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Sample records for hypothalamic magnocellular vasopressin

  1. Differential sensitivity to nicotine among hypothalamic magnocellular neurons

    DEFF Research Database (Denmark)

    Mikkelsen, J D; Jacobsen, Julie; Kiss, Adrian Emil

    2012-01-01

    The magnocellular neurons in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) either contain vasopressin or oxytocin. Even though both hormones are released after systemic administration of nicotine, the mechanism through which the two populations of neurons are activated...... is not known. This study was carried out in the rat to investigate the effect of increasing doses of nicotine on subsets of magnocellular neurons containing either oxytocin or vasopressin....

  2. Electrophysiology of Hypothalamic Magnocellular Neurons In vitro: A Rhythmic Drive in Organotypic Cultures and Acute Slices.

    Science.gov (United States)

    Israel, Jean-Marc; Oliet, Stéphane H; Ciofi, Philippe

    2016-01-01

    Hypothalamic neurohormones are released in a pulsatile manner. The mechanisms of this pulsatility remain poorly understood and several hypotheses are available, depending upon the neuroendocrine system considered. Among these systems, hypothalamo-neurohypophyseal magnocellular neurons have been early-considered models, as they typically display an electrical activity consisting of bursts of action potentials that is optimal for the release of boluses of the neurohormones oxytocin and vasopressin. The cellular mechanisms underlying this bursting behavior have been studied in vitro, using either acute slices of the adult hypothalamus, or organotypic cultures of neonatal hypothalamic tissue. We have recently proposed, from experiments in organotypic cultures, that specific central pattern generator networks, upstream of magnocellular neurons, determine their bursting activity. Here, we have tested whether a similar hypothesis can be derived from in vitro experiments in acute slices of the adult hypothalamus. To this aim we have screened our electrophysiological recordings of the magnocellular neurons, previously obtained from acute slices, with an analysis of autocorrelation of action potentials to detect a rhythmic drive as we recently did for organotypic cultures. This confirmed that the bursting behavior of magnocellular neurons is governed by central pattern generator networks whose rhythmic drive, and thus probably integrity, is however less satisfactorily preserved in the acute slices from adult brains.

  3. Electrophysiology of hypothalamic magnocellular neurons in vitro: a rhythmic drive in organotypic cultures and acute slices

    Directory of Open Access Journals (Sweden)

    Jean-Marc eIsrael

    2016-03-01

    Full Text Available Hypothalamic neurohormones are released in a pulsatile manner. The mechanisms of this pulsatility remain poorly understood and several hypotheses are available, depending upon the neuroendocrine system considered. Among these systems, hypothalamo-neurohypophyseal magnocellular neurons have been early-considered models, as they typically display an electrical activity consisting of bursts of action potentials that is optimal for the release of boluses of the neurohormones oxytocin and vasopressin. The cellular mechanisms underlying this bursting behavior have been studied in vitro, using either acute slices of the adult hypothalamus, or organotypic cultures of neonatal hypothalamic tissue. We have recently proposed, from experiments in organotypic cultures, that specific central pattern generator networks, upstream of magnocellular neurons, determine their bursting activity. Here, we have tested whether a similar hypothesis can be derived from in vitro experiments in acute slices of the adult hypothalamus. To this aim we have screened our electrophysiological recordings of the magnocellular neurons, previously obtained from acute slices, with an analysis of autocorrelation of action potentials to detect a rhythmic drive as we recently did for organotypic cultures. This confirmed that the bursting behavior of magnocellular neurons is governed by central pattern generator networks whose rhythmic drive, and thus probably integrity, is however less satisfactorily preserved in the acute slices from adult brains.

  4. Hyperosmotic stimulus induces reversible angiogenesis within the hypothalamic magnocellular nuclei of the adult rat: a potential role for neuronal vascular endothelial growth factor

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    Vincent Anne

    2005-03-01

    Full Text Available Abstract Background In mammals, the CNS vasculature is established during the postnatal period via active angiogenesis, providing different brain regions with capillary networks of various densities that locally supply adapted metabolic support to neurons. Thereafter this vasculature remains essentially quiescent excepted for specific pathologies. In the adult rat hypothalamus, a particularly dense network of capillary vessels is associated with the supraoptic (SON and paraventricular (PVN nuclei containing the magnocellular neurons secreting vasopressin and oxytocin, two neurohormones involved in the control of the body fluid homoeostasis. In the seventies, it was reported that proliferation of astrocytes and endothelial cells occurs within these hypothalamic nuclei when strong metabolic activation of the vasopressinergic and oxytocinergic neurons was induced by prolonged hyperosmotic stimulation. The aim of the present study was to determine whether such proliferative response to osmotic stimulus is related to local angiogenesis and to elucidate the cellular and molecular mechanisms involved. Results Our results provide evidence that cell proliferation occurring within the SON of osmotically stimulated adult rats corresponds to local angiogenesis. We show that 1 a large majority of the SON proliferative cells is associated with capillary vessels, 2 this proliferative response correlates with a progressive increase in density of the capillary network within the nucleus, and 3 SON capillary vessels exhibit an increased expression of nestin and vimentin, two markers of newly formed vessels. Contrasting with most adult CNS neurons, hypothalamic magnocellular neurons were found to express vascular endothelial growth factor (VEGF, a potent angiogenic factor whose production was increased by osmotic stimulus. When VEGF was inhibited by dexamethasone treatment or by the local application of a blocking antibody, the angiogenic response was strongly

  5. Response of substances co-expressed in hypothalamic magnocellular neurons to osmotic challenges in normal and Brattleboro rats

    DEFF Research Database (Denmark)

    Bundzikova, J.; Pirnik, Z.; Zelena, D.

    2008-01-01

    The intention of this review is to emphasize the current knowledge about the extent and importance of the substances co-localized with magnocellular arginine vasopressin (AVP) and oxytocin (OXY) as potential candidates for the gradual clarification of their actual role in the regulation of hydrom...

  6. Magnocellular Neurons and Posterior Pituitary Function.

    Science.gov (United States)

    Brown, Colin H

    2016-09-15

    The posterior pituitary gland secretes oxytocin and vasopressin (the antidiuretic hormone) into the blood system. Oxytocin is required for normal delivery of the young and for delivery of milk to the young during lactation. Vasopressin increases water reabsorption in the kidney to maintain body fluid balance and causes vasoconstriction to increase blood pressure. Oxytocin and vasopressin secretion occurs from the axon terminals of magnocellular neurons whose cell bodies are principally found in the hypothalamic supraoptic nucleus and paraventricular nucleus. The physiological functions of oxytocin and vasopressin depend on their secretion, which is principally determined by the pattern of action potentials initiated at the cell bodies. Appropriate secretion of oxytocin and vasopressin to meet the challenges of changing physiological conditions relies mainly on integration of afferent information on reproductive, osmotic, and cardiovascular status with local regulation of magnocellular neurons by glia as well as intrinsic regulation by the magnocellular neurons themselves. This review focuses on the control of magnocellular neuron activity with a particular emphasis on their regulation by reproductive function, body fluid balance, and cardiovascular status. © 2016 American Physiological Society. Compr Physiol 6:1701-1741, 2016. Copyright © 2016 John Wiley & Sons, Inc.

  7. Effect of dietary salt intake on epithelial Na+ channels (ENaC) in vasopressin magnocellular neurosecretory neurons in the rat supraoptic nucleus.

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    Sharma, Kaustubh; Haque, Masudul; Guidry, Richard; Ueta, Yoichi; Teruyama, Ryoichi

    2017-09-01

    A growing body of evidence suggests that epithelial Na + channels (ENaCs) in the brain play a significant role in the regulation of blood pressure; however, the brain structures that mediate the effect are not well understood. Because vasopressin (VP) neurons play a pivotal role in coordinating neuroendocrine and autonomic responses to maintain cardiovascular homeostasis, a basic understanding of the regulation and activity of ENaC in VP neurons is of great interest. We show that high dietary salt intake caused an increase in the expression and activity of ENaC which resulted in the steady state depolarization of VP neurons. The results help us understand one of the mechanisms underlying how dietary salt intake affects the activity of VP neurons via ENaC activity. All three epithelial Na + channel (ENaC) subunits (α, β and γ) are located in vasopressin (VP) magnocellular neurons in the hypothalamic supraoptic (SON) and paraventricular nuclei. Our previous study demonstrated that ENaC mediates a Na + leak current that affects the steady state membrane potential in VP neurons. In the present study, we evaluated the effect of dietary salt intake on ENaC regulation and activity in VP neurons. High dietary salt intake for 7 days caused an increase in expression of β- and γENaC subunits in the SON and the translocation of αENaC immunoreactivity towards the plasma membrane. Patch clamp experiments on hypothalamic slices showed that the mean amplitude of the putative ENaC currents was significantly greater in VP neurons from animals that were fed a high salt diet compared with controls. The enhanced ENaC current contributed to the more depolarized basal membrane potential observed in VP neurons in the high salt diet group. These findings indicate that high dietary NaCl intake enhances the expression and activity of ENaCs, which augments synaptic drive by depolarizing the basal membrane potential close to the action potential threshold during hormonal demand. However

  8. Analysis of transcription factor mRNAs in identified oxytocin and vasopressin magnocellular neurons isolated by laser capture microdissection.

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    Madison Humerick

    Full Text Available The oxytocin (Oxt and vasopressin (Avp magnocellular neurons (MCNs in the hypothalamus are the only neuronal phenotypes that are present in the supraoptic nucleus (SON, and are characterized by their robust and selective expression of either the Oxt or Avp genes. In this paper, we take advantage of the differential expression of these neuropeptide genes to identify and isolate these two individual phenotypes from the rat SON by laser capture microdissection (LCM, and to analyze the differential expression of several of their transcription factor mRNAs by qRT-PCR. We identify these neuronal phenotypes by stereotaxically injecting recombinant Adeno-Associated Viral (rAAV vectors which contain cell-type specific Oxt or Avp promoters that drive expression of EGFP selectively in either the Oxt or Avp MCNs into the SON. The fluorescent MCNs are then dissected by LCM using a novel Cap Road Map protocol described in this paper, and the purified MCNs are extracted for their RNAs. qRT-PCR of these RNAs show that some transcription factors (RORA and c-jun are differentially expressed in the Oxt and Avp MCNs.

  9. The alpha(2)-adrenoceptors do not modify the activity of tyrosine hydroxylase, corticoliberine, and neuropeptide Y producing hypothalamic magnocellular neurons ion the Long Evans and Brattleboro rats

    DEFF Research Database (Denmark)

    Bundzikova, J; Pirnik, Z; Zelena, D

    2010-01-01

    The hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei are activated by body salt-fluid variations. Stimulation of alpha(2)-adrenoceptors by an agonist-xylazine (XYL) activates oxytocinergic but not vasopressinergic magnocellular neurons. In this study, tyrosine hydroxylase (TH), cort...

  10. Anatomy of melancholia: focus on hypothalamic-pituitary-adrenal axis overactivity and the role of vasopressin.

    LENUS (Irish Health Repository)

    Dinan, Timothy G

    2012-02-03

    Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis characterized by hypercortisolism, adrenal hyperplasia and abnormalities in negative feedback is the most consistently described biological abnormality in melancholic depression. Corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) are the main secretagogues of the HPA\\/stress system. Produced in the parvicellular division of the hypothalamic paraventricular nucleus the release of these peptides is influenced by inputs from monoaminergic neurones. In depression, anterior pituitary CRH1 receptors are down-regulated and response to CRH infusion is blunted. By contrast, vasopressin V3 receptors on the anterior pituitary show enhanced response to AVP stimulation and this enhancement plays a key role in maintaining HPA overactivity.

  11. Dehydration-induced release of vasopressin involves activation of hypothalamic histaminergic neurons.

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    Kjaer, A; Knigge, U; Rouleau, A; Garbarg, M; Warberg, J

    1994-08-01

    The hypothalamic neurotransmitter histamine (HA) induces arginine vasopressin (AVP) release when administered centrally. We studied and characterized this effect of HA with respect to receptor involvement. In addition, we studied the possible role of hypothalamic histaminergic neurons in the mediation of a physiological stimulus (dehydration) for AVP secretion. Intracerebroventricular administration of HA, the H1-receptor agonists 2(3-bromophenyl)HA and 2-thiazolylethylamine, or the H2-receptor agonists amthamine or 4-methyl-HA stimulated AVP secretion. The stimulatory action of HA on AVP was inhibited by pretreatment with the H1-receptor antagonist mepyramine or the H2-receptor antagonist cimetidine. Twenty-four hours of dehydration elevated the plasma osmolality from 298 +/- 3 to 310 +/- 3 mmol/liter and increased the plasma AVP concentration 4-fold. The hypothalamic content of HA and its metabolite tele-methyl-HA was elevated in response to dehydration, indicating an increased synthesis and release of hypothalamic HA. Dehydration-induced AVP secretion was lowered when neuronal HA synthesis was inhibited by the administration of (S) alpha-fluoromethylhistidine or when the animals were pretreated with the H3-receptor agonist R(alpha)methylhistamine, which inhibits the release and synthesis of HA, the H1-receptor antagonists mepyramine and cetirizine, or the H2-receptor antagonists cimetidine and ranitidine. We conclude that HA, via activation of both H1- and H2-receptors, stimulates AVP release and that HA is a physiological regulator of AVP secretion.

  12. Hypothalamic vasopressin response to stress and various physiological stimuli: Visualization in transgenic animal models

    Czech Academy of Sciences Publication Activity Database

    Ueta, Y.; Dayanithi, Govindan; Murphy, D.; Fujihara, H.

    2011-01-01

    Roč. 59, č. 2 (2011), s. 221-226 ISSN 0018-506X Institutional research plan: CEZ:AV0Z50390703 Keywords : vasopressin * green fluorescent protein * red fluorescent protein Subject RIV: FH - Neurology Impact factor: 3.865, year: 2011

  13. Induction of hypertension blunts baroreflex inhibition of vasopressin neurons in the rat.

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    Han, Su Young; Bouwer, Gregory T; Seymour, Alexander J; Korpal, Aaron K; Schwenke, Daryl O; Brown, Colin H

    2015-11-01

    Vasopressin secretion from the posterior pituitary gland is determined by action potential discharge of hypothalamic magnocellular neurosecretory cells. Vasopressin is a potent vasoconstrictor, but vasopressin levels are paradoxically elevated in some patients with established hypertension. To determine whether vasopressin neurons are excited in hypertension, extracellular single-unit recordings of vasopressin neurons from urethane-anaesthetized Cyp1a1-Ren2 rats with inducible angiotensin-dependent hypertension were made. The basal firing rate of vasopressin neurons was higher in hypertensive Cyp1a1-Ren2 rats than in non-hypertensive Cyp1a1-Ren2 rats. The increase in firing rate was specific to vasopressin neurons because oxytocin neuron firing rate was unaffected by the induction of hypertension. Intravenous injection of the α1-adrenoreceptor agonist, phenylephrine (2.5 μg/kg), transiently increased mean arterial blood pressure to cause a baroreflex-induced inhibition of heart rate and vasopressin neuron firing rate (by 52 ± 9%) in non-hypertensive rats. By contrast, intravenous phenylephrine did not inhibit vasopressin neurons in hypertensive rats, despite a similar increase in mean arterial blood pressure and inhibition of heart rate. Circulating angiotensin II can excite vasopressin neurons via activation of afferent inputs from the subfornical organ. However, the increase in vasopressin neuron firing rate and the loss of inhibition by intravenous phenylephrine were not blocked by intra-subfornical organ infusion of the angiotensin AT1 receptor antagonist, losartan. It can be concluded that increased vasopressin neuron activity at the onset of hypertension is driven, at least in part, by reduced baroreflex inhibition of vasopressin neurons and that this might exacerbate the increase in blood pressure at the onset of hypertension. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  14. GABAergic inhibition through synergistic astrocytic neuronal interaction transiently decreases vasopressin neuronal activity during hypoosmotic challenge.

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    Wang, Yu-Feng; Sun, Min-Yu; Hou, Qiuling; Hamilton, Kathryn A

    2013-04-01

    The neuropeptide vasopressin is crucial to mammalian osmotic regulation. Local hypoosmotic challenge transiently decreases and then increases vasopressin secretion. To investigate mechanisms underlying this transient response, we examined the effects of hypoosmotic challenge on the electrical activity of rat hypothalamic supraoptic nucleus (SON) vasopressin neurons using patch-clamp recordings. We found that 5 min exposure of hypothalamic slices to hypoosmotic solution transiently increased inhibitory postsynaptic current (IPSC) frequency and reduced the firing rate of vasopressin neurons. Recovery occurred by 10 min of exposure, even though the osmolality remained low. The γ-aminobutyric acid (GABA)A receptor blocker, gabazine, blocked the IPSCs and the hypoosmotic suppression of firing. The gliotoxin l-aminoadipic acid blocked the increase in IPSC frequency at 5 min and the recovery of firing at 10 min, indicating astrocytic involvement in hypoosmotic modulation of vasopressin neuronal activity. Moreover, β-alanine, an osmolyte of astrocytes and GABA transporter (GAT) inhibitor, blocked the increase in IPSC frequency at 5 min of hypoosmotic challenge. Confocal microscopy of immunostained SON sections revealed that astrocytes and magnocellular neurons both showed positive staining of vesicular GATs (VGAT). Hypoosmotic stimulation in vivo reduced the number of VGAT-expressing neurons, and increased co-localisation and molecular association of VGAT with glial fibrillary acidic protein that increased significantly by 10 min. By 30 min, neuronal VGAT labelling was partially restored, and astrocytic VGAT was relocated to the ventral portion while it decreased in the somatic zone of the SON. Thus, synergistic astrocytic and neuronal GABAergic inhibition could ensure that vasopressin neuron firing is only transiently suppressed under hypoosmotic conditions. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  15. Activity of the Hypothalamic-Pituitary-Adrenal System in Prenatally Stressed Male Rats on the Experimental Model of Post-Traumatic Stress Disorder.

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    Pivina, S G; Rakitskaya, V V; Akulova, V K; Ordyan, N E

    2016-03-01

    Using the experimental model of post-traumatic stress disorder (stress-restress paradigm), we studied the dynamics of activity of the hypothalamic-pituitary-adrenal system (HPAS) in adult male rats, whose mothers were daily subjected to restraint stress on days 15-19 of pregnancy. Prenatally stressed males that were subjected to combined stress and subsequent restress exhibited not only increased sensitivity of HPAS to negative feedback signals (manifested under restress conditions), but also enhanced stress system reactivity. These changes persisted to the 30th day after restress. Under basal conditions, the number of cells in the hypothalamic paraventricular nucleus of these animals expressing corticotropin-releasing hormone and vasopressin was shown to decrease progressively on days 1-30. By contrast, combined stress and restress in control animals were followed by an increase in the count of CRH-immunopositive cells in the magnocellular and parvocellular parts of the paraventricular nucleus and number of vasopressin-immunopositive cells in the magnocellular part of the nucleus (to the 10th day after restress). Our results indicate a peculiar level of functional activity of HPAS in prenatally stressed males in the stress-restress paradigm: decreased activity under basal conditions and enhanced reactivity during stress.

