM), and a mix of MSG and IMP (100mM and 0.5mM respectively). OXT had no effect on licking for NaCl, citric acid, or quinine. A possible effect of OXT on saccharin and MSG+IMP was difficult to interpret due to unexpectedly low lick rates to water (the vehicle for all taste solutions), likely caused by the use of a high OXT dose that suppressed licking and other behaviors. A subsequent experiment focused on another preferred tastant, sucrose, and employed a much lower OXT dose (0.1mg/kg). This modification, based on our measurements of plasma OXT following i.p. injection, permitted us to elevate plasma [OXT] sufficiently to preferentially activate taste bud cells. OXT at this low dose significantly reduced licking responses to 0.3M sucrose, and overall shifted the sucrose concentration - behavioral response curves rightward (mean EC50saline=0.362M vs. EC50OXT=0.466M). Males did not differ from females under any condition in this study. We propose that circulating oxytocin is another factor that modulates taste-based behavior. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Oxytocin and social affiliation in humans.

    Science.gov (United States)

    Feldman, Ruth

    2012-03-01

    A conceptual model detailing the process of bio-behavioral synchrony between the online physiological and behavioral responses of attachment partners during social contact is presented as a theoretical and empirical framework for the study of affiliative bonds. Guided by an ethological behavior-based approach, we suggest that micro-level social behaviors in the gaze, vocal, affective, and touch modalities are dynamically integrated with online physiological processes and hormonal response to create dyad-specific affiliations. Studies across multiple attachments throughout life are presented and demonstrate that the extended oxytocin (OT) system provides the neurohormonal substrate for parental, romantic, and filial attachment in humans; that the three prototypes of affiliation are expressed in similar constellations of social behavior; and that OT is stable over time within individuals, is mutually-influencing among partners, and that mechanisms of cross-generation and inter-couple transmission relate to coordinated social behavior. Research showing links between peripheral and genetic markers of OT with concurrent parenting and memories of parental care; between administration of OT to parent and infant's physiological readiness for social engagement; and between neuropeptides and the online synchrony of maternal and paternal brain response in social-cognitive and empathy networks support the hypothesis that human attachment develops within the matrix of biological attunement and close behavioral synchrony. The findings have conceptual implications for the study of inter-subjectivity as well as translational implications for the treatment of social disorders originating in early childhood, such as autism spectrum disorders, or those associated with disruptions to early bonding, such as postpartum depression or child abuse and neglect. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior. Copyright © 2012 Elsevier Inc. All

  11. The Haemophilus ducreyi LspA1 protein inhibits phagocytosis by using a new mechanism involving activation of C-terminal Src kinase.

    Science.gov (United States)

    Dodd, Dana A; Worth, Randall G; Rosen, Michael K; Grinstein, Sergio; van Oers, Nicolai S C; Hansen, Eric J

    2014-05-20

    Haemophilus ducreyi causes chancroid, a sexually transmitted infection. A primary means by which this pathogen causes disease involves eluding phagocytosis; however, the molecular basis for this escape mechanism has been poorly understood. Here, we report that the LspA virulence factors of H. ducreyi inhibit phagocytosis by stimulating the catalytic activity of C-terminal Src kinase (Csk), which itself inhibits Src family protein tyrosine kinases (SFKs) that promote phagocytosis. Inhibitory activity could be localized to a 37-kDa domain (designated YL2) of the 456-kDa LspA1 protein. The YL2 domain impaired ingestion of IgG-opsonized targets and decreased levels of active SFKs when expressed in mammalian cells. YL2 contains tyrosine residues in two EPIYG motifs that are phosphorylated in mammalian cells. These tyrosine residues were essential for YL2-based inhibition of phagocytosis. Csk was identified as the predominant mammalian protein interacting with YL2, and a dominant-negative Csk rescued phagocytosis in the presence of YL2. Purified Csk phosphorylated the tyrosines in the YL2 EPIYG motifs. Phosphorylated YL2 increased Csk catalytic activity, resulting in positive feedback, such that YL2 can be phosphorylated by the same kinase that it activates. Finally, we found that the Helicobacter pylori CagA protein also inhibited phagocytosis in a Csk-dependent manner, raising the possibility that this may be a general mechanism among diverse bacteria. Harnessing Csk to subvert the Fcγ receptor (FcγR)-mediated phagocytic pathway represents a new bacterial mechanism for circumventing a crucial component of the innate immune response and may potentially affect other SFK-involved cellular pathways. Phagocytosis is a critical component of the immune system that enables pathogens to be contained and cleared. A number of bacterial pathogens have developed specific strategies to either physically evade phagocytosis or block the intracellular signaling required for

  12. The influence of oxytocin on volitional and emotional ambivalence.

    Science.gov (United States)

    Preckel, Katrin; Scheele, Dirk; Eckstein, Monika; Maier, Wolfgang; Hurlemann, René

    2015-07-01

    Moral decisions and social relationships are often characterized by strong feelings of ambivalence which can be a catalyst for emotional distress and several health-related problems. The anterior cingulate cortex (ACC) has been identified as a key brain region in monitoring conflicting information, but the neurobiological substrates of ambivalence processing are still widely unknown. We have conducted two randomized, double-blind, placebo-controlled, functional magnetic resonance imaging experiments involving 70 healthy male volunteers to investigate the effects of the neuropeptide oxytocin (OXT) on neural and behavioral correlates of ambivalence. We chose moral decision-making and the imagery of partner infidelity as examples to probe volitional and emotional ambivalence. In both experiments, intranasal OXT diminished neural responses in the ACC to ambivalence. Under OXT, moral dilemma vignettes also elicited a reduced activation in the orbitofrontal cortex, and the imagery of partner infidelity was rated as less arousing. Interestingly, the OXT-induced differential activation in the ACC predicted the magnitude of arousal reduction. Taken together, our findings reveal an unprecedented role of OXT in causing a domain-general decrease of neural responses to ambivalence. By alleviating emotional distress, OXT may qualify as a treatment option for psychiatric disorders with heightened ambivalence sensitivity such as schizophrenia or obsessive-compulsive disorder. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  13. Different Neural Networks are Involved in Cross-Modal Non-Spatial Inhibition of Return (IOR: The Effect of the Sensory Modality of Behavioral Targets

    Directory of Open Access Journals (Sweden)

    Qi Chen

    2011-10-01

    Full Text Available We employed a novel cross-modal non-spatial inhibition of return (IOR paradigm with fMRI to investigate whether object concept is organized by supramodal or modality-specific systems. A precue-neutral cue-target sequence was presented and participants were asked to discriminate whether the target was a dog or a cat. The precue and the target could be either a picture or vocalization of a dog or a cat. The neutral cue (bird was always from the same modality as the precue. Behaviorally, for both visual and auditory targets, the main effect of cue validity was the only significant effect, p<0.01, with equivalent effects for within- and cross-modal IOR. Neurally, for visual targets, left inferior frontal gyrus and left medial temporal gyrus showed significantly higher neural activity in cued than uncued condition, irrespective of the precue-target relationship, indicating that the two areas are involved in inhibiting a supramodal representation of previously attended object concept. For auditory targets, left lateral occipital gyrus and right postcentral gyrus showed significantly higher neural activity in uncued than cued condition irrespective of the cue-target relationship, indicating that the two areas are involved in creating a new supramodal representation when a novel object concept appears.

  14. The Involvement of Mutual Inhibition of ERK and mTOR in PLCγ1-Mediated MMP-13 Expression in Human Osteoarthritis Chondrocytes

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    Zejun Liu

    2015-08-01

    Full Text Available The issue of whether ERK activation determines matrix synthesis or degradation in osteoarthritis (OA pathogenesis currently remains controversial. Our previous study shows that PLCγ1 and mTOR are involved in the matrix metabolism of OA cartilage. Investigating the interplays of PLCγ1, mTOR and ERK in matrix degradation of OA will facilitate future attempts to manipulate ERK in OA prevention and therapy. Here, cultured human normal chondrocytes and OA chondrocytes were treated with different inhibitors or transfected with expression vectors, respectively. The levels of ERK, p-ERK, PLCγ1, p-PLCγ1, mTOR, p-mTOR and MMP-13 were then evaluated by Western blotting analysis. The results manifested that the expression level of ERK in human OA chondrocytes was lower than that in human normal articular chondrocytes, and the up-regulation of ERK could promote matrix synthesis, including the decrease in MMP-13 level and the increase in Aggrecan level in human OA chondrocytes. Furthermore, the PLCγ1/ERK axis and a mutual inhibition of mTOR and ERK were observed in human OA chondrocytes. Interestingly, activated ERK had no inhibitory effect on MMP-13 expression in PLCγ1-transformed OA chondrocytes. Combined with our previous study, the non-effective state of ERK activation by PLCγ1 on MMP-13 may be partly attributed to the inhibition of the PLCγ1/mTOR axis on the PLCγ1/ERK axis. Therefore, the study indicates that the mutual inhibition of ERK and mTOR is involved in PLCγ1-mediated MMP-13 expression in human OA chondrocytes, with important implication for the understanding of OA pathogenesis as well as for its prevention and therapy.

  15. Taking the Focus Away from the Self: Low Individualism Mediates the Effect of Oxytocin on Creativity

    Science.gov (United States)

    Pfundmair, Michaela; Frey, Dieter; Hodgson, Timothy L.

    2017-01-01

    Recently, it has been shown that the hormone oxytocin can enable creative cognition. The aim of this investigation was to examine the psychological mechanism via which oxytocin influences creativity. Two opposing explanatory approaches suggested by previous research were investigated: It was predicted that the effect of oxytocin on creativity…

  16. Oxytocin differentially affects sucrose taking and seeking in male and female rats.

    Science.gov (United States)

    Zhou, Luyi; Ghee, Shannon M; See, Ronald E; Reichel, Carmela M

    2015-04-15

    Oxytocin has a modulatory role in natural and drug reward processes. While the role of oxytocin in pair bonding and reproduction has been extensively studied, sex differences in conditioned and unconditioned behavioral responses to oxytocin treatment have not been fully characterized. Here, we determined whether male and female rats would show similar dose response curves in response to acute oxytocin on measures of locomotor activity, sucrose seeking, and sucrose intake. Male and freely cycling female rats received vehicle or oxytocin (0.1, 0.3, 1, 3mg/kg, IP) injections before behavioral tests designed to assess general motor activity, as well as sucrose self-administration and seeking. Lower doses of oxytocin decreased motor activity in a novel environment in females relative to males. Likewise, lower doses of oxytocin in females decreased responding for sucrose during maintenance of sucrose self-administration and reinstatement to sucrose-conditioned cues. However, sucrose seeking in response to a sucrose prime was only decreased by the highest oxytocin dose in both sexes. In general, oxytocin had similar effects in both sexes. However, females were more sensitive to lower doses of oxytocin than males. These findings are consistent with the notion that oxytocin regulates many of the same behaviors in males and females, but that the effects are typically more profound in females. Therapeutic use of oxytocin should include sex as a factor in determining dose regimens. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Aspartate buffer and divalent metal ions affect oxytocin in aqueous solution and protect it from degradation

    DEFF Research Database (Denmark)

    Avanti, Christina; Oktaviani, Nur Alia; Hinrichs, Wouther L.J.

    2013-01-01

    Oxytocin is a peptide drug used to induce labor and prevent bleeding after childbirth. Due to its instability, transport and storage of oxytocin formulations under tropical conditions is problematic. In a previous study, we have found that the stability of oxytocin in aspartate buffered formulati...

  18. Endogenous peripheral oxytocin measures can give insight into the dynamics of social relationships: a review

    Directory of Open Access Journals (Sweden)

    Catherine eCrockford

    2014-03-01

    Full Text Available The neuropeptide, oxytocin, receives increasing attention due to its role in stress regulation and promoting affiliative social behavior. Research across mammals points to a complex pattern whereby social context and individual differences moderate the endogenous release of oxytocin as well as moderate the effects that exogenous administration of oxytocin has on social behavior. In addition to measuring central release of oxytocin or exogenous administration of oxytocin on social behavior, for example via inhalation, it is becoming evident that measuring endogenous peripheral oxytocin levels is an additional, informative tool. This is particularly so when oxytocin can be measured from non-invasively collected samples, such as in urine. Although it is still debated as to whether peripheral measures of oxytocin relate to central measures of oxytocin, anatomical and functional evidence indicate a link between the two. We argue that non-invasive measures of peripheral oxytocin hold several research and potential therapeutic advantages. Principally, study subjects can be sampled repeatedly in different social contexts where social history between interaction partners can be taken into account. Several hormones can be measured simultaneously allowing examination of the influence of oxytocin interactions with other hormones on motivational states. Valence of relationships as well as changes in relationship quality over time can be measured through endocrine responses. Also, the approach of identifying natural social contexts that are associated with endogenous oxytocin release offers the potential of behavioral therapy as an addition or alternative to chemical therapy in the field of mental health.

  19. Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal

    NARCIS (Netherlands)

    Riem, M.M.E.; van IJzendoorn, M.H.; Tops, M.; Boksem, M.A.S.; Rombouts, S.A.R.B.; Bakermans-Kranenburg, M.J.

    2013-01-01

    The neuropeptide oxytocin has been implicated in a variety of social processes. However, recent studies indicate that oxytocin does not enhance prosocial behavior in all people in all circumstances. Here, we investigate effects of intranasal oxytocin administration on intrinsic functional brain

  20. Aspartate buffer and divalent metal ions affect oxytocin in aqueous solution and protect it from degradation

    NARCIS (Netherlands)

    Avanti, Christina; Oktaviani, Nur Alia; Hinrichs, Wouter L J; Frijlink, Henderik W; Mulder, Frans A A

    2013-01-01

    Oxytocin is a peptide drug used to induce labor and prevent bleeding after childbirth. Due to its instability, transport and storage of oxytocin formulations under tropical conditions is problematic. In a previous study, we have found that the stability of oxytocin in aspartate buffered formulation

  1. MDMA ('Ecstasy'), oxytocin and vasopressin modulate social preference in rats: A role for handling and oxytocin receptors.

    Science.gov (United States)

    Ramos, Linnet; Hicks, Callum; Caminer, Alex; Couto, Kalliu; Narlawar, Rajeshwar; Kassiou, Michael; McGregor, Iain S

    In laboratory rats, peripheral administration of the neuropeptides oxytocin (OT) and vasopressin (AVP) induces similar prosocial effects (i.e. increased adjacent lying) to the party drug 3,4-methylenedioxymethamphetamine (MDMA), which are sensitive to vasopressin V 1A receptor (V 1A R) antagonism. Here, we employed a social preference paradigm to further compare the prosocial effects of OT, AVP and MDMA. We also investigated the possible involvement of the V 1A R and oxytocin receptor (OTR) in rodent social preference. The social preference paradigm measures investigation times towards an empty wire cage (presented for 4min) followed by an identical cage containing a novel rat (also presented for 4min). Social preference is defined as greater investigation time towards the inhabited cage than the empty cage. Results indicated that well-handled rats exhibited no social preference at baseline, while intraperitoneally injected MDMA (5mg/kg), OT (0.5mg/kg) and AVP (0.005mg/kg) increased social preference. However, this effect was primarily due to reduced investigation of the empty cage. In contrast, rats that received minimal prior handling displayed a social preference at baseline, while MDMA (5mg/kg), OT (0.5mg/kg) and AVP (0.005mg/kg) reduced investigation times towards both the empty and inhabited cages. Lower doses of MDMA, OT and AVP were ineffective. The OTR antagonist Compound 25 (C25, 5mg/kg), but not the V 1A R antagonist SR49059 (1mg/kg), reduced the baseline social preference seen in minimally-handled rats and prevented the social preference induced by OT and AVP (but not MDMA) in well-handled rats. Overall, these results further confirm prosocial actions of MDMA, OT and AVP, which are dependent on handling history. These findings also indicate that social preference is sensitive to OTR rather than V 1A R modulation. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Rab3A Inhibition of Ca2+ -Dependent Dopamine Release From PC12 Cells Involves Interaction With Synaptotagmin I.

    Science.gov (United States)

    Dai, Zhipan; Tang, Xia; Chen, Jia; Tang, Xiaochao; Wang, Xianchun

    2017-11-01

    Rab3 and synaptotagmin have been suggested to play important roles in the regulation of neurotransmitter release and, however, the molecular mechanism has not been completely clear. Here, we studied the effects of Rab3A and synaptotagmin I (Syt I) on dopamine release using PC12 cells as a model system. Rab3A was demonstrated to have effects on both Ca 2+ -independent and Ca 2+ -dependent dopamine releases from the PC12 cells. Application of Rab3A (up to 2500 nM) gradually decreased the amount of Ca 2+ -dependently released dopamine, indicating that Rab3A is a negative modulator that was further supported by the increase in dopamine release caused by Rab3A knockdown. Syt I knockdown weakened the Ca 2+ -dependent dopamine release, suggesting that Syt I plays a positive regulatory role in the cellular process. Treatment of the Syt I-knocked down PC12 cells with Rab3A further decreased Ca 2+ -dependent dopamine release and, however, the decrease magnitude was significantly reduced compared with that before Syt I knockdown, thus for the first time demonstrating that the inhibitory effect of Rab3A on Ca 2+ -dependent dopamine release involves the interaction with Syt I. This work has shed new light on the molecular mechanism for Rab3 and synaptotamin regulation of neurotransmitter release. J. Cell. Biochem. 118: 3696-3705, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. Inhibition of GABAergic Neurotransmission by HIV-1 Tat and Opioid Treatment in the Striatum Involves μ-opioid Receptors

    Directory of Open Access Journals (Sweden)

    Changqing Xu

    2016-11-01

    Full Text Available Due to combined antiretroviral therapy (cART, human immunodeficiency virus type 1 (HIV-1 is considered a chronic disease with high prevalence of mild forms of neurocognitive impairments, also referred to as HIV-associated neurocognitive disorders (HAND. Although opiate drug use can exacerbate HIV-1 Tat-induced neuronal damage, it remains unknown how and to what extent opioids interact with Tat on the GABAergic system. We conducted whole-cell recordings in mouse striatal slices and examined the effects of HIV-1 Tat in the presence and absence of morphine (1 μM and damgo (1 μM on GABAergic neurotransmission. Results indicated a decrease in the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs and miniature IPSCs (mIPSCs by Tat (5 – 50 nM in a concentration-dependent manner. The significant Tat-induced decrease in IPSCs was abolished when removing extracellular and/or intracellular calcium. Treatment with morphine or damgo alone significantly decreased the frequency, but not amplitude of IPSCs. Interestingly, morphine but not damgo indicated an additional downregulation of the mean frequency of mIPSCs in combination with Tat. Pretreatment with naloxone (1 μM and CTAP (1 μM prevented the Tat-induced decrease in sIPSCs frequency but only naloxone prevented the combined Tat and morphine effect on mIPSCs frequency. Results indicate a Tat- or opioid-induced decrease in GABAergic neurotransmission via µ-opioid receptors with combined Tat and morphine effects involving additional opioid receptor-related mechanisms. Exploring the interactions between Tat and opioids on the GABAergic system may help to guide future research on HAND in the context of opiate drug use.

  4. Inhibition of hydrogen sulfide on the proliferation of vascular smooth muscle cells involved in the modulation of calcium sensing receptor in high homocysteine

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yuwen; Wang, Xiyao [Department of Clinical Laboratory, The second Affiliated Hospital of Harbin Medical University, Harbin 150081 (China); Liang, Xiaohui [Department of Radiology, Central Hospital of the Red Cross, Harbin 150080 (China); Wu, Jichao; Dong, Shiyun; Li, Hongzhu [Department of Pathophysiology, Harbin Medical University, Harbin 150081 (China); Jin, Meili [Department of Clinical Laboratory, The second Affiliated Hospital of Harbin Medical University, Harbin 150081 (China); Sun, Dianjun [Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150086 (China); Zhang, Weihua [Department of Pathophysiology, Harbin Medical University, Harbin 150081 (China); Zhong, Xin, E-mail: xzhong1111@163.com [Department of Pathophysiology, Harbin Medical University, Harbin 150081 (China)

    2016-09-10

    Hyperhomocysteinemia induces the proliferation of vascular smooth muscle cells (VSMCs). Hydrogen sulfide (H{sub 2}S) inhibits the phenotype switch of VSMCs and calcium-sensing receptor (CaSR) regulated the production of endogenous H{sub 2}S. However, whether CaSR inhibits the proliferation of VSMCs by regulating the endogenous cystathionine-gamma-lyase (CSE, a major enzyme that produces H{sub 2}S) pathway in high homocysteine (HHcy) has not been previously investigated. The intracellular calcium concentration, the concentration of H{sub 2}S, the cell viability, the proliferation and the expression of proteins of cultured VSMCs from rat thoracic aortas were measured, respectively. The results showed that the [Ca{sup 2+}]{sub i} and the expression of p-CaMK and CSE increased upon treatment with CaSR agonist. In HHcy, the H{sub 2}S concentration decrease, the proliferation and migration rate increased, the expression of Cyclin D1, PCNA, Osteopontin and p-Erk1/2 increased while the α-SM actin, P21{sup Cip/WAK−1} and Calponin decreased. The CaSR agonist or exogenous H{sub 2}S significantly reversed the changes of VSMCs caused by HHcy. In conclusion, our results demonstrated that CaSR regulate the endogenous CSE/H{sub 2}S is related to the PLC-IP{sub 3} receptor and CaM signal pathways which inhibit the proliferation of VSMCs, and the latter is involved in the Erk1/2 dependent signal pathway in high homocysteine. - Highlights: • CaSR activation increased the production of endogenous H{sub 2}S in high homocysteine VSMCs. • CaSR modulated the CSE/H{sub 2}S are related to the PLC-IP{sub 3}R and Ca{sup 2+}-CaM signal pathways. • Inhibition of H{sub 2}S on the proliferation of VSMCs is involved in the Erk1/2 pathway. • Explore the potential roles of CaSR in regulating VSMCs proliferation in high homocysteine.

  5. Approaches Mediating Oxytocin Regulation of the Immune System.

    Science.gov (United States)

    Li, Tong; Wang, Ping; Wang, Stephani C; Wang, Yu-Feng

    2016-01-01

    The hypothalamic neuroendocrine system is mainly composed of the neural structures regulating hormone secretion from the pituitary gland and has been considered as the higher regulatory center of the immune system. Recently, the hypothalamo-neurohypophysial system (HNS) emerged as an important component of neuroendocrine-immune network, wherein the oxytocin (OT)-secreting system (OSS) plays an essential role. The OSS, consisting of OT neurons in the supraoptic nucleus, paraventricular nucleus, their several accessory nuclei and associated structures, can integrate neural, endocrine, metabolic, and immune information and plays a pivotal role in the development and functions of the immune system. The OSS can promote the development of thymus and bone marrow, perform immune surveillance, strengthen immune defense, and maintain immune homeostasis. Correspondingly, OT can inhibit inflammation, exert antibiotic-like effect, promote wound healing and regeneration, and suppress stress-associated immune disorders. In this process, the OSS can release OT to act on immune system directly by activating OT receptors or through modulating activities of other hypothalamic-pituitary-immune axes and autonomic nervous system indirectly. However, our understandings of the role of the OSS in neuroendocrine regulation of immune system are largely incomplete, particularly its relationship with other hypothalamic-pituitary-immune axes and the vasopressin-secreting system that coexists with the OSS in the HNS. In addition, it remains unclear about the relationship between the OSS and peripherally produced OT in immune regulation, particularly intrathymic OT that is known to elicit central immunological self-tolerance of T-cells to hypophysial hormones. In this work, we provide a brief review of current knowledge of the features of OSS regulation of the immune system and of potential approaches that mediate OSS coordination of the activities of entire neuroendocrine-immune network.

  6. Increased Serum and Urinary Oxytocin Concentrations after Nasal Administration in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Andrea Temesi

    2017-09-01

    Full Text Available In recent years more and more studies have revealed the effect of extraneous oxytocin on the social behavior of dogs. The distribution of administered oxytocin in different physiologically relevant compartments is important because this knowledge forms the basis for the timing of behavior tests after the administration. Most behavioral studies rely on the non-invasive intranasal application of oxytocin. The aim of this study was to determine the time course of intranasal administered oxytocin secretion into blood and urine and also establish a connection between intranasal received oxytocin and urinary cortisol in dogs. In our experiment, four dogs received three puffs, 12 IU intranasal oxytocin treatment, two dogs received three puffs intranasal placebo treatment. Blood and urine samples were collected immediately prior to the administration then regularly during 4 h. After nasal oxytocin application, the serum oxytocin concentration increased, reached a maximum 15 min after the treatment and then rapidly returned to baseline levels 45 min later. The peak urinary oxytocin concentration occurred between 45 and 60 min after administration and returned to baseline levels slowly. We found considerable differences among individuals in the secretion of oxytocin in both the serum and the urinary oxytocin concentration measurements. Our results confirm that intranasally administered oxytocin passes into the blood stream. The time course of intranasally administered oxytocin secretion is similar to the time course of intravenously administered oxytocin secretion, and the peak values are also similar in both the serum and the urinary oxytocin concentration measurements, although there are large individual differences.

  7. Evidence for a role of the oxytocin system, indexed by genetic variation in CD38, in the social bonding effects of expressed gratitude.

    Science.gov (United States)

    Algoe, Sara B; Way, Baldwin M

    2014-12-01

    Oxytocin is thought to play a central role in promoting close social bonds via influence on social interactions. The current investigation targeted interactions involving expressed gratitude between members of romantic relationships because recent evidence suggests gratitude and its expression provides behavioral and psychological 'glue' to bind individuals closer together. Specifically, we took a genetic approach to test the hypothesis that social interactions involving expressed gratitude would be associated with variation in a gene, CD38, which has been shown to affect oxytocin secretion. A polymorphism (rs6449182) that affects CD38 expression was significantly associated with global relationship satisfaction, perceived partner responsiveness and positive emotions (particularly love) after lab-based interactions, observed behavioral expression of gratitude toward a romantic partner in the lab, and frequency of expressed gratitude in daily life. A separate polymorphism in CD38 (rs3796863) previously associated with plasma oxytocin levels and social engagement was also associated with perceived responsiveness in the benefactor after an expression of gratitude. The combined influence of the two polymorphisms was associated with a broad range of gratitude-related behaviors and feelings. The consistent pattern of findings suggests that the oxytocin system is associated with solidifying the glue that binds adults into meaningful and important relationships. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  8. Emotion recognition and oxytocin in patients with schizophrenia

    Science.gov (United States)

    Averbeck, B. B.; Bobin, T.; Evans, S.; Shergill, S. S.

    2012-01-01

    Background Studies have suggested that patients with schizophrenia are impaired at recognizing emotions. Recently, it has been shown that the neuropeptide oxytocin can have beneficial effects on social behaviors. Method To examine emotion recognition deficits in patients and see whether oxytocin could improve these deficits, we carried out two experiments. In the first experiment we recruited 30 patients with schizophrenia and 29 age- and IQ-matched control subjects, and gave them an emotion recognition task. Following this, we carried out a second experiment in which we recruited 21 patients with schizophrenia for a double-blind, placebo-controlled cross-over study of the effects of oxytocin on the same emotion recognition task. Results In the first experiment we found that patients with schizophrenia had a deficit relative to controls in recognizing emotions. In the second experiment we found that administration of oxytocin improved the ability of patients to recognize emotions. The improvement was consistent and occurred for most emotions, and was present whether patients were identifying morphed or non-morphed faces. Conclusions These data add to a growing literature showing beneficial effects of oxytocin on social–behavioral tasks, as well as clinical symptoms. PMID:21835090

  9. Oxytocin receptor gene variation predicts subjective responses to MDMA.

    Science.gov (United States)

    Bershad, Anya K; Weafer, Jessica J; Kirkpatrick, Matthew G; Wardle, Margaret C; Miller, Melissa A; de Wit, Harriet

    2016-12-01

    3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") enhances desire to socialize and feelings of empathy, which are thought to be related to increased oxytocin levels. Thus, variation in the oxytocin receptor gene (OXTR) may influence responses to the drug. Here, we examined the influence of a single OXTR nucleotide polymorphism (SNP) on responses to MDMA in humans. Based on findings that carriers of the A allele at rs53576 exhibit reduced sensitivity to oxytocin-induced social behavior, we hypothesized that these individuals would show reduced subjective responses to MDMA, including sociability. In this three-session, double blind, within-subjects study, healthy volunteers with past MDMA experience (N = 68) received a MDMA (0, 0.75 mg/kg, and 1.5 mg/kg) and provided self-report ratings of sociability, anxiety, and drug effects. These responses were examined in relation to rs53576. MDMA (1.5 mg/kg) did not increase sociability in individuals with the A/A genotype as it did in G allele carriers. The genotypic groups did not differ in responses at the lower MDMA dose, or in cardiovascular or other subjective responses. These findings are consistent with the idea that MDMA-induced sociability is mediated by oxytocin, and that variation in the oxytocin receptor gene may influence responses to the drug.

  10. The influence of oxytocin on interpersonal rhythmic synchronization and social bonding

    DEFF Research Database (Denmark)

    Gebauer, Line; Witek, Maria; Hansen, Niels Chr.

    oxytocin. In this study we investigated the role of oxytocin on interpersonal rhythmic synchronization, and its relation to pro-social effects, using an interactive finger tapping setup. Pairs of two tapped together, and both participants in each pair received either oxytocin or a non-active placebo...... as nasal spray. Our preliminary analyses showed trends in which intranasally administered oxytocin improved interpersonal synchronization. In this poster we present the full data set and analysis of the effect of oxytocin on interpersonal synchronization and social bonding....

  11. Social evolution. Oxytocin-gaze positive loop and the coevolution of human-dog bonds.

    Science.gov (United States)

    Nagasawa, Miho; Mitsui, Shouhei; En, Shiori; Ohtani, Nobuyo; Ohta, Mitsuaki; Sakuma, Yasuo; Onaka, Tatsushi; Mogi, Kazutaka; Kikusui, Takefumi

    2015-04-17

    Human-like modes of communication, including mutual gaze, in dogs may have been acquired during domestication with humans. We show that gazing behavior from dogs, but not wolves, increased urinary oxytocin concentrations in owners, which consequently facilitated owners' affiliation and increased oxytocin concentration in dogs. Further, nasally administered oxytocin increased gazing behavior in dogs, which in turn increased urinary oxytocin concentrations in owners. These findings support the existence of an interspecies oxytocin-mediated positive loop facilitated and modulated by gazing, which may have supported the coevolution of human-dog bonding by engaging common modes of communicating social attachment. Copyright © 2015, American Association for the Advancement of Science.

  12. Morus alba and active compound oxyresveratrol exert anti-inflammatory activity via inhibition of leukocyte migration involving MEK/ERK signaling.

    Science.gov (United States)

    Chen, Yi-Ching; Tien, Yin-Jing; Chen, Chun-Houh; Beltran, Francesca N; Amor, Evangeline C; Wang, Ran-Juh; Wu, Den-Jen; Mettling, Clément; Lin, Yea-Lih; Yang, Wen-Chin

    2013-02-23

    Morus alba has long been used in traditional Chinese medicine to treat inflammatory diseases; however, the scientific basis for such usage and the mechanism of action are not well understood. This study investigated the action of M. alba on leukocyte migration, one key step in inflammation. Gas chromatography-mass spectrometry (GC-MS) and cluster analyses of supercritical CO2 extracts of three Morus species were performed for chemotaxonomy-aided plant authentication. Phytochemistry and CXCR4-mediated chemotaxis assays were used to characterize the chemical and biological properties of M. alba and its active compound, oxyresveratrol. fluorescence-activated cell sorting (FACS) and Western blot analyses were conducted to determine the mode of action of oxyresveratrol. Chemotaxonomy was used to help authenticate M. alba. Chemotaxis-based isolation identified oxyresveratrol as an active component in M. alba. Phytochemical and chemotaxis assays showed that the crude extract, ethyl acetate fraction and oxyresveratrol from M. alba suppressed cell migration of Jurkat T cells in response to SDF-1. Mechanistic study indicated that oxyresveratrol diminished CXCR4-mediated T-cell migration via inhibition of the MEK/ERK signaling cascade. A combination of GC-MS and cluster analysis techniques are applicable for authentication of the Morus species. Anti-inflammatory benefits of M. alba and its active compound, oxyresveratrol, may involve the inhibition of CXCR-4-mediated chemotaxis and MEK/ERK pathway in T and other immune cells.

  13. Oxytocin and MDMA ('Ecstasy') enhance social reward in rats.

    Science.gov (United States)

    Ramos, Linnet; Hicks, Callum; Caminer, Alex; Goodwin, Jack; McGregor, Iain S

    2015-07-01

    Oxytocin (OT), vasopressin (AVP) and 3,4 methylenedioxymethamphetamine (MDMA, 'Ecstasy') all increase social interaction in rats, perhaps by enhancing the rewarding value of social encounters. Here, we used the conditioned place preference (CPP) paradigm to assess the intrinsic rewarding effects of OT, AVP and MDMA, and whether these effects are enhanced by the presence of a conspecific, or a dynamic, tactile object (a tennis ball). Adult male rats received conditioning sessions in a CPP apparatus twice a day (vehicle at 10 a.m., drug at 3 p.m.). Experiment 1 involved conditioning with OT (0.5 mg/kg, intraperitoneal (i.p.)), AVP (0.005 mg/kg, i.p.) or MDMA (5 mg/kg, i.p.). Experiments 2 and 3 involved conditioning with the same treatments but in the presence of a conspecific receiving the same treatment (social-CPP) or in the presence of a tennis ball (object-CPP), respectively. Conditioned place preference was assessed 24 h, 2 weeks and 4 weeks later. OT, AVP and MDMA did not produce a conventional CPP. However, when the conditioning environment also contained a conspecific both OT and MDMA induced a significant CPP lasting for at least 4 weeks. Rats given OT and MDMA also developed a more modest yet significant CPP for the environment where they encountered a tennis ball. These results indicate that OT and MDMA can augment the rewarding effects of social interaction, but also interaction with a dynamic and tactile non-social object. AVP does not condition social- or object-CPPs and may promote social proximity by inducing generalized anxiety and defensive aggregation.

  14. Characterization of the oxytocin system regulating affiliative behavior in female prairie voles.

    Science.gov (United States)

    Ross, H E; Cole, C D; Smith, Y; Neumann, I D; Landgraf, R; Murphy, A Z; Young, L J

    2009-09-15

    Oxytocin regulates partner preference formation and alloparental behavior in the socially monogamous prairie vole (Microtus ochrogaster) by activating oxytocin receptors in the nucleus accumbens of females. Mating facilitates partner preference formation, and oxytocin-immunoreactive fibers in the nucleus accumbens have been described in prairie voles. However, there has been no direct evidence of oxytocin release in the nucleus accumbens during sociosexual interactions, and the origin of the oxytocin fibers is unknown. Here we show for the first time that extracellular concentrations of oxytocin are increased in the nucleus accumbens of female prairie vole during unrestricted interactions with a male. We further show that the distribution of oxytocin-immunoreactive fibers in the nucleus accumbens is conserved in voles, mice and rats, despite remarkable species differences in oxytocin receptor binding in the region. Using a combination of site-specific and peripheral infusions of the retrograde tracer Fluorogold, we demonstrate that the nucleus accumbens oxytocin-immunoreactive fibers likely originate from paraventricular and supraoptic hypothalamic neurons. This distribution of retrogradely labeled neurons is consistent with the hypothesis that striatal oxytocin fibers arise from collaterals of magnocellular neurons of the neurohypophysial system. If correct, this may serve to coordinate peripheral and central release of oxytocin with appropriate behavioral responses associated with reproduction, including pair bonding after mating, and maternal responsiveness following parturition and during lactation.

  15. Neuroendocrine and cardiovascular parameters during simulation of stress-induced rise in circulating oxytocin in the rat.

    Science.gov (United States)

    Ondrejcakova, M; Bakos, J; Garafova, A; Kovacs, L; Kvetnansky, R; Jezova, D

    2010-07-01

    Physiological functions of oxytocin released during stress are not well understood. We have (1) investigated the release of oxytocin during chronic stress using two long-term stress models and (2) simulated stress-induced oxytocin secretion by chronic treatment with oxytocin via osmotic minipumps. Plasma oxytocin levels were significantly elevated in rats subjected to acute immobilization stress for 120 min, to repeated immobilization for 7 days and to combined chronic cold stress exposure for 28 days with 7 days immobilization. To simulate elevation of oxytocin during chronic stress, rats were implanted with osmotic minipumps subcutaneously and treated with oxytocin (3.6 microg/100 g body weight/day) or vehicle for 2 weeks. Chronic subcutaneous oxytocin infusion led to an increase in plasma oxytocin, adrenocorticotropic hormone, corticosterone, adrenal weights and heart/body weight ratio. Oxytocin treatment had no effect on the incorporation of 5-bromo-2-deoxyuridine into DNA in the heart ventricle. Mean arterial pressure response to intravenous phenylephrine was reduced in oxytocin-treated animals. Decrease in adrenal tyrosin hydroxylase mRNA following oxytocin treatment was not statistically significant. Oxytocin treatment failed to modify food intake and slightly increased water consumption. These data provide evidence on increased concentrations of oxytocin during chronic stress. It is possible that the role of oxytocin released during stress is in modulating hypothalamic-pituitary-adrenocortical axis and selected sympathetic functions.

  16. Targeting the Oxytocin System to Treat Addictive Disorders: Rationale and Progress to Date

    Science.gov (United States)

    Lee, Mary R.; Rohn, Matthew C.H.; Tanda, Gianluigi; Leggio, Lorenzo

    2016-01-01

    The neuropeptide oxytocin plays a role in reward, stress, social affiliation, learning and memory processes. As such there is increasing interest in oxytocin as a potential treatment for addictions. The oxytocin system is itself altered by acute or chronic exposure to drugs of abuse. A large number of preclinical studies in rodents have investigated the effect of oxytocin on various drug-induced behaviors to determine whether oxytocin can reverse the neuroadaptations occurring with repeated drug and alcohol use. In addition, the mechanisms by which oxytocin acts to modify the behavioral response to drugs of abuse are beginning to be understood. More recently, a few small clinical studies have been conducted in cocaine, cannabis and alcohol dependence. This review summarizes the preclinical as well as clinical literature to date on the oxytocin system and its relevance to drug and alcohol addiction. PMID:26932552

  17. Investigation of Oxytocin Secretion in Anorexia Nervosa and Bulimia Nervosa: Relationships to Temperament Personality Dimensions.

    Science.gov (United States)

    Monteleone, Alessio Maria; Scognamiglio, Pasquale; Volpe, Umberto; Di Maso, Virginia; Monteleone, Palmiero

    2016-01-01

    Published studies suggested an implication of oxytocin in some temperament characteristics of personality. Therefore, we measured oxytocin secretion in 23 women with anorexia nervosa (AN), 27 with bulimia nervosa (BN) and 19 healthy controls and explored the relationships between circulating oxytocin and patients' personality traits. Plasma oxytocin levels were significantly reduced in AN women but not in BN ones. In healthy women, the attachment subscale scores of the reward dependence temperament and the harm avoidance (HA) scores explained 82% of the variability in circulating oxytocin. In BN patients, plasma oxytocin resulted to be negatively correlated with HA, whereas no significant correlations emerged in AN patients. These findings confirm a dysregulation of oxytocin production in AN but not in BN and show, for the first time, a disruption of the associations between hormone levels and patients' temperament traits, which may have a role in certain deranged behaviours of eating disorder patients. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

  18. Inhibition of hypoxia-associated response and kynurenine production in response to hyperbaric oxygen as mechanisms involved in protection against experimental cerebral malaria.

    Science.gov (United States)

    Bastos, Marcele F; Kayano, Ana Carolina A V; Silva-Filho, João Luiz; Dos-Santos, João Conrado K; Judice, Carla; Blanco, Yara C; Shryock, Nathaniel; Sercundes, Michelle K; Ortolan, Luana S; Francelin, Carolina; Leite, Juliana A; Oliveira, Rafaella; Elias, Rosa M; Câmara, Niels O S; Lopes, Stefanie C P; Albrecht, Letusa; Farias, Alessandro S; Vicente, Cristina P; Werneck, Claudio C; Giorgio, Selma; Verinaud, Liana; Epiphanio, Sabrina; Marinho, Claudio R F; Lalwani, Pritesh; Amino, Rogerio; Aliberti, Julio; Costa, Fabio T M

    2018-03-20

    Cerebral malaria (CM) is a multifactorial syndrome involving an exacerbated proinflammatory status, endothelial cell activation, coagulopathy, hypoxia, and accumulation of leukocytes and parasites in the brain microvasculature. Despite significant improvements in malaria control, 15% of mortality is still observed in CM cases, and 25% of survivors develop neurologic sequelae for life-even after appropriate antimalarial therapy. A treatment that ameliorates CM clinical signs, resulting in complete healing, is urgently needed. Previously, we showed a hyperbaric oxygen (HBO)-protective effect against experimental CM. Here, we provide molecular evidence that HBO targets brain endothelial cells by decreasing their activation and inhibits parasite and leukocyte accumulation, thus improving cerebral microcirculatory blood flow. HBO treatment increased the expression of aryl hydrocarbon receptor over hypoxia-inducible factor 1-α (HIF-1α), an oxygen-sensitive cytosolic receptor, along with decreased indoleamine 2,3-dioxygenase 1 expression and kynurenine levels. Moreover, ablation of HIF-1α expression in endothelial cells in mice conferred protection against CM and improved survival. We propose that HBO should be pursued as an adjunctive therapy in CM patients to prolong survival and diminish deleterious proinflammatory reaction. Furthermore, our data support the use of HBO in therapeutic strategies to improve outcomes of non-CM disorders affecting the brain.-Bastos, M. F., Kayano, A. C. A. V., Silva-Filho, J. L., Dos-Santos, J. C. K., Judice, C., Blanco, Y. C., Shryock, N., Sercundes, M. K., Ortolan, L. S., Francelin, C., Leite, J. A., Oliveira, R., Elias, R. M., Câmara, N. O. S., Lopes, S. C. P., Albrecht, L., Farias, A. S., Vicente, C. P., Werneck, C. C., Giorgio, S., Verinaud, L., Epiphanio, S., Marinho, C. R. F., Lalwani, P., Amino, R., Aliberti, J., Costa, F. T. M. Inhibition of hypoxia-associated response and kynurenine production in response to hyperbaric oxygen

  19. Oxytocin increases the influence of public service advertisements.

    Directory of Open Access Journals (Sweden)

    Pei-Ying Lin

    Full Text Available This paper presents a neurophysiologic model of effective public service advertisements (PSAs and reports two experiments that test the model. In Experiment 1, we show that after watching 16 PSAs participants who received oxytocin, compared to those given a placebo, donated to 57% more causes, donated 56% more money, and reported 17% greater concern for those in the ads. In Experiment 2, we measured adrenocorticotropin hormone (ACTH and oxytocin levels in blood before and after participants watched a PSA. As predicted by the model, donations occurred when participants had increases in both ACTH and oxytocin. Our results indicate that PSAs with social content that cause OT release will be more effective than those that do not. Our results also explain why some individuals do not respond to PSAs.

  20. Oxytocin increases the influence of public service advertisements.

    Science.gov (United States)

    Lin, Pei-Ying; Grewal, Naomi Sparks; Morin, Christophe; Johnson, Walter D; Zak, Paul J

    2013-01-01

    This paper presents a neurophysiologic model of effective public service advertisements (PSAs) and reports two experiments that test the model. In Experiment 1, we show that after watching 16 PSAs participants who received oxytocin, compared to those given a placebo, donated to 57% more causes, donated 56% more money, and reported 17% greater concern for those in the ads. In Experiment 2, we measured adrenocorticotropin hormone (ACTH) and oxytocin levels in blood before and after participants watched a PSA. As predicted by the model, donations occurred when participants had increases in both ACTH and oxytocin. Our results indicate that PSAs with social content that cause OT release will be more effective than those that do not. Our results also explain why some individuals do not respond to PSAs.

  1. Measuring virgin female aggression in the female intruder test (FIT): effects of oxytocin, estrous cycle, and anxiety.

    Science.gov (United States)

    de Jong, Trynke R; Beiderbeck, Daniela I; Neumann, Inga D

    2014-01-01

    The costs of violence and aggression in our society have stimulated the scientific search for the predictors and causes of aggression. The majority of studies have focused on males, which are considered to be more aggressive than females in most species. However, rates of offensive behavior in girls and young women are considerable and are currently rising in Western society. The extrapolation of scientific results from males to young, non-maternal females is a priori limited, based on the profound sex differences in brain areas and functioning of neurotransmitters involved in aggression. Therefore, we established a paradigm to assess aggressive behavior in young virgin female rats, i.e. the female intruder test (FIT). We found that approximately 40% of un-manipulated adult (10-11 weeks old) female Wistar rats attack an intruder female during the FIT, independent of their estrous phase or that of their intruder. In addition, adolescent (7-8 weeks old) female rats selected for high anxiety behavior (HABs) displayed significantly more aggression than non-selected (NAB) or low-anxiety (LAB) rats. Intracerebroventricular infusion of oxytocin (OXT, 0.1 µg/5 µl) inhibited aggressive behavior in adult NAB and LAB, but not HAB females. Adolescent NAB rats that had been aggressive towards their intruder showed increased pERK immunoreactivity (IR) in the hypothalamic attack area and reduced pERK-IR in OXT neurons in the paraventricular hypothalamic nucleus compared to non-aggressive NAB rats. Taken together, aggressive behavior in young virgin female rats is partly dependent on trait anxiety, and appears to be under considerable OXT control.

  2. Measuring virgin female aggression in the female intruder test (FIT: effects of oxytocin, estrous cycle, and anxiety.

    Directory of Open Access Journals (Sweden)

    Trynke R de Jong

    Full Text Available The costs of violence and aggression in our society have stimulated the scientific search for the predictors and causes of aggression. The majority of studies have focused on males, which are considered to be more aggressive than females in most species. However, rates of offensive behavior in girls and young women are considerable and are currently rising in Western society. The extrapolation of scientific results from males to young, non-maternal females is a priori limited, based on the profound sex differences in brain areas and functioning of neurotransmitters involved in aggression. Therefore, we established a paradigm to assess aggressive behavior in young virgin female rats, i.e. the female intruder test (FIT. We found that approximately 40% of un-manipulated adult (10-11 weeks old female Wistar rats attack an intruder female during the FIT, independent of their estrous phase or that of their intruder. In addition, adolescent (7-8 weeks old female rats selected for high anxiety behavior (HABs displayed significantly more aggression than non-selected (NAB or low-anxiety (LAB rats. Intracerebroventricular infusion of oxytocin (OXT, 0.1 µg/5 µl inhibited aggressive behavior in adult NAB and LAB, but not HAB females. Adolescent NAB rats that had been aggressive towards their intruder showed increased pERK immunoreactivity (IR in the hypothalamic attack area and reduced pERK-IR in OXT neurons in the paraventricular hypothalamic nucleus compared to non-aggressive NAB rats. Taken together, aggressive behavior in young virgin female rats is partly dependent on trait anxiety, and appears to be under considerable OXT control.

  3. Oxytocin Reduces Cocaine Cued Fos Activation in a Regionally Specific Manner

    Science.gov (United States)

    Leong, Kah-Chung; Freeman, Linnea R; Berini, Carole R; Ghee, Shannon M; See, Ronald E

    2017-01-01

    Abstract Background Oxytocin may be a possible treatment for multiple neuropsychiatric disorders, including cocaine addiction. Little is known about the site-specific effects of oxytocin on various drug addiction-related brain regions. Furthermore, sexually dimorphic effects of oxytocin on neural function in the addiction circuit have not been established. Here, we studied Fos expression following cocaine-cued reinstatement in both male and female rats. Methods Male and female rats underwent self-administration, extinction, and reinstatement tests. On test days, rats were given oxytocin or vehicle, and lever pressing was measured in response to conditioned cocaine cues. Rats were perfused and Fos staining measured in the central amygdala, medial prefrontal cortex, nucleus accumbens core, and subthalamic nucleus. Fos/oxytocin double labeling occurred in the paraventricular nucleus of the hypothalamus. Results Rats reinstated to cocaine cues relative to extinction responding and oxytocin reduced cocaine seeking. Oxytocin combined with contingent cue presentations increased Fos+ oxytocin cell bodies within the paraventricular nucleus of the hypothalamus relative to vehicle. Fos expression robustly increased in the central amygdala following oxytocin administration. Oxytocin reversed cue-induced Fos expression in the medial prefrontal cortex, nucleus accumbens core, and subthalamic nucleus. Central oxytocin infusion also attenuated reinstated cocaine seeking. Conclusions Oxytocin decreased reinstated cocaine seeking, increased Fos activation in the paraventricular nucleus of the hypothalamus and central amygdala, but normalized cue-induced Fos activation in the medial prefrontal cortex, nucleus accumbens core, and subthalamic nucleus, thereby demonstrating regionally specific activation patterns. No sex differences were seen for the effects of oxytocin on cocaine seeking and Fos activation, indicating that oxytocin acts on similar central neural circuits critical to

  4. The role of oxytocin in cardiovascular regulation

    Directory of Open Access Journals (Sweden)

    J. Gutkowska

    2014-03-01

    Full Text Available Studies of body volume expansion have indicated that lesions of the anteroventral third ventricle and median eminence block the release of atrial natriuretic peptide (ANP into the circulation. Detailed analysis of the lesions showed that activation of oxytocin (OT-ergic neurons is responsible for ANP release, and it has become clear that activation of neuronal circuitry elicits OT secretion into the circulation, activating atrial OT receptors and ANP release from the heart. Subsequently, we have uncovered the entire functional OT system in the rat and the human heart. An abundance of OT has been observed in the early development of the fetal heart, and the capacity of OT to generate cardiomyocytes (CMs has been demonstrated in various types of stem cells. OT treatment of mesenchymal stem cells stimulates paracrine factors beneficial for cardioprotection. Cardiovascular actions of OT include: i lowering blood pressure, ii negative inotropic and chronotropic effects, iii parasympathetic neuromodulation, iv vasodilatation, v anti-inflammatory activity, vi antioxidant activity, and vii metabolic effects. OT actions are mediated by nitric oxide and ANP. The beneficial actions of OT may include the increase in glucose uptake by CMs and stem cells, reduction in CM hypertrophy, oxidative stress, and mitochondrial protection of several cell types. In experimentally induced myocardial infarction in rats, continuous in vivo OT delivery improves cardiac healing and cardiac work, reduces inflammation, and stimulates angiogenesis. Because OT plays anti-inflammatory and cardioprotective roles and improves vascular and metabolic functions, it demonstrates potential for therapeutic use in various pathologic conditions.

  5. The role of oxytocin in cardiovascular regulation

    International Nuclear Information System (INIS)

    Gutkowska, J.; Jankowski, M.; Antunes-Rodrigues, J.

    2014-01-01

    Studies of body volume expansion have indicated that lesions of the anteroventral third ventricle and median eminence block the release of atrial natriuretic peptide (ANP) into the circulation. Detailed analysis of the lesions showed that activation of oxytocin (OT)-ergic neurons is responsible for ANP release, and it has become clear that activation of neuronal circuitry elicits OT secretion into the circulation, activating atrial OT receptors and ANP release from the heart. Subsequently, we have uncovered the entire functional OT system in the rat and the human heart. An abundance of OT has been observed in the early development of the fetal heart, and the capacity of OT to generate cardiomyocytes (CMs) has been demonstrated in various types of stem cells. OT treatment of mesenchymal stem cells stimulates paracrine factors beneficial for cardioprotection. Cardiovascular actions of OT include: i) lowering blood pressure, ii) negative inotropic and chronotropic effects, iii) parasympathetic neuromodulation, iv) vasodilatation, v) anti-inflammatory activity, vi) antioxidant activity, and vii) metabolic effects. OT actions are mediated by nitric oxide and ANP. The beneficial actions of OT may include the increase in glucose uptake by CMs and stem cells, reduction in CM hypertrophy, oxidative stress, and mitochondrial protection of several cell types. In experimentally induced myocardial infarction in rats, continuous in vivo OT delivery improves cardiac healing and cardiac work, reduces inflammation, and stimulates angiogenesis. Because OT plays anti-inflammatory and cardioprotective roles and improves vascular and metabolic functions, it demonstrates potential for therapeutic use in various pathologic conditions

  6. The role of oxytocin in cardiovascular regulation

    Energy Technology Data Exchange (ETDEWEB)

    Gutkowska, J.; Jankowski, M. [University of Montreal, CHUM Research Centre, Faculty of Medicine, Department of Medicine, Laboratory of Cardiovascular Biochemistry, Montreal, Quebec, Canada, Laboratory of Cardiovascular Biochemistry, Department of Medicine, Faculty of Medicine, University of Montreal, CHUM Research Centre, Montreal, Quebec (Canada); Antunes-Rodrigues, J. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Fisiologia, Ribeirão Preto, SP, Brasil, Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2014-03-03

    Studies of body volume expansion have indicated that lesions of the anteroventral third ventricle and median eminence block the release of atrial natriuretic peptide (ANP) into the circulation. Detailed analysis of the lesions showed that activation of oxytocin (OT)-ergic neurons is responsible for ANP release, and it has become clear that activation of neuronal circuitry elicits OT secretion into the circulation, activating atrial OT receptors and ANP release from the heart. Subsequently, we have uncovered the entire functional OT system in the rat and the human heart. An abundance of OT has been observed in the early development of the fetal heart, and the capacity of OT to generate cardiomyocytes (CMs) has been demonstrated in various types of stem cells. OT treatment of mesenchymal stem cells stimulates paracrine factors beneficial for cardioprotection. Cardiovascular actions of OT include: i) lowering blood pressure, ii) negative inotropic and chronotropic effects, iii) parasympathetic neuromodulation, iv) vasodilatation, v) anti-inflammatory activity, vi) antioxidant activity, and vii) metabolic effects. OT actions are mediated by nitric oxide and ANP. The beneficial actions of OT may include the increase in glucose uptake by CMs and stem cells, reduction in CM hypertrophy, oxidative stress, and mitochondrial protection of several cell types. In experimentally induced myocardial infarction in rats, continuous in vivo OT delivery improves cardiac healing and cardiac work, reduces inflammation, and stimulates angiogenesis. Because OT plays anti-inflammatory and cardioprotective roles and improves vascular and metabolic functions, it demonstrates potential for therapeutic use in various pathologic conditions.

  7. Concurrent Oxytocin in Women Needing Second Dinoprostone

    International Nuclear Information System (INIS)

    Sher, Z.; Ashraf, M.; Irum, N.; Bashir, S.; Khaliq, N.; Yaqub, S.

    2015-01-01

    Objective: To reduce average induction delivery internal in patients with poor Bishop score without compromising fetomaternal outcome (in terms of birth weight, NICU admission, maternal complications and mode of delivery). Study Design: A descriptive study. Place and Duration of Study: Department of Obstetrics and Gynaecology, Pakistan Atomic Energy Commission (PAEC) General Hospital, Islamabad, from February to December 2009. Methodology: All patients needing 2nd dinoprostone pessary for induction of labour were included in the study. Patients with gestation below 37 weeks, those with intra-uterine growth restriction, bad obstetric history, previous uterine scar and patients in whom Bishop score improved for amniotomy after 1st dinoprostone pessary, were excluded. Data was collected on a special proforma where all variables were defined. Results:Out of 90 patients, 44 (48.8 percentage) had spontaneous vertex deliveries and 12 (13.3 percentage) had instrumental deliveries so a total vaginal deliveries occurred in 56 (62.2 percentage) patients. Thirty four patients (37.8 percentage) had emergency caesarean sections. Main indication for cesarean was failure to progress in 1st stage of labour followed by fetal distress. There were 3 failed inductions. Only 2 patients had hyperstimulation. NICU admission were 8 and all babies were discharged healthy from nursery with no case of early neonatal death. Conclusion:Concurrent oxytocin with 2nd dinoprostone in patients with poor Bishop scores (initial scores 2 and 3) resulted in more vaginal birth and comparatively shorter induction delivery time with almost negligible fetomaternal complications. (author)

  8. Cumulative risk on the oxytocin receptor gene (OXTR) underpins empathic communication difficulties at the first stages of romantic love.

    Science.gov (United States)

    Schneiderman, Inna; Kanat-Maymon, Yaniv; Ebstein, Richard P; Feldman, Ruth

    2014-10-01

    Empathic communication between couples plays an important role in relationship quality and individual well-being and research has pointed to the role of oxytocin in providing the neurobiological substrate for pair-bonding and empathy. Here, we examined links between genetic variability on the oxytocin receptor gene (OXTR) and empathic behaviour at the initiation of romantic love. Allelic variations on five OXTR single nucleotide polymorphisms (SNPs) previously associated with susceptibility to disorders of social functioning were genotyped in 120 new lovers: OXTRrs13316193, rs2254298, rs1042778, rs2268494 and rs2268490. Cumulative genetic risk was computed by summing risk alleles on each SNP. Couples were observed in support-giving interaction and behaviour was coded for empathic communication, including affective congruence, maintaining focus on partner, acknowledging partner's distress, reciprocal exchange and non-verbal empathy. Hierarchical linear modelling indicated that individuals with high OXTR risk exhibited difficulties in empathic communication. OXTR risk predicted empathic difficulties above and beyond the couple level, relationship duration, and anxiety and depressive symptoms. Findings underscore the involvement of oxytocin in empathic behaviour during the early stages of social affiliation, and suggest the utility of cumulative risk and plasticity indices on the OXTR as potential biomarkers for research on disorders of social dysfunction and the neurobiology of empathy. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  9. The Oxytocin Receptor (OXTR) Contributes to Prosocial Fund Allocations in the Dictator Game and the Social Value Orientations Task

    Science.gov (United States)

    Israel, Salomon; Lerer, Elad; Shalev, Idan; Uzefovsky, Florina; Riebold, Mathias; Laiba, Efrat; Bachner-Melman, Rachel; Maril, Anat; Bornstein, Gary; Knafo, Ariel; Ebstein, Richard P.

    2009-01-01

    Background Economic games observe social decision making in the laboratory that involves real money payoffs. Previously we have shown that allocation of funds in the Dictator Game (DG), a paradigm that illustrates costly altruistic behavior, is partially determined by promoter-region repeat region variants in the arginine vasopressin 1a receptor gene (AVPR1a). In the current investigation, the gene encoding the related oxytocin receptor (OXTR) was tested for association with the DG and a related paradigm, the Social Values Orientation (SVO) task. Methodology/Principal Findings Association (101 male and 102 female students) using a robust-family based test between 15 single tagging SNPs (htSNPs) across the OXTR was demonstrated with both the DG and SVO. Three htSNPs across the gene region showed significant association with both of the two games. The most significant association was observed with rs1042778 (p = 0.001). Haplotype analysis also showed significant associations for both DG and SVO. Following permutation test adjustment, significance was observed for 2–5 locus haplotypes (pprosocial decision making converges with a large body of animal research showing that oxytocin is an important social hormone across vertebrates including Homo sapiens. Individual differences in prosocial behavior have been shown by twin studies to have a substantial genetic basis and the current investigation demonstrates that common variants in the oxytocin receptor gene, an important element of mammalian social circuitry, underlie such individual differences. PMID:19461999

  10. Prevention of postpartum haemorrhage with the oxytocin analogue carbetocin.

    Science.gov (United States)

    Rath, Werner

    2009-11-01

    Postpartum haemorrhage is the leading cause of maternal mortality worldwide: 67-80% of cases are caused by uterine atony. Preventive measures include prophylactic drug use to aid uterine contraction after delivery, thus avoiding severe blood loss and reducing maternal morbidity and mortality. Carbetocin is a synthetic analogue of oxytocin with a half-life approximately 4-10 times longer than that reported for oxytocin. It combines the safety and tolerability profile of oxytocin with the sustained uterotonic activity of injectable ergot alkaloids. Furthermore, carbetocin can be administered as a single dose injection either intravenously or intramuscularly rather than as an infusion over several hours as is the case with oxytocin. Carbetocin is currently indicated for prevention of uterine atony after delivery by caesarean section in spinal or epidural anaesthesia. Data from three randomised controlled trials in caesarean delivery and a meta-analysis indicate that carbetocin significantly reduces the need for additional uterotonic agents or uterine massage to prevent excessive bleeding compared with placebo or oxytocin. The risk of headache, tremor, hypotension, flushing, nausea, abdominal pain, pruritus and feeling of warmth was similar in women who received carbetocin or oxytocin. The findings from two more recent double-blind randomised trials and one retrospective study suggest that carbetocin may also represent a good alternative to conventional uterotonic agents for prevention of postpartum haemorrhage after vaginal deliveries. A reduced need for additional uterotonics was observed with carbetocin vs. oxytocin in high-risk women and carbetocin was at least as effective as syntometrine in low-risk women. In these studies of vaginal deliveries, carbetocin was associated with a low incidence of adverse effects and demonstrated a better tolerability profile than syntometrine. Carbetocin had a long duration of action compared with intravenous oxytocin alone and a

  11. Gastroparesis is associated with oxytocin deficiency, oesophageal dysmotility with hyperCCKemia, and autonomic neuropathy with hypergastrinemia

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    Uvnäs-Moberg Kerstin

    2009-02-01

    Full Text Available Abstract Background Gastrointestinal (GI dysmotility and autonomic neuropathy are common problems among diabetics with largely unknown aetiology. Many peptides are involved in the autonomic nervous system regulating the GI tract. The aim of this study was to examine if concentrations of oxytocin, cholecystokinin (CCK, gastrin and vasopressin in plasma differ between diabetics with normal function and dysfunction in GI motility. Methods Nineteen patients with symptoms from the GI tract who had been examined with gastric emptying scintigraphy, oesophageal manometry, and deep-breathing test were included. They further received a fat-rich meal, after which blood samples were collected and plasma frozen until analysed for hormonal concentrations. Results There was an increase in postprandial oxytocin plasma concentration in the group with normal gastric emptying (p = 0.015 whereas subjects with delayed gastric emptying had no increased oxytocin secretion (p = 0.114. Both CCK and gastrin levels increased after the meal, with no differences between subjects with normal respective delayed gastric emptying. The concentration of vasopressin did not increase after the meal. In patients with oesophageal dysmotility the basal level of CCK tended to be higher (p = 0.051 and those with autonomic neuropathy had a higher area under the curve (AUC of gastrin compared to normal subjects (p = 0.007. Conclusion Reduced postprandial secretion of oxytocin was found in patients with delayed gastric emptying, CCK secretion was increased in patients with oesophageal dysmotility, and gastrin secretion was increased in patients with autonomic neuropathy. The findings suggest that disturbed peptide secretion may be part of the pathophysiology of digestive complications in diabetics.

  12. The role of oxytocin receptor gene (OXTR) DNA methylation (DNAm) in human social and emotional functioning: a systematic narrative review.