  16. Magnocellular pathway for rotation invariant Neocognitron.

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    Ting, C H

    1993-03-01

    In the mammalian visual system, magnocellular pathway and parvocellular pathway cooperatively process visual information in parallel. The magnocellular pathway is more global and less particular about the details while the parvocellular pathway recognizes objects based on the local features. In many aspects, Neocognitron may be regarded as the artificial analogue of the parvocellular pathway. It is interesting then to model the magnocellular pathway. In order to achieve "rotation invariance" for Neocognitron, we propose a neural network model after the magnocellular pathway and expand its roles to include surmising the orientation of the input pattern prior to recognition. With the incorporation of the magnocellular pathway, a basic shift in the original paradigm has taken place. A pattern is now said to be recognized when and only when one of the winners of the magnocellular pathway is validified by the parvocellular pathway. We have implemented the magnocellular pathway coupled with Neocognitron parallel on transputers; our simulation programme is now able to recognize numerals in arbitrary orientation.

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

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    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.

  18. The accessory magnocellular neurosecretory system of the rostral human hypothalamus

    DEFF Research Database (Denmark)

    Møller, Morten; Busch, Johannes R.; Jacobsen, Christina

    2018-01-01

    magnocellular neurons were often located along the blood vessels and projections of some of these neurons penetrated the vascular endothelium. The accessory magnocellular cell bodies expressed either neurophysin I or neurophysin II immunoreactivity. Summarizing, the accessory magnocellular system in the human......The morphology and neurophysin expression of the magnocellular accessory neuroendocrine system located in the rostral human hypothalamus is investigated in a series of brains obtained at autopsy. The hypothalami were fixed in formalin and embedded in paraffin, or after cryoprotection, frozen...

  19. Physiology of spontaneous [Ca2+](i) oscillations in the isolated vasopressin and oxytocin neurones of the rat supraoptic nucleus

    Czech Academy of Sciences Publication Activity Database

    Kortus, Štěpán; Srinivasan, Ch.; Forostyak, O.; Ueta, Y.; Syková, E.; Chvátal, A.; Zápotocký, Martin; Verkhratsky, A.; Dayanithi, G.

    2016-01-01

    Roč. 59, č. 6 (2016), s. 280-288 ISSN 0143-4160 R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : magnocellular neurosecretory cells * supraoptic nucleus * vasopressin * oxytocin * transgenic rats * Ca2+ oscillations Subject RIV: FH - Neurology Impact factor: 3.707, year: 2016

  20. The hypothalamic slice approach to neuroendocrinology.

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    Hatton, G I

    1983-07-01

    The magnocellular peptidergic cells of the supraoptic and paraventricular nuclei comprise much of what is known as the hypothalamo-neurohypophysial system and is involved in several functions, including body fluid balance, parturition and lactation. While we have learned much from experiments in vivo, they have not produced a clear understanding of some of the crucial features associated with the functioning of this system. In particular, questions relating to the osmosensitivity of magnocellular neurones and the mechanism(s) by which their characteristic firing patterns are generated have not been answered using the older approaches. Electrophysiological studies with brain slices present direct evidence for osmosensitivity, and perhaps even osmoreceptivity, of magnocellular neurones. Other evidence indicates that the phasic bursting patterns of activity associated with vasopressin-releasing neurones (a) occur in the absence of patterned chemical synaptic input, (b) may be modulated by electrotonic conduction across gap junctions connecting magnocellular neurones and (c) are likely to be generated by endogenous membrane currents. These results make untenable the formerly held idea that phasic bursting activity is dependent upon recurrent synaptic inhibition.

  1. Co-localization and regulation of basic fibroblast growth factor and arginine vasopressin in neuroendocrine cells of the rat and human brain

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    Gonzalez Ana M

    2010-08-01

    Full Text Available Abstract Background Adult rat hypothalamo-pituitary axis and choroid plexus are rich in basic fibroblast growth factor (FGF2 which likely has a role in fluid homeostasis. Towards this end, we characterized the distribution and modulation of FGF2 in the human and rat central nervous system. To ascertain a functional link between arginine vasopressin (AVP and FGF2, a rat model of chronic dehydration was used to test the hypothesis that FGF2 expression, like that of AVP, is altered by perturbed fluid balance. Methods Immunohistochemistry and confocal microscopy were used to examine the distribution of FGF2 and AVP neuropeptides in the normal human brain. In order to assess effects of chronic dehydration, Sprague-Dawley rats were water deprived for 3 days. AVP neuropeptide expression and changes in FGF2 distribution in the brain, neural lobe of the pituitary and kidney were assessed by immunohistochemistry, and western blotting (FGF2 isoforms. Results In human hypothalamus, FGF2 and AVP were co-localized in the cytoplasm of supraoptic and paraventricular magnocellular neurons and axonal processes. Immunoreactive FGF2 was associated with small granular structures distributed throughout neuronal cytoplasm. Neurohypophysial FGF2 immunostaining was found in axonal processes, pituicytes and Herring bodies. Following chronic dehydration in rats, there was substantially-enhanced FGF2 staining in basement membranes underlying blood vessels, pituicytes and other glia. This accompanied remodeling of extracellular matrix. Western blot data revealed that dehydration increased expression of the hypothalamic FGF2 isoforms of ca. 18, 23 and 24 kDa. In lateral ventricle choroid plexus of dehydrated rats, FGF2 expression was augmented in the epithelium (Ab773 as immunomarker but reduced interstitially (Ab106 immunostaining. Conclusions Dehydration altered FGF2 expression patterns in AVP-containing magnocellular neurons and neurohypophysis, as well as in choroid

  2. Visual Magnocellular Function in Perceptual Disorders

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    David P. Crewther

    2011-05-01

    Full Text Available Developmental disorders such as autism spectrum disorders (ASD, dyslexia, schizophrenia and dyscalculia have also been reported to show abnormal visual perception. Central to the four disorders are observations of altered global/local perception, motion sensation and grouping that are suggestive of a magnocellular abnormality(s. Such psychophysical observations do not easily yield neurophysiological mechanisms that can explain the altered perception/vision. Nonlinear visual evoked potentials have allowed the separation of magnocellular (M and parvocellular (P contributions to the VEP (Klistorner et al., 1997. Using these tools we compare the patterns of abnormality in groups with visual disorders. The second order kernel responses of the VEP in autistic tendency show interference between P and M nonlinearities at high contrast (Sutherland & Crewther, 2010 resulting in a delay of completion of firing. While afferent latencies of M and P cortical activation are not different in ASD, the delay in completion may allow a revision of the ideas surrounding the “magnocellular advantage” which relate to the alterations observed in global and local perception.

  3. Hypothalamic vasopressinergic projections innervate central amygdala GABAergic neurons: implications for anxiety and stress coping

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    Vito Salvador Hernandez

    2016-11-01

    Full Text Available The arginine-vasopressin (AVP-containing hypothalamic magnocellular neurosecretory neurons (VPMNNs are known for their role in hydro-electrolytic balance control via their projections to neurohypophysis. Recently, projections from these same neurons to hippocampus, habenula, and other brain regions, in which vasopressin infusion modulates contingent social and emotionally-affected behaviors, have been reported. Here, we present evidence that VPMNN collaterals also project to the amygdaloid complex, and establish synaptic connections with neurons in central amygdala (CeA. The density of AVP innervation in amygdala was substantially increased in adult rats that had experienced neonatal maternal separation (MS, consistent with our previous observations that MS enhances VPMNN number in the paraventricular (PVN and supraoptic (SON nuclei of the hypothalamus. In the CeA, V1a AVP receptor mRNA was only observed in GABAergic neurons, demonstrated by complete co-localization of V1a transcripts in neurons expressing Gad1 and Gad2 transcripts in CeA using the RNAscope method. V1b and V2 receptors mRNA were not detected, using the same method. Water-deprivation for 24 hrs, which increased the metabolic activity of VPMNNs, also increased anxiety-like behavior measured using the elevated plus maze test, and this effect was mimicked by bilateral microinfusion of VP into the CeA. Anxious behavior induced by either water deprivation or VP infusion was reversed by CeA infusion of V1a antagonist. VPMNNs are thus a newly discovered source of central amygdala inhibitory circuit modulation, through which both early-life and adult stress coping signals are conveyed from the hypothalamus to the amygdala.

  4. Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells

    OpenAIRE

    Merkle, Florian T.; Maroof, Asif; Wataya, Takafumi; Sasai, Yoshiki; Studer, Lorenz; Eggan, Kevin; Schier, Alexander F.

    2015-01-01

    Hypothalamic neurons orchestrate many essential physiological and behavioral processes via secreted neuropeptides, and are relevant to human diseases such as obesity, narcolepsy and infertility. We report the differentiation of human pluripotent stem cells into many of the major types of neuropeptidergic hypothalamic neurons, including those producing pro-opiolemelanocortin, agouti-related peptide, hypocretin/orexin, melanin-concentrating hormone, oxytocin, arginine vasopressin, corticotropin...

  5. Vasopressin differentially modulates aggression and anxiety in adolescent hamsters administered anabolic steroids.

    Science.gov (United States)

    Morrison, Thomas R; Ricci, Lesley A; Melloni, Richard H

    2016-11-01

    Adolescent Syrian hamsters (Mesocricetus auratus) treated with anabolic/androgenic steroids display increased offensive aggression and decreased anxiety correlated with an increase in vasopressin afferent development, synthesis, and neural signaling within the anterior hypothalamus. Upon withdrawal from anabolic/androgenic steroids, this neurobehavioral relationship shifts as hamsters display decreased offensive aggression and increased anxiety correlated with a decrease in anterior hypothalamic vasopressin. This study investigated the hypothesis that alterations in anterior hypothalamic vasopressin neural signaling modulate behavioral shifting between adolescent anabolic/androgenic steroid-induced offensive aggression and anxiety. To test this, adolescent male hamsters were administered anabolic/androgenic steroids and tested for offensive aggression or anxiety following direct pharmacological manipulation of vasopressin V1A receptor signaling within the anterior hypothalamus. Blockade of anterior hypothalamic vasopressin V1A receptor signaling suppressed offensive aggression and enhanced general and social anxiety in hamsters administered anabolic/androgenic steroids during adolescence, effectively reversing the pattern of behavioral response pattern normally observed during the adolescent exposure period. Conversely, activation of anterior hypothalamic vasopressin V1A receptor signaling enhanced offensive aggression in hamsters exposed to anabolic/androgenic steroids during adolescence. Together, these findings suggest that the state of vasopressin neural development and signaling in the anterior hypothalamus plays an important role in behavioral shifting between aggression and anxiety following adolescent exposure to anabolic/androgenic steroids. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Thirst is associated with suppression of LHB outputs and active stress coping: Is there a role for a non-canonical vasopressin-glutamate pathway?

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    Limei eZhang

    2016-03-01

    Full Text Available Water-homeostasis is a fundamental physiological process for terrestrial life. In vertebrates, thirst drives water intake, but the neuronal circuits that connect the physiology of water regulation with emotional context are poorly understood. Vasopressin (VP is a prominent messenger in this circuit, as well as L-glutamate. We have investigated the role of a VP circuit and interaction between thirst and motivational behaviors evoked by life-threatening stimuli in rats. We demonstrate a direct pathway from hypothalamic paraventricular VP-expressing, glutamatergic magnocellular neurons to the medial division of lateral habenula (LHbM, a region containing GABAergic neurons. In vivo recording and juxtacellular labeling revealed that GABAergic neurons in the LHbM had locally branching axons, and received VP-positive axon terminal contacts on their dendrites. Water deprivation significantly reduced freezing and immobility behaviors evoked by innate fear and behavioral despair respectively, accompanied by decreased Fos expression in the lateral habenula. Our results reveal a novel VP-expressing hypothalamus to the LHbM circuit that is likely to evoke GABA-mediated inhibition in the LHbM, which promotes escape behavior during stress coping.

  7. Effects of nitric oxide on magnocellular neurons of the supraoptic nucleus involve multiple mechanisms

    Directory of Open Access Journals (Sweden)

    M.P. da Silva

    2014-02-01

    Full Text Available Physiological evidence indicates that the supraoptic nucleus (SON is an important region for integrating information related to homeostasis of body fluids. Located bilaterally to the optic chiasm, this nucleus is composed of magnocellular neurosecretory cells (MNCs responsible for the synthesis and release of vasopressin and oxytocin to the neurohypophysis. At the cellular level, the control of vasopressin and oxytocin release is directly linked to the firing frequency of MNCs. In general, we can say that the excitability of these cells can be controlled via two distinct mechanisms: 1 the intrinsic membrane properties of the MNCs themselves and 2 synaptic input from circumventricular organs that contain osmosensitive neurons. It has also been demonstrated that MNCs are sensitive to osmotic stimuli in the physiological range. Therefore, the study of their intrinsic membrane properties became imperative to explain the osmosensitivity of MNCs. In addition to this, the discovery that several neurotransmitters and neuropeptides can modulate their electrical activity greatly increased our knowledge about the role played by the MNCs in fluid homeostasis. In particular, nitric oxide (NO may be an important player in fluid balance homeostasis, because it has been demonstrated that the enzyme responsible for its production has an increased activity following a hypertonic stimulation of the system. At the cellular level, NO has been shown to change the electrical excitability of MNCs. Therefore, in this review, we focus on some important points concerning nitrergic modulation of the neuroendocrine system, particularly the effects of NO on the SON.

  8. Radioimmunoassay in assessment of function of the hypothalamo-neurohypophyseal system in patients with hypothalamic syndromes

    International Nuclear Information System (INIS)

    Slavnov, V.N.; Markov, V.V.; Rudichenko, V.M.

    1991-01-01

    Radioimmunoassay of vasopressin was conducted before and after drug tests and exercise for assessment of function of the hypothalamo-neurohypophyseal system in 165 patients with hypothalamic syndromes. It was shown that radioimmunoassay gave the adequate information for assessment of function of hypothalamo-neurohypophyseal system on the base of study of basal and stimulated vasopressin secretion. It permits to make an individual choice of the most effective drug for therapy of the hypothalamic syndrome of neuroendocrine-metabolic type

  9. Role of fructose and fructokinase in acute dehydration-induced vasopressin gene expression and secretion in mice.

    Science.gov (United States)

    Song 宋志林, Zhilin; Roncal-Jimenez, Carlos A; Lanaspa-Garcia, Miguel A; Oppelt, Sarah A; Kuwabara, Masanari; Jensen, Thomas; Milagres, Tamara; Andres-Hernando, Ana; Ishimoto, Takuji; Garcia, Gabriela E; Johnson, Ginger; MacLean, Paul S; Sanchez-Lozada, Laura-Gabriela; Tolan, Dean R; Johnson, Richard J

    2017-02-01

    Fructose stimulates vasopressin in humans and can be generated endogenously by activation of the polyol pathway with hyperosmolarity. We hypothesized that fructose metabolism in the hypothalamus might partly control vasopressin responses after acute dehydration. Wild-type and fructokinase-knockout mice were deprived of water for 24 h. The supraoptic nucleus was evaluated for vasopressin and markers of the aldose reductase-fructokinase pathway. The posterior pituitary vasopressin and serum copeptin levels were examined. Hypothalamic explants were evaluated for vasopressin secretion in response to exogenous fructose. Water restriction increased serum and urine osmolality and serum copeptin in both groups of mice, although the increase in copeptin in wild-type mice was larger than that in fructokinase-knockout mice. Water-restricted, wild-type mice showed an increase in vasopressin and aldose reductase mRNA, sorbitol, fructose and uric acid in the supraoptic nucleus. In contrast, fructokinase-knockout mice showed no change in vasopressin or aldose reductase mRNA, and no changes in sorbitol or uric acid, although fructose levels increased. With water restriction, vasopressin in the pituitary of wild-type mice was significantly less than that of fructokinase-knockout mice, indicating that fructokinase-driven vasopressin secretion overrode synthesis. Fructose increased vasopressin release in hypothalamic explants that was not observed in fructokinase-knockout mice. In situ hybridization documented fructokinase mRNA in the supraoptic nucleus, paraventricular nucleus and suprachiasmatic nucleus. Acute dehydration activates the aldose reductase-fructokinase pathway in the hypothalamus and partly drives the vasopressin response. Exogenous fructose increases vasopressin release in hypothalamic explants dependent on fructokinase. Nevertheless, circulating vasopressin is maintained and urinary concentrating is not impaired. This study increases our understanding of the

  10. Magnocellular involvement in flanked-letter identification relates to the allocation of attention

    NARCIS (Netherlands)

    Omtzigt, D.; Hendriks, A.W.C.J.

    2004-01-01

    To verify the hypothesis that the magnocellular system is important to flanked-letter identification [Neuropsychologia 40 (2002) 1881] because it subserves attention allocation, we conducted three letter-naming experiments in which we manipulated magnocellular involvement (colour vs. luminance

  11. Altered astrocyte glutamate transporter regulation of hypothalamic neurosecretory neurons in heart failure rats.

    Science.gov (United States)

    Potapenko, Evgeniy S; Biancardi, Vinicia C; Zhou, Yiqiang; Stern, Javier E

    2012-08-01

    Neurohumoral activation, which includes augmented plasma levels of the neurohormone vasopressin (VP), is a common finding in heart failure (HF) that contributes to morbidity and mortality in this disease. While an increased activation of magnocellular neurosecretory cells (MNCs) and enhanced glutamate function in HF is well documented, the precise underlying mechanisms remain to be elucidated. Here, we combined electrophysiology and protein measurements to determine whether altered glial glutamate transporter function and/or expression occurs in the hypothalamic supraoptic nucleus (SON) during HF. Patch-clamp recordings obtained from MNCs in brain slices show that pharmacological blockade of astrocyte glutamate transporter 1 (GLT1) function [500 μM dihydrokainate (DHK)], resulted in a persistent N-methyl-D-aspartate receptor (NMDAR)-mediated inward current (tonic I(NMDA)) in sham rats, an effect that was significantly smaller in MNCs from HF rats. In addition, we found a diminished GLT1 protein content in plasma membrane (but not cytosolic) fractions of SON punches in HF rats. Conversely, astrocyte GLAST expression was significantly higher in the SON of HF rats, while nonselective blockade of glutamate transport activity (100 μM TBOA) evoked an enhanced tonic I(NMDA) activation in HF rats. Steady-state activation of NMDARs by extracellular glutamate levels was diminished during HF. Taken together, these results support a shift in the relative expression and function of two major glial glutamate transporters (from GLT1 to GLAST predominance) during HF. This shift may act as a compensatory mechanism to preserve an adequate basal glutamate uptake level in the face of an enhanced glutamatergic afferent activity in HF rats.

  12. In vivo somatostatin, vasopressin, and oxytocin synthesis in diabetic rat hypothalamus

    International Nuclear Information System (INIS)

    Fernstrom, J.D.; Fernstrom, M.H.; Kwok, R.P.

    1990-01-01

    The in vivo labeling of somatostatin-14, somatostatin-28, arginine vasopressin, and oxytocin was studied in rat hypothalamus after third ventricular administration of [35S]cysteine to streptozotocin-diabetic and normal rats. Immunoreactive somatostatin levels in hypothalamus were unaffected by diabetes, as was the incorporation of [35S]cysteine into hypothalamic somatostatin-14 and somatostatin-28. In contrast, immunoreactive vasopressin levels in hypothalamus and posterior pituitary (and oxytocin levels in posterior pituitary) were below normal in diabetic rats. Moreover, [35S]cysteine incorporation into hypothalamic vasopressin and oxytocin (probably mainly in the paraventricular nucleus because of its proximity to the third ventricular site of label injection) was significantly above normal. The increments in vasopressin and oxytocin labeling were reversed by insulin administration. In vivo cysteine specific activity and the labeling of acid-precipitable protein did not differ between normal and diabetic animals; effects of diabetes on vasopressin and oxytocin labeling were therefore not caused by simple differences in cysteine specific activity. These results suggest that diabetes (1) does not influence the production of somatostatin peptides in hypothalamus but (2) stimulates the synthesis of vasopressin and oxytocin. For vasopressin at least, the increase in synthesis may be a compensatory response to the known increase in its secretion that occurs in uncontrolled diabetes

  13. Enhanced NMDA receptor-mediated intracellular calcium signaling in magnocellular neurosecretory neurons in heart failure rats.

    Science.gov (United States)

    Stern, Javier E; Potapenko, Evgeniy S

    2013-08-15

    An enhanced glutamate excitatory function within the hypothalamic supraoptic and paraventricluar nuclei is known to contribute to increased neurosecretory and presympathetic neuronal activity, and hence, neurohumoral activation, during heart failure (HF). Still, the precise mechanisms underlying enhanced glutamate-driven neuronal activity in HF remain to be elucidated. Here, we performed simultaneous electrophysiology and fast confocal Ca²⁺ imaging to determine whether altered N-methyl-d-aspartate (NMDA) receptor-mediated changes in intracellular Ca²⁺ levels (NMDA-ΔCa²⁺) occurred in hypothalamic magnocellular neurosecretory cells (MNCs) in HF rats. We found that activation of NMDA receptors resulted in a larger ΔCa²⁺ in MNCs from HF when compared with sham rats. The enhanced NMDA-ΔCa²⁺ was neither dependent on the magnitude of the NMDA-mediated current (voltage clamp) nor on the degree of membrane depolarization or firing activity evoked by NMDA (current clamp). Differently from NMDA receptor activation, firing activity evoked by direct membrane depolarization resulted in similar changes in intracellular Ca²⁺ in sham and HF rats. Taken together, our results support a relatively selective alteration of intracellular Ca²⁺ homeostasis and signaling following activation of NMDA receptors in MNCs during HF. The downstream functional consequences of such altered ΔCa²⁺ signaling during HF are discussed.

  14. Endocrine Disruption of Vasopressin Systems and Related Behaviors

    Directory of Open Access Journals (Sweden)

    Heather B. Patisaul

    2017-06-01

    Full Text Available Endocrine disrupting chemicals (EDCs are chemicals that interfere with the organizational or activational effects of hormones. Although the vast majority of the EDC literature focuses on steroid hormone signaling related impacts, growing evidence from a myriad of species reveals that the nonapeptide hormones vasopressin (AVP and oxytocin (OT may also be EDC targets. EDCs shown to alter pathways and behaviors coordinated by AVP and/or OT include the plastics component bisphenol A (BPA, the soy phytoestrogen genistein (GEN, and various flame retardants. Many effects are sex specific and likely involve action at nuclear estrogen receptors. Effects include the elimination or reversal of well-characterized sexually dimorphic aspects of the AVP system, including innervation of the lateral septum and other brain regions critical for social and other non-reproductive behaviors. Disruption of magnocellular AVP function has also been reported in rats, suggesting possible effects on hemodynamics and cardiovascular function.

  15. Vasopressin and Vasopressin Antagonists in Heart Failure

    DEFF Research Database (Denmark)

    Vishram-Nielsen, Julie K; Gustafsson, Finn

    2017-01-01

    Despite the introduction of multiple new pharmacological agents over the past three decades in the field of heart failure (HF), overall prognosis remains poor. Hyponatremia is prevalent in HF patients and has been suggested as a contributor to poor response to standard therapy. Elevated levels...... by the V2 receptors in the renal collecting tubules. The optimal use of VRAs is yet to be determined, especially in patients with congestive HF. Although long-term effects on improvement in mortality have not been shown in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan...

  16. Cerebrospinal fluid levels of corticotropin-releasing hormone in women with functional hypothalamic amenorrhea.

    Science.gov (United States)

    Berga, S L; Loucks-Daniels, T L; Adler, L J; Chrousos, G P; Cameron, J L; Matthews, K A; Marcus, M D

    2000-04-01

    Women with functional hypothalamic amenorrhea are anovulatory because of reduced gonadotropin-releasing hormone drive. Several studies have documented hypercortisolemia, which suggests that functional hypothalamic amenorrhea is stress-induced. Further, with recovery (resumption of ovulation), cortisol decreased and gonadotropin-releasing hormone drive increased. Corticotropin-releasing hormone can increase cortisol and decrease gonadotropin-releasing hormone. To determine its role in functional hypothalamic amenorrhea, we measured corticotropin-releasing hormone in cerebrospinal fluid along with arginine vasopressin, another potent adrenocorticotropic hormone secretagog, and beta-endorphin, which is released by corticotropin-releasing hormone and can inhibit gonadotropin-releasing hormone. Corticotropin-releasing hormone, vasopressin, and beta-endorphin levels were measured in cerebrospinal fluid from 14 women with eumenorrhea and 15 women with functional hypothalamic amenorrhea. Levels of corticotropin-releasing hormone in cerebrospinal fluid and of vasopressin were comparable and beta-endorphin levels were lower in women with functional hypothalamic amenorrhea. In women with established functional hypothalamic amenorrhea, increased cortisol and reduced gonadotropin-releasing hormone are not sustained by elevated cerebrospinal-fluid corticotropin-releasing hormone, vasopressin, or beta-endorphin. These data do not exclude a role for these factors in the initiation of functional hypothalamic amenorrhea.

  17. Examination of the biological half-life and organ d;stribution of tritiated lysin-vasopressin in Brattleboro rats

    International Nuclear Information System (INIS)

    Laczi, F.; Laszlo, F.

    1980-01-01

    15 μCi tritiated lysin-vasopressin (spec. act. 3.5 Ci per mmol) was administered to control and Brattleboro rats, suffering from hereditary hypothalamic diabetes insipidus. The biological half-life and the distribution of the labelled compound in the different organs were determined. The biological half-life demonstrated no significant difference, however, the vasopressin content of the small intestine was higher in the Brattleboro rats. In the other organs no significant difference was found. It can be concluded that the hereditary diabetes insipidus is not due to faster elimination of circulating vasopressin. (L.E.)

  18. Examination of the biological half-life and organ d; stribution of tritiated lysin-vasopressin in Brattleboro rats

    Energy Technology Data Exchange (ETDEWEB)

    Laczi, F; Laszlo, F [Szegedi Orvostudomanyi Egyetem Szeged (Hungary). 1. Belgyogyaszati Klinika; Keri, Gy; Teplan, I [Semmelweis Orvostudomanyi Egyetem, Budapest (Hungary)

    1980-04-01

    15 ..mu..Ci tritiated lysin-vasopressin (spec. act. 3.5 Ci per mmol) was administered to control and Brattleboro rats, suffering from hereditary hypothalamic diabetes insipidus. The biological half-life and the distribution of the labelled compound in the different organs were determined. The biological half-life demonstrated no significant difference, however, the vasopressin content of the small intestine was higher in the Brattleboro rats. In the other organs no significant difference was found. It can be concluded that the hereditary diabetes insipidus is not due to faster elimination of circulating vasopressin.

  19. Identifying Dyscalculia Symptoms Related to Magnocellular Reasoning Using Smartphones.

    Science.gov (United States)

    Knudsen, Greger Siem; Babic, Ankica

    2016-01-01

    This paper presents a study that has developed a mobile software application for assisting diagnosis of learning disabilities in mathematics, called dyscalculia, and measuring correlations between dyscalculia symptoms and magnocellular reasoning. Usually, software aids for dyscalculic individuals are focused on both assisting diagnosis and teaching the material. The software developed in this study however maintains a specific focus on the former, and in the process attempts to capture alleged correlations between dyscalculia symptoms and possible underlying causes of the condition. Classification of symptoms is performed by k-Nearest Neighbor algorithm classifying five parameters evaluating user's skills, returning calculated performance in each category as well as correlation strength between detected symptoms and magnocellular reasoning abilities. Expert evaluations has found the application to be appropriate and productive for its intended purpose, proving that mobile software is a suitable and valuable tool for assisting dyscalculia diagnosis and identifying root causes of developing the condition.

  20. Population dynamics in vasopressin cells.

    Science.gov (United States)

    Leng, Gareth; Brown, Colin; Sabatier, Nancy; Scott, Victoria

    2008-01-01

    Most neurons sense and code change, and when presented with a constant stimulus they adapt, so as to be able to detect a fresh change. However, for some things it is important to know their absolute level; to encode such information, neurons must sustain their response to an unchanging stimulus while remaining able to respond to a change in that stimulus. One system that encodes the absolute level of a stimulus is the vasopressin system, which generates a hormonal signal that is proportional to plasma osmolality. Vasopressin cells sense plasma osmolality and secrete appropriate levels of vasopressin from the neurohypophysis as needed to control water excretion; this requires sustained secretion under basal conditions and the ability to increase (or decrease) secretion should plasma osmolality change. Here we explore the mechanisms that enable vasopressin cells to fulfill this function, and consider how coordination between the cells might distribute the secretory load across the population of vasopressin cells. 2008 S. Karger AG, Basel.

  1. Visual Temporal Processing in Dyslexia and the Magnocellular Deficit Theory: The Need for Speed?

    Science.gov (United States)

    McLean, Gregor M. T.; Stuart, Geoffrey W.; Coltheart, Veronika; Castles, Anne

    2011-01-01

    A controversial question in reading research is whether dyslexia is associated with impairments in the magnocellular system and, if so, how these low-level visual impairments might affect reading acquisition. This study used a novel chromatic flicker perception task to specifically explore "temporal" aspects of magnocellular functioning…

  2. Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells.

    Science.gov (United States)

    Merkle, Florian T; Maroof, Asif; Wataya, Takafumi; Sasai, Yoshiki; Studer, Lorenz; Eggan, Kevin; Schier, Alexander F

    2015-02-15

    Hypothalamic neurons orchestrate many essential physiological and behavioral processes via secreted neuropeptides, and are relevant to human diseases such as obesity, narcolepsy and infertility. We report the differentiation of human pluripotent stem cells into many of the major types of neuropeptidergic hypothalamic neurons, including those producing pro-opiolemelanocortin, agouti-related peptide, hypocretin/orexin, melanin-concentrating hormone, oxytocin, arginine vasopressin, corticotropin-releasing hormone (CRH) or thyrotropin-releasing hormone. Hypothalamic neurons can be generated using a 'self-patterning' strategy that yields a broad array of cell types, or via a more reproducible directed differentiation approach. Stem cell-derived human hypothalamic neurons share characteristic morphological properties and gene expression patterns with their counterparts in vivo, and are able to integrate into the mouse brain. These neurons could form the basis of cellular models, chemical screens or cellular therapies to study and treat common human diseases. © 2015. Published by The Company of Biologists Ltd.

  3. Vasopressin and oxytocin neurons of the human supraoptic and paraventricular nucleus: size changes in relation to age and sex

    NARCIS (Netherlands)

    Ishunina, T. A.; Swaab, D. F.

    1999-01-01

    The hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei consist of arginine vasopressin (AVP)- and oxytocin (OT)-synthesizing neurons that send projections to the neurohypophysis, whereas the PVN also projects to other brain areas. A growing body of evidence in animals suggests the

  4. Neuromorphic model of magnocellular and parvocellular visual paths: spatial resolution

    International Nuclear Information System (INIS)

    Aguirre, Rolando C; Felice, Carmelo J; Colombo, Elisa M

    2007-01-01

    Physiological studies of the human retina show the existence of at least two visual information processing channels, the magnocellular and the parvocellular ones. Both have different spatial, temporal and chromatic features. This paper focuses on the different spatial resolution of these two channels. We propose a neuromorphic model, so that they match the retina's physiology. Considering the Deutsch and Deutsch model (1992), we propose two configurations (one for each visual channel) of the connection between the retina's different cell layers. The responses of the proposed model have similar behaviour to those of the visual cells: each channel has an optimum response corresponding to a given stimulus size which decreases for larger or smaller stimuli. This size is bigger for the magno path than for the parvo path and, in the end, both channels produce a magnifying of the borders of a stimulus

  5. Visual temporal processing in dyslexia and the magnocellular deficit theory: the need for speed?

    Science.gov (United States)

    McLean, Gregor M T; Stuart, Geoffrey W; Coltheart, Veronika; Castles, Anne

    2011-12-01

    A controversial question in reading research is whether dyslexia is associated with impairments in the magnocellular system and, if so, how these low-level visual impairments might affect reading acquisition. This study used a novel chromatic flicker perception task to specifically explore temporal aspects of magnocellular functioning in 40 children with dyslexia and 42 age-matched controls (aged 7-11). The relationship between magnocellular temporal resolution and higher-level aspects of visual temporal processing including inspection time, single and dual-target (attentional blink) RSVP performance, go/no-go reaction time, and rapid naming was also assessed. The Dyslexia group exhibited significant deficits in magnocellular temporal resolution compared with controls, but the two groups did not differ in parvocellular temporal resolution. Despite the significant group differences, associations between magnocellular temporal resolution and reading ability were relatively weak, and links between low-level temporal resolution and reading ability did not appear specific to the magnocellular system. Factor analyses revealed that a collective Perceptual Speed factor, involving both low-level and higher-level visual temporal processing measures, accounted for unique variance in reading ability independently of phonological processing, rapid naming, and general ability.

  6. A radioimmunoassay for vasopressin

    International Nuclear Information System (INIS)

    Glaenzer, K.

    1989-01-01

    Described are the development and RIA experimental clinical use of determination for an antidiuretic hormone, 8-arginine vasopressin. The lower limits of detection for this RIA were 0.3 pg/ml in the plasma and 0.6 pg/ml in the urine. For purposes of reference, plasma AVP levels were determined in 50 normal volunteers and found to average 1.2 ± 0.6 pg/ml in females and 1.7 ± 0.7 pg/ml in males. The average AVP excretion with the urine ws 73 ± 43 ng/day. AVP levels determined in urine and plasma samples from patients showing diabetes insipidus centralis or healthy subjects that had not been offered any drink for 24 hours provided evidence in confirmation of supposed physiological interactions. The plasma AVP concentrations of subjects, in which the osmotic processes were impaired by the effects of contrast media used for X-ray examinations, proved to be far above the maximum antidiuretic concentrations and were also very likely to be within the effective range for cardiovascular influences. A series of further examinations was to throw some light on the question whether dramatic surges in ADH during and after surgical replacement of the mitral valve would be accompagnied by the occurrence of a hypoosmolar syndrome. Other examinations were to give insights into the particular role of AVP in the regulation of blood pressure. The last series of examinations had the aim to elucidate the interactions between the angiotensin-renin system and AVP secretion, which were studied in healthy volunteers using the tilting table test both before and during suppression of angiotensin II formation by captopril. There was no conclusive evidence from these examinations that angiotensin II mediates the stimulation of plasma AVP under the conditions of passive orthostatism. (orig./MG) With 24 figs., 8 tabs [de

  7. Hypothalamic demyelination causing panhypopituitarism.

    Science.gov (United States)

    Dixon-Douglas, Julia; Burgess, John; Dreyer, Michael

    2018-05-01

    Hypothalamic involvement in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is rare and endocrinopathies involving the hypothalamic-pituitary axis in patients with demyelinating conditions have rarely been reported. We present two cases of MS/NMOSD with associated hypothalamic-pituitary involvement and subsequent hypopituitarism, including the first report of a patient with hypothalamic demyelination causing panhypopituitarism. Differential diagnoses, including alemtuzumab-related and primary pituitary pathology are discussed. © 2018 Royal Australasian College of Physicians.

  8. Study on the biological half-life and organ-distribution of tritiated lysine-vasopressin in Brattleboro rats

    International Nuclear Information System (INIS)

    Laczi, F.; Laszlo, F.A.; Keri, Gy.; Teplan, I.

    1980-01-01

    The biological half-life and organ-distribution of tritiated lysine-vasopressin were determined in R-Amsterdam rats, and in homozygous and heterozygous Brattleboro rats with hereditary central diabetes insipidus. It was found that the biological half-life of the tritiated lysin-vasopressin in the Brattleboro rats did not differ significantly from that found in the R-Amsterdam rats. The highest radioactivities were observed in the neuro- and adenohypophyses and in the kidneys of both the R-Amsterdam and the Brattleboro rats. The accumulation of tritiated LVP was higher in the small intestine of the Brattleboro rats than in that of the R-Amsterdam animals. The results have led to the conclusion that the accelerated elimination of vasopressin and its pathologic organ-accumulation are probably not involved in the water metabolism disturbance of Brattleboro rats with hereditary hypothalamic diabetes insipidus. (author)

  9. Cellular plasticity in the supraoptic and paraventricular nuclei after prolonged dehydration in the desert rodent Meriones shawi: Vasopressin and GFAP immunohistochemical study.

    Science.gov (United States)

    Gamrani, Halima; Elgot, Abdeljalil; El Hiba, Omar; Fèvre-Montange, Michelle

    2011-02-23

    Supraoptic (SON) and paraventricular (PVN) nuclei are part of the hypothalamic-neurohypophysial system, they constitute the main source for vasopressin and they represent also obvious examples of activity-dependent neuroglial plasticity. Certain physiological conditions such as dehydration are accompanied by a structural remodeling of the neurons, their synaptic inputs and their surrounding glia. In the present work, an adult Meriones shawi (a rodent adapted to desert life) is used as an animal model. Using GFAP and vasopressin expressions as indicators successively of astrocytes and neuronal activations, the effect of a prolonged episode of water deprivation on the SON and PVN, hypothalamus nuclei were examined. We studied the immunoreactivity of GFAP and vasopressin in various hydration states (total deprivation of drinking water for 1 and 2months compared to hydrated animals). Prolonged dehydration produces an important decrease of GFAP immunoreactivity in both SON and PVN after 1 and 2months of water restriction. This decrease is accompanied by increased vasopressin immunoreactivity following the same periods of water deprivation. These findings may explain a real communication between vasopressin neurons and their surrounding astrocytes, thus the retraction of astrocytes and their processes is accompanied by an enhancement of vasopressin neuron density and their projecting fibers in response to this osmotic stress situation. Furthermore, these data could open further investigations concerning the possible involvement of the communication between astrocytes and vasopressin neurons in both PVN and SON in the regulation of Meriones hydrous balance and resistance to dehydration. Copyright © 2010. Published by Elsevier B.V.