    Science.gov (United States)

    Maud, Catherine; Ryan, Joanne; McIntosh, Jennifer E; Olsson, Craig A

    2018-05-29

    The neuropeptide Oxytocin (OXT) plays a central role in birthing, mother-infant bonding and a broad range of related social behaviours in mammals. More recently, interest has extended to epigenetic programming of genes involved in oxytocinergic neurotransmission. This review brings together early findings in a rapidly developing field of research, examining relationships between DNA methylation (DNAm) of the Oxytocin Receptor Gene (OXTR) and social and emotional behaviour in human populations. A systematic search across Web of Knowledge/Science, Scopus, Medline and EMBASE captured all published studies prior to June 2017 examining the association between OXTR DNAm and human social and emotional outcomes. Search terms included 'oxytocin gene' or 'oxytocin receptor gene' and 'epigenetics' or 'DNA methylation'. Any article with a focus on social and emotional functioning was then identified from this set by manual review. Nineteen studies met eligibility criteria. There was considerable heterogeneity of study populations, tissue samples, instrumentation, measurement, and OXTR site foci. Only three studies examined functional consequences of OXTR DNAm on gene expression and protein synthesis. Increases in OXTR DNAm were associated with callous-unemotional traits in youth, social cognitive deficits in Autistic Spectrum Disorder (ASD), rigid thinking in anorexia nervosa, affect regulation problems, and problems with facial and emotional recognition. In contrast, reductions in DNAm were associated with perinatal stress, postnatal depression, social anxiety and autism in children. Consistent with an emerging field of inquiry, there is not yet sufficient evidence to draw conclusions about the role of OXTR DNAm in human social and emotional behaviour. However, taken together, findings point to increased OXTR DNAm in general impairments in social, cognitive and emotional functioning, and decreased OXTR DNAm in specific patterns of impairment related to mood and anxiety

  13. A New Population of Parvocellular Oxytocin Neurons Controlling Magnocellular Neuron Activity and Inflammatory Pain Processing.

    Science.gov (United States)

    Eliava, Marina; Melchior, Meggane; Knobloch-Bollmann, H Sophie; Wahis, Jérôme; da Silva Gouveia, Miriam; Tang, Yan; Ciobanu, Alexandru Cristian; Triana Del Rio, Rodrigo; Roth, Lena C; Althammer, Ferdinand; Chavant, Virginie; Goumon, Yannick; Gruber, Tim; Petit-Demoulière, Nathalie; Busnelli, Marta; Chini, Bice; Tan, Linette L; Mitre, Mariela; Froemke, Robert C; Chao, Moses V; Giese, Günter; Sprengel, Rolf; Kuner, Rohini; Poisbeau, Pierrick; Seeburg, Peter H; Stoop, Ron; Charlet, Alexandre; Grinevich, Valery

    2016-03-16

    Oxytocin (OT) is a neuropeptide elaborated by the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Magnocellular OT neurons of these nuclei innervate numerous forebrain regions and release OT into the blood from the posterior pituitary. The PVN also harbors parvocellular OT cells that project to the brainstem and spinal cord, but their function has not been directly assessed. Here, we identified a subset of approximately 30 parvocellular OT neurons, with collateral projections onto magnocellular OT neurons and neurons of deep layers of the spinal cord. Evoked OT release from these OT neurons suppresses nociception and promotes analgesia in an animal model of inflammatory pain. Our findings identify a new population of OT neurons that modulates nociception in a two tier process: (1) directly by release of OT from axons onto sensory spinal cord neurons and inhibiting their activity and (2) indirectly by stimulating OT release from SON neurons into the periphery. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Extinction of fear is facilitated by social presence: Synergism with prefrontal oxytocin.

    Science.gov (United States)

    Brill-Maoz, Naama; Maroun, Mouna

    2016-04-01

    This study addressed the question of whether extinction in pairs would have a beneficial effect on extinction of fear conditioning. To that end, we established an experimental setting for extinction in which we trained animals to extinguish contextual fear memory in pairs. Taking advantage of the role of oxytocin (OT) in the medial prefrontal cortex (mPFC) in the mediation of memory extinction and social interaction, we also sought to study its role in social interaction-induced effects on extinction. Our results clearly show that the social presence of another animal in the extinction context facilitates extinction, and that this facilitation is mediated through mPFC-OT. Our results suggest that social interaction may be a positive regulator of fear inhibition, implying that social interaction may be an easy, accessible therapeutic tool for the treatment of fear-associated disorders. Copyright © 2016. Published by Elsevier Ltd.

  15. Selective inhibition of extracellular oxidants liberated from human neutrophils--A new mechanism potentially involved in the anti-inflammatory activity of hydroxychloroquine.

    Science.gov (United States)

    Jančinová, Viera; Pažoureková, Silvia; Lucová, Marianna; Perečko, Tomáš; Mihalová, Danica; Bauerová, Katarína; Nosáľ, Radomír; Drábiková, Katarína

    2015-09-01

    Hydroxychloroquine is used in the therapy of rheumatoid arthritis or lupus erythematosus. Although these diseases are often accompanied by activation of neutrophils, there are still few data relating to the impact of hydroxychloroquine on these cells. We investigated the effect of orally administered hydroxychloroquine on neutrophil oxidative burst in rats with adjuvant arthritis. In human neutrophils, extra- and intracellular formation of oxidants, mobilisation of intracellular calcium and the phosphorylation of proteins regulating NADPH oxidase assembly were analysed. Administration of hydroxychloroquine decreased the concentration of oxidants in blood of arthritic rats. The inhibition was comparable with the reference drug methotrexate, yet it was not accompanied by a reduction in neutrophil count. When both drugs were co-applied, the effect became more pronounced. In isolated human neutrophils, treatment with hydroxychloroquine resulted in reduced mobilisation of intracellular calcium, diminished concentration of external oxidants and in decreased phosphorylation of Ca(2+)-dependent protein kinase C isoforms PKCα and PKCβII, which regulate activation of NADPH oxidase on plasma membrane. On the other hand, no reduction was observed in intracellular oxidants or in the phosphorylation of p40(phox) and PKCδ, two proteins directing the oxidase assembly to intracellular membranes. Hydroxychloroquine reduced neutrophil-derived oxidants potentially involved in tissue damage and protected those capable to suppress inflammation. The observed effects may represent a new mechanism involved in the anti-inflammatory activity of this drug. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Involvement of Nrf2-Mediated Upregulation of Heme Oxygenase-1 in Mollugin-Induced Growth Inhibition and Apoptosis in Human Oral Cancer Cells

    Directory of Open Access Journals (Sweden)

    Young-Man Lee

    2013-01-01

    Full Text Available Although previous studies have shown that mollugin, a bioactive phytochemical isolated from Rubia cordifolia L. (Rubiaceae, exhibits antitumor effects, its biological activity in oral cancer has not been reported. We thus investigated the effects and putative mechanism of apoptosis induced by mollugin in human oral squamous cell carcinoma cells (OSCCs. Results show that mollugin induces cell death in a dose-dependent manner in primary and metastatic OSCCs. Mollugin-induced cell death involved apoptosis, characterized by the appearance of nuclear shrinkage, flow cytometric analysis of sub-G1 phase arrest, and annexin V-FITC and propidium iodide staining. Western blot analysis and RT-PCR revealed that mollugin suppressed activation of NF-κB and NF-κB-dependent gene products involved in antiapoptosis (Bcl-2 and Bcl-xl, invasion (MMP-9 and ICAM-1, and angiogenesis (FGF-2 and VEGF. Furthermore, mollugin induced the activation of p38, ERK, and JNK and the expression of heme oxygenase-1 (HO-1 and nuclear factor E2–related factor 2 (Nrf2. Mollugin-induced growth inhibition and apoptosis of HO-1 were reversed by an HO-1 inhibitor and Nrf2 siRNA. Collectively, this is the first report to demonstrate the effectiveness of mollugin as a candidate for a chemotherapeutic agent in OSCCs via the upregulation of the HO-1 and Nrf2 pathways and the downregulation of NF-κB.

  17. The Inhibition of microRNA-128 on IGF-1-Activating mTOR Signaling Involves in Temozolomide-Induced Glioma Cell Apoptotic Death.

    Directory of Open Access Journals (Sweden)

    Peng-Hsu Chen

    Full Text Available Temozolomide (TMZ, an alkylating agent of the imidazotetrazine series, is a first-line chemotherapeutic drug used in the clinical therapy of glioblastoma multiforme, the most common and high-grade primary glioma in adults. Micro (miRNAs, which are small noncoding RNAs, post-transcriptionally regulate gene expressions and are involved in gliomagenesis. However, no studies have reported relationships between TMZ and miRNA gene regulation. We investigated TMZ-mediated miRNA profiles and its molecular mechanisms underlying the induction of glioma cell death. By performing miRNA microarray and bioinformatics analyses, we observed that expression of 248 miRNAs was altered, including five significantly upregulated and 17 significantly downregulated miRNAs, in TMZ-treated U87MG cells. miR-128 expression levels were lower in different glioma cells and strongly associated with poor survival. TMZ treatment significantly upregulated miR-128 expression. TMZ significantly enhanced miR-128-1 promoter activity and transcriptionally regulated miR-128 levels through c-Jun N-terminal kinase 2/c-Jun pathways. The overexpression and knockdown of miR-128 expression significantly affected TMZ-mediated cell viability and apoptosis-related protein expression. Furthermore, the overexpression of miR-128 alone enhanced apoptotic death of glioma cells through caspase-3/9 activation, poly(ADP ribose polymerase degradation, reactive oxygen species generation, mitochondrial membrane potential loss, and non-protective autophagy formation. Finally, we identified that key members in mammalian target of rapamycin (mTOR signaling including mTOR, rapamycin-insensitive companion of mTOR, insulin-like growth factor 1, and PIK3R1, but not PDK1, were direct target genes of miR-128. TMZ inhibited mTOR signaling through miR-128 regulation. These results indicate that miR-128-inhibited mTOR signaling is involved in TMZ-mediated cytotoxicity. Our findings may provide a better understanding

  18. Neonatal oxytocin manipulations have long-lasting, sexually dimorphic effects on vasopressin receptors.

    Science.gov (United States)

    Bales, K L; Plotsky, P M; Young, L J; Lim, M M; Grotte, N; Ferrer, E; Carter, C S

    2007-01-05

    Developmental exposure to oxytocin (OT) or oxytocin antagonists (OTAs) has been shown to cause long-lasting and often sexually dimorphic effects on social behaviors in prairie voles (Microtus ochrogaster). Because regulation of social behavior in monogamous mammals involves central receptors for OT, arginine vasopressin (AVP), and dopamine, we examined the hypothesis that the long-lasting, developmental effects of exposure to neonatal OT or OTA might reflect changes in the expression of receptors for these peptides. On postnatal day 1, prairie voles were injected intraperitoneally with either OT (1 mg/kg), an OTA (0.1 mg/kg), saline vehicle, or were handled only. At approximately 60 days of age, vasopressin V1a receptors, OT receptors (OTR) and dopamine D2 receptor binding were quantified using receptor autoradiography in brain tissue taken from males and females. Significant treatment effects on V1a binding were found in the bed nucleus of the stria terminalis (BNST), cingulate cortex (CgCtx), mediodorsal thalamus (MdThal), medial preoptic area of the hypothalamus (MPOA), and lateral septum (LS). The CgCtx, MPOA, ventral pallidum, and LS also showed significant sex by treatment interactions on V1a binding. No significant treatment or sex differences were observed for D2 receptor binding. No significant treatment difference was observed for OTR receptor binding, and only a marginal sex difference. Changes in the neuropeptide receptor expression, especially the V1a receptor, may help to explain sexually dimorphic changes in behavior that follow comparable neonatal manipulations.

  19. Stress, sex, and addiction: potential roles of corticotropin-releasing factor, oxytocin, and arginine-vasopressin.

    Science.gov (United States)

    Bisagno, Verónica; Cadet, Jean Lud

    2014-09-01

    Stress sensitivity and sex are predictive factors for the development of neuropsychiatric disorders. Life stresses are not only risk factors for the development of addiction but also are triggers for relapse to drug use. Therefore, it is imperative to elucidate the molecular mechanisms underlying the interactions between stress and drug abuse, as an understanding of this may help in the development of novel and more effective therapeutic approaches to block the clinical manifestations of drug addiction. The development and clinical course of addiction-related disorders do appear to involve neuroadaptations within neurocircuitries that modulate stress responses and are influenced by several neuropeptides. These include corticotropin-releasing factor, the prototypic member of this class, as well as oxytocin and arginine-vasopressin that play important roles in affiliative behaviors. Interestingly, these peptides function to balance emotional behavior, with sexual dimorphism in the oxytocin/arginine-vasopressin systems, a fact that might play an important role in the differential responses of women and men to stressful stimuli and the specific sex-based prevalence of certain addictive disorders. Thus, this review aims to summarize (i) the contribution of sex differences to the function of dopamine systems, and (ii) the behavioral, neurochemical, and anatomical changes in brain stress systems.

  20. Estrogen receptor-α36 is involved in epigallocatechin-3-gallate induced growth inhibition of ER-negative breast cancer stem/progenitor cells

    Directory of Open Access Journals (Sweden)

    Xiaohua Pan

    2016-02-01

    Full Text Available Epigallocatechin-3-gallate (EGCG is a type of catechin extracted from green tea, which is reported to have anticancer effects. EGCG is also reported to inhibit the cancer stem/progenitor cells in several estrogen receptor (ER-negative breast cancer cell lines, such as SUM-149, SUM-190 and MDA-MB-231. And all these cancer cells are highly expressed a new variant of ER-α, ER-α36. The aim of our present study is to determine the role of ER-α36 in the growth inhibitory activity of EGCG towards ER-negative breast cancer MDA-MB-231 and MDA-MB-436 cells. We found that EGCG potently inhibited the growth of cancer stem/progenitor cells in MDA-MB-231 and MDA-MB-436 cells, and also reduced the expression of ER-α36 in these cells. However, in ER-α36 knocked-down MDA-MB-231 and MDA-MB-436 cells, no significant inhibitory effects of EGCG on cancer stem/progenitor cells were observed. We also found that down-regulation of ER-α36 expression was in accordance with down-regulation of EGFR, which further verified a loop between ER-α36 and EGFR. Thus, our study indicated ER-α36 is involved in EGCG's inhibitory effects on ER-negative breast cancer stem/progenitor cells, which supports future preclinical and clinical evaluation of EGCG as a therapeutic option for ER-α36 positive breast cancer.

  1. Comparative Proteomic Analysis Provides insight into the Key Proteins as Possible Targets Involved in Aspirin Inhibiting Biofilm Formation of Staphylococcus xylosus

    Directory of Open Access Journals (Sweden)

    Chang-Geng Xu

    2017-08-01

    Full Text Available Staphylococcus xylosus is an opportunistic pathogen that causes infection in humans and cow mastitis. And S. xylosus possesses a strong ability to form biofilms in vitro. As biofilm formation facilitates resistance to antimicrobial agents, the discovery of new medicinal properties for classic drugs is highly desired. Aspirin, which is the most common active component of non-steroidal anti-inflammatory compounds, affects the biofilm-forming capacity of various bacterial species. We have found that aspirin effectively inhibits biofilm formation of S. xylosus by Crystal violet (CV staining and scanning electron microscopy analyses. The present study sought to elucidate possible targets of aspirin in suppressing S. xylosus biofilm formation. Based on an isobaric tag for relative and absolute quantitation (iTRAQ fold-change of >1.2 or <0.8 (P-value < 0.05, 178 differentially expressed proteins, 111 down-regulated and 67 up-regulated, were identified after application of aspirin to cells at a 1/2 minimal inhibitory concentration. Gene ontology analysis indicated enrichment in metabolic processes for the majority of the differentially expressed proteins. We then used the Kyoto Encyclopedia of Genes and Genomes (KEGG pathway database to analyze a large number of differentially expressed proteins and identified genes involved in biosynthesis of amino acids pathway, carbon metabolism (pentose phosphate and glycolytic pathways, tricarboxylic acid cycle and nitrogen metabolism (histidine metabolism. These novel proteins represent candidate targets in aspirin-mediated inhibition of S. xylosus biofilm formation at sub-MIC levels. The findings lay the foundation for further studies to identify potential aspirin targets.

  2. Inhibition of human prostate cancer cells proliferation by a selective alpha1-adrenoceptor antagonist labedipinedilol-A involves cell cycle arrest and apoptosis

    International Nuclear Information System (INIS)

    Liou, S.-F.; Lin, H.-H.; Liang, J.-C.; Chen, I.-J.; Yeh, J.-L.

    2009-01-01

    In this research, we conducted an in vitro analysis to evaluate the prostate cancer cells response to labedipinedilol-A in order to determine the effect of this selective α 1 -adrenoceptor antagonist to suppress prostate cancer cell growth by affecting cell proliferation and apoptosis. Here, we report that treatment of androgen-sensitive (LNCaP) and androgen-insensitive (PC-3) prostate cancer cells with labedipinedilol-A inhibited cell proliferation in concentration-dependent and time-dependent manners. Moreover, norepinephrine-stimulated proliferation of both cell lines are markedly inhibited by labedipinedilol-A. The probable involvement of α 1 -adrenoceptors in this cellular response is suggested. Labedipinedilol-A-induced growth inhibition was associated with G 0 /G 1 arrest, and G 2 /M arrest depending upon concentrations. Cell cycle blockade was associated with reduced amounts of cyclin D1/2, cyclin E, Cdk2, Cdk4, and Cdk6 and increased levels of the Cdk inhibitory proteins (Cip1/p21 and Kip1/p27). In addition, labedipinedilol-A also induced apoptosis in PC-3 cells, as determined by using Hoechst 33342 staining, DNA fragmentation, and Annexin V staining assay. Furthermore, labedipinedilol-A triggered the mitochondrial apoptotic pathway, as indicated by increasing the expression of Bax, but decreasing the level of Bcl-2, resulting in mitochondrial membrane potential loss, cytochrome c release, and activation of caspase-9 and -3. We further investigated the role of MAPK cascades in the anti-proliferative and apoptosis effects of labedipinedilol-A, and confirmed that labedipinedilol-A could activate JNK1/2 but not p38 in both cell lines. Unlike JNK1/2, however, labedipinedilol-A treatment resulted in down-regulation of phospho-ERK1/2 expression. We concluded that labedipinedilol-A possessed the growth-suppressive and apoptotic effects on LNCaP and PC-3 cells by its α 1 -adrenoceptor blockade, and the apoptotic effects of labedipinedilol-A primarily through

  3. Oxytocin modulates GABAAR subunits to confer neuroprotection in stroke in vitro.

    Science.gov (United States)

    Kaneko, Yuji; Pappas, Colleen; Tajiri, Naoki; Borlongan, Cesar V

    2016-10-21

    Oxytocin protects against ischemia-induced inflammation and oxidative stress, and is associated with GABA (γ-aminobutyric acid, an inhibitory neurotransmitter) signaling transduction in neurons. However, the molecular mechanism by which oxytocin affords neuroprotection, especially the interaction between oxytocin receptor and GABA A receptor (GABA A R), remains to be elucidated. Primary rat neural cells were exposed to oxytocin before induction of experimental acute stroke model via oxygen-glucose deprivation-reperfusion (OGD/R) injury. Pretreatment with oxytocin increased cell viability, decreased the cell damage against oxidative stress, and prevented the release of high mobility group box1 during OGD/R. However, introduction of oxytocin during OGD/R did not induce neuroprotection. Although oxytocin did not affect the glutathione-related cellular metabolism before OGD, oxytocin modulated the expression levels of GABA A R subunits, which function to remove excessive neuronal excitability via chloride ion influx. Oxytocin-pretreated cells significantly increased the chloride ion influx in response to GABA and THIP (δ-GABA A R specific agonist). This study provides evidence that oxytocin regulated GABA A R subunits in affording neuroprotection against OGD/R injury.

  4. The Role of Oxytocin in Parenting and as Augmentative Pharmacotherapy: Critical Issues and Bold Conjectures.

    Science.gov (United States)

    van IJzendoorn, M H; Bakermans-Kranenburg, M J

    2016-08-01

    Despite the sometimes heated debate about the validity of human oxytocin studies, experimental oxytocin research with intranasal administration is a growing field with promising preliminary findings. The effects of intranasally administered oxytocin compared to placebo on brain neural activity have been supported in animal studies and in human studies of neural resting state. In several studies, oxytocin sniffs have been shown to lead to down-regulation of amygdala activation in response to infant attachment vocalisations. Meta-analytic evidence shows that oxytocin enhances the salience of (emotional) stimuli, lowers stress and arousal, and elevates empathic concern and tender care, in particular for offspring and in-group members. Less firm evidence points at the amnestic effects of oxytocin. We also note that the average effect sizes of oxytocin experiments are small to modest, and that most studies include a small number of subjects and thus are seriously underpowered, which implies a high risk for publication bias and nonreplicability. Nevertheless, we argue that the power of within-subjects experiments with oxytocin has been underestimated. Much more work is needed, however, to create a firm knowledge base of the neural and behavioural effects of oxytocin. Human oxytocin research is still taking place in the context of discovery, in which bold conjectures are being generated. In the context of justification, these conjectures should subsequently be subjected to stringent attempts at refutations before we jump to theoretical or clinical conclusions. For this context of justification, we propose a multisite multiple replications project on the social stimuli salience enhancing effect of oxytocin. Clinical application of oxytocin is premature. Meta-analytically, the use of oxytocin in clinical groups tends to show only effectiveness in changing symptomatology in individuals with autism spectrum disorders but, even then, it is not yet a validated therapy and its

  5. Antiaggressive activity of central oxytocin in male rats

    NARCIS (Netherlands)

    Calcagnoli, F.; de Boer, S.F.; Althaus, M.; den Boer, J.A.; Koolhaas, J.M.

    2013-01-01

    A substantial body of research suggests that the neuropeptide oxytocin promotes social affiliative behaviors in a wide range of animals including humans. However, its antiaggressive action has not been unequivocally demonstrated in male laboratory rodents. Our primary goal was to examine the

  6. The role of oxytocin in male and female reproductive behavior

    NARCIS (Netherlands)

    Veening, J.G.; Jong, T.R. de; Waldinger, M.D.; Korte, S.M.; Olivier, B.

    2015-01-01

    Oxytocin (OT) is a nonapeptide with an impressive variety of physiological functions. Among them, the 'prosocial' effects have been discussed in several recent reviews, but the direct effects on male and female sexual behavior did receive much less attention so far. As our contribution to honor the

  7. Effect of estradiol and oxytocin on ovine cervical relaxation

    African Journals Online (AJOL)

    Yomi

    2012-02-07

    Feb 7, 2012 ... The aim of this study was to examine the effect of estradiol (E2) and oxytocin ... Artificial insemination (AI) is a good way for the use of superior rams in reproduction but the conception rates in ... successful in sheep industry because it is costly, time .... during luteolysis and its abrogation in early pregnancy.

  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. Helping Oxytocin Deliver: Considerations in the Development of Oxytocin-Based Therapeutics for Brain Disorders.

    Directory of Open Access Journals (Sweden)

    Kai eMacdonald

    2013-03-01

    Full Text Available Concerns regarding a drought in psychopharmacology have risen from many quarters. From one perspective, the wellspring of bedrock medications for anxiety disorders, depression, and schizophrenia was serendipitously discovered over thirty year ago, the swell of pharmaceutical investment in drug discovery has receded, and the pipeline’s flow of medications with unique mechanisms of action (i.e. glutamatergic agents, CRF antagonists has slowed to a trickle. Might oxytocin (OT-based therapeutics be an oasis? Though a large basic science literature and a slowly increasing number of studies in human diseases support this hope, the bulk of extant OT studies in humans are single-dose studies on normals, and do not directly relate to improvements in human brain-based diseases. Instead, these studies have left us with a field pregnant with therapeutic possibilities, but barren of definitive treatments. In this clinically-oriented review, we discuss the extant OT literature with an eye toward helping OT deliver on its promise as a therapeutic agent. To this end, we identify ten key questions that we believe future OT research should address. From this overview, several conclusions are clear: 1 the OT system represents an extremely promising target for novel CNS drug development; 2 there is a pressing need for rigorous, randomized controlled clinical trials targeting actual patients; and 3 in order to inform the design and execution of these vital trials, we need further translational studies addressing the questions posed in this review. Looking forward, we extend a cautious hope that the next decade of OT research will birth oxytocin-targetted therapeutics that can truly deliver on this system’s therapeutic potential.

  10. Providing straw to allow exploratory behaviour in a pig experimental system does not modify putative indicators of positive welfare: peripheral oxytocin and serotonin.

    Science.gov (United States)

    Marcet Rius, M; Cozzi, A; Bienboire-Frosini, C; Teruel, E; Chabaud, C; Monneret, P; Leclercq, J; Lafont-Lecuelle, C; Pageat, P

    2018-01-22

    Numerous studies have shown that providing straw to pigs can reduce undesirable behaviours such as aggression, tail biting and stereotypy. The measurement of various neuromodulators can be helpful in assessing the development of positive behaviours and overall animal welfare. The oxytocin release is frequently linked to positive emotions and positive welfare. It has been suggested that oxytocin modulates the serotoninergic system. This study aims to investigate the potential effect of straw provision in pigs on peripheral levels of oxytocin and serotonin. In total, 18 mini-pigs were involved in an exploratory study conducted in two parallel groups, Enriched (n=10) and Control (n=8) groups. Pigs were divided by group and housed in pens of two individuals. Straw was provided continuously only in Enriched group and renewed each day for 2 weeks. Two blood samples were drawn from each animal 5 to 10 min before providing the straw, and 15 min after providing straw, during the 1st week, to analyse peripheral changes in oxytocin and serotonin before and after straw provision, and determine the existence of a putative short-term effect. The same procedure was carried out for Control group, without straw provision. Long-term effects of straw provision were also examined using blood samples drawn at the same hour from each animal in the 2nd and 3rd weeks. During this time, animals had the permanent possibility to explore the straw in Enriched group but not in Control group. At the end of each week, one animal-keeper completed two visual analogue scales for each mini-pig regarding the difficulty/ease to work with and handle it and its trust in humans. Results showed peripheral oxytocin increases in both groups after 2 weeks (P=0.02). Results did not demonstrate any effect of providing straw to allow exploratory behaviour on peripheral serotonin. Other results were not significant. This preliminary study explored the relationship between peripheral oxytocin and serotonin and

  11. Stimulation of Oxytocin Receptor during Early Reperfusion Period Protects the Heart against Ischemia/Reperfusion Injury: the Role of Mitochondrial ATPSensitive Potassium Channel, Nitric Oxide, and Prostaglandins

    Directory of Open Access Journals (Sweden)

    Alireza Imani

    2015-10-01

    Full Text Available Postconditioning is a simple and safe strategy for cardioprotection and infarct size limitation. Ourprevious study showed that oxytocin (OT exerts postconditioning effect on ischemic/reperfused isolated ratheart. The aim of this study was to investigate the involvement of OT receptor, mitochondrial ATP-sensitivepotassium channel (mKATP, nitric oxide (NO and cyclooxygenase (COX pathways in OTpostconditioning. Isolated rat hearts were divided into10 groups and underwent 30 min of regional ischemiafollowed by 120 min of reperfusion (n =6. In I/R (ischemia/reperfusion group, ischemia and reperfusionwere induced without any treatment. In OT group, oxytocin was perfused 5 min prior to beginning ofreperfusion for 25 min. In groups 3-6, atosiban (oxytocin receptor blocker, L-NAME (N-Nitro-L-ArginineMethyl Ester, non-specific nitric oxide synthase inhibitor, 5-HD (5-hydroxydecanoate, mKATP inhibitorand indomethacin (cyclooxygenase inhibitor were infused prior to oxytocin administration. In others, thementioned inhibitors were perfused prior to ischemia without oxytocin infusion. Infarct size, ventricularhemodynamic, coronary effluent, malondialdehyde (MDA and lactate dehydrogenase (LDH were measuredat the end of reperfusion. OT perfusion significantly reduced infarct size, MDA and LDH in comparison withIR group. Atosiban, 5HD, L-NAME and indomethacin abolished the postconditioning effect of OT. Perfusionof the inhibitors alone prior to ischemia had no effect on infarct size, hemodynamic parameters, coronaryeffluent and biochemical markers as compared with I/R group. In conclusion, this study indicates thatpostconditioning effects of OT are mediated by activation of mKATP and production of NO andProstaglandins (PGs.

  12. De-masking oxytocin-deficiency in craniopharyngioma and assessing its link with affective function.

    Science.gov (United States)

    Gebert, Dorothea; Auer, Matthias K; Stieg, Mareike R; Freitag, Martin T; Lahne, Madlén; Fuss, Johannes; Schilbach, Katharina; Schopohl, Jochen; Stalla, Günter K; Kopczak, Anna

    2018-02-01

    Despite the high prevalence of panhypopituitarism and diabetes insipidus in patients with craniopharyngioma (CP), little is known about the functioning of the neuropeptide oxytocin in these patients. This is of special interest as tumor-associated lesions often impair sites critical for oxytocin production and release, and affective dysfunction in CP links with elsewhere reported prosocial, antidepressant and anxiolytic oxytocin effects. Using a prospective study-design, we tested whether oxytocin is reduced in CP-patients, and whether altered oxytocin levels account for affective and emotional dysfunction. 26 adult CP-patients and 26 healthy controls matched in sex and age underwent physical exercise, a stimulus previously shown to induce oxytocin release. Baseline and stimulated salivary oxytocin levels, as well as empathy, depression and anxiety scores were measured. Results showed that patients overall did not present with lower baseline oxytocin levels than controls (F[1,30]=0.21, p=0.649), but baseline oxytocin levels were indeed reduced in patients with hypothalamic damage, as assessed by MRI-based grading (F[2,9.79]=4.54, p=0.040). In response to exercise-induced stimulation, all CP-patients showed a blunted oxytocin-release compared to controls (F[1,30]=9.36, p=0.005). DI was not associated with oxytocin levels. Regarding affective function, unexpectedly, higher baseline oxytocin was related to higher trait anxiety (b=2.885, t(43)=2.421, p=0.020, CI[.478; 5.292]); the positive link with higher depression failed to reach statistical significance (b=1.928, t(43)=1.949, p=0.058, CI[-0.070; 3.927]). A blunted oxytocin-release was linked with higher state anxiety (b=-0.133, t(43)=-2.797, p=0.008, CI[-0.230; -0.037]). Empathy was not associated with oxytocin measures. In conclusion, we observed reduced baseline oxytocin levels only in CP-patients with hypothalamic damage. Exercise-induced stimulation de-masked an oxytocin-deficiency in all CP-patients. Baseline

  13. Why social attachment and oxytocin protect against addiction and stress: Insights from the dynamics between ventral and dorsal corticostriatal systems.

    Science.gov (United States)

    Tops, Mattie; Koole, Sander L; IJzerman, Hans; Buisman-Pijlman, Femke T A

    2014-04-01

    The present article advances a neurobiological model of the reciprocal associations between social attachment and drug abuse, and social attachment and chronic stress, as overlapping systems are involved in stress coping and social attachment. In terms of coping, responding to a novel stressor or challenge involves initial novelty processing and activation of learning mechanisms that allow habituation to the stressor through familiarization. Similarly, social attachments are initially formed by being attracted by rewarding properties of an as-yet novel individual, and subsequently developing feelings of attachment towards the familiarized individual. Attachment and familiarization increase the availability of "internal working models" for the control of behavior and emotion, which may explain why secure attachments are associated with increased resilience in the face of stress, accompanied by less reactive reward responding (i.e., increased resilience against drug addiction). The present article seeks to illuminate the role of the neuropeptide oxytocin, which may be involved in the overlapping mechanisms of stable attachment formation and stress coping by shifting processing from novelty and reward seeking to appreciation of familiarity. Oxytocin may accomplish this by facilitating a ventral-to-dorsal shift in activation in corticostriatal loops, which produces a shift from a reactive reward drive (wanting) to stable appreciation of familiar social aspects ("liking" or "loving"). The authors suggest that through dopaminergic, serotonergic and endogenous opioid mechanisms, oxytocin is involved in shifting the balance between wanting and liking in corticostriatal loops by facilitating consolidation of social information from ventral reactive reward systems to dorsal internal working models that aid in prospectively selecting optimal actions in the future, increasing resilience in the face of stress and addiction. © 2013.