  10. Yellow filters can improve magnocellular function: motion sensitivity, convergence, accommodation, and reading.

    Science.gov (United States)

    Ray, N J; Fowler, S; Stein, J F

    2005-04-01

    The magnocellular system plays an important role in visual motion processing, controlling vergence eye movements, and in reading. Yellow filters may boost magnocellular activity by eliminating inhibitory blue input to this pathway. It was found that wearing yellow filters increased motion sensitivity, convergence, and accommodation in many children with reading difficulties, both immediately and after three months using the filters. Motion sensitivity was not increased using control neutral density filters. Moreover, reading-impaired children showed significant gains in reading ability after three months wearing the filters compared with those who had used a placebo. It was concluded that yellow filters can improve magnocellular function permanently. Hence, they should be considered as an alternative to corrective lenses, prisms, or exercises for treating poor convergence and accommodation, and also as an aid for children with reading problems.

  11. Cortical projection patterns of magnocellular basal nucleus subdivisions as revealed by anterogradely transported Phaseolus vulgaris leucoagglutinin

    NARCIS (Netherlands)

    Luiten, P.G.M.; Gaykema, R.P.A.; Traber, J.; Spencer Jr., D.G.

    1987-01-01

    The present paper deals with a detailed analysis of cortical projections from the magnocellular basal nucleus (MBN) and horizontal limb of the diagonal band of Broca (HDB) in the rat. The MBN and HDB were injected iontophoretically with the anterograde tracer Phaseolus vulgaris leucoagglutinin

  12. Impaired Driving Performance as Evidence of a Magnocellular Deficit in Dyslexia and Visual Stress.

    Science.gov (United States)

    Fisher, Carri; Chekaluk, Eugene; Irwin, Julia

    2015-11-01

    High comorbidity and an overlap in symptomology have been demonstrated between dyslexia and visual stress. Several researchers have hypothesized an underlying or causal influence that may account for this relationship. The magnocellular theory of dyslexia proposes that a deficit in visuo-temporal processing can explain symptomology for both disorders. If the magnocellular theory holds true, individuals who experience symptomology for these disorders should show impairment on a visuo-temporal task, such as driving. Eighteen male participants formed the sample for this study. Self-report measures assessed dyslexia and visual stress symptomology as well as participant IQ. Participants completed a drive simulation in which errors in response to road signs were measured. Bivariate correlations revealed significant associations between scores on measures of dyslexia and visual stress. Results also demonstrated that self-reported symptomology predicts magnocellular impairment as measured by performance on a driving task. Results from this study suggest that a magnocellular deficit offers a likely explanation for individuals who report high symptomology across both conditions. While conclusions about the impact of these disorders on driving performance should not be derived from this research alone, this study provides a platform for the development of future research, utilizing a clinical population and on-road driving assessment techniques. Copyright © 2015 John Wiley & Sons, Ltd.

  13. [Relationship between magnocellular function and reading skills in children: a study using visual evoked potentials].

    Science.gov (United States)

    Kobayashi, Tomoka; Inagaki, Masumi; Yamazaki, Hiroko; Kita, Yosuke; Kaga, Makiko; Oka, Akira

    2014-11-01

    Developmental dyslexia (DD) is a neurodevelopmental disorder that is characterized by difficulties with accurate and/or fluent word recognition and by poor spelling and decoding abilities. The magnocellular deficit theory is one of several hypotheses that have been proposed to explain the pathophysiology of DD. In this study, we investigated magnocellular system dysfunction in Japanese dyslexic children. Subjects were 19 dyslexic children (DD group) and 19 aged-matched healthy children (TD group). They were aged between 7 and 16 years. Reversed patterns of black and white sinusoidal gratings generated at a low spatial frequency, high reversal frequency of 7.5 Hz, and low contrasts were used specifically to stimulate the magnocellular system. We recorded visual evoked potentials (VEP) from the occipital area and examined their relationship with reading and naming tasks, such as the time to read hiragana characters, rapid automatized naming of pictured objects, and phonological manipulation. Compared to the TD group, the DD group showed a significantly lower peak amplitude of VEPs through the complex demodulation method. Structural equation modeling showed that VEP peak amplitudes were related to the rapid automatized naming of pictured objects, and better rapid automatized naming resulted in higher reading skills. There was no correlation between VEP findings and the capacity for phonological manipulation. VEPs in response to the magnocellular system are useful for understanding the pathophysiology of DD. Single phonological deficit may not be sufficient to cause DD.

  14. Heterologous radioimmunoassay for arginine vasopressin

    International Nuclear Information System (INIS)

    Shimamoto, K.; Murase, T.; Yamaji, T.

    1976-01-01

    A sensitive and specific radioimmunoassay for arginine vasopressin (AVP) was developed utilizing the antisera against lysine vasopressin (LVP) in combination with a labeled AVP. The assay employs an acetone extraction procedure and detects as little as 0.8 pg. per millimeter of AVP in human plasma. In normal subjects, the mean (+- S.D.) plasma concentration of AVP was 4.9 +- 1.2 pg. per milliliter after fluid deprivation and 1.2 +- 0.4 pg. per milliliter after water loading. Plasma AVP levels correlated significantly with plasma osmolalities. In four patients with diabetes insipidus, plasma AVP concentrations ranged from less than 0.8 to 1.2 pg. per milliliter, whereas six patients with the syndrome of inappropriate ADH secretion showed plasma levels of AVP which correspond to those of the dehydrated state in normal subjects or greater, although plasma osmolalities were low in all cases. It was concluded that the present radioimmunoassay method for AVP provides a useful way of assessing neurohypophyseal function in man

  15. The radioimmunological determination of vasopressin in urine

    International Nuclear Information System (INIS)

    Horn, M.J. van der.

    1981-01-01

    This thesis describes the development of a radioimmunoassay (RIA) for antidiuretic hormone (ADH) or vasopressin, which can be used for the quantitative measurement of the urinary excretion of the hormone in man during physiological and pathological conditions. The final RIA method, using approximately 5 pg 125 I-AVP diluted (1 : 50,000) antiserum 121 and charcoal-dextran separation of the antibody-bound and free fractions, is found to be specific for vasopressin and closely related substances; the sensitivity is 9 pg. The validity is demonstrated and the results of measurements of vasopressin excretion in urine from 39 normal subjects, including 4 children are presented. (Auth.)

  16. Magnocellular Bias in Exogenous Attention to Biologically Salient Stimuli as Revealed by Manipulating Their Luminosity and Color.

    Science.gov (United States)

    Carretié, Luis; Kessel, Dominique; García-Rubio, María J; Giménez-Fernández, Tamara; Hoyos, Sandra; Hernández-Lorca, María

    2017-10-01

    Exogenous attention is a set of mechanisms that allow us to detect and reorient toward salient events-such as appetitive or aversive-that appear out of the current focus of attention. The nature of these mechanisms, particularly the involvement of the parvocellular and magnocellular visual processing systems, was explored. Thirty-four participants performed a demanding digit categorization task while salient (spiders or S) and neutral (wheels or W) stimuli were presented as distractors under two figure-ground formats: heterochromatic/isoluminant (exclusively processed by the parvocellular system, Par trials) and isochromatic/heteroluminant (preferentially processed by the magnocellular system, Mag trials). This resulted in four conditions: SPar, SMag, WPar, and WMag. Behavioral (RTs and error rates in the task) and electrophysiological (ERPs) indices of exogenous attention were analyzed. Behavior showed greater attentional capture by SMag than by SPar distractors and enhanced modulation of SMag capture as fear of spiders reported by participants increased. ERPs reflected a sequence from magnocellular dominant (P1p, ≃120 msec) to both magnocellular and parvocellular processing (N2p and P2a, ≃200 msec). Importantly, amplitudes in one N2p subcomponent were greater to SMag than to SPar and WMag distractors, indicating greater magnocellular sensitivity to saliency. Taking together, results support a magnocellular bias in exogenous attention toward distractors of any nature during initial processing, a bias that remains in later stages when biologically salient distractors are present.

  17. Role of Nitric Oxide in the Regulation of Renin and Vasopressin Secretion

    Science.gov (United States)

    Reid, Ian A.

    1994-01-01

    Research during recent years has established nitric oxide as a unique signaling molecule that plays important roles in the regulation of the cardiovascular, nervous, immune, and other systems. Nitric oxide has also been implicated in the control of the secretion of hormones by the pancreas, hypothalamus, and anterior pituitary gland, and evidence is accumulating that it contributes to the regulation of the secretion of renin and vasopressin, hormones that play key roles in the control of sodium and water balance. Several lines of evidence have implicated nitric oxide in the control of renin secretion. The enzyme nitric oxide synthase is present in vascular and tubular elements of the kidney, particularly in cells of the macula densa, a structure that plays an important role in the control of renin secretion. Guanylyl cyclase, a major target for nitric oxide, is also present in the kidney. Drugs that inhibit nitric oxide synthesis generally suppress renin release in vivo and in vitro, suggesting a stimulatory role for the L-arginine/nitric oxide pathway in the control of renin secretion. Under some conditions, however, blockade of nitric oxide synthesis increases renin secretion. Recent studies indicate that nitric oxide not only contributes to the regulation of basal renin secretion, but also participates in the renin secretory responses to activation of the renal baroreceptor, macula densa, and beta adrenoceptor mechanisms that regulate renin secretion. Histochemical and immunocytochemical studies have revealed the presence of nitric oxide synthase in the supraoptic and paraventricular nuclei of the hypothalamus and in the posterior pituitary gland. Colocalization of nitric oxide synthase and vasopressin has been demonstrated in some hypothalamic neurons. Nitric oxide synthase activity in the hypothalamus and pituitary is increased by maneuvers known to stimulate vasopressin secretion, including salt loading and dehydration, Administration of L-arginine and nitric

  18. The increase in the cardiodepressant activity and vasopressin concentration in the sella turcica venous blood during vagal afferents stimulation or after angiotensin II infusion

    International Nuclear Information System (INIS)

    Goraca, A.; Orlowska-Majdak, M.; Traczyk, W.Z.

    1996-01-01

    It has previously been demonstrated that the cardiodepressant activity is present in the bovine hypothalamic extract and in the fluid incubating the posterior pituitary lobe i n situ . The present study was an attempt to reveal if the cardiodepressant factor and vasopressin were simultaneously released from the pituitary into blood. The samples of venous blood flowing from the sella turcica and, for comparison, from the posterior paw were collected in anesthetized rats. Blood from the sella turcica was collected with a fine cannula inserted into the internal maxillary vein. The concentration of vasopressin in blood plasma was determined by radioimmunoassay and cardiodepressant activity-using a biological test on a spontaneously discharged pacemaker tissue of the right auricle of the right heart atrium. Stimulation of the central ends of the cut vagus nerves or intra-arterial infusion of angiotensin II simultaneously caused an increase in the cardiodepressant activity and vasopressin concentration in the sella turcica venous blood. The cardiodepressant activity and vasopressin concentration was also enhanced to some degree in blood outflowing from the posterior paw. Present results indicate that both vasopressin and the cardiodepressant factor are released into blood from the posterior pituitary lobe. (author). 37 refs, 4 figs

  19. The increase in the cardiodepressant activity and vasopressin concentration in the sella turcica venous blood during vagal afferents stimulation or after angiotensin II infusion

    Energy Technology Data Exchange (ETDEWEB)

    Goraca, A.; Orlowska-Majdak, M.; Traczyk, W.Z. [Akademia Medyczna, Lodz (Poland). Katedra Fizjologii

    1996-12-31

    It has previously been demonstrated that the cardiodepressant activity is present in the bovine hypothalamic extract and in the fluid incubating the posterior pituitary lobe {sup i}n situ{sup .} The present study was an attempt to reveal if the cardiodepressant factor and vasopressin were simultaneously released from the pituitary into blood. The samples of venous blood flowing from the sella turcica and, for comparison, from the posterior paw were collected in anesthetized rats. Blood from the sella turcica was collected with a fine cannula inserted into the internal maxillary vein. The concentration of vasopressin in blood plasma was determined by radioimmunoassay and cardiodepressant activity-using a biological test on a spontaneously discharged pacemaker tissue of the right auricle of the right heart atrium. Stimulation of the central ends of the cut vagus nerves or intra-arterial infusion of angiotensin II simultaneously caused an increase in the cardiodepressant activity and vasopressin concentration in the sella turcica venous blood. The cardiodepressant activity and vasopressin concentration was also enhanced to some degree in blood outflowing from the posterior paw. Present results indicate that both vasopressin and the cardiodepressant factor are released into blood from the posterior pituitary lobe. (author). 37 refs, 4 figs.

  20. Comparison of ex vivo stability of copeptin and vasopressin

    NARCIS (Netherlands)

    Heida, Judith E; Boesten, Lianne S M; Ettema, Esmée M; Muller Kobold, Anneke C.; Franssen, Casper F M; Gansevoort, Ron T; Zittema, Debbie

    BACKGROUND: Copeptin, part of the vasopressin precursor, is increasingly used as marker for vasopressin and is claimed to have better ex vivo stability. However, no study has directly compared the ex vivo stability of copeptin and vasopressin. METHODS: Blood of ten healthy volunteers was collected

  1. Hypothalamic glioma masquerading as craniopharyngioma

    Directory of Open Access Journals (Sweden)

    Sameer Vyas

    2013-01-01

    Full Text Available Hypothalamic glioma account for 10-15% of supratentorial tumors in children. They usually present earlier (first 5 years of age than craniopharyngioma. Hypothalamic glioma poses a diagnostic dilemma with craniopharyngioma and other hypothalamic region tumors, when they present with atypical clinical or imaging patterns. Neuroimaging modalities especially MRI plays a very important role in scrutinizing the lesions in the hypothalamic region. We report a case of a hypothalamic glioma masquerading as a craniopharyngioma on imaging along with brief review of both the tumors.

  2. Vasopressin and the Neurogenetics of Parental Care.

    Science.gov (United States)

    Snyder-Mackler, Noah; Tung, Jenny

    2017-07-05

    Making robust connections between genetic variation, neurophysiology, and social behavior remains a challenge. A study by Bendesky et al. (2017) tackles this challenge by dissecting the genetic architecture of parental care in deer mice to discover an important contribution of vasopressin signaling to the evolution of nest building. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Continuous vasopressin replacement in diabetes insipidus.

    OpenAIRE

    Ralston, C; Butt, W

    1990-01-01

    Five children who developed diabetes insipidus as a manifestation of severe brain injury received continuous intravenous treatment with a solution containing both aqueous vasopressin and appropriate crystalloid replacement. Polyuria, hypernatraemia, and decreased urine osmolalities were safely corrected in all patients within eight to 28 hours.

  4. Vasopressin in perioperative management of congenital ...

    African Journals Online (AJOL)

    Perioperative care of infants with diaphragmatic hernias can be a challenge because of pulmonary hypertension and systemic hypotension. The objective of this study was to report the usefulness of vasopressin infusion in improving pulmonary and systemic haemodynamics in an infant with congenital diaphragmatic hernia.

  5. Computed tomography in hypothalamic hamartoma

    International Nuclear Information System (INIS)

    Mori, Koreaki; Takeuchi, Juji; Hanakita, Junya; Handa, Hajime; Nakano, Yoshihisa.

    1981-01-01

    Two cases of hypothalamic hamartoma were reported. Hypothalamic hamartoma is a rate tumor. The onset of symptoms is in infancy and early childhood. Clinical symptoms are composed of convulsive seizures, laughing spells and precocious puberty. CT finding of hypothalamic hamartoma is a mass in the suprasellar and interpeduncular cisterns which has the same density as the surrounding normal brain. The mass is not enhanced by injection of the contrast material and is easily differentiated from other masses in the suprasellar region. (author)

  6. MR appearance of hypothalamic hamartoma

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, F.J.; Leibrock, L.G.; Huseman, C.A.; Makos, M.M.

    1988-02-01

    Hypothalamic hamartoma is the most common detectable cerebral lesion causing precocious puberty. Two histologically confirmed cases were studied by computerized tomography (CT) and magnetic resonance (MR) imaging. T2 weighted, sagittal MR images were superior to CT in delineating the tumor from surrounding grey matter. The lesion was isointense to grey matter on T1 weighted images allowing exclusion of other hypothalamic tumors. MR will undoubtedly become the imaging modality of choice in the detection of hypothalamic hamartoma.

  7. A test of the magnocellular deficit theory of dyslexia in an adult sample.

    Science.gov (United States)

    Stuart, Geoffrey W; McAnally, Ken I; McKay, Adam; Johnston, Michael; Castles, Anne

    2006-12-01

    An influential theory of dyslexia is based on the premise that individuals with the disorder have impaired sensitivity to rapidly changing stimuli in the visual and auditory modalities, due to a dysfunction in the magnocellular channel of the visual system and its analogue in the auditory pathway. The deficit in the auditory system is thought to cause difficulties in the segmentation of speech and the formation of accurate phonological representations, leading to problems in making the grapheme-phoneme correspondences necessary for reading. In a sample of 13 adults with a history of severe reading difficulty and 18 controls, visual contrast thresholds were measured in response to an 8-Hz flickering Gaussian blob as well as a slowly modulated 8 cycles/deg Gaussian windowed grating. Auditory thresholds were measured in response to a 4-s burst of white noise, the 2nd or 3rd second of which was amplitude modulated at 100 Hz or 1 Hz. The adult reading difficulty group exhibited normal thresholds to rapidly changing stimuli in both modalities and to the slowly modulated visual stimulus, but some showed reduced sensitivity to the 1-Hz amplitude-modulated auditory stimulus. Sensitivity to amplitude modulation at slower rates has been shown to be important for segmentation of the speech stream and so may be implicated in the reading difficulty of the affected individuals. A magnocellular deficit cannot explain this impaired sensitivity, which may be the result of a reduced echoic memory span.

  8. COX-2 disruption leads to increased central vasopressin stores and impaired urine concentrating ability in mice

    DEFF Research Database (Denmark)

    Norregaard, Rikke; Madsen, Kirsten Morill; Hansen, Pernille Bl

    2011-01-01

    It was hypothesized that cyclooxygenase-2 (COX-2) activity promotes urine concentrating ability through stimulation of vasopressin (AVP) release after water deprivation (WD). COX-2-deficient (COX-2(-/-), C57BL/6) and wild-type (WT) mice were water deprived for 24 h, and water balance, central AVP m...... osmolality in COX-2(-/-) mice irrespective of gender. Hypothalamic AVP mRNA level increased and was unchanged between COX-2(-/-) and WT after WD. AVP peptide content was higher in COX-2(-/-) compared with WT. At baseline, plasma AVP concentration was elevated in conscious chronically catheterized COX-2......(-/-) mice, but after WD plasma AVP was unchanged between COX-2(-/-) and WT mice (43 ± 11 vs. 70 ± 16 pg/ml). Renal V2 receptor abundance was downregulated in COX-2(-/-) mice. Medullary interstitial osmolality increased and did not differ between COX-2(-/-) and WT after WD. Aquaporin-2 (AQP2; cortex...

  9. Further neuroendocrine evidence of enhanced vasopressin V3 receptor responses in melancholic depression.

    LENUS (Irish Health Repository)

    Dinan, T G

    2012-02-03

    BACKGROUND: In situations of chronic stress vasopressin plays an important role in regulating the hypothalamic-pituitary adrenal axis. The aim of the current study was to investigate the role of anterior pituitary vasopressin V3 receptors in maintaining the hypercortisolism seen in melancholic depression. METHOD: Fourteen patients with major depression and 14 age- and sex-matched healthy comparison subjects were recruited. Desmopressin (ddAVP) 10 microg was given intravenously and ACTH and cortisol release was monitored for 120 min. RESULTS: The mean +\\/- S.E.M. ACTH response in the depressives was 28.4 +\\/- 4.3 ng\\/l and in the healthy subjects was 18.8 +\\/- 4.9 ng\\/l (P = 0.04). The mean +\\/- S.E.M. cortisol response in the depressives was 261.8 +\\/- 46.5 nmol\\/l and in the healthy subjects was 107.3 +\\/- 26.1 nmol\\/l (P < 0.01). CONCLUSIONS: Patients with major depression have augmented ACTH and cortisol responses to desmopressin indicating enhanced V3 responsivity.

  10. Perinatal exposure to organohalogen pollutants decreases vasopressin content and its mRNA expression in magnocellular neuroendocrine cells activated by osmotic stress in adult rats

    Science.gov (United States)

    Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are environmental pollutants that produce neurotoxicity and neuroendocrine disruption. They affect the vasopressinergic system but their disruptive mechanisms are not well understood. Our group reported t...

  11. Bilateral inferior petrosal sinus sampling using vasopressin

    Directory of Open Access Journals (Sweden)

    Narendra Kotwal

    2016-01-01

    Full Text Available Context: Anatomical localization of pituitary adenoma can be challenging in adrenocorticotropic hormone (ACTH-dependent Cushing's syndrome, and bilateral inferior petrosal sinus sampling (BIPSS is considered gold standard in this regard. Stimulation using corticotrophin-releasing hormone (CRH improves the sensitivity of BIPSS, however, same is not easily available in India. Therefore, we undertook this study of BIPPS using vasopressin as agent for stimulation owing to its ability to stimulate V3 receptors present on corticotrophs. Aims: To study the tumor localization and lateralization in difficult to localize cases of ACTH-dependent Cushing's syndrome by bilateral inferior petrosal sinus sampling using vasopressin for corticotroph stimulation. Settings and Design: Prospective observational study. Subjects and Methods: Six patients (5 females meeting inclusion criteria underwent BIPSS using vasopressin for stimulation. Results: All six patients had nonsuppressible overnight and low dose dexamethasone suppression test with elevated plasma ACTH levels suggestive of ACTH-dependent Cushing's syndrome. High dose dexamethasone suppression test showed suppressible cortisol in two cases, and microadenoma was seen in two patients on magnetic resonance imaging pituitary. Contrast enhanced computed tomography of the abdomen showed left adrenal hyperplasia in one case and anterior mediastinal mass with bilateral adrenal hyperplasia another. Using BIPSS four patients were classified as having Cushing's disease that was confirmed histopathologically following surgery. Of the remaining two, one had primary pigmented nodular adrenocortical disease, and another had thymic carcinoid with ectopic ACTH production as the cause of Cushing's syndrome. No serious adverse events were noted. Conclusions: Vasopressin may be used instead of CRH and desmopressin for stimulation in BIPSS.

  12. Dietary exposure to the PCB mixture aroclor 1254 may compromise osmoregulation by altering central vasopressin release

    Energy Technology Data Exchange (ETDEWEB)

    Coburn, C G [Environmental Toxicology, Univ. of California at Riverside, CA (United States); Gillard, E; Curras-Collazo, M [Cell Biology and Neuroscience, Univ. of California at Riverside, CA (United States)

    2004-09-15

    Despite the importance of systemic osmoregulation, the potential deleterious effects of persistent organochlorines, such as polychlorinated biphenyls (PCBs), on body fluid regulation has not been thoroughly investigated. In an effort to ameliorate this deficit, the current study explores the toxic effects of PCBs on osmoregulation, and in particular, on the activity of the magnocellular neuroendocrine cell (MNC) system of the hypothalamus. MNCs of the supraoptic nucleus (SON) release oxytocin (OXY) and vasopressin (VP) from terminals in the neurohypophysis in response to dehydration. The latter is released to effect water conservation in response to dehydration via its action upon the kidney and through extra-renal actions. MNCs also secrete VP from their cell bodies and dendrites locally i.e., into the extracellular space of the SON. Although it has been shown that both intranuclear and systemic release rise in response to dehydration the physiological significance of intranuclear release has not been fully elucidated. We chose to use voluntary ingestion as the route of PCB exposure since it is more reflective of natural exposure compared to ip injection. One unexpected observation that resulted from pilot studies using ip injection of PCBs was the deleterious effects of the vehicle (corn oil) resulting in pooling of lipid within the abdominal cavity, mottling of the liver, fatty liver and general discoloration of all abdominal viscera at time of sacrifice. Therefore, all work described in this series of experiments have employed voluntary ingestion of the toxin. Work described in this paper suggests that PCBs in concentrations reflecting realistic lifetime exposure levels may negatively impact homeostatic mechanisms responsible for body water balance by altering somatodendritic (intranuclear) VP secretion in response to dehydration in vivo. The downstream consequences of such influence is currently under investigation, and preliminary evidence suggests that the

  13. Evaluation of magnocellular pathway abnormalities in schizophrenia: a frequency doubling technology study and clinical implications

    Directory of Open Access Journals (Sweden)

    Fabiana Benites Vaz de Lima

    2013-04-01

    Full Text Available BACKGROUND: Visual processing deficits have been reported for patients with schizophrenia. Previous studies demonstrated differences in early-stage processing of schizophrenics, although the nature, extent, and localization of the disturbance are unknown. The magnocellular and parvocellular visual pathways are associated with transient and sustained channels, but their respective contributions to schizophrenia-related visual deficits remains controversial. PURPOSE: The aim of this study was to evaluate magnocellular dysfunction in schizophrenia using frequency doubling technology. METHODS: Thirty-one patients with schizophrenia and 34 healthy volunteers were examined. Frequency doubling technology testing was performed in one session, consisting of a 15-minute screening strategy followed by the C-20 program for frequency doubling technology. RESULTS: Schizophrenic patients showed lower global mean sensitivity (30,97 ± 2,25 dB compared with controls (32,17 ± 3,08 dB, p<0.009. Although there was no difference in the delta sensitivity of hemispheres, there was a difference in sensitivity analysis of the fibers crossing the optic chiasm, with lower mean sensitivity in the patient group (28,80 dB versus controls (30,66 dB. The difference was higher in fibers that do not cross the optic chiasm, with lower mean sensitivity in patients (27,61 dB versus controls (30,26 dB, p<0.005. CONCLUSIONS: Our results suggest that there are differences between global sensitivity and fiber sensitivity measured by frequency doubling technology. The different sensitivity of fibers that do not cross the optic chiasm is consistent with most current etiological hypotheses for schizophrenia. The decreased sensitivity responses in the optic radiations may significantly contribute to research assessing early-stage visual processing deficits for patients with schizophrenia.

  14. Acid-sensing ion channels in rat hypothalamic vasopressin neurons of the supraoptic nucleus

    Czech Academy of Sciences Publication Activity Database

    Ohbuchi, T.; Sato, K.; Suzuki, H.; Okada, Y.; Dayanithi, Govindan; Murphy, D.; Ueta, Y.

    2010-01-01

    Roč. 588, č. 12 (2010), s. 2147-2162 ISSN 0022-3751 Institutional research plan: CEZ:AV0Z50390703 Keywords : hypothalamus * ASIC * oxytocin Subject RIV: FH - Neurology Impact factor: 5.139, year: 2010

  15. Astrocytes Modulate a Postsynaptic NMDA–GABAA-Receptor Crosstalk in Hypothalamic Neurosecretory Neurons

    Science.gov (United States)

    Potapenko, Evgeniy S.; Biancardi, Vinicia C.; Zhou, Yiqiang

    2013-01-01

    A dynamic balance between the excitatory and inhibitory neurotransmitters glutamate and GABA is critical for maintaining proper neuronal activity in the brain. This balance is partly achieved via presynaptic interactions between glutamatergic and GABAAergic synapses converging into the same targets. Here, we show that in hypothalamic magnocellular neurosecretory neurons (MNCs), a direct crosstalk between postsynaptic NMDA receptors (NMDARs) and GABAA receptors (GABAARs) contributes to the excitatory/inhibitory balance in this system. We found that activation of NMDARs by endogenous glutamate levels controlled by astrocyte glutamate transporters, evokes a transient and reversible potentiation of postsynaptic GABAARs. This inter-receptor crosstalk is calcium-dependent and involves a kinase-dependent phosphorylation mechanism, but does not require nitric oxide as an intermediary signal. Finally, we found the NMDAR–GABAAR crosstalk to be blunted in rats with heart failure, a pathological condition in which the hypothalamic glutamate–GABA balance is tipped toward an excitatory predominance. Together, our findings support a novel form of glutamate–GABA interactions in MNCs, which involves crosstalk between NMDA and GABAA postsynaptic receptors, whose strength is controlled by the activity of local astrocytes. We propose this inter-receptor crosstalk to act as a compensatory, counterbalancing mechanism to dampen glutamate-mediated overexcitation. Finally, we propose that an uncoupling between NMDARs and GABAARs may contribute to exacerbated neuronal activity and, consequently, sympathohumoral activation in such disease conditions as heart failure. PMID:23303942

  16. Medical therapy of hypothalamic diseases

    International Nuclear Information System (INIS)

    Werder, K. von; Mueller, O.A.

    1985-01-01

    Hormonal disturbances caused by hypothalamic pathology can be treated effectively by target hormone replacement in the case of failure of glandotropic hormone secretion. Hyposomatotropism in children has to be substituted by parenteral administration of growth hormone. In addition gonadotropins respectively gonadotropin releasing factor have to be given in order to restore fertility in hypothalamic hypogonadism. Posterior pituitary failure can be adequately replaced by administration of analogues of antidiuretic hormone. Hypothalamic pathology causing hypersecretion of anterior pituitary hormones may also be accessable to medical treatment. This pertains particularly to hyperprolactinemia and precocious puberty. However, there is no medical therapy so far for hypothalamic disturbances leading to veterative dysfunction like disturbances of temperature regulation and control of thirst and polyphagia. In this situation symptomatic correction of the abnormality represents the only possibility to keep these patients alive. (Author)

  17. Hypothalamic lipophagy and energetic balance

    OpenAIRE

    Singh, Rajat

    2011-01-01

    Autophagy is a conserved cellular turnover process that degrades unwanted cytoplasmic material within lysosomes. Through ?in bulk? degradation of cytoplasmic proteins and organelles, including lipid droplets, autophagy helps provide an alternative fuel source, in particular, when nutrients are scarce. Recent work demonstrates a role for autophagy in hypothalamic agouti-related peptide (AgRP) neurons in regulation of food intake and energy balance. The induction of autophagy in hypothalamic ne...

  18. [Functional hypothalamic amenorrhea].

    Science.gov (United States)

    Stárka, Luboslav; Dušková, Michaela

    2015-10-01

    Functional hypothalamic amenorrhea (FHA) besides pregnancy and syndrome of polycystic ovary is one of the most common causes of secondary amenorrhea. FHA results from the aberrations in pulsatile gonadotropin-releasing hormone (GnRH) secretion, which in turn causes impairment of the gonadotropins (follicle-stimulating hormone and luteinizing hormone). FHA is a form of the defence of organism in situations where life functions are more important than reproductive function. FHA is reversible; it can be normalized after ceasing the stress situation. There are three types of FHA: weight loss related, stress-related, and exercise-related amenorrhea. The final consequences are complex hormonal changes manifested by profound hypoestrogenism. Additionally, these patients present mild hypercortisolemia, low serum insulin levels, low insulin-like growth factor 1 (IGF-1) and low total triiodothyronine. Women health in this disorder is disturbed in several aspects including the skeletal system, cardiovascular system, and mental problems. Patients manifest a decrease in bone mass density, which is related to an increase in fracture risk. Therefore, osteopenia and osteoporosis are the main long-term complications of FHA. Cardiovascular complications include endothelial dysfunction and abnormal changes in the lipid profile. FHA patients present significantly higher depression and anxiety and also sexual problems compared to healthy subjects.

  19. Multiple Causal Links Between Magnocellular-Dorsal Pathway Deficit and Developmental Dyslexia.

    Science.gov (United States)

    Gori, Simone; Seitz, Aaron R; Ronconi, Luca; Franceschini, Sandro; Facoetti, Andrea

    2016-10-17

    Although impaired auditory-phonological processing is the most popular explanation of developmental dyslexia (DD), the literature shows that the combination of several causes rather than a single factor contributes to DD. Functioning of the visual magnocellular-dorsal (MD) pathway, which plays a key role in motion perception, is a much debated, but heavily suspected factor contributing to DD. Here, we employ a comprehensive approach that incorporates all the accepted methods required to test the relationship between the MD pathway dysfunction and DD. The results of 4 experiments show that (1) Motion perception is impaired in children with dyslexia in comparison both with age-match and with reading-level controls; (2) pre-reading visual motion perception-independently from auditory-phonological skill-predicts future reading development, and (3) targeted MD trainings-not involving any auditory-phonological stimulation-leads to improved reading skill in children and adults with DD. Our findings demonstrate, for the first time, a causal relationship between MD deficits and DD, virtually closing a 30-year long debate. Since MD dysfunction can be diagnosed much earlier than reading and language disorders, our findings pave the way for low resource-intensive, early prevention programs that could drastically reduce the incidence of DD. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. The effect of magnocellular-based visual-motor intervention on Chinese children with developmental dyslexia

    Directory of Open Access Journals (Sweden)

    Yi eQian

    2015-10-01

    Full Text Available Magnocellular(M deficit theory points out that the core deficit of developmental dyslexia (DD is the impairment in M pathway, which has been evidenced in many previous studies. Based on the M deficit, some researchers found that visual intervention focusing on M deficit improved dyslexics’ M function as well as reading abilities. However, the number and reliability of these training studies were limited. Therefore, the present study conducted an M-based visual-motor intervention on Chinese children with DD to investigate the relationship between M deficit and Chinese DD. Intervention programs included coherent motion detection, visual search, visual tracking and juggling, which were related to M function. The results showed that M function and phonological awareness of training dyslexic group were improved to a normal level as age-matched normal children after intervention, while non-training dyslexics did not. It supported M deficit theory, and suggested M deficit might be the core deficit of Chinese DD.

  1. Sensitive radioimmunoassay for plasma arginine vasopressin

    International Nuclear Information System (INIS)

    Thibonnier, M.; Soto, M.E.; Corvol, P.; Milliez, P.; Marchetti, J.; Menard, J.

    1980-01-01

    Using an ion exchange resin, a sensitive radioimmunoassay for plasma arginine vasopressin (AVP) was developed. This assay was characterized by the absence of blank values, an excellent recovery rate, great sensitivity (0.1 pg of AVP was significantly detected) and reproducibility. In 8 normal men, plasma AVP after overnight dehydration was 1.57+-0.17 pg/ml, and dropped to 0.58+-0.11 pg/ml after 20 ml/kg oral water loading. Significant correlations between plasma AVP levels and plasma or urinary osmolality confirm the validity of this assay. In complete pituitary diabetes insipidus (n=4) plasma AVP was undetectable whereas it was frankly increased in Schwartz-Bartter syndrome (3 to 33 pg/ml, n=8) [fr

  2. Control of sodium excretion in patients with cranial diabetes insipidus maintained on desamino-[8-D-arginine]vasopressin.

    Science.gov (United States)

    Sutters, M; Brace, C; Hatfield, E; Whitehurst, A; Lightman, S L; Peart, W S

    1993-11-01

    1. We have studied the response of six patients with cranial diabetes insipidus and six age-matched control subjects to dietary sodium restriction during constant administration of the synthetic vasopressin analogue desamino-[8-D-arginine]vasopressin. 2. Urine flow increased on the first low salt day in the normal control subjects but not in the patients with cranial diabetes insipidus. Body weight fell 1.35 kg in the control subjects but was constant in the patients with cranial diabetes insipidus. 3. Urinary sodium excretion fell at the same rate in both groups. Diurnal variation of urinary sodium excretion and creatinine clearance was present in the control subjects but not in the patients with cranial diabetes insipidus. 4. Changes in plasma sodium concentration and osmolality were similar. Plasma protein concentration increased more in the control subjects (from 69.1 +/- 1.5 to 73 +/- 1.2 versus from 71.7 +/- 1 to 73.2 +/- 1.1 milligrams). The responses of plasma atrial natriuretic peptide, plasma renin activity and salivary aldosterone concentration were similar between the two groups. Salivary aldosterone concentration levels were consistently higher in the patients with cranial diabetes insipidus. 5. We confirm that the low salt diuresis is triggered by release from the antidiuretic activity of arginine vasopressin. In the patients with cranial diabetes insipidus extracellular fluid osmoregulation appeared to be achieved by the movement of water out of and sodium into the extracellular fluid. 6. Absent posterior pituitary function and hypothalamic disturbances did not alter renal sodium conservation.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Mechanosensing in hypothalamic osmosensory neurons.

    Science.gov (United States)

    Prager-Khoutorsky, Masha

    2017-11-01

    Osmosensory neurons are specialized cells activated by increases in blood osmolality to trigger thirst, secretion of the antidiuretic hormone vasopressin, and elevated sympathetic tone during dehydration. In addition to multiple extrinsic factors modulating their activity, osmosensory neurons are intrinsically osmosensitive, as they are activated by increased osmolality in the absence of neighboring cells or synaptic contacts. This intrinsic osmosensitivity is a mechanical process associated with osmolality-induced changes in cell volume. This review summarises recent findings revealing molecular mechanisms underlying the mechanical activation of osmosensory neurons and highlighting important roles of microtubules, actin, and mechanosensitive ion channels in this process. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Cerebral gigantism of hypothalamic origin.

    Science.gov (United States)

    Ranke, M B; Bierich, J R

    1983-04-01

    In five cases of Sotos Syndrome serum somatomedin activities were measured. In two of these cases elevated levels and an increased secretion of growth hormone was observed. In one case (index case) a suspected hypothalamic tumor mass could be excluded, but hydrocephalus with increased intracranial pressure was present. The pathogenesis of gigantism in this syndrome is discussed.

  5. Luminance noise as a novel approach for measuring contrast sensitivity within the magnocellular and parvocellular pathways.

    Science.gov (United States)

    Hall, Cierra M; McAnany, J Jason

    2017-07-01

    This study evaluated the extent to which different types of luminance noise can be used to target selectively the inferred magnocellular (MC) and parvocellular (PC) visual pathways. Letter contrast sensitivity (CS) was measured for three visually normal subjects for letters of different size (0.8°-5.3°) under established paradigms intended to target the MC pathway (steady-pedestal paradigm) and PC pathway (pulsed-pedestal paradigm). Results obtained under these paradigms were compared to those obtained in asynchronous static noise (a field of unchanging luminance noise) and asynchronous dynamic noise (a field of randomly changing luminance noise). CS was measured for letters that were high- and low-pass filtered using a range of filter cutoffs to quantify the object frequency information (cycles per letter) mediating letter identification, which was used as an index of the pathway mediating CS. A follow-up experiment was performed to determine the range of letter duration over which MC and PC pathway CS can be targeted. Analysis of variance indicated that the object frequencies measured under the static noise and steady-pedestal paradigms did not differ significantly (p ≥ 0.065), but differed considerably from those measured under the dynamic noise (both p noise, and in dynamic noise. These data suggest that the spatiotemporal characteristics of noise can be manipulated to target the inferred MC (static noise) and PC (dynamic noise) pathways. The results also suggest that CS within these pathways can be measured at long stimulus durations, which has potential importance in the design of future clinical CS tests.