  14. Prenatal stress puzzle, the oxytocin piece: Prenatal stress alters the behaviour and autonomic regulation in piglets, insights from oxytocin

    Science.gov (United States)

    Developmental changes in response to prenatal stressors (PNS) may represent an adaptive strategy to enhance survival traits in the offspring. Yet, PNS could be maladaptive for captive animals, causing anxiety and abnormal social development. Oxytocin (OT) reduces anxiety, whereas OT deficiencies are...

  15. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders.

    Science.gov (United States)

    Andari, Elissar; Duhamel, Jean-René; Zalla, Tiziana; Herbrecht, Evelyn; Leboyer, Marion; Sirigu, Angela

    2010-03-02

    Social adaptation requires specific cognitive and emotional competences. Individuals with high-functioning autism or with Asperger syndrome cannot understand or engage in social situations despite preserved intellectual abilities. Recently, it has been suggested that oxytocin, a hormone known to promote mother-infant bonds, may be implicated in the social deficit of autism. We investigated the behavioral effects of oxytocin in 13 subjects with autism. In a simulated ball game where participants interacted with fictitious partners, we found that after oxytocin inhalation, patients exhibited stronger interactions with the most socially cooperative partner and reported enhanced feelings of trust and preference. Also, during free viewing of pictures of faces, oxytocin selectively increased patients' gazing time on the socially informative region of the face, namely the eyes. Thus, under oxytocin, patients respond more strongly to others and exhibit more appropriate social behavior and affect, suggesting a therapeutic potential of oxytocin through its action on a core dimension of autism.

  16. Oxytocin Attenuates Neural Reactivity to Masked Threat Cues from the Eyes

    OpenAIRE

    Kanat, Manuela; Heinrichs, Markus; Schwarzwald, Ralf; Domes, Gregor

    2014-01-01

    The neuropeptide oxytocin has recently been shown to modulate covert attention shifts to emotional face cues and to improve discrimination of masked facial emotions. These results suggest that oxytocin modulates facial emotion processing at early perceptual stages prior to full evaluation of the emotional expression. Here, we used functional magnetic resonance imaging to examine whether oxytocin alters neural responses to backwardly masked angry and happy faces while controlling for attention...

  17. Oxytocin in pregnancy and the postpartum: relations to labor and its management

    Directory of Open Access Journals (Sweden)

    Marie ePrevost

    2014-01-01

    Full Text Available The purpose of this study was to examine variations in endogenous oxytocin levels in pregnancy and postpartum state. We also explored the associations between delivery variables and oxytocin levels. A final sample of 272 mothers in their first trimester of pregnancy were included for the study. Blood samples were drawn during the 1st trimester and 3rd trimester of pregnancy and at 8 weeks postpartum. Socio-demographic data were collected at each time point and medical files were consulted for delivery details. In most women, levels of circulating oxytocin increased from the 1st to 3rd trimester of pregnancy followed by a decrease in the postpartum period. Oxytocin levels varied considerably between individuals, ranging from 50 pg/mL to over 2000 pg/mL. Parity was the main predictor of oxytocin levels in the 3rd trimester of pregnancy and of oxytocin level changes from the 1st to the 3rd trimester of pregnancy. Oxytocin levels in the 3rd trimester of pregnancy predicted a self-reported negative labor experience and increased the chances of having an epidural. Intrapartum exogenous oxytocin was positively associated with levels of oxytocin during the postpartum period. Our exploratory results suggest that circulating oxytocin levels during the 3rd trimester of pregnancy may predict the type of labor a woman will experience. More importantly, the quantity of intrapartum exogenous oxytocin administered during labor predicted plasma oxytocin levels 2 months postpartum, suggesting a possible long-term effect of this routine intervention, the consequences of which are largely unknown.

  18. The role of oxytocin in the pathogenesis and treatment of schizophrenia

    Directory of Open Access Journals (Sweden)

    Jusiak Katarzyna

    2017-12-01

    Full Text Available Introduction: Until recently, oxytocin was mainly associated with the pathophysiology of childbirth and sexual functions, but lately this hormone has become the object of interest to psychiatry and psychology due to the significant influence of oxytocin on human behavior in the field of social and emotional functioning. Current scientific research focuses on the participation of oxytocin in the pathogenesis and therapy of mental disorders.

  19. Oxytocin increases bias, but not accuracy, in face recognition line-ups

    OpenAIRE

    Bate, Sarah; Bennetts, Rachel; Parris, Benjamin A.; Bindemann, Markus; Udale, Robert; Bussunt, Amanda

    2014-01-01

    Previous work indicates that intranasal inhalation of oxytocin improves face recognition skills, raising the possibility that it may be used in security settings. However, it is unclear whether oxytocin directly acts upon the core face-processing system itself, or indirectly improves face recognition via affective or social salience mechanisms. In a double-blind procedure, 60 participants received either an oxytocin or placebo nasal spray before completing the One-in-Ten task – a standardized...

  20. Restoring effects of oxytocin on the attentional preference for faces in autism

    OpenAIRE

    Kanat, M; Spenthof, I; Riedel, A; van Elst, L T; Heinrichs, M; Domes, G

    2017-01-01

    Reduced attentional preference for faces and symptoms of social anxiety are common in autism spectrum disorders (ASDs). The neuropeptide oxytocin triggers anxiolytic functions and enhances eye gaze, facial emotion recognition and neural correlates of face processing in ASD. Here we investigated whether a single dose of oxytocin increases attention to faces in ASD. As a secondary question, we explored the influence of social anxiety on these effects. We tested for oxytocin's effects on attenti...

  1. Stress-induced oxytocin release and oxytocin cell number and size in prepubertal and adult male and female rats.

    Science.gov (United States)

    Minhas, Sumeet; Liu, Clarissa; Galdamez, Josselyn; So, Veronica M; Romeo, Russell D

    2016-08-01

    Studies indicate that adolescent exposure to stress is a potent environmental factor that contributes to psychological and physiological disorders, though the mechanisms that mediate these dysfunctions are not well understood. Periadolescent animals display greater stress-induced hypothalamic-pituitary-adrenal (HPA) axis responses than adults, which may contribute to these vulnerabilities. In addition to the HPA axis, the hypothalamo-neurohypophyseal tract (HNT) is also activated in response to stress. In adults, stress activates this system resulting in secretion of oxytocin from neurons in the supraoptic (SON) and paraventricular (PVN) nuclei. However, it is currently unknown whether a similar or different response occurs in prepubertal animals. Given the influence of these hormones on a variety of emotional behaviors and physiological systems known to change as an animal transitions into adulthood, we investigated stress-induced HPA and HNT hormonal responses before and after stress, as well as the number and size of oxytocin-containing cells in the SON and PVN of prepubertal (30d) and adult (70d) male and female rats. Though we found the well-established protracted adrenocorticotropic hormone and corticosterone response in prepubertal males and females, only adult males and prepubertal females showed a significant stress-induced increase in plasma oxytocin levels. Moreover, though we found no pubertal changes in the number of oxytocin cells, we did find a pubertal-related increase in oxytocin somal size in both the SON and PVN of males and females. Taken together, these data indicate that neuroendocrine systems can show different patterns of stress reactivity before and after adolescent development and that these responses can be further modified by sex. Given the impact of these hormones on a variety of systems, it will be imperative to further explore these changes in hormonal stress reactivity and their role in adolescent health. Copyright © 2016 Elsevier

  2. Oxytocin attenuates aversive response to nicotine and anxiety-like behavior in adolescent rats.

    Science.gov (United States)

    Lee, Hyunchan; Jang, Minji; Noh, Jihyun

    2017-02-01

    Initial tobacco use is initiated with rewarding and aversive properties of nicotine and aversive response to nicotine plays a critical role in nicotine dependency. Decrease of nicotine aversion increases the nicotine use that causes behavioral and neuronal changes of animals. Oxytocin influences drug abuse and reciprocally affect vulnerability to drug use. To assess the effect of oxytocin on initial nicotine aversion and anxiety, we examined voluntary oral nicotine intake and anxiety-like behavior following oxytocin treatment in adolescent rats. Sprague-Dawley male rats (4 weeks old) were used. For oxytocin administration, rats were injected subcutaneously with saline or oxytocin (0.01, 0.1 and 1mg/kg) according to the assigned groups. Voluntary oral nicotine consumption test was performed by two bottle free-choice paradigm. To examine anxiety-like behavior in rats, we performed a light/dark box test. Oxytocin not only significantly increased the nicotine intake but also alleviated nicotine aversion after acclimation to nicotine solution in a concentration dependent manner. Meanwhile, oxytocin significantly reduced anxiety-like behavior. We suggest that oxytocin itself mitigates aversive response toward initial nicotine intake and anxiety-like behavior. These results widen the psychophysiological perspective on oxytocin for better understanding of nicotine addiction related behaviors influenced by diverse social factors. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  3. Plasma Oxytocin Immunoreactive Products and Response to Trust in Patients with Social Anxiety Disorder

    Science.gov (United States)

    Hoge, EA; Lawson, EA; Metcalf, CA; Keshaviah, A; Zak, PJ; Pollack, MH; Simon, NM

    2013-01-01

    Background Generalized Social Anxiety Disorder (GSAD) is characterized by excessive fear and avoidance of several types of social and performance situations. The pathophysiology is not well understood, but research in animals and humans has provided evidence that oxytocin helps regulate normal social affiliative behavior. Previous work in healthy male subjects demonstrated a rise in plasma oxytocin after receiving a high trust signal. To examine the oxytocin system in GSAD, we measured plasma oxytocin in GSAD patients and controls, before and after the social “Trust Game,” a neuroeconomic test examining trust behavior and reaction to trust using real monetary incentives. Methods Thirty-nine subjects with GSAD and 28 healthy controls provided three blood samples for oxytocin measurement before the Trust Game, and one sample after the game. Plasma estradiol was also measured at baseline. The Trust Game protocol version prioritized the sending of a signal of high cooperation and trust to all participants. All analyses controlled for gender and estradiol levels. Results Mean oxytocin levels post-Trust Game (p=0.025), and overall (area under the curve, p=0.011) were lower in GSAD patients compared to controls, after controlling for sex and estradiol. There was no significant change in oxytocin levels after the Game in either group. Conclusions We report low plasma oxytocin levels in patients with generalized social anxiety disorder during a pro-social laboratory task paradigm. Additional research will be important to further examine the relationship between oxytocin and social behavior in GSAD. PMID:22807189

  4. The Neuropeptide Oxytocin Enhances Information Sharing and Group Decision Making Quality.

    Science.gov (United States)

    De Wilde, Tim R W; Ten Velden, Femke S; De Dreu, Carsten K W

    2017-01-11

    Groups can make better decisions than individuals when members cooperatively exchange and integrate their uniquely held information and insights. However, under conformity pressures group members are biased towards exchanging commonly known information, and away from exchanging unique information, thus undermining group decision-making quality. At the neurobiological level, conformity associates with the neuropeptide oxytocin. A double-blind placebo controlled study found no evidence for oxytocin induced conformity. Compared to placebo groups, three-person groups whose members received intranasal oxytocin, focused more on unique information (i) and repeated this information more often (ii). These findings reveal oxytocin as a neurobiological driver of group decision-making processes.

  5. Bisphenol A, Dichlorodiphenyltrichloroethane (DDT) and Vinclozolin Affect ex-vivo Uterine Contraction in Rats via Uterotonin (Prostaglandin F2?, Acetylcholine and Oxytocin) Related Pathways

    OpenAIRE

    Salleh, Naguib; Giribabu, Nelli; Feng, Angeline Oh Mei; Myint, Kyaimon

    2015-01-01

    Bisphenol-A (BPA), dichrolodiphenyltrichloroethane (DDT) and vinclozolin were found able to induce abnormal uterine contraction. The mechanisms involved remains unclear. We hypothesized that the effect of these compounds were mediated via the uterotonin pathways. Therefore, in this study, effects of BPA, vinclozolin and DDT-only and in combination with uterotonins (PGF-2?, acetylcholine and oxytocin) on the force and pattern of uterine contraction were observed. Methods: Uteri were harvested ...

  6. A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Qiaoyuan [Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510182 (China); Xu, Enwu [Department of Thoracic Surgery, General Hospital of Guangzhou Military Command of Chinese People' s Liberation Army, Guangzhou 510010 (China); Dai, Jiabin; Liu, Binbin; Han, Zhiyuan; Wu, Jianjun; Zhang, Shaozhu; Peng, Baoying [Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510182 (China); Zhang, Yajie [Department of Pathology, Guangzhou Medical University, Guangzhou 510182 (China); Jiang, Yiguo, E-mail: jiangyiguo@vip.163.com [Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510182 (China)

    2015-06-01

    Lung cancer is the most common form of cancer throughout the world. The specific targeting of long noncoding RNAs (lncRNAs) by resveratrol opened a new avenue for cancer chemoprevention. In this study, we found that 21 lncRNAs were upregulated and 19 lncRNAs were downregulated in lung cancer A549 cells with 25 μmol/L resveratrol treatment determined by microarray analysis. AK001796, the lncRNA with the most clearly altered expression, was overexpressed in lung cancer tissues and cell lines, but its expression was downregulated in resveratrol-treated lung cancer cells. By monitoring cell proliferation and growth in vitro and tumor growth in vivo, we observed a significant reduction in cell viability in lung cancer cells and a slow growth in the tumorigenesis following AK001796 knockdown. We also found that AK001796 knockdown caused a cell-cycle arrest, with significant increases in the percentage of cells in G{sub 0}/G{sub 1} in lung cancer cells. By using cell cycle pathway-specific PCR arrays, we detected changes in a number of cell cycle-related genes related to lncRNA AK001796 knockdown. We further investigated whether AK001796 participated in the anticancer effect of resveratrol and the results showed that reduced lncRNA AK001796 level potentially impaired the inhibitory effect of resveratrol on cell proliferation. To our knowledge, this is the first study to report the changes in an lncRNA expression profile induced by resveratrol in lung cancer. - Highlights: • LncRNA AK001796 played an oncogenic role in lung carcinogenesis. • LncRNA AK001796 was downregulated in resveratrol-treated lung cancer cells. • LncRNA AK001796 was involved in the inhibition of cell growth by resveratrol.

  7. A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer

    International Nuclear Information System (INIS)

    Yang, Qiaoyuan; Xu, Enwu; Dai, Jiabin; Liu, Binbin; Han, Zhiyuan; Wu, Jianjun; Zhang, Shaozhu; Peng, Baoying; Zhang, Yajie; Jiang, Yiguo

    2015-01-01

    Lung cancer is the most common form of cancer throughout the world. The specific targeting of long noncoding RNAs (lncRNAs) by resveratrol opened a new avenue for cancer chemoprevention. In this study, we found that 21 lncRNAs were upregulated and 19 lncRNAs were downregulated in lung cancer A549 cells with 25 μmol/L resveratrol treatment determined by microarray analysis. AK001796, the lncRNA with the most clearly altered expression, was overexpressed in lung cancer tissues and cell lines, but its expression was downregulated in resveratrol-treated lung cancer cells. By monitoring cell proliferation and growth in vitro and tumor growth in vivo, we observed a significant reduction in cell viability in lung cancer cells and a slow growth in the tumorigenesis following AK001796 knockdown. We also found that AK001796 knockdown caused a cell-cycle arrest, with significant increases in the percentage of cells in G 0 /G 1 in lung cancer cells. By using cell cycle pathway-specific PCR arrays, we detected changes in a number of cell cycle-related genes related to lncRNA AK001796 knockdown. We further investigated whether AK001796 participated in the anticancer effect of resveratrol and the results showed that reduced lncRNA AK001796 level potentially impaired the inhibitory effect of resveratrol on cell proliferation. To our knowledge, this is the first study to report the changes in an lncRNA expression profile induced by resveratrol in lung cancer. - Highlights: • LncRNA AK001796 played an oncogenic role in lung carcinogenesis. • LncRNA AK001796 was downregulated in resveratrol-treated lung cancer cells. • LncRNA AK001796 was involved in the inhibition of cell growth by resveratrol

  8. EMF radiations (1800 MHz)-inhibited early seedling growth of maize (Zea mays) involves alterations in starch and sucrose metabolism.

    Science.gov (United States)

    Kumar, Arvind; Singh, Harminder Pal; Batish, Daizy R; Kaur, Shalinder; Kohli, Ravinder Kumar

    2016-07-01

    The present study investigated the impact of 1800-MHz electromagnetic field radiations (EMF-r), widely used in mobile communication, on the growth and activity of starch-, sucrose-, and phosphate-hydrolyzing enzymes in Zea mays seedlings. We exposed Z. mays to modulated continuous wave homogenous EMF-r at specific absorption rate (SAR) of 1.69±0.0 × 10(-1) W kg(-1) for ½, 1, 2, and 4 h. The analysis of seedlings after 7 days revealed that short-term exposure did not induce any significant change, while longer exposure of 4 h caused significant growth and biochemical alterations. There was a reduction in the root and coleoptile length with more pronounced effect on coleoptile growth (23 % reduction on 4-h exposure). The contents of photosynthetic pigments and total carbohydrates declined by 13 and 18 %, respectively, in 4-h exposure treatments compared to unexposed control. The activity of starch-hydrolyzing enzymes-α- and β-amylases-increased by ∼92 and 94 %, respectively, at an exposure duration of 4 h, over that in the control. In response to 4-h exposure treatment, the activity of sucrolytic enzymes-acid invertases and alkaline invertases-was increased by 88 and 266 %, whereas the specific activities of phosphohydrolytic enzymes (acid phosphatases and alkaline phosphatases) showed initial increase up to ≤2 h duration and then declined at >2 h exposure duration. The study concludes that EMF-r-inhibited seedling growth of Z. mays involves interference with starch and sucrose metabolism.

  9. Proteasome inhibitors activate autophagy involving inhibition of PI3K-Akt-mTOR pathway as an anti-oxidation defense in human RPE cells.

    Directory of Open Access Journals (Sweden)

    Bingrong Tang

    Full Text Available The two major intracellular protein degradation systems, the ubiquitin-proteasome system (UPS and autophagy, work collaboratively in many biological processes including development, apoptosis, aging, and countering oxidative injuries. We report here that, in human retinal pigment epithelial cells (RPE, ARPE-19 cells, proteasome inhibitors, clasto-lactacystinβ-lactone (LA or epoxomicin (Epo, at non-lethal doses, increased the protein levels of autophagy-specific genes Atg5 and Atg7 and enhanced the conversion of microtubule-associated protein light chain (LC3 from LC3-I to its lipidative form, LC3-II, which was enhanced by co-addition of the saturated concentration of Bafilomycin A1 (Baf. Detection of co-localization for LC3 staining and labeled-lysosome further confirmed autophagic flux induced by LA or Epo. LA or Epo reduced the phosphorylation of the protein kinase B (Akt, a downstream target of phosphatidylinositol-3-kinases (PI3K, and mammalian target of rapamycin (mTOR in ARPE-19 cells; by contrast, the induced changes of autophagy substrate, p62, showed biphasic pattern. The autophagy inhibitor, Baf, attenuated the reduction in oxidative injury conferred by treatment with low doses of LA and Epo in ARPE-19 cells exposed to menadione (VK3 or 4-hydroxynonenal (4-HNE. Knockdown of Atg7 with siRNA in ARPE-19 cells reduced the protective effects of LA or Epo against VK3. Overall, our results suggest that treatment with low levels of proteasome inhibitors confers resistance to oxidative injury by a pathway involving inhibition of the PI3K-Akt-mTOR pathway and activation of autophagy.

  10. Statin-induced inhibition of breast cancer proliferation and invasion involves attenuation of iron transport: intermediacy of nitric oxide and antioxidant defence mechanisms.

    Science.gov (United States)

    Kanugula, Anantha Koteswararao; Gollavilli, Paradesi Naidu; Vasamsetti, Sathish Babu; Karnewar, Santosh; Gopoju, Raja; Ummanni, Ramesh; Kotamraju, Srigiridhar

    2014-08-01

    Accumulating evidence from in vitro, in vivo, clinical and epidemiological studies shows promising results for the use of statins against many cancers including breast carcinoma. However, the molecular mechanisms responsible for the anti-proliferative and anti-invasive properties of statins still remain elusive. In this study, we investigated the involvement of nitric oxide, iron homeostasis and antioxidant defence mechanisms in mediating the anti-proliferative and anti-invasive properties of hydrophobic statins in MDA-MB-231, MDA-MB-453 and BT-549 metastatic triple negative breast cancer cells. Fluvastatin and simvastatin significantly increased cytotoxicity which was reversed with mevalonate. Interestingly, fluvastatin downregulated transferrin receptor (TfR1), with a concomitant depletion of intracellular iron levels in these cells. Statin-induced effects were mimicked by geranylgeranyl transferase inhibitor (GGTI-298) but not farnesyl transferase inhibitor (FTI-277). Further, it was observed that TfR1 downregulation is mediated by increased nitric oxide levels via inducible nitric oxide synthase (iNOS) expression. NOS inhibitors (asymmetric dimethylarginine and 1400W) counteracted and sepiapterin, a precursor of tetrahydrobiopterin, exacerbated statin-induced depletion of intracellular iron levels. Notably, fluvastatin increased manganese superoxide dismutase (by repressing the transcription factor DNA damage-binding protein 2), catalase and glutathione which, in turn, diminished H2 O2 levels. Fluvastatin-induced downregulation of TfR1, matrix metalloproteinase-2, -9 and inhibition of invasion were reversed in the presence of aminotriazole, a specific inhibitor of catalase. Finally, we conclude that fluvastatin, by altering iron homeostasis, nitric oxide generation and antioxidant defence mechanisms, induces triple negative breast cancer cell death. © 2014 FEBS.

  11. Caffeic acid attenuates the inflammatory stress induced by glycated LDL in human endothelial cells by mechanisms involving inhibition of AGE-receptor, oxidative, and endoplasmic reticulum stress.

    Science.gov (United States)

    Toma, Laura; Sanda, Gabriela M; Niculescu, Loredan S; Deleanu, Mariana; Stancu, Camelia S; Sima, Anca V

    2017-09-10

    Type 2 diabetes mellitus is a worldwide epidemic and its atherosclerotic complications determine the high morbidity and mortality of diabetic patients. Caffeic acid (CAF), a phenolic acid present in normal diets, is known for its antioxidant properties. The aim of this study was to investigate CAF's anti-inflammatory properties and its mechanism of action, using cultured human endothelial cells (HEC) incubated with glycated low-density lipoproteins (gLDL). Levels of the receptor for advanced glycation end-products (RAGE), inflammatory stress markers (C reactive protein, CRP; vascular cell adhesion molecule-1, VCAM-1; monocyte chemoattractant protein-1, MCP-1), and oxidative stress and endoplasmic reticulum stress (ERS) markers were evaluated in gLDL-exposed HEC, in the presence/absence of CAF. RAGE silencing or blocking, specific inhibitors for oxidative stress (apocynin, N-acetyl-cysteine), and ERS (salubrinal) were used. The results showed that: (i) gLDL induced CRP synthesis and secretion through mechanisms involving NADPH oxidase-dependent oxidative stress and ERS in HEC; (ii) gLDL-RAGE interaction, oxidative stress, and ERS stimulated the secretion of VCAM-1 and MCP-1 in HEC; and (iii) CAF reduced the secretion of CRP, VCAM-1, and MCP-1 in gLDL-exposed HEC by inhibiting RAGE expression, oxidative stress, and ERS. In conclusion, CAF might be a promising alternative to ameliorate a wide spectrum of disorders due to its complex mechanisms of action resulting in anti-inflammatory and antioxidative properties. © 2017 BioFactors, 43(5):685-697, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

  12. Urinary and plasma oxytocin changes in response to MDMA or intranasal oxytocin administration.

    Science.gov (United States)

    Francis, Sunday M; Kirkpatrick, Matthew G; de Wit, Harriet; Jacob, Suma

    2016-12-01

    The neuropeptide oxytocin (OT) has received increased experimental attention for its putative role in both normal social functioning and several psychiatric disorders that are partially characterized by social dysfunction (e.g., autism spectrum disorders: ASD). Many human experimental studies measure circulating plasma levels of OT in order to examine the relationship between the hormone and behavior. Urinary OT (uOT) assays offer a simple, easy, and non-invasive method to measure peripheral hormone levels, but the correspondence between uOT and plasma OT (pOT) levels is unclear. Here, we conducted two within-subjects, double-blind studies exploring changes in uOT and pOT levels following administration of two drugs: MDMA, an oxytocin-releasing drug (Study 1), and intranasal oxytocin (INOT: Study 1 and 2). In Study 1, 14 adult participants (2 females) were each administered either oral 1.5mg/kg MDMA or 40IU INOT across two different study sessions. In Study 2, 10 male participants (adolescents and young adults) diagnosed with ASD received either 40IU INOT or placebo across two different sessions. In both studies, blood and urine samples were collected before and after drug administration at each study session. For Study 1, 10 participants provided valid plasma and urine samples for the MDMA session, and 8 provided valid samples for the INOT session. For Study 2, all 10 participants provided valid samples for both INOT and placebo sessions. Pre- and post-administration levels of pOT and uOT were compared. Additionally, correlations between percent change from baseline uOT and pOT levels were examined. Study 1: Plasma OT and uOT levels significantly increased after administration of MDMA and INOT. Furthermore, uOT levels were positively correlated with pOT levels following administration of MDMA (r=0.57, p=0.042) but not INOT (r=0.51, p=0.097). Study 2: There was a significant increase in uOT levels after administration of INOT, but not after administration of

  13. Effect of maternal renin-angiotensin-aldosterone system activation on social coping strategies and gene expression of oxytocin and vasopressin in the brain of rat offspring in adulthood.

    Science.gov (United States)

    Senko, Tomáš; Svitok, Pavel; Kršková, Lucia

    2017-10-01

    The intrauterine condition in which the mammalian foetus develops has an important role in prenatal programming. The aim of this study was to determine the extent to which activation of the maternal renin-angiotensin-aldosterone system (RAAS) could influence social behaviour strategies in offspring via changes in social neurotransmitters in the brain. Pregnant female Wistar rats were implanted with osmotic minipumps which continually released angiotensin II for 14 days at concentration of 2 μg/kg/h. The adult offspring (angiotensin and control groups) underwent a social interaction test. The mRNA expression of vasopressin, oxytocin and the oxytocin receptor in selected brain areas was measured by in situ hybridisation. Prenatal exposure to higher levels of angiotensin II resulted in a strong trend toward decreased total social interaction time and significantly decreased time spent in close proximity and frequency of mutual sniffing. The angiotensin group showed no changes in oxytocin mRNA expression in the hypothalamic paraventricular or supraoptic nuclei, but this group had reduced vasopressin mRNA expression in the same areas. We concluded that maternal activation of RAAS (via higher levels of angiotensin II) caused inhibition of some socio-cohesive indicators and decreased vasopressinergic activity of offspring. Taken together, these results suggest a reactive rather than proactive social coping strategy.

  14. Intranasal Oxytocin Selectively Modulates Social Perception, Craving, and Approach Behavior in Subjects With Alcohol Use Disorder.

    Science.gov (United States)

    Mitchell, Jennifer M; Arcuni, Peter A; Weinstein, Dawn; Woolley, Josh D

    2016-01-01

    A pharmacotherapy that both improves social abilities and promotes abstinence may be particularly helpful for the treatment of alcohol use disorder. Recent clinical and preclinical evidence suggests that oxytocin has prosocial and antiaddiction effects. We performed a pilot, laboratory-based, preclinical trial of oxytocin in subjects with alcohol abuse (as per Diagnostic and Statistical Manual of Mental Disorders, 4 Edition criteria) to evaluate therapeutic potential and assess tolerability. Social perceptual ability, cue-induced craving, and approach bias for alcohol and appetitive imagery were quantified after intranasal oxytocin and placebo administration to 32 nontreatment-seeking individuals with alcohol abuse in a double-blind, crossover study. Because attachment style can moderate the effects of oxytocin, we also explored whether attachment style moderated oxytocin's effects on our behavioral measures. Oxytocin significantly improved recognition of easier items on a social perception task, but had no significant group-level effect on cue-induced craving. However, oxytocin effects on craving were moderated by attachment anxiety, with oxytocin reducing craving in more anxiously attached individuals and increasing craving in less anxiously attached individuals. Subjects did not display an approach bias to alcohol images on the placebo day, preventing meaningful analysis of this measure. Subjects did display an approach bias to appetitive images on the placebo day, which was significantly reduced by oxytocin administration. No adverse reactions were observed. Intranasal oxytocin has potential to improve social perception, reduce cue-induced alcohol cravings, and reduce appetitive approach bias in subjects with alcohol abuse, and can be safely tolerated in this population. The effects of oxytocin are complex, however, and require further investigation.

  15. Oxytocin Receptor (OXTR Polymorphisms and Attachment in Human Infants

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    Frances S Chen

    2011-08-01

    Full Text Available Ordinary variations in human infants’ attachment behaviors—their proclivity to seek and accept comfort from caregivers—are associated with a wide range of individual differences in psychological functioning in adults. The current investigation examined variation in the oxytocin receptor (OXTR gene as one possible source of these variations in infant attachment. One hundred and seventy-six infants (77 Caucasian, 99 non-Caucasian were classified as securely or insecurely attached based on their behavior in the Strange Situation (Ainsworth et al., 1976. The A allele at OXTR rs2254298 was associated with attachment security in the non-Caucasian infants (p < .005. These findings underscore the importance of oxytocin in the development of human social behavior and support its role in social stress-regulation and the development of trust.

  16. 2-(1H-Benzimidazol-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol, a Benzimidazole Derivative, Inhibits T Cell Proliferation Involving H+/K+-ATPase Inhibition

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    Jin Liu

    2014-10-01

    Full Text Available In this study, a benzimidazole derivative named BMT-1 is revealed as a potential immunomodulatory agent. BMT-1 inhibits the activity of H+/K+-ATPases from anti-CD3/CD28 activated T cells. Furthermore, inhibition the H+/K+-ATPases by use of BMT-1 should lead to intracellular acidification, inhibiting T cell proliferation. To explore this possibility, the effect of BMT-1 on intracellular pH changes was examined by using BCECF as a pH-dependent fluorescent dye. Interestingly, increases in the pHi were observed in activated T cells, and T cells treated with BMT-1 showed a more acidic intracellular pH. Finally, BMT-1 targeted the H+/K+-ATPases and inhibited the proliferative response of anti-CD3/CD28-stimulated T cells. A cell cycle analysis indicated that BMT-1 arrested the cell cycle progression of activated T cells from the G1 to the S phase without affecting CD25 expression or interleukin-2 (IL-2 production; treating IL-2-dependent PBMCs with BMT-1 also led to the inhibition of cell proliferation. Taken together, these findings demonstrate that BMT-1 inhibits the proliferation of T cells by interfering with H+/K+-ATPases and down-regulating intracellular pHi. This molecule may be an interesting lead compound for the development of new immunomodulatory agents.

  17. Microbial symbionts accelerate wound healing via the neuropeptide hormone oxytocin.

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    Theofilos Poutahidis

    Full Text Available Wound healing capability is inextricably linked with diverse aspects of physical fitness ranging from recovery after minor injuries and surgery to diabetes and some types of cancer. Impact of the microbiome upon the mammalian wound healing process is poorly understood. We discover that supplementing the gut microbiome with lactic acid microbes in drinking water accelerates the wound-healing process to occur in half the time required for matched control animals. Further, we find that Lactobacillus reuteri enhances wound-healing properties through up-regulation of the neuropeptide hormone oxytocin, a factor integral in social bonding and reproduction, by a vagus nerve-mediated pathway. Bacteria-triggered oxytocin serves to activate host CD4+Foxp3+CD25+ immune T regulatory cells conveying transplantable wound healing capacity to naive Rag2-deficient animals. This study determined oxytocin to be a novel component of a multi-directional gut microbe-brain-immune axis, with wound-healing capability as a previously unrecognized output of this axis. We also provide experimental evidence to support long-standing medical traditions associating diet, social practices, and the immune system with efficient recovery after injury, sustained good health, and longevity.