  6. Comparative anatomy of the mammalian hypothalamic suprachiasmatic nucleus.

    Science.gov (United States)

    Cassone, V M; Speh, J C; Card, J P; Moore, R Y

    1988-01-01

    A detailed analysis of the cytoarchitecture, retinohypothalamic tract (RHT) projections, and immunohistochemical localization of major cell and fiber types within the hypothalamic suprachiasmatic nuclei (SCN) was conducted in five mammalian species: two species of opossum, the domestic cat, the guinea pig, and the house mouse. Cytoarchitectural and immunohistochemical studies were conducted in three additional species of marsupial mammals and in the domestic pig. The SCN in this diverse transect of mammalian taxonomy bear striking similarities. First, the SCN are similar in location, lying close to the third ventricle (3V) dorsal to the optic chiasm (OC), with a cytoarchitecture characterized by small, tightly packed neurons. Second, in all groups studied, the SCN receive bilateral retinal input. Third, the SCN contain immunohistochemically similar elements. These similarities suggest that the SCN developed characteristic features early in mammalian phylogeny. Some details of SCN organization vary among the species studied. In marsupials, vasopressin-like immunoreactive (VP-LI) and vasoactive intestinal polypeptide-like immunoreactive (VIP-LI) cells codistribute primarily in the dorsomedial aspects of the SCN, while in eutherians, VP-LI and VIP-LI cells are separated into SCN subnuclei. Furthermore, the marsupial RHT projects to the periventricular dorsomedial region, whereas the eutherian RHT projects more ventrally in the SCN into the zone that typically contains VIP-LI perikarya.

  7. The vasopressin receptor of the blood-brain barrier in the rat hippocampus is linked to calcium signalling

    DEFF Research Database (Denmark)

    Hess, J.; Jensen, Claus V.; Diemer, Nils Henrik

    1991-01-01

    Neuropathology, vasopressin receptor, VI subtype, blood-brain barrier, cerebral endothelium, hippocampus, Fura-2......Neuropathology, vasopressin receptor, VI subtype, blood-brain barrier, cerebral endothelium, hippocampus, Fura-2...

  8. Bariatric Surgery in Hypothalamic Obesity

    OpenAIRE

    Bingham, Nathan C.; Rose, Susan R.; Inge, Thomas H.

    2012-01-01

    Craniopharyngiomas (CP) are epithelial neoplasms generally found in the area of the pituitary and hypothalamus. Despite benign histology, these tumors and/or their treatment often result in significant, debilitating disorders of endocrine, neurological, behavioral, and metabolic systems. Severe obesity is observed in a high percentage of patients with CP resulting in significant comorbidities and negatively impacting quality of life. Obesity occurs as a result of hypothalamic damage and disru...

  9. Vasopressin as a target for antidepressant development: an assessment of the available evidence.

    LENUS (Irish Health Repository)

    Scott, Lucinda V

    2012-02-03

    Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is one of the key biological abnormalities described in major depressive disorder, occurring in 30-50% of depressed subjects. Corticotropin-releasing hormone (CRH) and vasopressin (AVP) are the main regulators of this stress system, with the two neuropeptides acting synergistically in bringing about adrenocorticotropin (ACTH) release from the anterior pituitary and cortisol from the adrenal gland. Based on the demonstration of elevated cerebrospinal fluid levels of CRH in depressives, and other evidence, it has been postulated that excess CRH and the resultant increased HPA forward drive form the basis of neuroendocrine dysregulation in depression. However, there is an accumulating body of evidence to support a significant role for AVP in the regulation of pituitary-adrenal activity in health and also in depressive disorder. This review, based on a Medline search from 1980 to 2001, focuses on the functional neuroanatomy, receptor pharmacology, VP synergism with CRH, and the data from clinical and pre-clinical studies that support an important role for AVP in the pathophysiology of major depression. We suggest that future antidepressants may target the vasopressinergic system.

  10. The effect of acute heat exposure on rat pituitary corticotroph activation: the role of vasopressin.

    Directory of Open Access Journals (Sweden)

    Nebojsa Jasnic

    2010-04-01

    Full Text Available The increased ambient temperature affects the function of hypothalamic-pituitary-adrenal (HPA axis. Since thecorrelation among vasopressin (VP, adrenocorticotropic hormone (ACTH and corticosterone (CORT responses to variousstressors have been long recognized, the aim of this study was to reveal the aforementioned hormones production andmorphology of the pituitary gland after exposure to acute heat. Rats were exposed to high ambient temperature (38°C for20 or 60 minutes. The circulating hormones were determined by an ELISA test or chemiluminescence's method. The resultsobtained show the elevation in ACTH and CORT secretion depending on the duration of heat exposure. The VP concentrationincreased only after prolonged exposure to heat (60 min. The pituitary morphology was examined by routine and fluorescentimmunohistochemistry as well as electron microscopy. Observed changes in the anterior and posterior pituitarywell corresponded to circulating hormones, regarding the volume density of ACTH-immunopositive cells, percentage ofACTH immunopositive area v. total area and number of VP-immunopositive containing varicose fibers per total area. Acuteheat exposure also induced changes in shapes of ACTH-immunopositive cells. Cells appeared stellate with numerous slendercytoplasmic processes and degranulated, which is the most obvious after 20 min. In addition, immunopositivity ofendothelial and anterior pituitary cells for VP suggests its influence on ACTH secretion.

  11. The effect of acute heat exposure on rat pituitary corticotroph activation: the role of vasopressin.

    Directory of Open Access Journals (Sweden)

    Sinisa Djurasevic

    2011-04-01

    Full Text Available The increased ambient temperature affects the function of hypothalamic-pituitary-adrenal (HPA axis. Since the correlation among vasopressin (VP, adrenocorticotropic hormone (ACTH and corticosterone (CORT responses to various stressors have been long recognized, the aim of this study was to reveal the aforementioned hormones production and morphology of the pituitary gland after exposure to acute heat. Rats were exposed to high ambient temperature (38 °C for 20 or 60 minutes. The circulating hormones were determined by an ELISA test or chemiluminescence's method. The results obtained show the elevation in ACTH and CORT secretion depending on the duration of heat exposure. The VP concentration increased only after prolonged exposure to heat (60 min. The pituitary morphology was examined by routine and fluorescent immunohistochemistry as well as electron microscopy. Observed changes in the anterior and posterior pituitary well corresponded to circulating hormones, regarding the volume density of ACTH-immunopositive cells, percentage of ACTH immunopositive area v. total area and number of VP-immunopositive containing varicose fibers per total area. Acute heat exposure also induced changes in shapes of ACTH-immunopositive cells. Cells appeared stellate with numerous slender cytoplasmic processes and degranulated, which is the most obvious after 20 min. In addition, immunopositivity of endothelial and anterior pituitary cells for VP suggests its influence on ACTH secretion.

  12. Social Context, Stress, Neuropsychiatric Disorders, and the Vasopressin 1b Receptor

    Directory of Open Access Journals (Sweden)

    Heather K. Caldwell

    2017-10-01

    Full Text Available The arginine vasopressin 1b receptor (Avpr1b is involved in the modulation of a variety of behaviors and is an important part of the mammalian hormonal stress axis. The Avpr1b is prominent in hippocampal CA2 pyramidal cells and in the anterior pituitary corticotrophs. Decades of research on this receptor has demonstrated its importance to the modulation of social recognition memory, social forms of aggression, and modulation of the hypothalamic-pituitary-adrenal axis, particularly under conditions of acute stress. Further, work in humans suggests that the Avpr1b may play a role in human neuropsychiatric disorders and its modulation may have therapeutic potential. This paper reviews what is known about the role of the Avpr1b in the context of social behaviors, the stress axis, and human neuropsychiatric disorders. Further, possible mechanisms for how Avpr1b activation within the hippocampus vs. Avpr1b activation within anterior pituitary may interact with one another to affect behavioral output are proposed.

  13. A review of the nonpressor and nonantidiuretic actions of the hormone vasopressin

    Directory of Open Access Journals (Sweden)

    Gaurang P Mavani

    2015-03-01

    Full Text Available The pressor and antidiuretic actions of arginine vasopressin (AVP have been well documented. This review focuses on the less widely appreciated actions of AVP which also have important physiologic functions and when better understood may provide important insights into common disease states. These actions include effects on pain perception and bone structure as well as important relationships to the varied components of metabolic syndrome. These include effects on blood glucose, lipid levels, and blood pressure. AVP may also play a role in the progression of chronic kidney disease and effect physiologic changes relating to aging, abnormal social behavior and cognitive function. Important cellular responses including cell proliferation, inflammation and control of infection and their relationship to AVP are described. Finally, the effects of AVP on hemostasis and the hypothalamic-pituitary-adrenal access are noted. The goal of this summary of the various actions of AVP is to direct attention to the potential benefits of research in these underemphasized areas of importance.

  14. Radioimmunological detection of vasopressin in urine extracts

    International Nuclear Information System (INIS)

    Buengner, R.

    1983-01-01

    After initial measures had been taken to ensure that ion exchange chromatography would yield a sufficiently high recovery of labelled and non-labelled hormone as well as to eliminate all intervening factors it was possible to use the described extraction procedure in connection with the RIA introduced by Freisenhausen et al. At the clinical level, the technique was employed to assess the post-operative release of AVP (argenine vasopressin) in 24-hour urine samples obtained from patients subjected to hypophysectomy. In a total of 10 patients, where hypophysectomy had been performed for different clinical reasons, the AVP values were seen to be significantly decreased for the first three hours after surgical intervention. They recovered slightly during the following three hours to remain at an average level of 2 pg / 400 μl urine. The extraction procedure described can be used to determine levels of AVP approaching the limit of detection - either due to large volumes of urine or very low concentrations of AVP. (orig./MG) [de

  15. Radioimmunoassay of arginine vasopressin in human plasma

    International Nuclear Information System (INIS)

    Uhlich, E.; Weber, P.; Groeschel-Stewart, U.; Roeschlau, T.; Wuerzburg Univ.

    1975-01-01

    Antibodies for the radioimmunoassay of arginine vasopressin (AVP) described here were produced in rabbits using synthetic AVP coupled to rabbit γ-globulin with carbodiimide. In three out of six rabbits, significant antibody titres were obtained. Using the best antisera produced, 40% of labelled AVP was bound at a final dilution of 1 : 50,000. After iodination of synthetic AVP with 125 I using the chloramin-T method, a gel filtration on Sephadex G-25 was performed to purify the iodinated AVP. For separation of antibody bound and free hormone, a second antibody precipitation was used. There was no crossreactivity with oxytocin. AVP was extracted from plasma after ammoniumsulfate precipitation of the proteins by adsorption to Florisil. The recovery of AVP added to plasma in amounts of 5-25 pg/ml was 60 +- 15% (n = 6). The minimum amount of AVP detectable was 1 pg per ml plasma. The plasma level in normal adults under standard conditions was 3.4 +- 2.2 pg/ml. This is in agreement with data recently published by other researchers. The applicability and reproducibility was further tested in measurements of samples taken hourly during the entire day under water diuresis and after hormonal stimulation of AVP. (orig.) [de

  16. Involvement of hypothalamus autoimmunity in patients with autoimmune hypopituitarism: role of antibodies to hypothalamic cells.

    Science.gov (United States)

    De Bellis, A; Sinisi, A A; Pane, E; Dello Iacovo, A; Bellastella, G; Di Scala, G; Falorni, A; Giavoli, C; Gasco, V; Giordano, R; Ambrosio, M R; Colao, A; Bizzarro, A; Bellastella, A

    2012-10-01

    Antipituitary antibodies (APA) but not antihypothalamus antibodies (AHA) are usually searched for in autoimmune hypopituitarism. Our objective was to search for AHA and characterize their hypothalamic target in patients with autoimmune hypopituitarism to clarify, on the basis of the cells stained by these antibodies, the occurrence of autoimmune subclinical/clinical central diabetes insipidus (CDI) and/or possible joint hypothalamic contribution to their hypopituitarism. We conducted a cross-sectional cohort study. Ninety-five APA-positive patients with autoimmune hypopituitarism, 60 without (group 1) and 35 with (group 2) lymphocytic hypophysitis, were studied in comparison with 20 patients with postsurgical hypopituitarism and 50 normal subjects. AHA by immunofluorescence and posterior pituitary function were evaluated; then AHA-positive sera were retested by double immunofluorescence to identify the hypothalamic cells targeted by AHA. AHA were detected at high titer in 12 patients in group 1 and in eight patients in group 2. They immunostained arginine vasopressin (AVP)-secreting cells in nine of 12 in group 1 and in four of eight in group 2. All AVP cell antibody-positive patients presented with subclinical/clinical CDI; in contrast, four patients with GH/ACTH deficiency but with APA staining only GH-secreting cells showed AHA targeting CRH- secreting cells. The occurrence of CDI in patients with lymphocytic hypophysitis seems due to an autoimmune hypothalamic involvement rather than an expansion of the pituitary inflammatory process. To search for AVP antibody in these patients may help to identify those of them prone to develop an autoimmune CDI. The detection of AHA targeting CRH-secreting cells in some patients with GH/ACTH deficiency but with APA targeting only GH-secreting cells indicates that an autoimmune aggression to hypothalamus is jointly responsible for their hypopituitarism.

  17. Vasopressin in chronic kidney disease, in particular ADPKD : Causal factor or innocent bystander?

    NARCIS (Netherlands)

    Zittema, Debbie

    2016-01-01

    Vasopressin is an important hormone for water regulation of the body. When dehydration occurs, vasopressin secretion leads to water reabsorption in the kidney to prevent water loss. However, vasopressin seems to have deleterious effects on the kidney as well. In autosomal dominant polycystic kidney

  18. Potential Deleterious Effects of Vasopressin in Chronic Kidney Disease and Particularly Autosomal Dominant Polycystic Kidney Disease

    NARCIS (Netherlands)

    Meijer, E.; Boertien, W. E.; Zietse, R.; Gansevoort, R. T.

    2011-01-01

    The antidiuretic hormone vasopressin is crucial for regulating free water clearance in normal physiology. However, it has also been hypothesized that vasopressin has deleterious effects on the kidney. Vasopressin is elevated in animals and patients with chronic kidney disease. Suppression of

  19. Inner capillary diameter of hypothalamic paraventricular nucleus of female rat increases during lactation

    Directory of Open Access Journals (Sweden)

    Cortés-Sol Albertina

    2013-01-01

    Full Text Available Abstract Background The role of the endothelial cell (EC in blood flow regulation within the central nervous system has been little studied. Here, we explored EC participation in morphological changes of the anterior hypothalamic paraventricular nucleus (PVN microvasculature of female rats at two reproductive stages with different metabolic demand (virginity and lactation. We measured the inner capillary diameter (ICD of 800 capillaries from either the magnocellular or parvocellular regions. The space occupied by neural (somas, dendrites and axons and glial, but excluding vascular elements of the neurovascular compartment was also measured in 100-μm2 sample fields of both PVN subdivisions. Results The PVN of both groups of animals showed ICDs that ranged from 3 to 10 microns. The virgin group presented mostly capillaries with small ICD, whereas the lactating females exhibited a significant increment in the percentage of capillaries with larger ICD. The space occupied by the neural and glial elements of the neurovascular compartment did not show changes with lactation. Conclusions Our findings suggest that during lactation the microvasculature of the PVN of female rats undergoes dynamic, transitory changes in blood flow as represented by an increment in the ICD through a self-cytoplasmic volume modification reflected by EC changes. A model of this process is proposed.

  20. Quantitative light microscopic autoradiographic localization of binding sites labelled with [3H]vasopressin antagonist d(CH2)5Tyr(Me)VP in the rat brain, pituitary and kidney

    International Nuclear Information System (INIS)

    Leeuwen, F.W. van; Beek, E.M. van der; Heerikhuize, J.J. van; Wolters, P.; Meulen, G. van der; Wan, Yieh-Ping

    1987-01-01

    Binding sites for the vasopressin (VP) antagonist d(CH 2 ) 5 Tyr(Me)VP, were located in various brain areas (e.g. the lateral septum, amygdala, choroid plexus and nucleus of the solitary tract) using light microscopic autoradiography. A number of areas (e.g. suprachiasmatic and arcuate nucleus, pineal gland) which previously showed no VP binding were labelled in the present study. The olfactory nucleus and ventromedial hypothalamic nucleus were not labelled. It therefore appears that d(CH 2 ) 5 Tyr(Me)VP is capable of discriminating between VP and oxytocin binding sites and more sensitive means of detecting VP binding sites than VP alone. (Author)

  1. Bariatric surgery in hypothalamic obesity

    Directory of Open Access Journals (Sweden)

    Nathan eBingham

    2012-02-01

    Full Text Available Craniopharyngiomas (CP are epithelial neoplasms generally found in the area of the pituitary and hypothalamus. Despite benign histology, these tumors and/or their treatment often result in significant, debilitating disorders of endocrine, neurological, behavioral, and metabolic systems. Severe obesity is observed in a high percentage of patients with CP resulting in significant comorbidities and negatively impacting quality of life. Obesity occurs as a result of hypothalamic damage and disruption of normal homeostatic mechanisms regulating energy balance. Such pathological weight gain, termed hypothalamic obesity (HyOb, is often severe and refractory to therapy.Unfortunately, neither lifestyle intervention nor pharmacotherapy has proven truly effective in the treatment of CP-HyOb. Given the limited choices and poor results of these treatments, several groups have examined bariatric surgery as a treatment alternative for patients with CP-HyOb. While a large body of evidence exists supporting the use of bariatric surgery in the treatment of exogenous obesity and its comorbidities, its role in the treatment of HyOb has yet to be well defined. To date, the existing literature on bariatric surgery in CP-HyOb is largely limited to case reports and series with short term follow-up. Here we review the current reports on the use of bariatric surgery in the treatment of CP-HyOb. We also compare these results to those reported for other populations of HyOb, including Prader-Willi Syndrome and patients with melanocortin signaling defects. While initial reports of bariatric surgery in CP-HyOb are promising, their limited scope makes it difficult to draw any substantial conclusions as to the long term safety and efficacy of bariatric surgery in CP-HyOb. There continues to be a need for more robust, controlled, prospective trials with long term follow-up in order to better define the role of bariatric surgery in the treatment of all types of hypothalamic

  2. Immunohistochemical evaluation of vasopressin expression in breast fibrocystic disease and ductal carcinoma in situ (DCIS).