  18. Inhibition of Phosphodiesterase 4 by FCPR03 Alleviates Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice: Involvement of p38 and JNK Signaling Pathways

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    Hui Yu

    2018-02-01

    Full Text Available Inflammatory responses induced by peripheral administration of lipopolysaccharide (LPS triggers depressive-like behavioral syndrome in rodents. Inhibition of phosphodiesterase 4 (PDE4 produces a robust anti-inflammatory effect in inflammatory cells. Unfortunately, archetypal PDE4 inhibitors cause intolerable gastrointestinal side-effects, such as vomiting and nausea. N-isopropyl-3-(cyclopropylmethoxy-4-difluoromethoxy benzamide (FCPR03 is a novel, selective PDE4 inhibitor with little, or no, emetic potency. Our previous studies show that FCPR03 is effective in attenuating neuroinflammation in mice treated with LPS. However, whether FCPR03 could exert antidepressant-like effect induced by LPS is largely unknown. In the present study, mice injected intraperitoneally (i.p. with LPS was established as an in vivo animal model of depression. The antidepressant-like activities of FCPR03 were evaluated using a tail suspension test, forced swimming test, and sucrose preference test. We demonstrated that administration of FCPR03 (1 mg/kg produced antidepressant-like effects in mice challenged by LPS, as evidenced by decreases in the duration of immobility in the forced swim and tail suspension tests, while no significant changes in locomotor activity were observed. FCPR03 also increased sucrose preference in mice treated with LPS. In addition, treatment with FCPR03 abolished the downregulation of brain-derived neurotrophic factor induced by LPS and decreased the level of corticosterone in plasma. Meanwhile, periphery immune challenge by LPS induced enhanced phosphorylation of p38-mitogen activated protein kinase (p38 and c-Jun N-terminal kinase (JNK in both the cerebral cortex and hippocampus in mice. Interestingly, treatment with FCPR03 significantly blocked the role of LPS and reduced the levels of phosphorylated p38 and JNK. Collectively, these results indicate that FCPR03 shows antidepressant-like effects in mice challenged by LPS, and the p38/JNK

  19. [Association between oxytocin augmentation intervals and the risk of postpartum haemorrhage].

    Science.gov (United States)

    Loscul, C; Chantry, A-A; Caubit, L; Deneux-Tharaux, C; Goffinet, F; Le Ray, C

    2016-09-01

    To study the association between the duration of oxytocin augmentation intervals and the risk of postpartum haemorrhage (PPH) among primiparous women in spontaneous labour. Retrospective cohort including primiparous women in spontaneous labour who received oxytocin during labour (n=454). Oxytocin augmentation intervals were dichotomized in intervalsoxytocin augmentation intervals. The association between oxytocin augmentation intervals and PPH was analyzed using univariate and multivariate analysis. Oxytocin augmentation intervals were shorter than 20minutes for 43.8% of the study population. The rate of PPH was higher (9.1% vs 3.5%; P=0.014), and the use of sulprostone was more frequent (6.5% vs 3.5%; P=0.013) if oxytocin augmentation intervals were shorter than 20minutes in comparison with intervals≥20minutes. The association between oxytocin augmentation intervals and PPH remains significant after adjustment on other PPH risk factors (adjusted OR=3.48, 95% CI [1.45-8.34]). The rate of adverse neonatal issue, defined by arterial pH at birth≤7.10 and/or 5minutes score d'Apgar≤7, was higher if oxytocin augmentation intervals wereoxytocin with augmentation intervals shorter than 20minutes. Copyright © 2016. Published by Elsevier Masson SAS.

  20. Use of oxytocin during Caesarean section at Princess Marina Hospital, Botswana: An audit of clinical practice

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    Billy M. Tsima

    2013-02-01

    Full Text Available Background: Oxytocin is widely used for the prevention of postpartum haemorrhage. In the setting of Caesarean section (CS, the dosage and mode of administrating oxytocin differs according to different guidelines. Inappropriate oxytocin doses have been identified ascontributory to some cases of maternal deaths. The main aim of this study was to audit the current standard of clinical practice with regard to the use of oxytocin during CS at a referral hospital in Botswana.Methods: A clinical audit of pregnant women having CS and given oxytocin at the time of the operation was conducted over a period of three months. Data included indications for CS, oxytocin dose regimen, prescribing clinician’s designation, type of anaesthesia for the CS and estimated blood loss.Results: A total of 139 case records were included. The commonest dose was 20 IU infusion (31.7%. The potentially dangerous regimen of 10 IU intravenous bolus of oxytocin was used in 12.9% of CS. Further doses were utilized in 57 patients (41%. The top three indications forCS were fetal distress (36 patients, 24.5%, dystocia (32 patients, 21.8% and a previous CS (25 patients, 17.0%. Estimated blood loss ranged from 50 mL – 2000 mL.Conclusion: The use of oxytocin during CS in the local setting does not follow recommended practice. This has potentially harmful consequences. Education and guidance through evidencebased national guidelines could help alleviate the problem.

  1. Lack of association between human plasma oxytocin and interpersonal trust in a Prisoner's Dilemma paradigm.

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    James C Christensen

    Full Text Available Expanding interest in oxytocin, particularly the role of endogenous oxytocin in human social behavior, has created a pressing need for replication of results and verification of assay methods. In this study, we sought to replicate and extend previous results correlating plasma oxytocin with trust and trustworthy behavior. As a necessary first step, the two most commonly used commercial assays were compared in human plasma via the addition of a known quantity of exogenous oxytocin, with and without sample extraction. Plasma sample extraction was found to be critical in obtaining repeatable concentrations of oxytocin. In the subsequent trust experiment, twelve samples in duplicate, from each of 82 participants, were collected over approximately six hours during the performance of a Prisoner's Dilemma task paradigm that stressed human interpersonal trust. We found no significant relationship between plasma oxytocin concentrations and trusting or trustworthy behavior. In light of these findings, previous published work that used oxytocin immunoassays without sample extraction should be reexamined and future research exploring links between endogenous human oxytocin and trust or social behavior should proceed with careful consideration of methods and appropriate biofluids for analysis.

  2. Induction of oviposition by the administration of oxytocin in hawksbill turtles.

    Science.gov (United States)

    Kawazu, Isao; Kino, Masakatsu; Maeda, Konomi; Yamaguchi, Yasuhiro; Sawamukai, Yutaka

    2014-12-01

    We set out to develop an oviposition induction technique for captive female hawksbill turtles Eretmochelys imbricata. The infertile eggs of nine females were induced to develop by the administration of follicle-stimulating hormone, after which we investigated the effects of administering oxytocin on oviposition. Seven of the turtles were held in a stationary horizontal position on a retention stand, and then oxytocin was administrated (0.6-0.8 units/kg of body weight; 5 mL). The seven turtles were retained for a mandatory 2 h period after oxytocin administration, and were then returned to the holding tanks. As the control, normal saline (5 mL) was administered to the other two turtles, followed by the administration of oxytocin after 24 h. The eggs in oviducts of all nine turtles were observed by ultrasonography at 24 h after oxytocin administration. The control experiment validated that stationary retention and normal saline administration had no effect on egg oviposition. Eight of the turtles began ovipositing eggs at 17-43 min after oxytocin administration, while one began ovipositing in the holding tank immediately after retention. All turtles finished ovipositing eggs within 24 h of oxytocin administration. This report is the first to demonstrate successful induced oviposition in sea turtles. We suggest that the muscles in the oviducts of hawksbill turtles may respond to relatively lower doses of oxytocin (inducing contractions) compared to land and freshwater turtles (4-40 units/kg) based on existing studies.

  3. Working hard for oneself or others: Effects of oxytocin on reward motivation in social anxiety disorder.

    Science.gov (United States)

    Fang, Angela; Treadway, Michael T; Hofmann, Stefan G

    2017-07-01

    There is some evidence to suggest that oxytocin promotes social behavior, especially for disorders characterized by social dysfunction, such as social anxiety disorder (SAD). The goal of this study was to examine the effect of oxytocin on reward motivation in SAD. We tested whether oxytocin promotes prosocial, or antisocial, self-directed decisions, and whether its effects depended on social anxiety severity and attachment. Fifty-two males with SAD received 24 international units of oxytocin or placebo, and completed a reward motivation task that measured willingness to work for self vs. other monetary rewards. Although there was no main drug effect, social anxiety severity moderated the effect of oxytocin. Less socially anxious individuals who received oxytocin worked harder for other vs. own rewards, compared to high socially anxious individuals. Attachment did not moderate this effect. Among people with SAD, oxytocin enhances prosocial behaviors in individuals with relatively lower levels of social anxiety. National Institutes of Health ClinicalTrials.gov Registry #NCT01856530. https://clinicaltrials.gov/ct2/show/NCT01856530?term=oxytocin+pro-social&rank=2. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Relations between plasma oxytocin and cortisol: The stress buffering role of social support

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    Robyn J. McQuaid

    2016-06-01

    Full Text Available Stress responses in humans can be attenuated by exogenous oxytocin administration, and these stress-buffering properties may be moderated by social factors. Yet, the influence of acute stressors on circulating endogenous oxytocin levels have been inconsistent, and limited information is available concerning the influence of social support in moderating this relationship. In the current investigation, undergraduate women (N = 67 were assessed in the Trier Social Stress Test (TSST with either social support available from a close female friend or no social support being available. An additional set of women served as controls. The TSST elicited marked elevations of state anxiety and negative emotions, which were largely attenuated among women who received social support. Furthermore, baseline oxytocin levels were inversely related to women's general feelings of distrust, as well as basal plasma cortisol levels. Despite these associations, oxytocin levels were unaffected by the TSST, and this was the case irrespective of oral contraceptive use or estrogen levels. In contrast, plasma cortisol elevations were elicited by the psychosocial stressor, but only in women using oral contraceptives, an effect that was prevented when social support was available. Taken together, these data provisionally suggest that changes in plasma oxytocin might not accompany the stress attenuating effects of social support on cortisol levels. Moreover, as plasma oxytocin might not reliably reflect brain oxytocin levels, the linkage between oxytocin and prosocial behaviors remains tenuous.

  5. Effects of oxytocin on fertility of red sokoto goats treated with ...

    African Journals Online (AJOL)

    The objective of this study was to evaluate the effects of oxytocin (OX) administration on conception rates in does. Red Sokoto (RS) does (n = 38) were equally allocated into 2 groups; I: does treated with prostaglandin plus normal saline (PGNS) and II: does treated with prostaglandin plus oxytocin (PGOX). Does were ...

  6. Hypooxytocinaemia in obese Zucker rats relates to oxytocin degradation in liver and adipose tissue

    Czech Academy of Sciences Publication Activity Database

    Gajdošechová, L.; Kršková, K.; Segarra, A. B.; Špolcová, Andrea; Suski, M.; Olszanecki, R.; Zórad, S.

    2014-01-01

    Roč. 220, č. 3 (2014), s. 333-343 ISSN 0022-0795 Institutional support: RVO:61388963 Keywords : oxytocin * obesity * insulin resistance * oxytocinase * oxytocin receptor Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.718, year: 2014

  7. THE EFFECTIVENESS OF COMBINATION OF OXYTOCIN AND ENDORPHIN MASSAGE ON UTERINE INVOLUTION IN PRIMIPAROUS MOTHERS

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    Nurmala Sari

    2017-10-01

    Full Text Available Background: One of the puerperal complication is uterine subinvolution that can cause bleeding to maternal death. Oxytocin massage can stimulate oxytocin hormone that plays a role in the process of uterine involution. Endorphine massage can increase the release of oxytocin and endorphine hormone that give a sense of calm and comfort. It also increases production of oxytocin hormone that can improve the process of uterine involution. Objective: To prove the effectiveness of a combination of oxytocin massage and endorphine massage to uterine involution in primiparaous mothers during postpartum period. Methods: This was a quasy-experimental study with pretest-posttest with control group design. Total samples were 44 normal postpartum mothers selected using purposive sampling technique, which were randomly assigned in four groups, namely: 1 oxytocin massage group, 2 endorphin massage group, 3 combined oxytocin-endorphin massage group, and 4 control group. The data were analyzed using univariate, bivariate and One Way Anova to test the effectiveness of the intervention. Results: There were statistically significant differences of fundal height before and after intervention among the four groups (p=<0.05. Conclusion: The combination of oxytocin massage and endorphine massage proved most effective in accelerating uterine involution in normal postpartum mothers.

  8. Nasal Oxytocin for Social Deficits in Childhood Autism: A Randomized Controlled Trial

    Science.gov (United States)

    Dadds, Mark R.; MacDonald, Elayne; Cauchi, Avril; Williams, Katrina; Levy, Florence; Brennan, John

    2014-01-01

    The last two decades have witnessed a surge in research investigating the application of oxytocin as a method of enhancing social behaviour in humans. Preliminary evidence suggests oxytocin may have potential as an intervention for autism. We evaluated a 5-day "live-in" intervention using a double-blind randomized control trial. 38 male…

  9. Oxytocin is associated with PTSD's anxious arousal symptoms in Chinese male earthquake survivors

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    Chengqi Cao

    2014-12-01

    Full Text Available Background: Posttraumatic stress disorder (PTSD is a complex and severe mental disorder triggered by exposure to an extraordinarily traumatic event. Human and animal studies have implied the functional role of the oxytocin system in the development of PTSD (Cochran, Fallon, Hill, & Frazier, 2013; Koch et al., 2014; Olff, 2012. Specification of the role of the oxytocin system in the emergence and progression of PTSD symptomatology would provide evidence to inform both theory and clinical practice. Methods: This study examined the association between oxytocin serum levels and PTSD symptoms. A total of 106 Chinese male adults who suffered from the deadly 2008 Wenchuan earthquake participated in this study. PTSD symptoms were measured with PTSD Checklist for DSM-5 (PCL-5, and serum oxytocin level was determined with ELISA oxytocin kits. Results: The mean score on the PCL-5 was 19.30 (SD=14.50, range: 1–65 in this sample. The mean oxytocin level was 101.59 pg/ml (SD=55.89, range: 31.50–286.71. The results indicated that although the oxytocin was not associated with total PTSD symptoms, it was associated with PTSD's anxious arousal symptoms. Conclusion: These findings support that the oxytocin may play an important functional role in the development of PTSD and contribute to the extant knowledge on the genetic basis of the PTSD symptoms.

  10. Radioimmunoassay measurement of plasma oxytocin and vasopressin in cows during machine milking

    Energy Technology Data Exchange (ETDEWEB)

    Landgraf, R; Wehowsky, G; Schulz, J; Schulze, H; Bothur, D [Forschungsinstitut fuer Koerperkultur und Sport, Leipzig (German Democratic Republic); Karl-Marx-Universitaet, Leipzig (German Democratic Republic). Sektion Tierproduktion und Veterinaermedizin)

    1982-07-01

    The response of plasma oxytocin and vasopressin to machine milking in cows was studied by radioimmunoassay. Depending on the method of machine milking used, plasma oxytocin increased to a greater or lesser degree after teat cup application. Plasma vasopressin was not affected by the milking procedures.

  11. Oxytocin eliminates the own-race bias in face recognition memory.

    Science.gov (United States)

    Blandón-Gitlin, Iris; Pezdek, Kathy; Saldivar, Sesar; Steelman, Erin

    2014-09-11

    The neuropeptide Oxytocin influences a number of social behaviors, including processing of faces. We examined whether Oxytocin facilitates the processing of out-group faces and reduce the own-race bias (ORB). The ORB is a robust phenomenon characterized by poor recognition memory of other-race faces compared to the same-race faces. In Experiment 1, participants received intranasal solutions of Oxytocin or placebo prior to viewing White and Black faces. On a subsequent recognition test, whereas in the placebo condition the same-race faces were better recognized than other-race faces, in the Oxytocin condition Black and White faces were equally well recognized, effectively eliminating the ORB. In Experiment 2, Oxytocin was administered after the study phase. The ORB resulted, but Oxytocin did not significantly reduce the effect. This study is the first to show that Oxytocin can enhance face memory of out-group members and underscore the importance of social encoding mechanisms underlying the own-race bias. This article is part of a Special Issue entitled Oxytocin and Social Behav. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Sex hormones and oxytocin augmentation strategies in schizophrenia : A quantitative review

    NARCIS (Netherlands)

    Heringa, Sophie M; Begemann, Marieke J H; Goverde, Angelique J; Sommer, Iris E C

    2015-01-01

    INTRODUCTION: Sex differences in incidence, onset and course of schizophrenia suggest sex hormones play a protective role in the pathophysiology. Such a role is also proposed for oxytocin, another important regulator of reproduction function. Evidence on the efficacy of sex hormones and oxytocin in

  13. Can oxytocin augmentation modify the risk of epidural analgesia by maternal age in cesarean sections?

    Science.gov (United States)

    Rossen, Janne; Klungsøyr, Kari; Albrechtsen, Susanne; Løkkegård, Ellen; Rasmussen, Steen; Bergholt, Thomas; Skjeldestad, Finn E

    2018-03-07

    Maternal age is an established risk factor for cesarean section; epidural analgesia and oxytocin augmentation may modify this association. We investigated the effects and interactions of oxytocin augmentation, epidural analgesia and maternal age on the risk of cesarean section. In all, 416 386 nulliparous women with spontaneous onset of labor, ≥37 weeks of gestation and singleton infants with a cephalic presentation during 2000-2011 from Norway and Denmark were included [Ten-group classification system (Robson) group 1]. In this case-control study the main exposure was maternal age; epidural analgesia, oxytocin augmentation, birthweight and time period were explanatory variables. Chi-square test and logistic regression were used to estimate associations and interactions. The cesarean section rate increased consistently with advancing maternal age, both overall and in strata of epidural analgesia and oxytocin augmentation. We observed strong interactions between maternal age, oxytocin augmentation and epidural analgesia for the risk of cesarean section. Women with epidural analgesia generally had a reduced adjusted odds ratio when oxytocin was used compared with when it was not used. In Norway, this applied to all maternal age groups but in Denmark only for women ≥30 years. Among women without epidural, oxytocin augmentation was associated with an increased odds ratio for cesarean section in Denmark, whereas no difference was observed in Norway. Oxytocin augmentation in nulliparous women with epidural analgesia is associated with a reduced risk of cesarean section in labor with spontaneous onset. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

  14. Consequence of oxytocin injections on minerals concentration in Sahiwal cow milk

    International Nuclear Information System (INIS)

    Hameed, A.; Anjum, F.M.; Zahoor, T.; Jamil, A.

    2010-01-01

    The major objective of this study was to find out the consequence of exogenous administration of oxytocin to Sahiwal cow, local breed of Pakistan (to enhance milk let down) on mineral composition. Milk samples were collected from two groups of eight animals under controlled atmosphere and feeding input. The analysis of fodder and feed samples were also carried out to support this study. Means of macro and micro minerals of fodder and feed samples were determined. One group of Sahiwal cows was subjected to intramuscular injection of oxytocin (20 IU). The milk obtained from oxytocin injected animals possessed significantly higher sodium and chloride with increment in ash content. Lactose content decreased by 0.39% and ash content increased by 0.08% in milk treated with oxytocin injections. Oxytocin administration increased the level of Na (19.74%), Cl (9.39%) and Cu (146.89%) while K content decreased (10.06%). (author)

  15. Oxytocin increases extrapancreatic glucagon secretion and glucose production in pancreatectomized dogs

    International Nuclear Information System (INIS)

    Altszuler, N.; Puma, F.; Winkler, B.; Fontan, N.; Saudek, C.D.

    1986-01-01

    Infusion of oxytocin into normal dogs increases plasma levels of insulin and glucagon and glucose production and uptake. To determine whether infused oxytocin also increases glucagon secretion from extrapancreatic sites, pancreatectomized dogs, off insulin of 18 hr, were infused with oxytocin and plasma glucagon, and glucose production and uptake were measured using the [6- 3 H]glucose primer-infusion technique. The diabetic dogs, in the control period, had elevated plasma glucose and glucagon levels, an increased rate of glucose production, and a relative decrease in glucose uptake (decreased clearance). Infusion of oxytocin (500 μU/kg/min) caused a rise in plasma glucagon and glucose levels, increased glucose production, and further decreased glucose clearance. it is concluded that oxytocin can stimulate secretion of extrapancreatic glucagon, which contributes to the increased glucose production

  16. Social instability stress in adolescent male rats reduces social interaction and social recognition performance and increases oxytocin receptor binding.

    Science.gov (United States)

    Hodges, Travis E; Baumbach, Jennet L; Marcolin, Marina L; Bredewold, Remco; Veenema, Alexa H; McCormick, Cheryl M

    2017-09-17

    Social experiences in adolescence are essential for displaying context-appropriate social behaviors in adulthood. We previously found that adult male rats that underwent social instability stress (SS) in adolescence had reduced social interactions with unfamiliar peers compared with non-stressed controls (CTL). Here we determined whether SS altered social recognition and social reward and brain oxytocin and vasopressin receptor density in adolescence. We confirmed that SS rats spent less time interacting with unfamiliar peers than did CTL rats (p=0.006). Furthermore, CTL rats showed a preference for novel over familiar conspecifics in a social recognition test whereas SS rats did not, which may reflect reduced recognition, impaired memory, or reduced preference for novelty in SS rats. The reward value of social interactions was not affected by SS based on conditioned place preference tests and based on the greater time SS rats spent investigating stimulus rats than did CTL rats when the stimulus rat was behind wire mesh (p=0.03). Finally, oxytocin receptor binding density was higher in the dorsal lateral septum and nucleus accumbens shell in SS rats compared with CTL rats (p=0.02, p=0.01, respectively). No effect of SS was found for vasopressin 1a receptor binding density in any of the brain regions analyzed. We discuss the extent to which the differences in social behavior exhibited after social instability in adolescence involve changes in social salience and social competency, and the possibility that changes in oxytocin signaling in the brain underlie the differences in social behavior. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. The oxytocin receptor (OXTR contributes to prosocial fund allocations in the dictator game and the social value orientations task.

    Directory of Open Access Journals (Sweden)

    Salomon Israel

    Full Text Available BACKGROUND: Economic games observe social decision making in the laboratory that involves real money payoffs. Previously we have shown that allocation of funds in the Dictator Game (DG, a paradigm that illustrates costly altruistic behavior, is partially determined by promoter-region repeat region variants in the arginine vasopressin 1a receptor gene (AVPR1a. In the current investigation, the gene encoding the related oxytocin receptor (OXTR was tested for association with the DG and a related paradigm, the Social Values Orientation (SVO task. METHODOLOGY/PRINCIPAL FINDINGS: Association (101 male and 102 female students using a robust-family based test between 15 single tagging SNPs (htSNPs across the OXTR was demonstrated with both the DG and SVO. Three htSNPs across the gene region showed significant association with both of the two games. The most significant association was observed with rs1042778 (p = 0.001. Haplotype analysis also showed significant associations for both DG and SVO. Following permutation test adjustment, significance was observed for 2-5 locus haplotypes (p<0.05. A second sample of 98 female subjects was subsequently and independently recruited to play the dictator game and was genotyped for the three significant SNPs found in the first sample. The rs1042778 SNP was shown to be significant for the second sample as well (p = 0.004, Fisher's exact test. CONCLUSIONS: The demonstration that genetic polymorphisms for the OXTR are associated with human prosocial decision making converges with a large body of animal research showing that oxytocin is an important social hormone across vertebrates including Homo sapiens. Individual differences in prosocial behavior have been shown by twin studies to have a substantial genetic basis and the current investigation demonstrates that common variants in the oxytocin receptor gene, an important element of mammalian social circuitry, underlie such individual differences.

  18. Preventing PTSD with oxytocin: effects of oxytocin administration on fear neurocircuitry and PTSD symptom development in recently trauma-exposed individuals

    NARCIS (Netherlands)

    Frijling, Jessie L.

    2017-01-01

    Background: Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder which develops in approximately 10% of trauma-exposed individuals. Currently, there are few early preventive interventions available for PTSD. Intranasal oxytocin administration early posttrauma may prevent PTSD

  19. Peripheral administration of oxytocin increases social affiliation in the naked mole-rat (Heterocephalus glaber).

    Science.gov (United States)

    Mooney, Skyler J; Douglas, Natasha R; Holmes, Melissa M

    2014-04-01

    The neuropeptide oxytocin regulates a wide variety of social behaviors across diverse species. However, the types of behaviors that are influenced by this hormone are constrained by the species in question and the social organization that a particular species exhibits. Therefore, the present experiments investigated behaviors regulated by oxytocin in a eusocial mammalian species by using the naked mole-rat (Heterocephalus glaber). In Experiment 1, adult non-breeding mole-rats were given intraperitoneal injections of either oxytocin (1mg/kg or 10mg/kg) or saline on alternate days. Animals were then returned to their colony and behavior was recorded for minutes 15-30 post-injection. Both doses of oxytocin increased huddling behavior during this time period. In Experiment 2, animals received intraperitoneal injections of either oxytocin (1mg/kg), an oxytocin-receptor antagonist (0.1mg/kg), a cocktail of oxytocin and the antagonist, or saline across 4 testing days in a counterbalanced design. Animals were placed in either a 2-chamber arena with a familiar conspecific or in a small chamber with 1week old pups from their home colony and behaviors were recorded for minutes 15-30 post-injection. Oxytocin increased investigation of, and time spent in close proximity to, a familiar conspecific; these effects were blocked by the oxytocin antagonist. No effects were seen on pup-directed behavior. These data suggest that oxytocin is capable of modulating affiliative-like behavior in this eusocial species. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Plasma oxytocin concentrations during late pregnancy and parturition in the dog.

    Science.gov (United States)

    Klarenbeek, M; Okkens, A C; Kooistra, H S; Mol, J A; M M Bevers; Taverne, M A M

    2007-11-01

    While oxytocin is widely used in the treatment of dystocia in dogs, there is little information about its secretion before and during normal unassisted whelping. We therefore measured plasma oxytocin concentrations during late pregnancy and the expulsive stage of parturition. Blood samples were collected from eight dogs at 3-min intervals during a 42-min period between the 2nd and 14th day before whelping and during parturition after the birth of 1-3 pups. The litters consisted of 5-15 pups and the progression of the expulsive stage was linear and nearly parallel in the eight bitches. The overall mean (+/-S.D.) plasma oxytocin concentration during late pregnancy was 3.6+/-2.1pg/ml. Mean values in individual dogs ranged from 1.2 to 7.4 pg/ml, but the intra-animal variation was rather small. During the expulsive stage the overall mean (+/-S.D.) plasma oxytocin concentration was 12.9+/-13.9 pg/ml, with mean values in individual dogs ranging from 3.5 to 46 pg/ml. The mean area under the oxytocin curve for parturient dogs was significantly higher (Pdogs. During the expulsive stage, the peak plasma oxytocin level in individual dogs ranged between 10 and 117 pg/ml. In six of the eight dogs a pup was born during blood collection and in five of these animals the plasma oxytocin concentration increased temporarily during periods of abdominal straining and expulsion. However, straining efforts and expulsion were not consistently associated with a rise in the circulating oxytocin level. It is concluded that in the dog plasma oxytocin levels are higher and more variable during the expulsive stage of parturition than during late pregnancy. Interrelationships between the secretion pattern of oxytocin, the level of uterine contractility, and the progress of fetal expulsion in dogs need further exploration.

  1. Postprandial oxytocin secretion is associated with severity of anxiety and depressive symptoms in anorexia nervosa.

    Science.gov (United States)

    Lawson, Elizabeth A; Holsen, Laura M; Santin, McKale; DeSanti, Rebecca; Meenaghan, Erinne; Eddy, Kamryn T; Herzog, David B; Goldstein, Jill M; Klibanski, Anne

    2013-05-01

    Anorexia nervosa, a psychiatric disorder characterized by self-induced starvation, is associated with endocrine dysfunction and comorbid anxiety and depression. Animal data suggest that oxytocin may have anxiolytic and antidepressant effects. We have reported increased postprandial oxytocin levels in women with active anorexia nervosa and decreased levels in weight-recovered women with anorexia nervosa compared to healthy controls. A meal may represent a significant source of stress in patients with disordered eating. We therefore investigated the association between postprandial oxytocin secretion and symptoms of anxiety and depression in anorexia nervosa. We performed a cross-sectional study of 35 women (13 women with active anorexia nervosa, 9 with weight-recovered anorexia nervosa, and 13 healthy controls). Anorexia nervosa was diagnosed according to DSM-IV-TR criteria. Serum oxytocin and cortisol and plasma leptin levels were measured fasting and 30, 60, and 120 minutes after a standardized mixed meal. The area under the curve (AUC) and, for oxytocin, postprandial nadir and peak levels were determined. Anxiety and depressive symptoms were assessed using the Spielberger State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory II (BDI-II). The study was conducted from January 2009 to March 2011. In women with anorexia nervosa, oxytocin AUC and postprandial nadir and peak levels were positively associated with STAI trait and STAI premeal and postmeal state scores. Oxytocin AUC and nadir levels were positively associated with BDI-II scores. After controlling for cortisol AUC, all of the relationships remained significant. After controlling for leptin AUC, most of the relationships remained significant. Oxytocin secretion explained up to 51% of the variance in STAI trait and 24% of the variance in BDI-II scores. Abnormal postprandial oxytocin secretion in women with anorexia nervosa is associated with increased symptoms of anxiety and depression. This

  2. A New Perspective on the Pathophysiology of Borderline Personality Disorder: A Model of the Role of Oxytocin.

    Science.gov (United States)

    Herpertz, Sabine C; Bertsch, Katja

    2015-09-01

    Borderline personality disorder is characterized by three domains of dysfunction: affect dysregulation, behavioral dyscontrol, and interpersonal hypersensitivity. Interpersonal hypersensitivity is associated with a (pre)attentive bias toward negative social information and, on the level of the brain, enhanced bottom-up emotion generation, while affect dysregulation results from abnormal top-down processes. Additionally, the problems of patients with borderline personality disorder in interpersonal functioning appear to be related to alterations in the (social) reward and empathy networks. There is increasing evidence that the oxytocinergic system may be involved in these domains of dysfunction and may thus contribute to borderline psychopathology and even open new avenues for targeted pharmacotherapeutic approaches. From studies in healthy and clinical subjects (including first studies with borderline personality disorder patients), the authors provide a conceptual framework for future research in borderline personality disorder that is based on oxytocinergic modulation of the following biobehavioral mechanisms: 1) the brain salience network favoring adaptive social approach behavior, 2) the affect regulation circuit normalizing top-down processes, 3) the mesolimbic circuit improving social reward experiences, and 4) modulating brain regions involved in cognitive and emotional empathy. In addition, preliminary data point to interactions between the oxytocin and cannabinoid system, with implications for pain processing. These mechanisms, which the authors believe to be modulated by oxytocin, may not be specific for borderline personality disorder but rather may be common to a host of psychiatric disorders in which disturbed parent-infant attachment is a major etiological factor.

  3. Oxytocin as an Indicator of Psychological and Social Well-Being in Domesticated Animals: A Critical Review

    Directory of Open Access Journals (Sweden)

    Jean-Loup Rault

    2017-09-01

    Full Text Available Oxytocin is often portrayed as a hormone specific to social behavior, reflective of positive welfare states, and linked to mental states. Research on oxytocin in domesticated animal species has been few to date but is rapidly increasing (in dog, pig, cattle, sheep, with direct implications for animal welfare. This review evaluates the evidence for the specificity of oxytocin as an indicator of: 1. Social, 2. Positive, and 3. Psychological well-being. Oxytocin has most often been studied in socially relevant paradigms, with a lack of non-social control paradigms. Oxytocin research appears biased toward investigating positive valence, with a lack of control in valence or arousal. Oxytocin actions are modulated by the environmental and social contexts, which are important factors to consider. Limited evidence supports that oxytocin's actions are linked to psychological states; nevertheless whether this is a direct effect of oxytocin per se remains to be demonstrated. Overall, it is premature to judge oxytocin's potential as an animal welfare indicator given the few and discrepant findings and a lack of standardization in methodology. We cover potential causes for discrepancies and suggest solutions through appropriate methodological design, oxytocin sampling or delivery, analysis and reporting. Of particular interest, the oxytocinergic system as a whole remains poorly understood. Appreciation for the differences that social contact and group living pose in domesticated species and the way they interact with humans should be key considerations in using oxytocin as a psychosocial indicator of well-being.