    Science.gov (United States)

    North, William G; Wells, Wendy; Fay, Michael J; Mathew, Rennie S; Donnelly, Edward M; Memoli, Vincent A

    2003-01-01

    We previously found that expression of the vasopressin gene is a common feature of human breast cancer. In the present study we first examined 21 different cases of benign fibrocystic breast disease for vasopressin expression using immunohistochemistry and antibodies directed against vasopressin (anti-VP) and against vasopressin-associated glycopeptide (anti-VAG). All cases examined were negative for vasopressin gene expression using these antibodies. Alternatively, we examined 16 cases of breast ductal carcinoma in situ (DCIS) using the second of these antibodies (anti-VAG), and all of these cases were positive for vasopressin gene expression. Our results suggest that products of vasopressin gene expression are not markers of cellular proliferation in the breast, and might rather represent an early part of the carcinogenic process in this tissue.

  3. Neonatal oxytocin and vasopressin manipulation alter social behavior during the juvenile period in Mongolian gerbils.

    Science.gov (United States)

    Taylor, Jack H; Cavanaugh, Jon; French, Jeffrey A

    2017-07-01

    Oxytocin and vasopressin are important modulators of a wide variety of social behaviors, and increasing evidence is showing that these neuropeptides are important organizational effectors of later-life behavior as well. We treated day-old gerbil pups with oxytocin, vasopressin, an oxytocin receptor antagonist, a vasopressin V1a receptor antagonist, or saline control, and then measured received parental responsiveness during the early postnatal period and juvenile social behavior during weaning. Neonatal vasopressin treatment enhanced sociality in males, but not females, at both developmental time points. When pups were individually placed outside the nest, parents were more responsive to male pups treated with vasopressin compared with littermates, and vasopressin treated male pups exhibited increased play with littermates as juveniles. These results show that vasopressin during very early life can enhance social interactions throughout early development. © 2017 Wiley Periodicals, Inc.

  4. Computed tomography demonstration of a hypothalamic metastasis

    International Nuclear Information System (INIS)

    Chakeres, D.W.

    1983-01-01

    This case report describes a patient who presented with panhypopituitarism secondary to hypothalamic metastasis. A primary hypothalamic abnormality was suggested by computed tomographic (CT) demonstration of a small enhancing circular mass centered within the hypothalamus. Sellar radiographs and cerebral angiography were normal. (orig.)

  5. Computed tomography demonstration of a hypothalamic metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Chakeres, D.W.

    1983-05-01

    This case report describes a patient who presented with panhypopituitarism secondary to hypothalamic metastasis. A primary hypothalamic abnormality was suggested by computed tomographic (CT) demonstration of a small enhancing circular mass centered within the hypothalamus. Sellar radiographs and cerebral angiography were normal.

  6. Dietary sugars, not lipids, drive hypothalamic inflammation

    Directory of Open Access Journals (Sweden)

    Yuanqing Gao

    2017-08-01

    Conclusions: Combined overconsumption of fat and sugar, but not the overconsumption of fat per se, leads to excessive CML production in hypothalamic neurons, which, in turn, stimulates hypothalamic inflammatory responses such as microgliosis and eventually leads to neuronal dysfunction in the control of energy metabolism.

  7. Human platelet vasopressin receptor identification by direct ultraviolet photoaffinity labeling

    International Nuclear Information System (INIS)

    Thibonnier, M.

    1987-01-01

    Tritiated vasopressin ([ 3 H]AVP) was directly crosslinked to its human platelet receptor by using an ultraviolet irradiation procedure. After preincubation with [ 3 H]AVP, the hydrodynamic parameters of the hormone-receptor complexes solubilized with 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate were derived from Sephacryl S-300 superfine gel filtration and from sucrose density gradient ultracentrifugation experiments. The following values were obtained: Stoke's radius = 5.48 +/- 0.1 nm, apparent sedimentation coefficient = 5.55 +/- 0.1 S, and calculated molecular weight = 132,000. On sodium dodecyl sulfate-8% polyacrylamide slab gel electrophoresis under reducing conditions, [ 3 H]AVP preferentially and specifically labeled a 125,000-dalton protein. The labeling of this protein was suppressed by addition of excess cold vasopressin, whereas angiotensin II did not inhibit incorporation of tritiated vasopressin in this protein. These results suggest that direct UV-photoaffinity labelling with [ 3 H]AVP is a suitable tool for the purification of the human platelet vasopressin receptor

  8. Testosterone supplementation restores vasopressin innervation in the senescent rat brain

    NARCIS (Netherlands)

    Goudsmit, E.; Fliers, E.; Swaab, D. F.

    1988-01-01

    The vasopressin (AVP) innervation in the male rat brain is decreased in senescence. This decrease is particularly pronounced in brain regions where AVP fiber density is dependent on plasma levels of sex steroids. Since plasma testosterone levels decrease progressively with age in the rat, the

  9. Medial Amygdala and Aggressive Behavior : Interaction Between Testosterone and Vasopressin

    NARCIS (Netherlands)

    Koolhaas, J.M.; Roozendaal, B.; Boorsma, F.; Van Den Brink, T.H.C.

    1990-01-01

    This paper considers the functional significance of the testosterone-dependent vasopressinergic neurons of the medial amygdala (Ame) in intermale aggressive behavior of rats. Local microinfusion of vasopressin into the medial amygdala causes an increase in offensive behavior both in gonadally intact

  10. Vasopressin – Emerging Importance in Sepsis | Skowno | Southern ...

    African Journals Online (AJOL)

    Southern African Journal of Anaesthesia and Analgesia. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 9, No 1 (2003) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Vasopressin – Emerging ...

  11. Lysine-vasopressin analogues with glycoconjugates in position 8

    Czech Academy of Sciences Publication Activity Database

    Marcinkowska, A.; Borovičková, Lenka; Slaninová, Jiřina; Grzonka, Z.

    2006-01-01

    Roč. 80, č. 5 (2006), s. 759-766 ISSN 0137- 5083 Institutional research plan: CEZ:AV0Z40550506 Keywords : glycoconjugates * glycopeptides * lysine-vasopressin analogues Subject RIV: CC - Organic Chemistry Impact factor: 0.491, year: 2006

  12. Experimental cardiac arrest treatment with adrenaline, vasopressin, or placebo.

    Science.gov (United States)

    Palácio, Manoel Ângelo Gomes; Paiva, Edison Ferreira de; Azevedo, Luciano Cesar Pontes de; Timerman, Ari

    2013-12-01

    The effect of vasoconstrictors in prolonged cardiopulmonary resuscitation (CPR) has not been fully clarified. To evaluate adrenaline and vasopressin pressure effect, and observe the return of spontaneous circulation (ROSC). A prospective, randomized, blinded, and placebo-controlled study. After seven minutes of untreated ventricular fibrillation, pigs received two minutes cycles of CPR. Defibrillation was attempted (4 J/kg) once at 9 minutes, and after every cycle if a shockable rhythm was present, after what CPR was immediately resumed. At 9 minutes and every five minutes intervals, 0.02 mg/kg (n = 12 pigs) adrenaline, or 0.4 U/kg (n = 12) vasopressin, or 0.2 mL/kg (n = 8) 0.9% saline solution was administered. CPR continued for 30 minutes or until the ROSC. Coronary perfusion pressure increased to about 20 mmHg in the three groups. Following vasoconstrictors doses, pressure level reached 35 mmHg versus 15 mmHg with placebo (p < 0.001). Vasopressin effect remained at 15-20 mmHg after three doses versus zero with adrenaline or placebo. ROSC rate differed (p = 0.031) among adrenaline (10/12), vasopressin (6/12), and placebo (2/8). Time-to-ROSC did not differ (16 minutes), nor the number of doses previously received (one or two). There was no difference between vasoconstrictors, but against placebo, only adrenaline significantly increased the ROSC rate (p = 0.019). The vasoconstrictors initial pressure effect was equivalent and vasopressin maintained a late effect at prolonged resuscitation. Nevertheless, when compared with placebo, only adrenaline significantly increased the ROSC rate.

  13. The vasopressin deficient Brattleboro rats: A natural knockout model used in the search for CNS effects of vasopressin

    NARCIS (Netherlands)

    Bohus, B; de Wied, David; Urban, I.J.A.; Burbach, J.P.H.; De Wied, D.

    1999-01-01

    Behavioral neuroscience is using mon and more gene knockout techniques to produce animals with a specific deletion. These studies have their precedent in nature. A mutation may result in a limited genetic defect, as seen in the vasopressin (VP) deficiency in the Brattleboro rat. The mutation is in a

  14. Extrahypothalamic vasopressin and oxytocin in the human brain; presence of vasopressin cells in the bed nucleus of the stria terminalis

    NARCIS (Netherlands)

    Fliers, E.; Guldenaar, S. E.; van de Wal, N.; Swaab, D. F.

    1986-01-01

    In the present study, the distribution of extrahypothalamic vasopressin (VP) and oxytocin (OXT) in the human brain was investigated by means of immunocytochemistry. In the septum verum, few VP fibers were found in the nucleus septalis lateralis and medialis (NSL and NSM), and in the bed nucleus of

  15. Hypothalamic pathogenesis of type 2 diabetes.

    Science.gov (United States)

    Koshiyama, Hiroyuki; Hamamoto, Yoshiyuki; Honjo, Sachiko; Wada, Yoshiharu; Lkeda, Hiroki

    2006-01-01

    There have recently been increasing experimental and clinical evidences suggesting that hypothalamic dysregulation may be one of the underlying mechanisms of abnormal glucose metabolism. First, increased hypothalamic-pituitary-adrenal axis activity induced by uncontrollable excess stress may cause diabetes mellitus as well as dyslipidemia, visceral obesity, and osteoporosis with some resemblance to Cushing's disease. Second, several molecules are known to be expressed both in pancreas and hypothalamus; adenosine triphosphate-sensitive potassium channels, malonyl-CoA, glucokinase, and AMP-activated protein kinase. Those molecules appear to form an integrated hypothalamic system, which may sense hypothalamic fuel status, especially glucose level, and inhibit action of insulin on hepatic gluconeogenesis, thereby forming a brain-liver circuit. Third, hypothalamic resistance to insulin as an adiposity signal may be involved in pathogenesis of peripheral insulin resistance. The results with mice with a neuron-specific disruption of the insulin receptor gene or those lacking insulin receptor substrate 2 in hypothalamus supported this possibility. Finally, it has very recently been suggested that dysregulation of clock genes in hypothalamus may cause abnormal glucose metabolism. Taken together, it is plausible that some hypothalamic abnormality may underlie at least some portion of type 2 diabetes or insulin resistance in humans, and this viewpoint of hypothalamic pathogenesis of type 2 diabetes may lead to the development of new drugs for type 2 diabetes.

  16. Long-lasting enhancement of synaptic excitability of CA1/subiculum neurons of the rat ventral hippocampus by vasopressin and vasopressin(4-8)

    NARCIS (Netherlands)

    Gispen, W.H.; Chepkova, A.N.; French, P.; Wied, D. de; Ontskul, A.H.; Ramakers, G.M.J.; Skrebitski, V.G.; Urban, I.J.A.

    1995-01-01

    Vasopressin (VP) is axonally distributed in many brain structures, including the ventral hippocampus. Picogram quantities of VP injected into the hippocampus improve the passive avoidance response of rats, presumably by enhancing memory processes. Vasopressin is metabolized by the brain tissue into

  17. Reassessment of LRF radioimmunoassay in the plasma and hypothalamic extracts of rats and rams

    International Nuclear Information System (INIS)

    Caraty, A.; Reviers, M.-M. de; Pelletier, J.; Dubois, M.P.

    1980-01-01

    A highly sensitive and specific radioimmunoassay for LRF was applied to the measurement of endogenous LRF in various hypothalamic extracts. Specific antiserum was obtained by injecting LRF conjugated to human serum albumin with glutaraldehyde. Thyrotropin-releasing hormone, lysine vasopressin, oxytocin, noradrenaline, LH, FSH and cortical extracts did not appear to affect the assay, and the maximum cross-reaction observed with the LRF analogs tested was 8.5% with LRF 2-10. The best detection limit (0.4 pg/tube) was usually obtained when the labelled LRF had been purified by polyacrylamide gel electrophoresis. Within and between-assay coefficients of variation were 8.0 and 12.6% respectively (from B/Bo=20 to 80%). Synthetic LRF administered to rams by intravenous injection was readily detectable in the peripheral plasma. However, the direct measurement of plasma endogenous LRF may give misleading results due to non-specific interference by plasma factors. No endogenous LRF could be detected in plasma methanol or acetone extracts obtained from rats and rams in various physiological conditions. The inhibition curves parallel to the synthetic LRF curve were obtained by diluting the crude hypothalamic extracts of rams and rats, and a good correlation (r=0,997) with the Ramirez-McCann bioassay resulted, indicating that using radioimmunoassay to determine hypothalamic LRF content may be fruitful in studying hypothalamo-pituitary gonad interactions. The LRF content of rat and ovine hypothalami ranged from 2-8 to 20-80 ng of LRF, respectively

  18. The underlying physiological basis of the desert rodent Meriones shawi's survival to prolonged water deprivation: Central vasopressin regulation on peripheral kidney water channels AQPs-2.

    Science.gov (United States)

    Elgot, A; El Hiba, O; Belkouch, M; Gamrani, H

    2018-02-01

    Meriones shawi (M. shawi) is a particular semi-desert rodent known by its resistance to long periods of thirst. The aim of the present investigation is to clarify the underlying mechanisms allowing M. shawi to resist to hard conditions of dehydration. For this reason we used two different approaches: i) a morphometric study, which consists in measuring the effect of dehydration on body and kidneys weights as well as the report kidney weight/body weight, ii) By immunohistochemistry, we proceed to study the effect of dehydration on the immunoreactivity of central vasopressin (AVP) and the kidney aquaporin-2 (AQP-2) which is a channel protein that allows water to permeate across cell membranes. Our results showed both a body mass decrease accompanied by a remarkable kidneys hypertrophy. The immunohistochemical study showed a significant increase of AQP-2 immunoreactivity in the medullar part of Meriones kidneys allowing probably to Meriones a great ability to water retention. Consistently, we demonstrate that the increased AQP-2 expression occurred together with an increase in vasopressin (AVP) expression in both hypothalamic supraoptic (SON) and paraventricular nucleus (PVN), which are a major hub in the osmotic control circuitry. These various changes seen either in body weight and kidneys or at the cellular level might be the basis of peripheral control of body water homeostasis, providing to M. shawia strong resistance against chronic dehydration. Copyright © 2017 Elsevier GmbH. All rights reserved.

  19. 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.

  20. Vasopressin and Oxytocin Reduce Food Sharing Behavior in Male, but Not Female Marmosets in Family Groups

    Directory of Open Access Journals (Sweden)

    Jack H. Taylor

    2017-07-01

    Full Text Available Oxytocin (OT is critical for lactation and maternal care, but OT and the related nonapeptide vasopressin are important for caregiving behaviors in fathers and alloparents as well. This experiment tested the effects of vasopressin and OT on food sharing in marmoset families. We treated caregivers (parents, siblings with intranasal vasopressin, OT, or saline, and then paired them with the youngest marmoset in the family. Caregivers were given preferred food, and then observed for food sharing and aggressive behavior with young marmosets. OT reduced food sharing from male alloparents to youngest siblings, and fathers that received vasopressin refused to share food with their youngest offspring more often than when treated with OT. Vasopressin increased aggressive vocalizations directed toward potential food recipients in all classes of caregivers. These results indicate that vasopressin and OT do not always enhance prosocial behavior: modulation of food sharing depends on both sex and parental status.

  1. Oxytocin and vasopressin are dysregulated in Williams Syndrome, a genetic disorder affecting social behavior.

    Directory of Open Access Journals (Sweden)

    Li Dai

    Full Text Available The molecular and neural mechanisms regulating human social-emotional behaviors are fundamentally important but largely unknown; unraveling these requires a genetic systems neuroscience analysis of human models. Williams Syndrome (WS, a condition caused by deletion of ~28 genes, is associated with a gregarious personality, strong drive to approach strangers, difficult peer interactions, and attraction to music. WS provides a unique opportunity to identify endogenous human gene-behavior mechanisms. Social neuropeptides including oxytocin (OT and arginine vasopressin (AVP regulate reproductive and social behaviors in mammals, and we reasoned that these might mediate the features of WS. Here we established blood levels of OT and AVP in WS and controls at baseline, and at multiple timepoints following a positive emotional intervention (music, and a negative physical stressor (cold. We also related these levels to standardized indices of social behavior. Results revealed significantly higher median levels of OT in WS versus controls at baseline, with a less marked increase in AVP. Further, in WS, OT and AVP increased in response to music and to cold, with greater variability and an amplified peak release compared to controls. In WS, baseline OT but not AVP, was correlated positively with approach, but negatively with adaptive social behaviors. These results indicate that WS deleted genes perturb hypothalamic-pituitary release not only of OT but also of AVP, implicating more complex neuropeptide circuitry for WS features and providing evidence for their roles in endogenous regulation of human social behavior. The data suggest a possible biological basis for amygdalar involvement, for increased anxiety, and for the paradox of increased approach but poor social relationships in WS. They also offer insight for translating genetic and neuroendocrine knowledge into treatments for disorders of social behavior.

  2. Distribution of oxytocin and co-localization with arginine vasopressin in the brain of mice.

    Science.gov (United States)

    Otero-García, Marcos; Agustín-Pavón, Carmen; Lanuza, Enrique; Martínez-García, Fernando

    2016-09-01

    Oxytocin (OT) and vasopressin (AVP) play a major role in social behaviours. Mice have become the species of choice for neurobiology of social behaviour due to identification of mouse pheromones and the advantage of genetically modified mice. However, neuroanatomical data on nonapeptidergic systems in mice are fragmentary, especially concerning the central distribution of OT. Therefore, we analyse the immunoreactivity for OT and its neurophysin in the brain of male and female mice (strain CD1). Further, we combine immunofluorescent detection of OT and AVP to locate cells co-expressing both peptides and their putative axonal processes. The results indicate that OT is present in cells of the neurosecretory paraventricular (Pa) and supraoptic hypothalamic nuclei (SON). From the anterior SON, OTergic cells extend into the medial amygdala, where a sparse cell population occupies its ventral anterior and posterior divisions. Co-expression of OT and AVP in these nuclei is rare. Moreover, a remarkable OTergic cell group is found near the ventral bed nucleus of the stria terminalis (BST), distributed between the anterodorsal preoptic nucleus and the nucleus of anterior commissure (ADP/AC). This cell group, the rostral edge of the Pa and the periventricular hypothalamus display frequent OT + AVP double labelling, with a general dominance of OT over AVP immunoreactivity. Fibres with similar immunoreactivity profile innervate the accumbens shell and core, central amygdala and portions of the intervening BST. These data, together with data in the literature on rats, suggest that the projections of ADP/AC nonapeptidergic cells onto these brain centres could promote pup-motivated behaviours and inhibit pup avoidance during motherhood.

  3. Sodium-calcium exchanger and R-type Ca2+ channels mediate spontaneous [Ca2+](i) oscillations in magnocellular neurones of the rat supraoptic nucleus

    Czech Academy of Sciences Publication Activity Database

    Kortus, Štěpán; Srinivasan, Ch.; Forostyak, O.; Zápotocký, Martin; Ueta, Y.; Syková, E.; Chvátal, A.; Verkhratsky, A.; Dayanithi, G.