  4. Oxytocin differently regulates pressor responses to stress in WKY and SHR rats: the role of central oxytocin and V1a receptors.

    Science.gov (United States)

    Wsol, A; Szczepanska-Sadowska, E; Kowalewski, S; Puchalska, L; Cudnoch-Jedrzejewska, A

    2014-01-01

    The role of central oxytocin in the regulation of cardiovascular parameters under resting conditions and during acute stress was investigated in male normotensive Wistar-Kyoto (WKY; n = 40) and spontaneously hypertensive rats (SHR; n = 28). In Experiment 1, mean arterial blood pressure (MABP) and heart rate (HR) were recorded in WKY and SHR rats at rest and after an air-jet stressor during intracerebroventricular (ICV) infusions of vehicle, oxytocin or oxytocin receptor (OTR) antagonist. In Experiment 2, the effects of vehicle, oxytocin and OTR antagonist were determined in WKY rats after prior administration of a V1a vasopressin receptor (V1aR) antagonist. Resting MABP and HR were not affected by any of the ICV infusions either in WKY or in SHR rats. In control experiments (vehicle), the pressor response to stress was significantly higher in SHR. Oxytocin enhanced the pressor response to stress in the WKY rats but reduced it in SHR. During V1aR blockade, oxytocin infusion entirely abolished the pressor response to stress in WKY rats. Combined blockade of V1aR and OTR elicited a significantly greater MABP response to stress than infusion of V1a antagonist and vehicle. This study reveals significant differences in the regulation of blood pressure in WKY and SHR rats during alarming stress. Specifically, the augmentation of the pressor response to stress by exogenous oxytocin in WKY rats is caused by its interaction with V1aR, and endogenous oxytocin regulates the magnitude of the pressor response to stress in WKY rats by simultaneous interaction with OTR and V1aR.

  5. Sex-Specific Effects of Stress on Oxytocin Neurons Correspond With Responses to Intranasal Oxytocin.

    Science.gov (United States)

    Steinman, Michael Q; Duque-Wilckens, Natalia; Greenberg, Gian D; Hao, Rebecca; Campi, Katharine L; Laredo, Sarah A; Laman-Maharg, Abigail; Manning, Claire E; Doig, Ian E; Lopez, Eduardo M; Walch, Keenan; Bales, Karen L; Trainor, Brian C

    2016-09-01

    Oxytocin (OT) is considered to be a stress-buffering hormone, dampening the physiologic effects of stress. However, OT can also be anxiogenic. We examined acute and long-lasting effects of social defeat on OT neurons in male and female California mice. We used immunohistochemistry for OT and c-fos cells to examine OT neuron activity immediately after defeat (n = 6-9) and 2 weeks (n = 6-9) and 10 weeks (n = 4-5) later. We quantified Oxt messenger RNA with quantitative polymerase chain reaction (n = 5-9). Intranasal OT was administered to naïve and stressed mice tested in social interaction and resident-intruder tests (n = 8-14). Acute exposure to a third episode of defeat increased OT/c-fos colocalizations in the paraventricular nucleus of both sexes. In the medioventral bed nucleus of the stria terminalis, defeat increased Oxt messenger RNA, total OT neurons, and OT/c-fos colocalizations in female mice but not male mice. Intranasal OT failed to reverse stress-induced social withdrawal in female mice and reduced social interaction behavior in female mice naïve to defeat. In contrast, intranasal OT increased social interaction in stressed male mice and reduced freezing in the resident-intruder test. Social defeat induces long-lasting increases in OT production and OT/c-fos cells in the medioventral bed nucleus of the stria terminalis of female mice but not male mice. Intranasal OT largely reversed the effects of stress on behavior in male mice, but effects were mixed in female mice. These results suggest that changes in OT-sensitive networks contribute to sex differences in behavioral responses to stress. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  6. Study Protocol. ECSSIT – Elective Caesarean Section Syntocinon® Infusion Trial. A multi-centre randomised controlled trial of oxytocin (Syntocinon® 5 IU bolus and placebo infusion versus oxytocin 5 IU bolus and 40 IU infusion for the control of blood loss at elective caesarean section

    Directory of Open Access Journals (Sweden)

    Montgomery Alan A

    2009-08-01

    Full Text Available Abstract Background Caesarean section is one of the most commonly performed major operations in women throughout the world. Rates are escalating, with studies from the United States of America, the United Kingdom, China and the Republic of Ireland reporting rates between 20% and 25%. Operative morbidity includes haemorrhage, anaemia, blood transfusion and in severe cases, maternal death. The value of routine oxytocics in the third stage of vaginal birth has been well established and it has been assumed that these benefits apply to caesarean delivery as well. A slow bolus dose of oxytocin is recommended following delivery of the baby at caesarean section. Some clinicians use an additional infusion of oxytocin for a further period following the procedure. Intravenous oxytocin has a very short half-life (4–10 minutes therefore the potential advantage of an oxytocin infusion is that it maintains uterine contractility throughout the surgical procedure and immediate postpartum period, when most primary haemorrhages occur. The few trials to date addressing the optimal approach to preventing haemorrhage at caesarean section have been under-powered to evaluate clinically important outcomes. There has been no trial to date comparing the use of an intravenous slow bolus of oxytocin versus an oxytocin bolus and infusion. Methods and design A multi-centre randomised controlled trial is proposed. The study will take place in five large maternity units in Ireland with collaboration between academics and clinicians in the disciplines of obstetrics and anaesthetics. It will involve 2000 women undergoing elective caesarean section after 36 weeks gestation. The main outcome measure will be major haemorrhage (blood loss >1000 ml. A study involving 2000 women will have 80% power to detect a 36% relative change in the risk of major haemorrhage with two-sided 5% alpha. Discussion It is both important and timely that we evaluate the optimal approach to the management

  7. Study Protocol. ECSSIT – Elective Caesarean Section Syntocinon® Infusion Trial. A multi-centre randomised controlled trial of oxytocin (Syntocinon®) 5 IU bolus and placebo infusion versus oxytocin 5 IU bolus and 40 IU infusion for the control of blood loss at elective caesarean section

    Science.gov (United States)

    Murphy, Deirdre J; Carey, Michael; Montgomery, Alan A; Sheehan, Sharon R

    2009-01-01

    Background Caesarean section is one of the most commonly performed major operations in women throughout the world. Rates are escalating, with studies from the United States of America, the United Kingdom, China and the Republic of Ireland reporting rates between 20% and 25%. Operative morbidity includes haemorrhage, anaemia, blood transfusion and in severe cases, maternal death. The value of routine oxytocics in the third stage of vaginal birth has been well established and it has been assumed that these benefits apply to caesarean delivery as well. A slow bolus dose of oxytocin is recommended following delivery of the baby at caesarean section. Some clinicians use an additional infusion of oxytocin for a further period following the procedure. Intravenous oxytocin has a very short half-life (4–10 minutes) therefore the potential advantage of an oxytocin infusion is that it maintains uterine contractility throughout the surgical procedure and immediate postpartum period, when most primary haemorrhages occur. The few trials to date addressing the optimal approach to preventing haemorrhage at caesarean section have been under-powered to evaluate clinically important outcomes. There has been no trial to date comparing the use of an intravenous slow bolus of oxytocin versus an oxytocin bolus and infusion. Methods and design A multi-centre randomised controlled trial is proposed. The study will take place in five large maternity units in Ireland with collaboration between academics and clinicians in the disciplines of obstetrics and anaesthetics. It will involve 2000 women undergoing elective caesarean section after 36 weeks gestation. The main outcome measure will be major haemorrhage (blood loss >1000 ml). A study involving 2000 women will have 80% power to detect a 36% relative change in the risk of major haemorrhage with two-sided 5% alpha. Discussion It is both important and timely that we evaluate the optimal approach to the management of the third stage at

  8. Study protocol. ECSSIT - Elective Caesarean Section Syntocinon Infusion Trial. A multi-centre randomised controlled trial of oxytocin (Syntocinon) 5 IU bolus and placebo infusion versus oxytocin 5 IU bolus and 40 IU infusion for the control of blood loss at elective caesarean section.

    LENUS (Irish Health Repository)

    Murphy, Deirdre J

    2012-02-01

    BACKGROUND: Caesarean section is one of the most commonly performed major operations in women throughout the world. Rates are escalating, with studies from the United States of America, the United Kingdom, China and the Republic of Ireland reporting rates between 20% and 25%. Operative morbidity includes haemorrhage, anaemia, blood transfusion and in severe cases, maternal death. The value of routine oxytocics in the third stage of vaginal birth has been well established and it has been assumed that these benefits apply to caesarean delivery as well. A slow bolus dose of oxytocin is recommended following delivery of the baby at caesarean section. Some clinicians use an additional infusion of oxytocin for a further period following the procedure. Intravenous oxytocin has a very short half-life (4-10 minutes) therefore the potential advantage of an oxytocin infusion is that it maintains uterine contractility throughout the surgical procedure and immediate postpartum period, when most primary haemorrhages occur. The few trials to date addressing the optimal approach to preventing haemorrhage at caesarean section have been under-powered to evaluate clinically important outcomes. There has been no trial to date comparing the use of an intravenous slow bolus of oxytocin versus an oxytocin bolus and infusion. METHODS AND DESIGN: A multi-centre randomised controlled trial is proposed. The study will take place in five large maternity units in Ireland with collaboration between academics and clinicians in the disciplines of obstetrics and anaesthetics. It will involve 2000 women undergoing elective caesarean section after 36 weeks gestation. The main outcome measure will be major haemorrhage (blood loss >1000 ml). A study involving 2000 women will have 80% power to detect a 36% relative change in the risk of major haemorrhage with two-sided 5% alpha. DISCUSSION: It is both important and timely that we evaluate the optimal approach to the management of the third stage at

  9. Study protocol. ECSSIT - Elective Caesarean Section Syntocinon Infusion Trial. A multi-centre randomised controlled trial of oxytocin (Syntocinon) 5 IU bolus and placebo infusion versus oxytocin 5 IU bolus and 40 IU infusion for the control of blood loss at elective caesarean section.

    LENUS (Irish Health Repository)

    Murphy, Deirdre J

    2009-01-01

    BACKGROUND: Caesarean section is one of the most commonly performed major operations in women throughout the world. Rates are escalating, with studies from the United States of America, the United Kingdom, China and the Republic of Ireland reporting rates between 20% and 25%. Operative morbidity includes haemorrhage, anaemia, blood transfusion and in severe cases, maternal death. The value of routine oxytocics in the third stage of vaginal birth has been well established and it has been assumed that these benefits apply to caesarean delivery as well. A slow bolus dose of oxytocin is recommended following delivery of the baby at caesarean section. Some clinicians use an additional infusion of oxytocin for a further period following the procedure. Intravenous oxytocin has a very short half-life (4-10 minutes) therefore the potential advantage of an oxytocin infusion is that it maintains uterine contractility throughout the surgical procedure and immediate postpartum period, when most primary haemorrhages occur. The few trials to date addressing the optimal approach to preventing haemorrhage at caesarean section have been under-powered to evaluate clinically important outcomes. There has been no trial to date comparing the use of an intravenous slow bolus of oxytocin versus an oxytocin bolus and infusion. METHODS AND DESIGN: A multi-centre randomised controlled trial is proposed. The study will take place in five large maternity units in Ireland with collaboration between academics and clinicians in the disciplines of obstetrics and anaesthetics. It will involve 2000 women undergoing elective caesarean section after 36 weeks gestation. The main outcome measure will be major haemorrhage (blood loss >1000 ml). A study involving 2000 women will have 80% power to detect a 36% relative change in the risk of major haemorrhage with two-sided 5% alpha. DISCUSSION: It is both important and timely that we evaluate the optimal approach to the management of the third stage at

  10. NF-kappa B signaling pathway is involved in growth inhibition, G2/M arrest and apoptosis induced by Trichostatin A in human tongue carcinoma cells

    NARCIS (Netherlands)

    Yao, Jun; Duan, Li; Fan, Mingwen; Wu, Xinxing

    2006-01-01

    The HDAC inhibitor Trichostatin A (TSA) exhibits antiturnour activity in various tumour cells. However, little is known about the effect of TSA on growth of human tongue carcinoma cells. In this study, we observed that TSA concentration-dependently inhibited growth of human tongue carcinoma Tca8113

  11. Association between genetic variation in the oxytocin receptor gene and emotional withdrawal, but not between oxytocin pathway genes and diagnosis in psychotic disorders.

    Directory of Open Access Journals (Sweden)

    Marit eHaram

    2015-01-01

    Full Text Available Social dysfunction is common in patients with psychotic disorders. Oxytocin is a neuropeptide with a central role in social behaviour. This study aims to explore the relationship between oxytocin pathway genes and symptoms related to social dysfunction in patients with psychotic disorders. We performed association analyses between four oxytocin pathway genes (OXT, OXTR, AVP, CD38 and four areas of social behaviour-related psychopathology as measured by Positive and Negative Syndrome Scale (PANSS. For this purpose, we used both a polygenic risk score (PGRS and single OXTR candidate SNPs previously reported in the literature (rs53576, rs237902, rs2254298. A total of 734 subjects with DSM-IV psychotic spectrum disorders and 420 healthy controls were included. Oxytocin pathway PGRSs were calculated based on the independent Psychiatric Genomics Consortium study sample. There was a significant association between symptom of Emotional Withdrawal and the previously reported OXTR risk allele A in rs53576. No significant associations between oxytocin pathway gene variants and a diagnosis of psychotic disorder were found. Our findings indicate that while oxytocin pathway genes do not appear to contribute to the susceptibility to psychotic disorders, variations in the OXTR gene might play a role in the development of impaired social behaviour.

  12. Anti-Cancer Effect of Metabotropic Glutamate Receptor 1 Inhibition in Human Glioma U87 Cells: Involvement of PI3K/Akt/mTOR Pathway

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    Chi Zhang

    2015-01-01

    Full Text Available Background: Metabotropic glutamate receptors (mGluRs are G-protein-coupled receptors that mediate neuronal excitability and synaptic plasticity in the central nervous system, and emerging evidence suggests a role of mGluRs in the biology of cancer. Previous studies showed that mGluR1 was a potential therapeutic target for the treatment of breast cancer and melanoma, but its role in human glioma has not been determined. Methods: In the present study, we investigated the effects of mGluR1 inhibition in human glioma U87 cells using specific targeted small interfering RNA (siRNA or selective antagonists Riluzole and BAY36-7620. The anti-cancer effects of mGluR1 inhibition were measured by cell viability, lactate dehydrogenase (LDH release, TUNEL staining, cell cycle assay, cell invasion and migration assays in vitro, and also examined in a U87 xenograft model in vivo. Results: Inhibition of mGluR1 significantly decreased the cell viability but increased the LDH release in a dose-dependent fashion in U87 cells. These effects were accompanied with the induction of caspase-dependent apoptosis and G0/G1 cell cycle arrest. In addition, the results of Matrigel invasion and cell tracking assays showed that inhibition of mGluR1 apparently attenuated cell invasion and migration in U87 cells. All these anti-cancer effects were ablated by the mGluR1 agonist L-quisqualic acid. The results of western blot analysis showed that mGluR1 inhibition overtly decreased the phosphorylation of PI3K, Akt, mTOR and P70S6K, indicating the mitigated activation of PI3K/Akt/mTOR pathway. Moreover, the anti-tumor activity of mGluR1 inhibition in vivo was also demonstrated in a U87 xenograft glioma model in athymic nude mice. Conclusion: The remarkable efficiency of mGluR1 inhibition to induce cell death in U87 cells may find therapeutic application for the treatment of glioma patients.

  13. Variation in the oxytocin receptor gene is associated with increased risk for anxiety, stress and depression in individuals with a history of exposure to early life stress.

    Science.gov (United States)

    Myers, Amanda J; Williams, Leanne; Gatt, Justine M; McAuley-Clark, Erica Z; Dobson-Stone, Carol; Schofield, Peter R; Nemeroff, Charles B

    2014-12-01

    Oxytocin is a neuropeptide that is involved in the regulation of mood, anxiety and social biology. Genetic variation in the oxytocin receptor gene (OXTR) has been implicated in anxiety, depression and related stress phenotypes. It is not yet known whether OXTR interacts with other risk factors such as early life trauma to heighten the severity of experienced anxiety and depression. In this study, we examined genotypes in 653 individuals and tested whether SNP variation in OXTR correlates with severity of features of self-reported experience on the Depression Anxiety and Stress Scale (DASS), and whether this correlation is enhanced when early life trauma is taken into account. We also assessed the effects of OXTR SNPs on RNA expression levels in two separate brain tissue cohorts totaling 365 samples. A significant effect of OXTR genotype on DASS anxiety, stress and depression scores was found and ELS events, in combination with several different OXTR SNPs, were significantly associated with differences in DASS scores with one SNP (rs139832701) showing significant association or a trend towards association for all three measures. Several OXTR SNPs were correlated with alterations in OXTR RNA expression and rs3831817 replicated across both sets of tissues. These results support the hypothesis that the oxytocin system plays a role in the pathophysiology of mood and anxiety disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Changes in salivary oxytocin after inhalation of clary sage essential oil scent in term-pregnant women: a feasibility pilot study.

    Science.gov (United States)

    Tadokoro, Yuriko; Horiuchi, Shigeko; Takahata, Kaori; Shuo, Takuya; Sawano, Erika; Shinohara, Kazuyuki

    2017-12-08

    This pilot study using a quasi-experimental design was conducted to evaluate the feasibility (i.e., limited efficacy, practicality, and acceptability) of our intervention protocol involving inhalation of the scent of clary sage essential oil by pregnant women and measurement of their preinhalation and postinhalation oxytocin levels. Participants were women of singleton pregnancies between 38 and 40 gestation weeks (N = 11). The experiment group (n = 5) inhaled the scent of clary sage essential oil diluted 50-fold with 10 mL of odorless propylene glycol for 20 min. Regarding limited efficacy, the oxytocin level 15 min postinhalation increased in 3 women and was unmeasurable in 2. The control group (n = 6) inhaled similarly without the 50-fold dilution of clary sage essential oil. Their oxytocin level increased in 2 women, decreased in 2, and was unmeasurable in 2. Uterine contraction was not observed in both groups. Regarding practicality, 3 of the 11 women could not collect sufficient saliva. The cortisol level decreased in both groups postinhalation. The protocol had no negative effects. Regarding acceptability, burden of the protocol was not observed. Trial registration The Clinical Trials Registry of University Hospital Medical Information Network in Japan-UMIN000017830. Registered:  June 8, 2015.

  15. [ABIN1 is not involved in imatinib upregulating A20 to inhibit the activation of NF-κB pathway in Jurkat T cells].

    Science.gov (United States)

    Chen, Qian; Wang, Senlin; Lin, Chen; Chen, Shaohua; Zhao, Xiaoling; Li, Yangqiu

    2017-05-01

    Objective To investigate the effect of imatinib (IM) on the expressions of A20-binding inhibitor of NF-κB1 (ABIN1) and A20 in Jurkat T cells. Methods Jurkat T cells were treated with 25, 50 and 100 nmol/L IM for 24 hours. The mRNA and protein levels of ABIN1, A20 and NF-κB were detected by real-time quantitative PCR and Western blotting. Results IM significantly inhibited both mRNA and protein levels of ABIN1 and NF-κB, but raised the mRNA and protein levels of A20; while phorbol 12-myristate 13-acetate/ionomycin increased the expression levels of ABIN1 and A20 mRNA and protein. Conclusion IM could upregulate A20 protein to inhibit the activation of NF-κB pathway in Jurkat T cells, which was independent of the ABIN1 protein.

  16. Synthetic triterpenoid inhibition of human ghrelin O-acyltransferase: Involvement of a functionally required cysteine provides mechanistic insight into ghrelin acylation

    OpenAIRE

    McGovern-Gooch, Kayleigh R.; Mahajani, Nivedita S.; Garagozzo, Ariana; Schramm, Anthony J.; Hannah, Lauren G.; Sieburg, Michelle A.; Chisholm, John D.; Hougland, James L.

    2017-01-01

    The peptide hormone ghrelin plays a key role in regulating hunger and energy balance within the body. Ghrelin signaling presents a promising and unexploited target for development of small-molecule therapeutics to treat obesity, diabetes, and other health conditions. Inhibition of ghrelin O-acyltransferase (GOAT), which catalyzes an essential octanoylation step in ghrelin maturation, offers a potential avenue for controlling ghrelin signaling. Through screening a small molecule library, we ha...

  17. Inhibition of cancer cell growth by exposure to a specific time-varying electromagnetic field involves T-type calcium channels.

    Directory of Open Access Journals (Sweden)

    Carly A Buckner

    Full Text Available Electromagnetic field (EMF exposures affect many biological systems. The reproducibility of these effects is related to the intensity, duration, frequency, and pattern of the EMF. We have shown that exposure to a specific time-varying EMF can inhibit the growth of malignant cells. Thomas-EMF is a low-intensity, frequency-modulated (25-6 Hz EMF pattern. Daily, 1 h, exposures to Thomas-EMF inhibited the growth of malignant cell lines including B16-BL6, MDA-MB-231, MCF-7, and HeLa cells but did not affect the growth of non-malignant cells. Thomas-EMF also inhibited B16-BL6 cell proliferation in vivo. B16-BL6 cells implanted in syngeneic C57b mice and exposed daily to Thomas-EMF produced smaller tumours than in sham-treated controls. In vitro studies showed that exposure of malignant cells to Thomas-EMF for > 15 min promoted Ca(2+ influx which could be blocked by inhibitors of voltage-gated T-type Ca(2+ channels. Blocking Ca(2+ uptake also blocked Thomas-EMF-dependent inhibition of cell proliferation. Exposure to Thomas-EMF delayed cell cycle progression and altered cyclin expression consistent with the decrease in cell proliferation. Non-malignant cells did not show any EMF-dependent changes in Ca(2+ influx or cell growth. These data confirm that exposure to a specific EMF pattern can affect cellular processes and that exposure to Thomas-EMF may provide a potential anti-cancer therapy.

  18. Inhibition of cancer cell growth by exposure to a specific time-varying electromagnetic field involves T-type calcium channels.

    Science.gov (United States)

    Buckner, Carly A; Buckner, Alison L; Koren, Stan A; Persinger, Michael A; Lafrenie, Robert M

    2015-01-01

    Electromagnetic field (EMF) exposures affect many biological systems. The reproducibility of these effects is related to the intensity, duration, frequency, and pattern of the EMF. We have shown that exposure to a specific time-varying EMF can inhibit the growth of malignant cells. Thomas-EMF is a low-intensity, frequency-modulated (25-6 Hz) EMF pattern. Daily, 1 h, exposures to Thomas-EMF inhibited the growth of malignant cell lines including B16-BL6, MDA-MB-231, MCF-7, and HeLa cells but did not affect the growth of non-malignant cells. Thomas-EMF also inhibited B16-BL6 cell proliferation in vivo. B16-BL6 cells implanted in syngeneic C57b mice and exposed daily to Thomas-EMF produced smaller tumours than in sham-treated controls. In vitro studies showed that exposure of malignant cells to Thomas-EMF for > 15 min promoted Ca(2+) influx which could be blocked by inhibitors of voltage-gated T-type Ca(2+) channels. Blocking Ca(2+) uptake also blocked Thomas-EMF-dependent inhibition of cell proliferation. Exposure to Thomas-EMF delayed cell cycle progression and altered cyclin expression consistent with the decrease in cell proliferation. Non-malignant cells did not show any EMF-dependent changes in Ca(2+) influx or cell growth. These data confirm that exposure to a specific EMF pattern can affect cellular processes and that exposure to Thomas-EMF may provide a potential anti-cancer therapy.

  19. Radiation-induced enteropathy: Molecular basis of pentoxifylline–vitamin E anti-fibrotic effect involved TGF-β1 cascade inhibition

    International Nuclear Information System (INIS)

    Hamama, Saad; Gilbert-Sirieix, Marie; Vozenin, Marie-Catherine; Delanian, Sylvie

    2012-01-01

    Background: Radiation-induced fibrosis is a serious late complication of radiotherapy. Pentoxifylline–vitamin E has proven effective and safe in clinical trials in the treatment of fibrosis, while the molecular mechanism of its activity is yet unexplored. Methods: Ten patients suffering from radiation-induced enteropathy were treated with pentoxifylline–vitamin E combination with SOMA score as the primary endpoint. In parallel, primary smooth muscle cells isolated from intestinal samples isolated from humans with radiation enteropathy were incubated with pentoxifylline, trolox (vit. E hydrophilic analogous) or their combination. Activation of the TGF-β1/Smad and Rho/ROCK pathways was subsequently investigated using Q-RT-PCR, gene reporter, Western-blot, ELISA and immunohistochemistry. Results: Pentoxifylline–vitamin E combination induces regression of symptoms (SOMA) by −41% and −80% at 6 and 18 months. In vitro, pentoxifylline and trolox synergize to inhibit TGF-β1 protein and mRNA expression. This inhibitory action is mediated at the transcriptional level and leads to subsequent inhibition of TGF-β1/Smad targets (Col Iα1, FN1, PAI-1, CTGF), while it has no effect on the Rho/ROCK pathway. Conclusions: The anti-fibrotic effect of combined pentoxifylline–vitamin E is at least in part mediated by inhibition of the TGF-β1 cascade. It strengthens previous clinical data showing pentoxifylline–vitamin E synergy and supports its use as a first-line treatment of radiation-induced fibrosis.

  20. Oridonin effectively reverses the drug resistance of cisplatin involving induction of cell apoptosis and inhibition of MMP expression in human acute myeloid leukemia cells

    Directory of Open Access Journals (Sweden)

    Yuan Zhang

    2017-03-01

    Full Text Available Cisplatin is the first generation platinum-based chemotherapy agent. However, the extensive application of cisplatin inevitably causes drug resistance, which is a major obstacle to cancer chemotherapy. Oridonin is a diterpenoid isolated from Rabdosia rubescens with potent anticancer activity. The aim of our study is to investigate the role of oridonin to reverse the cisplatin-resistance in human acute myeloid leukemia (AML cells. The effect of oridonin on human AML cell proliferation was evaluated by MTT assay, cell migration and invasion were evaluated by transwell migration and invasion assays in cisplatin-resistant human AML cells. Furthermore, cell apoptosis was examined by flow cytometry. The inhibitive effect of oridonin in vivo was determined using xenografted nude mice. In addition, the expressions of MMP2 and MMP9 were detected by Western blot. There was a synergistic antitumor effect between cisplatin and oridonin on cisplatin-resistant human AML cells in vitro and in vivo. In addition, the combination of cisplatin and oridonin synergistically induced cell apoptosis. Furthermore, the combination treatment not only inhibited AML cell migration and invasion, but more significantly, decreased the expressions of MMP2 and MMP9 proteins. Our results suggest that the synergistic effect between both agents is likely to be driven by the inhibition of MMP expression and the resulting increased apoptosis.

  1. Procyanidins from evening primrose (Oenothera paradoxa) defatted seeds inhibit invasiveness of breast cancer cells and modulate the expression of selected genes involved in angiogenesis, metastasis, and apoptosis.

    Science.gov (United States)

    Lewandowska, Urszula; Szewczyk, Karolina; Owczarek, Katarzyna; Hrabec, Zbigniew; Podsędek, Anna; Sosnowska, Dorota; Hrabec, Elżbieta

    2013-01-01

    There is a growing interest in plant polyphenols (including flavanols) that exhibit pleiotropic biological activities such as antiinflammatory, antioxidant, and anticancer effects. Here, we report for the first time the inhibition of MDA-MB-231 breast cancer cell viability and invasiveness by an evening primrose flavanol preparation (EPFP). We observed a decrease in MDA-MB-231 viability of 50% vs. a control after 72 h of incubation with EPFP at a concentration of 58 μM gallic acid equivalents (GAE) and an inhibition of their invasiveness of 65% vs. a control at 75 μM GAE after 48 h of incubation. EPFP caused a 10-fold reduction in matrix metalloproteinase-9 (MMP-9) activity at 100 μM GAE. Furthermore, through modulation of mRNA expression, EPFP reduced the expression levels of the following proteins: antiapoptotic Bcl-2, angiogenic vascular endothelial growth factor (VEGF), and 2 transcription factors (c-Jun, c-Fos). Moreover, analysis by flow cytometry revealed that EPFP induced apoptosis in MDA-MB-231 cells. In conclusion, our data shows that EPFP inhibits cell viability by increasing apoptosis and decreases cell invasiveness by decreasing angiogenesis.

  2. Effects of acute doses of prosocial drugs methamphetamine and alcohol on plasma oxytocin levels.

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    Bershad, Anya K; Kirkpatrick, Matthew G; Seiden, Jacob A; de Wit, Harriet

    2015-06-01

    Many drugs, including alcohol and stimulants, demonstrably increase sociability and verbal interaction and are recreationally consumed in social settings. One drug, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), seems to produce its prosocial effects by increasing plasma oxytocin levels, and the oxytocin system has been implicated in responses to several other drugs of abuse. Here, we sought to investigate the effects of 2 other "social" drugs on plasma oxytocin levels--methamphetamine and alcohol. Based on their shared capacity to enhance sociability, we hypothesized that both methamphetamine and alcohol would increase plasma oxytocin levels. In study 1, 11 healthy adult volunteers attended 3 sessions during which they received methamphetamine (10 mg or 20 mg) or placebo under double-blind conditions. Subjective drug effects, cardiovascular effects, and plasma oxytocin levels were measured at regular intervals throughout the sessions. In study 2, 8 healthy adult volunteers attended a single session during which they received 1 beverage containing placebo, and then a beverage containing alcohol (0.8 g/kg). Subjective effects, breath alcohol levels, and plasma oxytocin levels were measured at regular intervals. Both methamphetamine and alcohol produced their expected physiological and subjective effects, but neither of these drugs increased plasma oxytocin levels. The neurobiological mechanisms mediating the prosocial effects of drugs such as alcohol and methamphetamine remain to be identified.

  3. Effects of Intranasal Oxytocin on Aggressive Responding in Antisocial Personality Disorder.

    Science.gov (United States)

    Alcorn, Joseph L; Rathnayaka, Nuvan; Swann, Alan C; Moeller, F Gerard; Lane, Scott D

    2015-12-01

    The oxytocin receptor is important in several domains of social behavior, and administration of oxytocin modulates social responding in several mammalian species, including humans. Oxytocin has both therapeutic and scientific potential for elucidating the neural and behavioral mechanisms governing social behavior. In the present study, operationally-defined aggressive behavior of six males with Antisocial Personality Disorder (ASPD) was measured following acute intranasal oxytocin dosing (12, 24, and 48 international units) and placebo, using a well-validated laboratory task of human aggression (Point-Subtraction Aggression Paradigm, or PSAP). The PSAP provides participants with concurrently available monetary-earning and operationally-defined aggressive response options, maintained by fixed ratio schedules of consequences. Shifts in response rates and inter-response time (IRT) distributions were observed on the aggressive response option following oxytocin doses, relative to placebo. Few changes were observed in monetary-reinforced responding. However, across participants the direction and magnitude of changes in aggressive responding were not systematically related to dose. No trends were observed between psychometric or physiological data and oxytocin dosing or aggressive behavior. While this report is to our knowledge the first to examine the acute effects of oxytocin in this population at high risk for violence and other forms of antisocial behavior, several limitations in the experimental design and the results cast the study as a preliminary report. Strategies for more extensive future projects are discussed.

  4. Basal salivary oxytocin level predicts extra- but not intra-personal dimensions of emotional intelligence.

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    Koven, Nancy S; Max, Laura K

    2014-06-01

    A wealth of literature suggests that oxytocin is an important mediator of social cognition, but much of the research to date has relied on pharmaceutical administration methods that can raise oxytocin to artificially high levels. The present study builds upon previous work by examining whether basal oxytocin level predicts intra- and extra-personal (i.e., self- and other-focused) elements of emotional intelligence (EI), independent of shared variance with current mood. The sample included 71 healthy young adults (46 women). Assessment measures included the Mayer-Salovey-Caruso Emotional Intelligence Test Version 2.0 (MSCEIT), the Trait Meta-Mood Scale, and the Profile of Mood States. Peripheral oxytocin levels were examined with enzyme-linked immunosorbent assay from saliva after solid phase extraction. Oxytocin level was unrelated to TMMS scores but was positively associated with performance in the Experiential EI domain of the MSCEIT. However, total mood disturbance was positively related to MSCEIT scores. Hierarchical regression analysis indicated that oxytocin level added unique variance to the prediction of MSCEIT performance beyond that of current mood. These results confirm an association between endogenous levels of oxytocin in healthy adults and a subset of EI abilities, including extra-personal emotion recognition and the channeling of emotions to enhance social proficiency. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Does oxytocin lead to emotional interference during a working memory paradigm?

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    Tollenaar, Marieke S; Ruissen, M; Elzinga, B M; de Bruijn, E R A

    2017-12-01

    Oxytocin administration may increase attention to emotional information. We hypothesized that this augmented emotional processing might in turn lead to interference on concurrent cognitive tasks. To test this hypothesis, we examined whether oxytocin administration would lead to heightened emotional interference during a working memory paradigm. Additionally, moderating effects of childhood maltreatment were explored. Seventy-eight healthy males received 24 IU of intranasal oxytocin or placebo in a randomized placebo-controlled double-blind between-subjects study. A working memory task was performed during which neutral, positive, and negative distractors were presented. The main outcome observed was that oxytocin did not enhance interference by emotional information during the working memory task. There was a non-significant trend for oxytocin to slow down performance irrespective of distractor valence, while accuracy was unaffected. Exploratory analyses showed that childhood maltreatment was related to lower overall accuracy, but in the placebo condition only. However, the maltreated group sample size was very small precluding any conclusions on its moderating effect. Despite oxytocin's previously proposed role in enhanced emotional processing, no proof was found that this would lead to reduced performance on a concurrent cognitive task. The routes by which oxytocin exerts its effects on cognitive and social-emotional processes remain to be fully elucidated.

  6. Oxytocin makes females, but not males, less forgiving following betrayal of trust.

    Science.gov (United States)

    Yao, Shuxia; Zhao, Weihua; Cheng, Rui; Geng, Yayuan; Luo, Lizhu; Kendrick, Keith M

    2014-11-01

    Although oxytocin has been shown to enhance trust behavior, to date no study has directly established whether oxytocin can modulate the effect of repair strategies on restoring damaged trust. In the current double-blind, between-subjects, placebo-controlled design study, two repair strategies were used to examine the effect of intranasal oxytocin administration on modulating trust restoration in a revised trust game. The results showed that although oxytocin had no overall effect on modulating trust restoration, it did have a significant gender specific effect. Female subjects showed less evidence for trust repair in the oxytocin compared with the placebo treatment group. This suggests that oxytocin may make female subjects exhibit more punitive behavior towards partners who violate their trust and less sensitive to repair strategies provided by them. Interestingly, this gender specific effect was more evident in the context of attempted trust repair using financial compensation. However, it also extended to both apology alone and no compensation conditions, but not to the fair one, in females exhibiting high trait forgiveness. Thus females with a more forgiving attitude towards betrayal may actually be more likely to punish betrayal following oxytocin treatment.

  7. Intranasal oxytocin increases neural responses to social reward in post-traumatic stress disorder.

    Science.gov (United States)

    Nawijn, Laura; van Zuiden, Mirjam; Koch, Saskia B J; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

    2017-02-01

    Therapeutic alliance and perceived social support are important predictors of treatment response for post-traumatic stress disorder (PTSD). Intranasal oxytocin administration may enhance treatment response by increasing sensitivity for social reward and thereby therapeutic alliance and perceived social support. As a first step to investigate this therapeutical potential, we investigated whether intranasal oxytocin enhances neural sensitivity to social reward in PTSD patients. Male and female police officers with (n = 35) and without PTSD (n = 37) were included in a double-blind, randomized, placebo-controlled cross-over fMRI study. After intranasal oxytocin (40 IU) and placebo administration, a social incentive delay task was conducted to investigate neural responses during social reward and punishment anticipation and feedback. Under placebo, PTSD patients showed reduced left anterior insula (AI) responses to social rewards (i.e. happy faces) compared with controls. Oxytocin administration increased left AI responses during social reward in PTSD patients, such that PTSD patients no longer differed from controls under placebo. Furthermore, in PTSD patients, oxytocin increased responses to social reward in the right putamen. By normalizing abberant insula responses and increasing putamen responses to social reward, oxytocin administration may enhance sensitivity for social support and therapeutic alliance in PTSD patients. Future studies are needed to investigate clinical effects of oxytocin. © The Author (2016). Published by Oxford University Press.

  8. Oxytocin facilitation of acceptance of social advice is dependent upon the perceived trustworthiness of individual advisors.

    Science.gov (United States)

    Luo, Ruixue; Xu, Lei; Zhao, Weihua; Ma, Xiaole; Xu, Xiaolei; Kou, Juan; Gao, Zhao; Becker, Benjamin; Kendrick, Keith M

    2017-09-01

    The neuropeptide oxytocin may increase social cohesion by making us more willing to trust others and/or to conform to their opinions. Here we investigated whether intranasal oxytocin can influence acceptance of advice given on solving everyday social problems by either individual expert (psychologist) or non-expert advisors with or without influencing their perceived likeability or trustworthiness. In a double-blind, between-subject, placebo-control design study in 160 male and female subjects, intranasal oxytocin (24IU) only significantly enhanced acceptance of advice given by female psychologists who were rated as the most trustworthy advisors. However, oxytocin itself did not alter either trustworthiness or likeability ratings. The oxytocin effect on acceptance of the female psychologist's advice was not maintained after a week, with subjects mainly reverting to their original solutions. These findings suggest that while oxytocin can transiently increase acceptance of advice from the most trustworthy individuals this is because it makes subjects more likely to conform to their opinions rather than enhancing their perceived trustworthiness or likeability. Thus in every day contexts oxytocin may primarily promote social cohesion by facilitating conformity towards the opinions of the most trusted individuals. Copyright © 2017. Published by Elsevier Ltd.

  9. Oxytocin decreases cocaine taking, cocaine seeking, and locomotor activity in female rats.

    Science.gov (United States)

    Leong, Kah-Chung; Zhou, Luyi; Ghee, Shannon M; See, Ronald E; Reichel, Carmela M

    2016-02-01

    Oxytocin has been shown to decrease cocaine taking and seeking in male rats, suggesting potential treatment efficacy for drug addiction. In the present study, we extended these findings to the assessment of cocaine seeking and taking in female rats. Further, we made direct comparisons of oxytocin's impact on cocaine induced locomotor activity in both males and females. In females, systemic oxytocin (0.3, 1.0, 3.0 mg/kg) attenuated lever pressing for cocaine during self-administration and oxytocin (1.0 mg/kg) attenuated cue-induced cocaine seeking following extinction. Cocaine increased baseline locomotor activity to a greater degree in females relative to males. Oxytocin (0.1, 0.3, 1.0, and 3.0 mg/kg) reduced cocaine-induced locomotor activity in females, but not significantly in males. These data illustrate sex similarities in oxytocin's attenuation of cocaine seeking, but sex differences in cocaine-induced locomotor effects. While reductions in cocaine seeking cannot be attributed to a reduction in locomotor activity in males, attenuation of locomotor function cannot be entirely ruled out as an explanation for a decrease in cocaine seeking in females suggesting that oxytocin's effect on cocaine seeking may be mediated by different mechanisms in male and females. PsycINFO Database Record (c) 2016 APA, all rights reserved.

  10. The effect of oxytocin on attention to angry and happy faces in chronic depression.

    Science.gov (United States)

    Domes, Gregor; Normann, Claus; Heinrichs, Markus

    2016-04-06

    Chronic depression is characterized by a high degree of early life trauma, psychosocial impairment, and deficits in social cognition. Undisturbed recognition and processing of facial emotions are basic prerequisites for smooth social interactions. Intranasal application of the neuropeptide oxytocin has been reported to enhance emotion recognition in neuropsychiatric disorders and healthy individuals. We therefore investigated whether oxytocin modulates attention to emotional faces in patients with chronic depression. In this double-blind, randomized, controlled study, 43 patients received a single dose of oxytocin or placebo nasal spray and were tested while fulfilling a facial dot probe task. We assessed reaction times to neutral probes presented at the location of one of two faces depicting happy, angry, or neutral expressions as a prime. When comparing reaction times to the congruent (prime and probe at the same location) with incongruent presentation of facial emotions, neither the placebo nor oxytocin group showed an attentional preference for emotional facial expressions in terms of a threat bias. However, oxytocin treatment did reveal two specific effects: it generally reduced the allocation of attention towards angry facial expressions, and it increased sustained attention towards happy faces, specifically under conditions of heightened awareness, i.e. trials with longer primes. We investigated a heterogeneous group of medicated male and female patients. We conclude that oxytocin does modulate basic factors of facial emotion processing in chronic depression. Our findings encourage further investigations assessing the therapeutic potential of oxytocin in chronic depression. EUDRA-CT 2010-020956-69 . Date registered: 23 February 2011.

  11. Oxytocin eliminates the own-race bias in face recognition memory☆

    Science.gov (United States)

    Blandón-Gitlin, Iris; Pezdek, Kathy; Saldivar, Sesar; Steelman, Erin

    2015-01-01

    The neuropeptide Oxytocin influences a number of social behaviors, including processing of faces. We examined whether Oxytocin facilitates the processing of out-group faces and reduce the own-race bias (ORB). The ORB is a robust phenomenon characterized by poor recognition memory of other-race faces compared to the same-race faces. In Experiment 1, participants received intranasal solutions of Oxytocin or placebo prior to viewing White and Black faces. On a subsequent recognition test, whereas in the placebo condition the same-race faces were better recognized than other-race faces, in the Oxytocin condition Black and White faces were equally well recognized, effectively eliminating the ORB. In Experiment 2, Oxytocin was administered after the study phase. The ORB resulted, but Oxytocin did not significantly reduce the effect. This study is the first to show that Oxytocin can enhance face memory of out-group members and underscore the importance of social encoding mechanisms underlying the own-race bias. PMID:23872107

  12. Early social environment affects the endogenous oxytocin system: a review and future directions

    Directory of Open Access Journals (Sweden)

    Emily eAlves

    2015-03-01

    Full Text Available Endogenous oxytocin plays an important role in a wide range of human functions including birth, milk ejection during lactation and facilitation of social interaction. There is increasing evidence that both variations in the oxytocin receptor (OXTR and concentrations of oxytocin are associated with differences in these functions. The causes for the differences that have been observed in tonic and stimulated oxytocin release remain unclear. Previous reviews have suggested that across the life course, these differences may be due to individual factors, e.g. genetic variation (of the OXTR, age or sex, or be the result of early environmental influences such as social experiences, stress or trauma partly by inducing epigenetic changes. This review has three aims. First, we briefly discuss the endogenous oxytocin system, including physiology, development, individual differences and function. Secondly, current models describing the relationship between the early life environment and the development of the oxytocin system in humans and animals are discussed. Finally, we describe research designs that can be used to investigate the effects of the early environment on the oxytocin system, identifying specific areas of research that need further attention.

  13. Oxytocin increases bias, but not accuracy, in face recognition line-ups.

    Science.gov (United States)

    Bate, Sarah; Bennetts, Rachel; Parris, Benjamin A; Bindemann, Markus; Udale, Robert; Bussunt, Amanda

    2015-07-01

    Previous work indicates that intranasal inhalation of oxytocin improves face recognition skills, raising the possibility that it may be used in security settings. However, it is unclear whether oxytocin directly acts upon the core face-processing system itself or indirectly improves face recognition via affective or social salience mechanisms. In a double-blind procedure, 60 participants received either an oxytocin or placebo nasal spray before completing the One-in-Ten task-a standardized test of unfamiliar face recognition containing target-present and target-absent line-ups. Participants in the oxytocin condition outperformed those in the placebo condition on target-present trials, yet were more likely to make false-positive errors on target-absent trials. Signal detection analyses indicated that oxytocin induced a more liberal response bias, rather than increasing accuracy per se. These findings support a social salience account of the effects of oxytocin on face recognition and indicate that oxytocin may impede face recognition in certain scenarios. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  14. Safety and Efficacy of Misoprostol versus Oxytocin for the Prevention of Postpartum Hemorrhage

    Directory of Open Access Journals (Sweden)

    Minoo Rajaei

    2014-01-01

    Full Text Available Postpartum hemorrhage (PPH is the commonest cause of maternal death worldwide. Studies suggest that the use of misoprostol may be beneficial in clinical settings where oxytocin is unavailable. The aim of this study was to compare the safety and efficacy of oxytocin and misoprostol when used in the prevention of PPH. In a double-blind randomized controlled trial, 400 pregnant women who had a vaginal delivery were assigned into two groups: to receive either 20 IU of oxytocin in 1000 mL Ringer’s solution and two placebo tablets or 400 mcg oral misoprostol (as two tablets and 2 mL normal saline in 1000 mL Ringer’s solution. The quantity of blood loss was higher in the oxytocin group in comparison to the misoprostol group. There was no significant difference in the decrease in hematocrit and hemoglobin between the two groups. Although there was no significant difference in the need for transfusions between the two groups, the patients in the oxytocin group had greater need for additional oxytocin. Results from this study indicate that it may be considered as an alternative for oxytocin in low resource clinical settings. This study is registered with ClinicalTrials.gov NCT01863706.

  15. Oxytocin mechanisms of stress response and aggression in a territorial finch.

    Science.gov (United States)

    Goodson, James L; Schrock, Sara E; Kingsbury, Marcy A

    2015-03-15

    All jawed vertebrates produce a form of oxytocin (OT), and in birds, mammals and fish, OT is strongly associated with affiliation. However, remarkably few data are available on the roles of OT and OT receptors (OTRs) in aggression. Because OT and OTRs exert anxiolytic effects in mammals (although context-specific) and modulate stress coping, we hypothesized that OTR activation is at least permissive for territorial aggression. Indeed, we find that peripheral injections of an OTR antagonist significantly reduce male-male and female-female aggression in a highly territorial finch. This finding suggests the hypothesis that aggression is accompanied by an increase in transcriptional (Fos) activity of OT neurons, but contrary to this hypothesis, we find that dominant male residents do not elevate OT-Fos colocalization following an aggressive encounter and that OT-Fos colocalization in the preoptic area and hypothalamus correlates negatively with aggression. Furthermore, OT-Fos colocalization increases dramatically in males that were aggressively subjugated or pursued by a human hand, likely reflecting OT modulation of stress response. Because OT inhibits the hypothalamo-pituitary-adrenal axis, the antagonist effects may reflect the fact that aggressive birds and mammals tend to be hyporesponsive to stress. If this is correct, then 1) the observed effects of OTR antagonism may reflect alterations in corticosterone feedback to the brain rather than centrally mediated OTR effects, and 2) the negative correlation between OT-Fos colocalization and aggression may reflect the fact that more aggressive, stress hyporesponsive males require less inhibition of the hypothalamo-pituitary-adrenal axis than do less aggressive males, despite the requirement of that inhibition for the normal display of aggression. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Protective Macroautophagy Is Involved in Vitamin E Succinate Effects on Human Gastric Carcinoma Cell Line SGC-7901 by Inhibiting mTOR Axis Phosphorylation.

    Directory of Open Access Journals (Sweden)

    Liying Hou

    Full Text Available Vitamin E succinate (VES, a potential cancer therapeutic agent, potently induces apoptosis and inhibits the growth of various cancer cells. Autophagy has been supposed to promote cancer cell survival or trigger cell death, depending on particular cancer types and tumor microenvironments. The role of autophagy in the growth suppressive effect of VES on gastric cancer cell is basically unknown. We aimed to determine whether and how autophagy affected the VES-induced inhibition of SGC-7901 human gastric carcinoma cell growth. SGC-7901 cells were treated with VES or pre-treated with autophagy inhibitor, chloroquine (CQ and 3-methyladenine (3-MA. Electron microscopy, fluorescence microscopy and Western blot were used to study whether VES induced autophagy reaction in SGC-7901 cells. Western blot evaluated the activities of the mammalian target of rapamycin (mTOR axis. Then we used 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT and flow cytometry to detect the level of cell viability and apoptosis. Collectively, our data indeed strongly support our hypothesis that VES treatment produced cytological variations that depict autophagy, increased the amount of intracellular green fluorescent protein-microtubule associated protein 1 light chain 3 (GFP-LC3 punctate fluorescence and the number of autophagic vacuoles. It altered the expression of endogenous autophagy marker LC3. VES activated the suppression of mTOR through inhibiting upstream regulators p38 MAPK and Akt. mTOR suppression consequently inhibited the activation of mTOR downstream targets p70S6K and 4E-BP-1. The activation of the upstream mTOR inhibitor AMPK had been up-regulated by VES. The results showed that pre-treatment SGC-7901 with autophagy inhibitors before VES treatment could increase the capacity of VES to reduce cell viability and to provoke apoptosis. In conclusion, VES-induced autophagy participates in SGC-7901 cell protection by inhibiting mTOR axis

  17. EGFR‑associated pathways involved in traditional Chinese medicine (TCM)‑1‑induced cell growth inhibition, autophagy and apoptosis in prostate cancer.

    Science.gov (United States)

    Wu, Zhaomeng; Zhu, Qingyi; Zhang, Yu; Yin, Yingying; Kang, Dan; Cao, Runyi; Tian, Qian; Lu, Shan; Liu, Ping

    2018-06-01

    Traditional Chinese medicine (TCM) has the synergistic effect of the combination of a single ingredient and a monomer, and systemic and local therapeutic effects in cancer treatment, through which TCM is able to enhance the curative effect and reduce the side effects. The present study analyzed the effect of TCM‑1 (an anti‑cancer TCM) on prostate cancer (PCa) cell lines, and studied in detail the mechanism of cell death induced by TCM‑1 in vitro and in vivo. From the present results, it was identified for the first time, to the best of our knowledge, that TCM‑1 arrested the cell cycle at the G1 phase, decreased cell viability and increased nuclear rupture in a dose‑dependent manner; these effects finally resulted in apoptosis in PCa cells. At the molecular level, the data demonstrated that TCM‑1 competitively acted on epidermal growth factor receptor (EGFR) with EGF, and suppressed the auto‑phosphorylation and activity of EGFR. Inhibition of EGFR further suppressed the downstream phosphatidylinositol 3‑kinase (PI3K)/RAC‑α serine/threonine‑protein kinase (AKT) and RAF proto‑oncogene serine/threonine‑protein kinase/extracellular signal regulated kinase signaling pathways and resulted in a decrease in the phosphorylated‑forkhead box protein O1 (at Ser256, Thr24 and Ser319) expression level, and induced cell growth inhibition and apoptosis by regulating the expression of apoptosis‑and cell cycle‑associated genes. In addition, TCM‑1 markedly inhibited the PI3K/AKT/serine/threonine‑protein kinase mTOR signaling pathway and induced cell autophagy by downregulating the phosphorylation of p70S6K and upregulating the levels of Beclin‑1 and microtubule‑associated protein light chain‑3II. In vivo, the TCM‑1‑treated group exhibited a significant decrease in tumor volume compared with the negative control group in subcutaneous xenograft nude mice by inhibiting EGFR‑associated signaling pathways. Therefore, the bio‑functions of

  18. The Protective Effects of Κ-Opioid Receptor Stimulation in Hypoxic Pulmonary Hypertension Involve Inhibition of Autophagy Through the AMPK-MTOR Pathway

    Directory of Open Access Journals (Sweden)

    Yaguang Zhou

    2017-12-01

    Full Text Available Background/Aims: In a previous study, we showed that κ-opioid receptor stimulation with the selective agonist U50,488H ameliorated hypoxic pulmonary hypertension (HPH. However, the roles that pulmonary arterial smooth muscle cell (PASMC proliferation, apoptosis, and autophagy play in κ-opioid receptor-mediated protection against HPH are still unknown. The goal of the present study was to investigate the role of autophagy in U50,488H-induced HPH protection and the underlying mechanisms. Methods: Rats were exposed to 10% oxygen for three weeks to induce HPH. After hypoxia, the mean pulmonary arterial pressure (mPAP and the right ventricular pressure (RVP were measured. Cell viability was monitored using the Cell Counting Kit-8 (CCK-8 assay. Cell apoptosis was detected by flow cytometry and Western blot. Autophagy was assessed by means of the mRFP-GFP-LC3 adenovirus transfection assay and by Western blot. Results: Inhibition of autophagy by the administration of chloroquine prevented the development of HPH in the rat model, as evidenced by significantly reduced mPAP and RVP, as well as decreased autophagy. U50,488H mimicked the effects of chloroquine, and the effects of U50,488H were blocked by nor-BNI, a selective κ-opioid receptor antagonist. In vitro experiments showed that the inhibition of autophagy by chloroquine was associated with decreased proliferation and increased apoptosis of PASMCs. Under hypoxia, U50,488H also significantly inhibited autophagy, reduced proliferation and increased apoptosis of PASMCs. These effects of U50,488H were blocked by nor-BNI. Moreover, exposure to hypoxic conditions significantly increased AMPK phosphorylation and reduced mTOR phosphorylation, and these effects were abrogated by U50,488H. The effects of U50,488H on PASMC autophagy were inhibited by AICAR, a selective AMPK agonist, or by rapamycin, a selective mTOR inhibitor. Conclusion: Our data provide evidence for the first time that κ-opioid receptor

  19. Dopamine and oxytocin interactions underlying behaviors: potential contributions to behavioral disorders.

    Science.gov (United States)

    Baskerville, Tracey A; Douglas, Alison J

    2010-06-01

    Dopamine is an important neuromodulator that exerts widespread effects on the central nervous system (CNS) function. Disruption in dopaminergic neurotransmission can have profound effects on mood and behavior and as such is known to be implicated in various neuropsychiatric behavioral disorders including autism and depression. The subsequent effects on other neurocircuitries due to dysregulated dopamine function have yet to be fully explored. Due to the marked social deficits observed in psychiatric patients, the neuropeptide, oxytocin is emerging as one particular neural substrate that may be influenced by the altered dopamine levels subserving neuropathologic-related behavioral diseases. Oxytocin has a substantial role in social attachment, affiliation and sexual behavior. More recently, it has emerged that disturbances in peripheral and central oxytocin levels have been detected in some patients with dopamine-dependent disorders. Thus, oxytocin is proposed to be a key neural substrate that interacts with central dopamine systems. In addition to psychosocial improvement, oxytocin has recently been implicated in mediating mesolimbic dopamine pathways during drug addiction and withdrawal. This bi-directional role of dopamine has also been implicated during some components of sexual behavior. This review will discuss evidence for the existence dopamine/oxytocin positive interaction in social behavioral paradigms and associated disorders such as sexual dysfunction, autism, addiction, anorexia/bulimia, and depression. Preliminary findings suggest that whilst further rigorous testing has to be conducted to establish a dopamine/oxytocin link in human disorders, animal models seem to indicate the existence of broad and integrated brain circuits where dopamine and oxytocin interactions at least in part mediate socio-affiliative behaviors. A profound disruption to these pathways is likely to underpin associated behavioral disorders. Central oxytocin pathways may serve as a

  20. Oxytocin Acts in Nucleus Accumbens to Attenuate Methamphetamine Seeking and Demand.

    Science.gov (United States)

    Cox, Brittney M; Bentzley, Brandon S; Regen-Tuero, Helaina; See, Ronald E; Reichel, Carmela M; Aston-Jones, Gary

    2017-06-01

    Evidence indicates that oxytocin, an endogenous peptide well known for its role in social behaviors, childbirth, and lactation, is a promising addiction pharmacotherapy. We employed a within-session behavioral-economic (BE) procedure in rats to examine oxytocin as a pharmacotherapy for methamphetamine (meth) addiction. The BE paradigm was modeled after BE procedures used to assess motivation for drugs in humans with addiction. The same BE variables assessed across species have been shown to predict later relapse behavior. Thus, the translational potential of preclinical BE studies is particularly strong. We tested the effects of systemic and microinfused oxytocin on demand for self-administered intravenous meth and reinstatement of extinguished meth seeking in male and female rats using a BE paradigm. Correlations between meth demand and meth seeking were assessed. Female rats showed greater demand (i.e., motivation) for meth compared with male rats. In both male and female rats, meth demand predicted reinstatement of meth seeking, and systemic oxytocin decreased demand for meth and attenuated reinstatement to meth seeking. Oxytocin was most effective at decreasing meth demand and seeking in rats with the strongest motivation for drug. Finally, these effects of systemic oxytocin were mediated by actions in the nucleus accumbens. Oxytocin decreases meth demand and seeking in both sexes, and these effects depend on oxytocin signaling in the nucleus accumbens. Overall, these data indicate that development of oxytocin-based therapies may be a promising treatment approach for meth addiction in humans. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. Effects of oxytocin on high intensity focused ultrasound (HIFU) ablation of adenomysis: A prospective study

    International Nuclear Information System (INIS)

    Zhang, Xin; Zou, Min; Zhang, Cai; He, Jia; Mao, Shihua; Wu, Qingrong; He, Min; Wang, Jian; Zhang, Ruitao; Zhang, Lian

    2014-01-01

    Objective: To investigate the effects of oxytocin on high-intensity focused ultrasound (HIFU) ablation for the treatment of adenomyosis. Materials and methods: Eighty-six patients with adenomyosis from three hospitals were randomly assigned to the oxytocin group or control group for HIFU treatment. During HIFU treatment, 80 units of oxytocin was added in 500 ml of 0.9% normal saline running at the rate of 2 ml/min (0.32 U/min) in the oxytocin group, while 0.9% normal saline was used in the control group. Both patients and HIFU operators were blinded to oxytocin or saline application. Treatment results, adverse effects were compared. Results: When using oxytocin, the non-perfused volume (NPV) ratio was 80.7 ± 11.6%, the energy-efficiency factor (EEF) was 8.1 ± 9.9 J/mm 3 , and the sonication time required to ablate 1 cm 3 was 30.0 ± 36.0 s/cm 3 . When not using oxytocin, the non-perfused volume ratio was 70.8 ± 16.7%, the EEF was 15.8 ± 19.6 J/mm 3 , and the sonication time required to ablate 1 cm 3 was 58.2 ± 72.7 S/cm 3 . Significant difference in the NPV ratio, EEF, and the sonication time required to ablate 1 cm 3 between the two groups was observed. No oxytocin related adverse effects occurred. Conclusion: Oxytocin could significantly decrease the energy for ablating adenomyosis with HIFU, safely enhance the treatment efficiency

  2. Restoring effects of oxytocin on the attentional preference for faces in autism.

    Science.gov (United States)

    Kanat, M; Spenthof, I; Riedel, A; van Elst, L T; Heinrichs, M; Domes, G

    2017-04-18

    Reduced attentional preference for faces and symptoms of social anxiety are common in autism spectrum disorders (ASDs). The neuropeptide oxytocin triggers anxiolytic functions and enhances eye gaze, facial emotion recognition and neural correlates of face processing in ASD. Here we investigated whether a single dose of oxytocin increases attention to faces in ASD. As a secondary question, we explored the influence of social anxiety on these effects. We tested for oxytocin's effects on attention to neutral faces as compared to houses in a sample of 29 autistic individuals and 30 control participants using a dot-probe paradigm with two different presentation times (100 or 500 ms). A single dose of 24 IU oxytocin was administered in a randomized, double-blind placebo-controlled, cross-over design. Under placebo, ASD individuals paid less attention to faces presented for 500 ms than did controls. Oxytocin administration increased the allocation of attention toward faces in ASD to a level observed in controls. Secondary analyses revealed that these oxytocin effects primarily occurred in ASD individuals with high levels of social anxiety who were characterized by attentional avoidance of faces under placebo. Our results confirm a positive influence of intranasal oxytocin on social attention processes in ASD. Further, they suggest that oxytocin may in particular restore the attentional preference for facial information in ASD individuals with high social anxiety. We conclude that oxytocin's anxiolytic properties may partially account for its positive effects on socio-cognitive functioning in ASD, such as enhanced eye gaze and facial emotion recognition.

  3. Oral misoprostol versus oxytocin in the management of third stage of labour

    International Nuclear Information System (INIS)

    Aziz, S.; Kazi, S.; Haq, G.; Soomro, N.

    2014-01-01

    Objectives: To compare oral misoprostol versus intramuscular oxytocin in the management of third stage of labour. Methods: The quasi-experimental study was conducted at the Obstetrics and Gynaecology Unit II, Civil Hospital, Karachi, from June 20 to December 19, 2006. A total of 70 patients diagnosed in active phase of labour who fulfilled the inclusion criteria were selected by non-probability convenience sampling. These patients were divided into 2 groups of 35 patients each, for Oxytocin (Group 1) and misoprostol (Group 2). Main and secondary outcome measures were analysed. SPSS 10 was used for statistical analysis. Results: Average amount of blood loss(ml) was 267.14+-140.35 with Oxytocin versus 302.86+-160.4, with Misoprostol, this difference was statistically insignificant (p=0.236). Average drop in haemoglobin concentration (g/dl) with Oxytocin was 1.55+-0.38 vs 1.66+-0.61 with Misoprostol (p=0.684). Drop in haematocrit (%) was 4.18+-0.64 with Oxytocin vs. 4.50+-0.92 with Misoprostol (p=0.133). There was also insignificant difference in duration of third stage of labour, between oxytocin and Misoprostol groups (5.37+-2.20 vs. 5.23+-2.46, p=0.451) Shivering, in Misoprostol group occured in n=11 (31.4%) vs n=3 (8.6%) with Oxytocin (p=0.017) and pyrexia in n=6 (17.1%) with misoprostol vs n=0, with oxytocin (p=0.025) thus significantly higher in misoprostol group. Conclusion: There were no major differences in oral misoprostol and intramuscular oxytocin in the management of third stage of labour. (author)

  4. Modulating the Oxytocin System During the Perinatal Period: A New Strategy for Neuroprotection of the Immature Brain?

    Directory of Open Access Journals (Sweden)

    Manuela Zinni

    2018-04-01

    Full Text Available Oxytocin is a neurohypophysal hormone known for its activity during labor and its role in lactation. However, the function of oxytocin (OTX goes far beyond the peripheral regulation of reproduction, and the central effects of OTX have been extensively investigated, since it has been recognized to influence the learning and memory processes. OTX has also prominent effects on social behavior, anxiety, and autism. Interaction between glucocorticoids, OTX, and maternal behavior may have long-term effects on the developmental program of the developing brain subjected to adverse events during pre and perinatal periods. OTX treatment in humans improves many aspects of social cognition and behavior. Its effects on the hypothalamic–pituitary–adrenal axis and inflammation appear to be of interest in neonates because these properties may confer benefits when the perinatal brain has been subjected to injury. Indeed, early life inflammation and abnormal adrenal response to stress have been associated with an abnormal white matter development. Recent investigations demonstrated that OTX is involved in the modulation of microglial reactivity in the developing brain. This review recapitulates state-of-the art data supporting the hypothesis that the OTX system could be considered as an innovative candidate for neuroprotection, especially in the immature brain.

  5. Lasting Adaptations in Social Behavior Produced by Social Disruption and Inhibition of Adult Neurogenesis

    Science.gov (United States)

    Opendak, Maya; Offit, Lily; Monari, Patrick; Schoenfeld, Timothy J.; Sonti, Anup N.; Cameron, Heather A.

    2016-01-01

    Research on social instability has focused on its detrimental consequences, but most people are resilient and respond by invoking various coping strategies. To investigate cellular processes underlying such strategies, a dominance hierarchy of rats was formed and then destabilized. Regardless of social position, rats from disrupted hierarchies had fewer new neurons in the hippocampus compared with rats from control cages and those from stable hierarchies. Social disruption produced a preference for familiar over novel conspecifics, a change that did not involve global memory impairments or increased anxiety. Using the neuropeptide oxytocin as a tool to increase neurogenesis in the hippocampus of disrupted rats restored preference for novel conspecifics to predisruption levels. Conversely, reducing the number of new neurons by limited inhibition of adult neurogenesis in naive transgenic GFAP–thymidine kinase rats resulted in social behavior similar to disrupted rats. Together, these results provide novel mechanistic evidence that social disruption shapes behavior in a potentially adaptive way, possibly by reducing adult neurogenesis in the hippocampus. SIGNIFICANCE STATEMENT To investigate cellular processes underlying adaptation to social instability, a dominance hierarchy of rats was formed and then destabilized. Regardless of social position, rats from disrupted hierarchies had fewer new neurons in the hippocampus compared with rats from control cages and those from stable hierarchies. Unexpectedly, these changes were accompanied by changes in social strategies without evidence of impairments in cognition or anxiety regulation. Restoring adult neurogenesis in disrupted rats using oxytocin and conditionally suppressing the production of new neurons in socially naive GFAP–thymidine kinase rats showed that loss of 6-week-old neurons may be responsible for adaptive changes in social behavior. PMID:27358459

  6. The effect of oxytocin on human-directed social behaviour in dogs (Canis familiaris).

    Science.gov (United States)

    Kis, Anna; Ciobica, Alin; Topál, József

    2017-08-01

    The oxytocin system has recently received increasing attention due to its effect on complex human behaviours. In parallel to this, over the past couple of decades, the human-analogue social behaviour of dogs has been intensively studied. Combining these two lines of research (e.g. studying the relationship between dog social behaviour and the oxytocin system) is a promising new research area. The present paper reviews the existing literature on how oxytocin is related to different aspects of human-directed social behaviour in dogs. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Examination of the Pharmacology of Oxytocin and Clinical Guidelines for Use in Labor.

    Science.gov (United States)

    Page, Katie; McCool, William F; Guidera, Mamie

    2017-07-01

    The use of exogenous oxytocin to induce or augment labor has increased in recent years. This literature-informed review examines the action of this medication and the potential associated complications, with an evaluation of current professional practice guidelines. A brief history of the use of exogenous oxytocin for labor induction or augmentation is presented. In addition, risk management strategies for the prevention of oxytocin-related adverse outcomes and subsequent litigation are identified. © 2017 by the American College of Nurse-Midwives.

  8. Effects of selective serotonin reuptake inhibitor treatment on plasma oxytocin and cortisol in major depressive disorder.

    Science.gov (United States)

    Keating, Charlotte; Dawood, Tye; Barton, David A; Lambert, Gavin W; Tilbrook, Alan J

    2013-04-29

    Oxytocin is known for its capacity to facilitate social bonding, reduce anxiety and for its actions on the stress hypothalamopituitary adrenal (HPA) axis. Since oxytocin can physiologically suppress activity of the HPA axis, clinical applications of this neuropeptide have been proposed in conditions where the function of the HPA axis is dysregulated. One such condition is major depressive disorder (MDD). Dysregulation of the HPA system is the most prominent endocrine change seen with MDD, and normalizing the HPA axis is one of the major targets of recent treatments. The potential clinical application of oxytocin in MDD requires improved understanding of its relationship to the symptoms and underlying pathophysiology of MDD. Previous research has investigated potential correlations between oxytocin and symptoms of MDD, including a link between oxytocin and treatment related symptom reduction. The outcomes of studies investigating whether antidepressive treatment (pharmacological and non-pharmacological) influences oxytocin concentrations in MDD, have produced conflicting outcomes. These outcomes suggest the need for an investigation of the influence of a single treatment class on oxytocin concentrations, to determine whether there is a relationship between oxytocin, the HPA axis (e.g., oxytocin and cortisol) and MDD. Our objective was to measure oxytocin and cortisol in patients with MDD before and following treatment with selective serotonin reuptake inhibitors, SSRI. We sampled blood from arterial plasma. Patients with MDD were studied at the same time twice; pre- and post- 12 weeks treatment, in an unblinded sequential design (clinicaltrials.govNCT00168493). Results did not reveal differences in oxytocin or cortisol concentrations before relative to following SSRI treatment, and there were no significant relationships between oxytocin and cortisol, or these two physiological variables and psychological symptom scores, before or after treatment. These outcomes

  9. Expression and activation of the oxytocin receptor in airway smooth muscle cells: Regulation by TNFα and IL-13

    Directory of Open Access Journals (Sweden)

    Siddiqui Salman

    2010-07-01

    Full Text Available Abstract Background During pregnancy asthma may remain stable, improve or worsen. The factors underlying the deleterious effect of pregnancy on asthma remain unknown. Oxytocin is a neurohypophyseal protein that regulates a number of central and peripheral responses such as uterine contractions and milk ejection. Additional evidence suggests that oxytocin regulates inflammatory processes in other tissues given the ubiquitous expression of the oxytocin receptor. The purpose of this study was to define the role of oxytocin in modulating human airway smooth muscle (HASMCs function in the presence and absence of IL-13 and TNFα, cytokines known to be important in asthma. Method Expression of oxytocin receptor in cultured HASMCs was performed by real time PCR and flow cytomery assays. Responses to oxytocin was assessed by fluorimetry to detect calcium signals while isolated tracheal rings and precision cut lung slices (PCLS were used to measure contractile responses. Finally, ELISA was used to compare oxytocin levels in the bronchoalveloar lavage (BAL samples from healthy subjects and those with asthma. Results PCR analysis demonstrates that OXTR is expressed in HASMCs under basal conditions and that both interleukin (IL-13 and tumor necrosis factor (TNFα stimulate a time-dependent increase in OXTR expression at 6 and 18 hr. Additionally, oxytocin increases cytosolic calcium levels in fura-2-loaded HASMCs that were enhanced in cells treated for 24 hr with IL-13. Interestingly, TNFα had little effect on oxytocin-induced calcium response despite increasing receptor expression. Using isolated murine tracheal rings and PCLS, oxytocin also promoted force generation and airway narrowing. Further, oxytocin levels are detectable in bronchoalveolar lavage (BAL fluid derived from healthy subjects as well as from those with asthma. Conclusion Taken together, we show that cytokines modulate the expression of functional oxytocin receptors in HASMCs suggesting a

  10. The Effect of Oxygen Inhalation Plus Oxytocin Compared with Oxytocin Only on Postpartum Haemorrhage: A Randomized Clinical Trial.

    Science.gov (United States)

    Suhrabi, Zainab; Taghinejad, Hamid; Direkvand-Moghadam, Ashraf; Akbari, Malihe

    2016-09-01

    Post Partum Haemorrhage (PPH) is the leading cause of maternal mortality across the world, mainly in the developing countries. The present study was conducted with the aim to investigate effect of oxygen inhalation plus oxytocin compared with oxytocin only on PPH. This study was a clinical trial which was performed in Shahid Mustafa Khomieni Teaching Hospital of Ilam (western Iran) from April 2012 to Nov 2013. One hundred and twenty pregnant women who were referred to delivery ward for normal vaginal delivery were selected with convenience sampling method and they were randomly assigned into two groups. For both groups management of the third stage of labour was done using 1000CC Ringer and 20 units of Oxytocin. In the intervention group, in addition to the routine administration, 8 liters of oxygen via face mask was used continuously until 2 hours after delivery. Blood loss was determined by regular weighing of the buttocks that were previously weighted. The difference was calculated before and after weighing (1 gram increasing of weight was considered to be equivalent to 1CC blood loss). Data were analysed by SPSS 16 version using Student- t and Chi-square tests. The two groups were homogenous in regard to all the base line variables. The study results indicated that the mean of blood loss were (256.16±97) ml at two hours after delivery in the control group and (149.5±46.49) ml in the intervention group. There was a significant difference between PPH of the two groups (poxytocin infusion during 2hours later resulted in a significant decreasing in the amount of bleeding after normal vaginal delivery.

  11. Molar concentrations of sorbitol and polyethylene glycol inhibit the Plasmodium aquaglyceroporin but not that of E. coli: involvement of the channel vestibules.

    Science.gov (United States)

    Song, Jie; Almasalmeh, Abdulnasser; Krenc, Dawid; Beitz, Eric

    2012-05-01

    The aquaglyceroporins of Escherichia coli, EcGlpF, and of Plasmodium falciparum, PfAQP, are probably the best characterized members of the solute-conducting aquaporin (AQP) subfamily. Their crystal structures have been elucidated and numerous experimental and theoretical analyses have been conducted. However, opposing reports on their rates of water permeability require clarification. Hence, we expressed EcGlpF and PfAQP in yeast, prepared protoplasts, and compared water and glycerol permeability of both aquaglyceroporins in the presence of different osmolytes, i.e. sucrose, sorbitol, PEG300, and glycerol. We found that water permeability of PfAQP strongly depends on the external osmolyte, with full inhibition by sorbitol, and increasing water permeability when glycerol, PEG300, and sucrose were used. EcGlpF expression did not enhance water permeability over that of non-expressing control protoplasts regardless of the osmolyte. Glycerol permeability of PfAQP was also inhibited by sorbitol, but to a smaller extent, whereas EcGlpF conducted glycerol independently of the osmolyte. Mixtures of glycerol and urea passed PfAQP equally well under isosmotic conditions, whereas under hypertonic conditions in a countercurrent with water, glycerol was clearly preferred over urea. We conclude that PfAQP has high and EcGlpF low water permeability, and explain the inhibiting effect of sorbitol on PfAQP by its binding to the extracellular vestibule. The preference for glycerol under hypertonic conditions implies that in a physiological setting, PfAQP mainly acts as a water/glycerol channel rather than a urea facilitator. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Choir versus Solo Singing: Effects on Mood, and Salivary Oxytocin and Cortisol Concentrations.

    Science.gov (United States)

    Schladt, T Moritz; Nordmann, Gregory C; Emilius, Roman; Kudielka, Brigitte M; de Jong, Trynke R; Neumann, Inga D

    2017-01-01

    The quantification of salivary oxytocin (OXT) concentrations emerges as a helpful tool to assess peripheral OXT secretion at baseline and after various challenges in healthy and clinical populations. Both positive social interactions and stress are known to induce OXT secretion, but the relative influence of either of these triggers is not well delineated. Choir singing is an activity known to improve mood and to induce feelings of social closeness, and may therefore be used to investigate the effects of positive social experiences on OXT system activity. We quantified mood and salivary OXT and cortisol (CORT) concentrations before, during, and after both choir and solo singing performed in a randomized order in the same participants (repeated measures). Happiness was increased, and worry and sadness as well as salivary CORT concentrations were reduced, after both choir and solo singing. Surprisingly, salivary OXT concentrations were significantly reduced after choir singing, but did not change in response to solo singing. Salivary OXT concentrations showed high intra-individual stability, whereas salivary CORT concentrations fluctuated between days within participants. The present data indicate that the social experience of choir singing does not induce peripheral OXT secretion, as indicated by unchanged salivary OXT levels. Rather, the reduction of stress/arousal experienced during choir singing may lead to an inhibition of peripheral OXT secretion. These data are important for the interpretation of future reports on salivary OXT concentrations, and emphasize the need to strictly control for stress/arousal when designing similar experiments.

  13. Oxytocin promotes bone formation during the alveolar healing process in old acyclic female rats.

    Science.gov (United States)

    Colli, Vilma Clemi; Okamoto, Roberta; Spritzer, Poli Mara; Dornelles, Rita Cássia Menegati

    2012-09-01

    OT was reported to be a direct regulator of bone mass in young rodents, and this anabolic effect on bone is a peripheral action of OT. The goal of this study was to investigate the peripheral action of oxytocin (OT) in the alveolar healing process in old female rats. Females Wistar rats (24-month-old) in permanent diestrus phase, received two ip (12h apart) injections of saline (NaCl 0.15M - control group) or OT (45μg/rat - treated group). Seven days later, the right maxillary incisor was extracted and analyses were performed up to 28 days of the alveolar healing process (35 days after saline or OT administration). Calcium and phosphorus plasma concentrations did not differ between the groups. The plasma biochemical bone formations markers, alkaline phosphatase (ALP) and osteocalcin were significantly higher in the treated group. Histomorphometric analyses confirmed bone formation as the treated group presented the highest mean value of post-extraction bone formation. Tartrate-resistant acid phosphatase (TRAP) was significantly reduced in the treated group indicating an anti-resorptive effect of OT. Immunohistochemistry reactions performed in order to identify the presence of osteocalcin and TRAP in the bone cells of the dental socket confirmed these outcomes. OT was found to promote bone formation and to inhibit bone resorption in old acyclic female rats during the alveolar healing process. Published by Elsevier Ltd.

  14. Body temperature and cardiac changes induced by peripherally administered oxytocin, vasopressin and the non-peptide oxytocin receptor agonist WAY 267,464: a biotelemetry study in rats

    Science.gov (United States)

    Hicks, C; Ramos, L; Reekie, T; Misagh, G H; Narlawar, R; Kassiou, M; McGregor, I S

    2014-01-01

    Background and Purpose There is current interest in oxytocin (OT) as a possible therapeutic in psychiatric disorders. However, the usefulness of OT may be constrained by peripheral autonomic effects, which may involve an action at both OT and vasopressin V1A receptors. Here, we characterized the cardiovascular and thermoregulatory effects of OT, vasopressin (AVP) and the non-peptide OT receptor agonist WAY 267,464 in rats, and assessed the relative involvement of the OT and V1A receptors in these effects. Experimental Approach Biotelemetry in freely moving male Wistar rats was used to examine body temperature and heart rate after OT (0.01 – 1 mg kg−1; i.p.), AVP (0.001 – 0.1 mg kg−1; i.p.) or WAY 267,464 (10 and 100 mg kg−1; i.p.). The actions of the OT receptor antagonist Compound 25 (C25, 5 and 10 mg kg−1) and V1A receptor antagonist SR49059 (1 and 10 mg kg−1) were studied, as well as possible V1A receptor antagonist effects of WAY 267,464. Key Results OT and AVP dose-dependently reduced body temperature and heart rate. WAY 267,464 had similar, but more modest, effects. SR49059, but not C25, prevented the hypothermia and bradycardia induced by OT and AVP. WAY 267,464 (100 mg·kg−1) prevented the effects of OT, and to some extent AVP. Conclusions and Implications Peripherally administered OT and AVP have profound cardiovascular and thermoregulatory effects that appear to principally involve the V1A receptor rather than the OT receptor. Additionally, WAY 267,464 is not a simple OT receptor agonist, as it has functionally relevant V1A antagonist actions. PMID:24641248

  15. Body temperature and cardiac changes induced by peripherally administered oxytocin, vasopressin and the non-peptide oxytocin receptor agonist WAY 267,464: a biotelemetry study in rats.

    Science.gov (United States)

    Hicks, C; Ramos, L; Reekie, T; Misagh, G H; Narlawar, R; Kassiou, M; McGregor, I S

    2014-06-01

    There is current interest in oxytocin (OT) as a possible therapeutic in psychiatric disorders. However, the usefulness of OT may be constrained by peripheral autonomic effects, which may involve an action at both OT and vasopressin V1A receptors. Here, we characterized the cardiovascular and thermoregulatory effects of OT, vasopressin (AVP) and the non-peptide OT receptor agonist WAY 267,464 in rats, and assessed the relative involvement of the OT and V1A receptors in these effects. Biotelemetry in freely moving male Wistar rats was used to examine body temperature and heart rate after OT (0.01 - 1 mg kg(-1); i.p.), AVP (0.001 - 0.1 mg kg(-1); i.p.) or WAY 267,464 (10 and 100 mg kg(-1); i.p.). The actions of the OT receptor antagonist Compound 25 (C25, 5 and 10 mg kg(-1)) and V1A receptor antagonist SR49059 (1 and 10 mg kg(-1)) were studied, as well as possible V1A receptor antagonist effects of WAY 267,464. OT and AVP dose-dependently reduced body temperature and heart rate. WAY 267,464 had similar, but more modest, effects. SR49059, but not C25, prevented the hypothermia and bradycardia induced by OT and AVP. WAY 267,464 (100 mg·kg(-1)) prevented the effects of OT, and to some extent AVP. Peripherally administered OT and AVP have profound cardiovascular and thermoregulatory effects that appear to principally involve the V1A receptor rather than the OT receptor. Additionally, WAY 267,464 is not a simple OT receptor agonist, as it has functionally relevant V1A antagonist actions. © 2014 The British Pharmacological Society.

  16. Involvement of up-regulated Necl-5/Tage4/PVR/CD155 in the loss of contact inhibition in transformed NIH3T3 cells

    International Nuclear Information System (INIS)

    Minami, Yukiko; Ikeda, Wataru; Kajita, Mihoko; Fujito, Tsutomu; Monden, Morito; Takai, Yoshimi

    2007-01-01

    Normal cells show contact inhibition of cell movement and proliferation, but this is lost following transformation. We found that Necl-5, originally identified as a poliovirus receptor and up-regulated in many cancer cells, enhances growth factor-induced cell movement and proliferation. We showed that when cells contact other cells, Necl-5 interacts in trans with nectin-3 and is removed by endocytosis from the cell surface, resulting in a reduction of cell movement and proliferation. We show here that up-regulation of the gene encoding Necl-5 by the oncogene V12-Ki-Ras causes enhanced cell movement and proliferation. Upon cell-cell contact, de novo synthesis of Necl-5 exceeds the rate of Necl-5 endocytosis, eventually resulting in a net increase in the amount of Necl-5 at the cell surface. In addition, expression of the gene encoding nectin-3 is markedly reduced in transformed cells. Thus, up-regulation of Necl-5 following transformation contributes to the loss of contact inhibition in transformed cells

  17. Dihydroartemisinin potentiates the anticancer effect of cisplatin via mTOR inhibition in cisplatin-resistant ovarian cancer cells: involvement of apoptosis and autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Xue [Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001 (China); Li, Ling [Department of Brain Cognition Computing Lab, University of Kent, Kent CT2 7NZ (United Kingdom); Jiang, Hong; Jiang, Keping; Jin, Ye [Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001 (China); Zheng, Jianhua, E-mail: zhengjianhua1115@126.com [Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001 (China)

    2014-02-14

    Highlights: • Phosphorylation of mTOR is abnormal activation in SKOV3/DDP ovarian cancer cells. • Downregulation of mTOR by DHA helps to sensitize the SKOV3/DDP cells to chemotherapy. • DHA has the potential of induce autophagy in cancer cells. - Abstract: Dihydroartemisinin (DHA) exhibits anticancer activity in tumor cells but its mechanism of action is unclear. Cisplatin (DDP) is currently the best known chemotherapeutic available for ovarian cancer. However, tumors return de novo with acquired resistance over time. Mammalian target of rapamycin (mTOR) is an important kinase that regulates cell apoptosis and autophagy, and its dysregulation has been observed in chemoresistant human cancers. Here, we show that compared with control ovarian cancer cells (SKOV3), mTOR phosphorylation was abnormally activated in cisplatin-resistant ovarian cancer cells (SKOV3/DDP) following cisplatin monotherapy. Treatment with cisplatin combined with DHA could enhance cisplatin-induced proliferation inhibition in SKOV3/DDP cells. This mechanism is at least partially due to DHA deactivation of mTOR kinase and promotion of apoptosis. Although autophagy was also induced by DHA, the reduced cell death was not found by suppressing autophagic flux by Bafilomycin A1 (BAF). Taken together, we conclude that inhibition of cisplatin-induced mTOR activation is one of the main mechanisms by which DHA dramatically promotes its anticancer effect in cisplatin-resistant ovarian cancer cells.

  18. Dihydroartemisinin potentiates the anticancer effect of cisplatin via mTOR inhibition in cisplatin-resistant ovarian cancer cells: involvement of apoptosis and autophagy

    International Nuclear Information System (INIS)

    Feng, Xue; Li, Ling; Jiang, Hong; Jiang, Keping; Jin, Ye; Zheng, Jianhua

    2014-01-01

    Highlights: • Phosphorylation of mTOR is abnormal activation in SKOV3/DDP ovarian cancer cells. • Downregulation of mTOR by DHA helps to sensitize the SKOV3/DDP cells to chemotherapy. • DHA has the potential of induce autophagy in cancer cells. - Abstract: Dihydroartemisinin (DHA) exhibits anticancer activity in tumor cells but its mechanism of action is unclear. Cisplatin (DDP) is currently the best known chemotherapeutic available for ovarian cancer. However, tumors return de novo with acquired resistance over time. Mammalian target of rapamycin (mTOR) is an important kinase that regulates cell apoptosis and autophagy, and its dysregulation has been observed in chemoresistant human cancers. Here, we show that compared with control ovarian cancer cells (SKOV3), mTOR phosphorylation was abnormally activated in cisplatin-resistant ovarian cancer cells (SKOV3/DDP) following cisplatin monotherapy. Treatment with cisplatin combined with DHA could enhance cisplatin-induced proliferation inhibition in SKOV3/DDP cells. This mechanism is at least partially due to DHA deactivation of mTOR kinase and promotion of apoptosis. Although autophagy was also induced by DHA, the reduced cell death was not found by suppressing autophagic flux by Bafilomycin A1 (BAF). Taken together, we conclude that inhibition of cisplatin-induced mTOR activation is one of the main mechanisms by which DHA dramatically promotes its anticancer effect in cisplatin-resistant ovarian cancer cells

  19. Coumarin or benzoxazinone bearing benzimidazolium and bis(benzimidazolium salts; involvement in transfer hydrogenation of acetophenone derivatives and hCA inhibition

    Directory of Open Access Journals (Sweden)

    Mert Olgun Karataş

    2015-10-01

    Full Text Available Four new salts of benzimidazolium and bis(benzimidazolium which include coumarin or benzoxazinone moieties were synthesized and the structures of the newly synthesized compounds were elucidated on the basis of spectral analyses such as 1H-NMR, 13C-NMR, HSQC, IR, LC-MS and elemental analysis. Benzimidazolium salts were used intensively as N-heterocyclic carbene (NHC precursors in the various catalytic reactions such as transfer hydrogenation (TH, C-H bond activation, Heck, Suzuki reaction etc. With the prospect of potential NHC precursor properties of the synthesized compounds, they were employed in the (TH reaction of p-substitute acetophenones (acetophenone, p-methyl acetophenone, p-chloro acetophenone and good yields were observed. Coumarin compounds are known as inhibitor of carbonic anhydrase and inhibition effects of the synthesized compounds on human carbonic anhydrases (hCA were investigated as in vitro. The in vitro results demonstrated that all compounds inhibited hCA I and hCA II activity. Among the synthesized compounds 1,4-bis(1-((6,8-dimethyl-2H-chromen-2-one-4-ylmethylbenzimidazolium-3-ylbutane dichloride was found to be the most active IC50= 5.55 mM and 6.06 mM for hCA I and hCA II, respectively.

  20. [Carbetocin versus Oxytocin during caesarean section for preventing postpartum haemorrhage].

    Science.gov (United States)

    Pizzagalli, F; Agasse, J; Marpeau, L

    2015-05-01

    The aim of the study was to compare the effectiveness of Carbetocin versus Oxyotcin during caesarean section for preventing postpartum haemorrhage. Prospective observational study (before/after design). Five hundred and forty patients who received an injection of Oxytocin were compared to 262 patients with single injection of 100 micrograms of Carbetocin. The primary outcome was to compare the differential hematocrit level between pre- and postoperative blood samples. The secondary outcome was to compare differential hemoglobin level and the use of complementary therapies for postpartum haemorrhage. We did not find any difference between the Oxytocin and Carbetocin groups on differential hematocrit level. There was no difference between the groups regarding the use of additionnal therapies (Sulproston injections, blood transfusions and surgery methods). The rate of postpartum haemorrhage was similar in the two groups (18.7% vs 21.6%; P=0.33). We found a lower percentage of patients with differential of hemoglobin level between 2 g/dL and 4 g/dL in the Carbetocin group (6.5% vs 15.6%, Poxytocin. Carbetocin seems to reduce the need for postoperative intravenous iron injection. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  1. Salubrious effects of oxytocin on social stress-induced deficits

    Science.gov (United States)

    Smith, Adam S.; Wang, Zuoxin

    2012-01-01

    Social relationships are a fundamental aspect of life, affecting social, psychological, physiological, and behavioral functions. While social interactions can attenuate stress and promote health, disruption, confrontations, isolation, or neglect in the social environment can each be major stressors. Social stress can impair the basal function and stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, impairing function of multiple biological systems and posing a risk to mental and physical health. In contrast, social support can ameliorate stress-induced physiological and immunological deficits, reducing the risk of subsequent psychological distress and improving an individual's overall well-being. For better clinical treatment of these physiological and mental pathologies, it is necessary to understand the regulatory mechanisms of stress-induced pathologies as well as determine the underlying biological mechanisms that regulate social buffering of the stress system. A number of ethologically relevant animal models of social stress and species that form strong adult social bonds have been utilized to study the etiology, treatment, and prevention of stress-related disorders. While undoubtedly a number of biological pathways contribute to the social buffering of the stress response, the convergence of evidence denotes the regulatory effects of oxytocin in facilitating social bond-promoting behaviors and their effect on the stress response. Thus, oxytocin may be perceived as a common regulatory element of the social environment, stress response, and stress-induced risks on mental and physical health. PMID:22178036

  2. Natural indoles, indole-3-carbinol and 3,3′-diindolymethane, inhibit T cell activation by staphylococcal enterotoxin B through epigenetic regulation involving HDAC expression

    International Nuclear Information System (INIS)

    Busbee, Philip B.; Nagarkatti, Mitzi; Nagarkatti, Prakash S.

    2014-01-01

    Staphylococcal enterotoxin B (SEB) is a potent exotoxin produced by the Staphylococcus aureus. This toxin is classified as a superantigen because of its ability to directly bind with MHC-II class molecules followed by activation of a large proportion of T cells bearing specific Vβ-T cell receptors. Commonly associated with classic food poisoning, SEB has also been shown to induce toxic shock syndrome, and is also considered to be a potential biological warfare agent because it is easily aerosolized. In the present study, we assessed the ability of indole-3-carbinol (I3C) and one of its byproducts, 3,3′-diindolylmethane (DIM), found in cruciferous vegetables, to counteract the effects of SEB-induced activation of T cells in mice. Both I3C and DIM were found to decrease the activation, proliferation, and cytokine production by SEB-activated Vβ8 + T cells in vitro and in vivo. Interestingly, inhibitors of histone deacetylase class I (HDAC-I), but not class II (HDAC-II), showed significant decrease in SEB-induced T cell activation and cytokine production, thereby suggesting that epigenetic modulation plays a critical role in the regulation of SEB-induced inflammation. In addition, I3C and DIM caused a decrease in HDAC-I but not HDAC-II in SEB-activated T cells, thereby suggesting that I3C and DIM may inhibit SEB-mediated T cell activation by acting as HDAC-I inhibitors. These studies not only suggest for the first time that plant-derived indoles are potent suppressors of SEB-induced T cell activation and cytokine storm but also that they may mediate these effects by acting as HDAC inhibitors. - Highlights: • I3C and DIM reduce SEB-induced T cell activation and inflammatory cytokines. • Inhibiting class I HDACs reduces T cell activation and inflammatory cytokines. • Inhibiting class II HDACs increases T cell activation and inflammatory cytokines. • I3C and DIM selectively reduce mRNA expression of class I HDACs. • Novel use and mechanism to counteract SEB

  3. Natural indoles, indole-3-carbinol and 3,3′-diindolymethane, inhibit T cell activation by staphylococcal enterotoxin B through epigenetic regulation involving HDAC expression

    Energy Technology Data Exchange (ETDEWEB)

    Busbee, Philip B.; Nagarkatti, Mitzi; Nagarkatti, Prakash S., E-mail: prakash@mailbox.sc.edu

    2014-01-01

    Staphylococcal enterotoxin B (SEB) is a potent exotoxin produced by the Staphylococcus aureus. This toxin is classified as a superantigen because of its ability to directly bind with MHC-II class molecules followed by activation of a large proportion of T cells bearing specific Vβ-T cell receptors. Commonly associated with classic food poisoning, SEB has also been shown to induce toxic shock syndrome, and is also considered to be a potential biological warfare agent because it is easily aerosolized. In the present study, we assessed the ability of indole-3-carbinol (I3C) and one of its byproducts, 3,3′-diindolylmethane (DIM), found in cruciferous vegetables, to counteract the effects of SEB-induced activation of T cells in mice. Both I3C and DIM were found to decrease the activation, proliferation, and cytokine production by SEB-activated Vβ8{sup +} T cells in vitro and in vivo. Interestingly, inhibitors of histone deacetylase class I (HDAC-I), but not class II (HDAC-II), showed significant decrease in SEB-induced T cell activation and cytokine production, thereby suggesting that epigenetic modulation plays a critical role in the regulation of SEB-induced inflammation. In addition, I3C and DIM caused a decrease in HDAC-I but not HDAC-II in SEB-activated T cells, thereby suggesting that I3C and DIM may inhibit SEB-mediated T cell activation by acting as HDAC-I inhibitors. These studies not only suggest for the first time that plant-derived indoles are potent suppressors of SEB-induced T cell activation and cytokine storm but also that they may mediate these effects by acting as HDAC inhibitors. - Highlights: • I3C and DIM reduce SEB-induced T cell activation and inflammatory cytokines. • Inhibiting class I HDACs reduces T cell activation and inflammatory cytokines. • Inhibiting class II HDACs increases T cell activation and inflammatory cytokines. • I3C and DIM selectively reduce mRNA expression of class I HDACs. • Novel use and mechanism to counteract

  4. Venom of the Peruvian snake Bothriopsis oligolepis: Detection of antibacterial activity and involvement of proteolytic enzymes and C-type lectins in growth inhibition of Staphylococcus aureus.

    Science.gov (United States)

    Sulca, M A; Remuzgo, C; Cárdenas, J; Kiyota, S; Cheng, E; Bemquerer, M P; Machini, M T

    2017-08-01

    There is a rising interest in snake venoms proteins (SVPs) because these macromolecules are related to pharmacological properties that manifest themselves during poisoning and can lead to secondary microbial infections. Interestingly, researchers have somehow neglected the antimicrobial activity of SVPs. The aims of this study were: (i) to verify whether the venom of the Peruvian snake Bothriopsis oligolepis displays such activity; (ii) to isolate and identify some of its antimicrobial constituents. Liquid growth inhibition assays revealed that the crude venom inhibited the growth of Gram-positive and Gram-negative bacteria, but not of Candida species. Fractionation of the venom by anion-exchange chromatography provided fractions P2, P4 and P8 active against S. aureus. Fractionation of P2 or P8 by gel-filtration chromatography and of P4 by RP-HPLC furnished the sub-fractions P2-I, P8-II and P4-II, respectively, being those fractions active against S. aureus. Analyses of these sub-fractions by SDS-PAGE under denaturing/reducing conditions evidenced SVPs with 59-73, 27 and 14-28 kDa, respectively.