    2016-01-01

    Roč. 59, č. 6 (2016), s. 289-298 ISSN 0143-4160 R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : magnocellular neurosecretory cells * voltage-gated Ca2+ channels * intracellular Ca2+ stores * Ca2+ imaging * Ca2+ oscillations Subject RIV: FH - Neurology Impact factor: 3.707, year: 2016

  4. Radioimmunoassay of arginine vasopressin (AVP) and clinical application

    International Nuclear Information System (INIS)

    Wagner, H.; Haeberle, M.; Franz, H.E.; Maier, V.

    1977-01-01

    The low circulating levels of vasopressin required an initial extraction procedure. The extraction method itself presented problems with the specificity and the reproducibility of the extracted hormone from serum. The presented paper describes the developement of a radioimmunoassay without an extraction procedure. The AVP was coupled with rabbit-albumin by gluteraldehyde condensation for the immunization of rabbits. Synthetic AVP was iodinated by the method of GREENWOOD and HUNTER (1963) and purified by the addition of Dowex. The antibody cannot differentiate between lysine- and arginine-, ornithine-, glycerine - vasopressin and oxytocin. 1 - 24 ACTH and gastrin did not crosscreact. Normal subjects were found to have 5.7 +- 4.4/uU/ml after a dehydration period of 12 hours. Subjects suffering from psychogenic polydipsia showed normal levels, however, different forms of stress yielded higher levels in normal subjects. In patients suffering from liver cirrhosis the values normalized when ascites was under control. (orig.) [de

  5. Effects of vasopressin on the isolated perfused human collecting tubule.

    Science.gov (United States)

    Yanagawa, N; Trizna, W; Bar-Khayim, Y; Fine, L G

    1981-05-01

    Cortical collecting tubules (CCT) were dissected from the surviving normal tissue of human kidneys removed at operation for either carcinoma or calculus. These CCT's were perfused in vitro shortly after the nephrectomy was performed. Transtubular potential differences in different tubules varied from +3.2 to -2.0 mV and were reduced towards zero by lowering the temperature or by adding ouabain to the bath. In the absence of vasopressin, tubules were essentially impermeable to water with extremely low net water fluxes even in the presence of a transtubular osmotic gradient. Addition of vasopressin to the bath caused the transtubular osmotic water permeability coefficient to increase to values of 125, 175, and 155 X 10(-4) cm/sec in three tubules thus studied. These results demonstrate close similarities between the human CCT and the more extensively studied rabbit CCT.

  6. Osmosensation in vasopressin neurons: changing actin density to optimize function.

    Science.gov (United States)

    Prager-Khoutorsky, Masha; Bourque, Charles W

    2010-02-01

    The proportional relation between circulating vasopressin concentration and plasma osmolality is fundamental for body fluid homeostasis. Although changes in the sensitivity of this relation are associated with pathophysiological conditions, central mechanisms modulating osmoregulatory gain are unknown. Here, we review recent data that sheds important light on this process. The cell autonomous osmosensitivity of vasopressin neurons depends on cation channels comprising a variant of the transient receptor potential vanilloid 1 (TRPV1) channel. Hyperosmotic activation is mediated by a mechanical process where sensitivity increases in proportion with actin filament density. Moreover, angiotensin II amplifies osmotic activation by a rapid stimulation of actin polymerization, suggesting that neurotransmitter-induced changes in cytoskeletal organization in osmosensory neurons can mediate central changes in osmoregulatory gain. (c) 2009 Elsevier Ltd. All rights reserved.

  7. Dietary sugars, not lipids, drive hypothalamic inflammation

    OpenAIRE

    Gao, Yuanqing; Bielohuby, Maximilian; Fleming, Thomas; Grabner, Gernot F.; Foppen, Ewout; Bernhard, Wagner; Guzm?n-Ruiz, Mara; Layritz, Clarita; Legutko, Beata; Zinser, Erwin; Garc?a-C?ceres, Cristina; Buijs, Ruud M.; Woods, Stephen C.; Kalsbeek, Andries; Seeley, Randy J.

    2017-01-01

    Objective: The hypothalamus of hypercaloric diet-induced obese animals is featured by a significant increase of microglial reactivity and its associated cytokine production. However, the role of dietary components, in particular fat and carbohydrate, with respect to the hypothalamic inflammatory response and the consequent impact on hypothalamic control of energy homeostasis is yet not clear. Methods: We dissected the different effects of high-carbohydrate high-fat (HCHF) diets and low-car...

  8. A genetic basis for functional hypothalamic amenorrhea.

    OpenAIRE

    Caronia, L.M.; Martin, C.; Welt, C.K.; Sykiotis, G.P.; Quinton, R.; Thambundit, A.; Avbelj, M.; Dhruvakumar, S.; Plummer, L.; Hughes, V.A.; Seminara, S.B.; Boepple, P.A.; Sidis, Y.; Crowley, W.F.; Martin, K.A.

    2011-01-01

    Background: Functional hypothalamic amenorrhea is a reversible form of gonadotropin-releasing hormone (GnRH) deficiency commonly triggered by stressors such as excessive exercise, nutritional deficits, or psychological distress. Women vary in their susceptibility to inhibition of the reproductive axis by such stressors, but it is unknown whether this variability reflects a genetic predisposition to hypothalamic amenorrhea. We hypothesized that mutations in genes involved in idiopathic hypogon...

  9. Experimental Cardiac Arrest Treatment with Adrenaline, Vasopressin, or Placebo

    Science.gov (United States)

    Palácio, Manoel Ângelo Gomes; de Paiva, Edison Ferreira; de Azevedo, Luciano Cesar Pontes; Timerman, Ari

    2013-01-01

    Background The effect of vasoconstrictors in prolonged cardiopulmonary resuscitation (CPR) has not been fully clarified. Objectives To evaluate adrenaline and vasopressin pressure effect, and observe the return of spontaneous circulation (ROSC). Methods A prospective, randomized, blinded, and placebo-controlled study. After seven minutes of untreated ventricular fibrillation, pigs received two minutes cycles of CPR. Defibrillation was attempted (4 J/kg) once at 9 minutes, and after every cycle if a shockable rhythm was present, after what CPR was immediately resumed. At 9 minutes and every five minutes intervals, 0.02 mg/kg (n = 12 pigs) adrenaline, or 0.4 U/kg (n = 12) vasopressin, or 0.2 mL/kg (n = 8) 0.9% saline solution was administered. CPR continued for 30 minutes or until the ROSC. Results Coronary perfusion pressure increased to about 20 mmHg in the three groups. Following vasoconstrictors doses, pressure level reached 35 mmHg versus 15 mmHg with placebo (p adrenaline or placebo. ROSC rate differed (p = 0.031) among adrenaline (10/12), vasopressin (6/12), and placebo (2/8). Time-to-ROSC did not differ (16 minutes), nor the number of doses previously received (one or two). There was no difference between vasoconstrictors, but against placebo, only adrenaline significantly increased the ROSC rate (p = 0.019). Conclusion The vasoconstrictors initial pressure effect was equivalent and vasopressin maintained a late effect at prolonged resuscitation. Nevertheless, when compared with placebo, only adrenaline significantly increased the ROSC rate. PMID:24173134

  10. Diabetes insipidus: celebrating a century of vasopressin therapy.

    Science.gov (United States)

    Qureshi, Sana; Galiveeti, Sneha; Bichet, Daniel G; Roth, Jesse

    2014-12-01

    Diabetes mellitus, widely known to the ancients for polyuria and glycosuria, budded off diabetes insipidus (DI) about 200 years ago, based on the glucose-free polyuria that characterized a subset of patients. In the late 19th century, clinicians identified the posterior pituitary as the site of pathology, and pharmacologists found multiple bioactivities there. Early in the 20th century, the amelioration of the polyuria with extracts of the posterior pituitary inaugurated a new era in therapy and advanced the hypothesis that DI was due to a hormone deficiency. Decades later, a subset of patients with polyuria unresponsive to therapy were recognized, leading to the distinction between central DI and nephrogenic DI, an early example of a hormone-resistant condition. Recognition that the posterior pituitary had 2 hormones was followed by du Vigneaud's Nobel Prize winning isolation, sequencing, and chemical synthesis of oxytocin and vasopressin. The pure hormones accelerated the development of bioassays and immunoassays that confirmed the hormone deficiency in vasopressin-sensitive DI and abundant levels of hormone in patients with the nephrogenic disorder. With both forms of the disease, acquired and inborn defects were recognized. Emerging concepts of receptors and of genetic analysis led to the recognition of patients with mutations in the genes for 1) arginine vasopressin (AVP), 2) the AVP receptor 2 (AVPR2), and 3) the aquaporin 2 water channel (AQP2). We recount here the multiple skeins of clinical and laboratory research that intersected frequently over the centuries since the first recognition of DI.

  11. GABAergic Signaling within a Limbic-Hypothalamic Circuit Integrates Social and Anxiety-Like Behavior with Stress Reactivity.

    Science.gov (United States)

    Myers, Brent; Carvalho-Netto, Eduardo; Wick-Carlson, Dayna; Wu, Christine; Naser, Sam; Solomon, Matia B; Ulrich-Lai, Yvonne M; Herman, James P

    2016-05-01

    The posterior hypothalamic nucleus (PH) stimulates autonomic stress responses. However, the role of the PH in behavioral correlates of psychiatric illness, such as social and anxiety-like behavior, is largely unexplored, as is the neurochemistry of PH connectivity with limbic and neuroendocrine systems. Thus, the current study tested the hypothesis that GABAergic signaling within the PH is a critical link between forebrain behavior-regulatory nuclei and the neuroendocrine hypothalamus, integrating social and anxiety-related behaviors with physiological stress reactivity. To address this hypothesis, GABAA receptor pharmacology was used to locally inhibit or disinhibit the PH immediately before behavioral measures of social and anxiety-like behavior in rats. Limbic connectivity of the PH was then established by simultaneous co-injection of anterograde and retrograde tracers. Further, the role of PH GABAergic signaling in neuroendocrine stress responses was tested via inhibition/disinhibition of the PH. These studies determined a prominent role for the PH in the expression of anxiety-related behaviors and social withdrawal. Histological analyses revealed divergent stress-activated limbic input to the PH, emanating predominantly from the prefrontal cortex, lateral septum, and amygdala. PH projections also targeted both parvicellular and magnocellular peptidergic neurons in the paraventricular and supraoptic hypothalamus. Further, GABAA receptor pharmacology determined an excitatory effect of the PH on neuroendocrine responses to stress. These data indicate that the PH represents an important stress-integrative center, regulating behavioral processes and connecting the limbic forebrain with neuroendocrine systems. Moreover, the PH appears to be uniquely situated to have a role in stress-related pathologies associated with limbic-hypothalamic dysfunction.

  12. A Genetic Basis for Functional Hypothalamic Amenorrhea

    Science.gov (United States)

    Caronia, Lisa M.; Martin, Cecilia; Welt, Corrine K.; Sykiotis, Gerasimos P.; Quinton, Richard; Thambundit, Apisadaporn; Avbelj, Magdalena; Dhruvakumar, Sadhana; Plummer, Lacey; Hughes, Virginia A.; Seminara, Stephanie B.; Boepple, Paul A.; Sidis, Yisrael; Crowley, William F.; Martin, Kathryn A.; Hall, Janet E.; Pitteloud, Nelly

    2011-01-01

    BACKGROUND Functional hypothalamic amenorrhea is a reversible form of gonadotropin-releasing hormone (GnRH) deficiency commonly triggered by stressors such as excessive exercise, nutritional deficits, or psychological distress. Women vary in their susceptibility to inhibition of the reproductive axis by such stressors, but it is unknown whether this variability reflects a genetic predisposition to hypothalamic amenorrhea. We hypothesized that mutations in genes involved in idiopathic hypogonadotropic hypogonadism, a congenital form of GnRH deficiency, are associated with hypothalamic amenorrhea. METHODS We analyzed the coding sequence of genes associated with idiopathic hypogonadotropic hypogonadism in 55 women with hypothalamic amenorrhea and performed in vitro studies of the identified mutations. RESULTS Six heterozygous mutations were identified in 7 of the 55 patients with hypothalamic amenorrhea: two variants in the fibroblast growth factor receptor 1 gene FGFR1 (G260E and R756H), two in the prokineticin receptor 2 gene PROKR2 (R85H and L173R), one in the GnRH receptor gene GNRHR (R262Q), and one in the Kall-mann syndrome 1 sequence gene KAL1 (V371I). No mutations were found in a cohort of 422 controls with normal menstrual cycles. In vitro studies showed that FGFR1 G260E, FGFR1 R756H, and PROKR2 R85H are loss-of-function mutations, as has been previously shown for PROKR2 L173R and GNRHR R262Q. CONCLUSIONS Rare variants in genes associated with idiopathic hypogonadotropic hypogonadism are found in women with hypothalamic amenorrhea, suggesting that these mutations may contribute to the variable susceptibility of women to the functional changes in GnRH secretion that characterize hypothalamic amenorrhea. Our observations provide evidence for the role of rare variants in common multifactorial disease. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00494169.) PMID:21247312

  13. A genetic basis for functional hypothalamic amenorrhea.

    Science.gov (United States)

    Caronia, Lisa M; Martin, Cecilia; Welt, Corrine K; Sykiotis, Gerasimos P; Quinton, Richard; Thambundit, Apisadaporn; Avbelj, Magdalena; Dhruvakumar, Sadhana; Plummer, Lacey; Hughes, Virginia A; Seminara, Stephanie B; Boepple, Paul A; Sidis, Yisrael; Crowley, William F; Martin, Kathryn A; Hall, Janet E; Pitteloud, Nelly

    2011-01-20

    Functional hypothalamic amenorrhea is a reversible form of gonadotropin-releasing hormone (GnRH) deficiency commonly triggered by stressors such as excessive exercise, nutritional deficits, or psychological distress. Women vary in their susceptibility to inhibition of the reproductive axis by such stressors, but it is unknown whether this variability reflects a genetic predisposition to hypothalamic amenorrhea. We hypothesized that mutations in genes involved in idiopathic hypogonadotropic hypogonadism, a congenital form of GnRH deficiency, are associated with hypothalamic amenorrhea. We analyzed the coding sequence of genes associated with idiopathic hypogonadotropic hypogonadism in 55 women with hypothalamic amenorrhea and performed in vitro studies of the identified mutations. Six heterozygous mutations were identified in 7 of the 55 patients with hypothalamic amenorrhea: two variants in the fibroblast growth factor receptor 1 gene FGFR1 (G260E and R756H), two in the prokineticin receptor 2 gene PROKR2 (R85H and L173R), one in the GnRH receptor gene GNRHR (R262Q), and one in the Kallmann syndrome 1 sequence gene KAL1 (V371I). No mutations were found in a cohort of 422 controls with normal menstrual cycles. In vitro studies showed that FGFR1 G260E, FGFR1 R756H, and PROKR2 R85H are loss-of-function mutations, as has been previously shown for PROKR2 L173R and GNRHR R262Q. Rare variants in genes associated with idiopathic hypogonadotropic hypogonadism are found in women with hypothalamic amenorrhea, suggesting that these mutations may contribute to the variable susceptibility of women to the functional changes in GnRH secretion that characterize hypothalamic amenorrhea. Our observations provide evidence for the role of rare variants in common multifactorial disease. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00494169.).

  14. Nutritional State-Dependent Ghrelin Activation of Vasopressin Neurons via Retrograde Trans-Neuronal–Glial Stimulation of Excitatory GABA Circuits

    Science.gov (United States)

    Haam, Juhee; Halmos, Katalin C.; Di, Shi

    2014-01-01

    Behavioral and physiological coupling between energy balance and fluid homeostasis is critical for survival. The orexigenic hormone ghrelin has been shown to stimulate the secretion of the osmoregulatory hormone vasopressin (VP), linking nutritional status to the control of blood osmolality, although the mechanism of this systemic crosstalk is unknown. Here, we show using electrophysiological recordings and calcium imaging in rat brain slices that ghrelin stimulates VP neurons in the hypothalamic paraventricular nucleus (PVN) in a nutritional state-dependent manner by activating an excitatory GABAergic synaptic input via a retrograde neuronal–glial circuit. In slices from fasted rats, ghrelin activation of a postsynaptic ghrelin receptor, the growth hormone secretagogue receptor type 1a (GHS-R1a), in VP neurons caused the dendritic release of VP, which stimulated astrocytes to release the gliotransmitter adenosine triphosphate (ATP). ATP activation of P2X receptors excited presynaptic GABA neurons to increase GABA release, which was excitatory to the VP neurons. This trans-neuronal–glial retrograde circuit activated by ghrelin provides an alternative means of stimulation of VP release and represents a novel mechanism of neuronal control by local neuronal–glial circuits. It also provides a potential cellular mechanism for the physiological integration of energy and fluid homeostasis. PMID:24790191

  15. Vasopressin and angiotensin II stimulate oxygen uptake in the perfused rat hindlimb

    DEFF Research Database (Denmark)

    Colquhoun, E Q; Hettiarachchi, M; Ye, J M

    1988-01-01

    Vasopressin and angiotensin II markedly stimulated oxygen uptake in the perfused rat hindlimb. The increase due to each agent approached 70% of the basal rate, and was greater than that produced by a maximal concentration of norepinephrine. Half-maximal stimulation occurred at 60 pM vasopressin, 0...

  16. Radioimmunoassay of [8-D-arginine] deamino-vasopressin (dDAVP)

    International Nuclear Information System (INIS)

    Slaninova, J.; Barth, T.

    1978-01-01

    Specific antibodies to [8-D-arginine] deamino-vasopressin (dDAVP) were prepared by immunizing pigs with the conjugate of [8-D-arginine] vasopressin (DVAP) and rabbit immunoglobulin. The specificity of the antibodies was studied by comparing their cross-reactivity with 20 analogues of neurohypophysial hormones. The sensitivity of the developed radioimmunoassay was 30 pg/ml. (authors)

  17. Mechanisms involved in dual vasopressin/apelin neuron dysfunction during aging.

    Directory of Open Access Journals (Sweden)

    Julie Sauvant

    Full Text Available Normal aging is associated with vasopressin neuron adaptation, but little is known about its effects on the release of apelin, an aquaretic peptide colocalized with vasopressin. We found that plasma vasopressin concentrations were higher and plasma apelin concentrations lower in aged rats than in younger adults. The response of AVP/apelin neurons to osmotic challenge was impaired in aged rats. The overactivity of vasopressin neurons was sustained partly by the increased expression of Transient receptor potential vanilloid2 (Trpv2, because central Trpv blocker injection reversed the age-induced increase in plasma vasopressin concentration without modifying plasma apelin concentration. The morphofunctional plasticity of the supraoptic nucleus neuron-astrocyte network normally observed during chronic dehydration in adults appeared to be impaired in aged rats as well. IL-6 overproduction by astrocytes and low-grade microglial neuroinflammation may contribute to the modification of neuronal functioning during aging. Indeed, central treatment with antibodies against IL-6 decreased plasma vasopressin levels and increased plasma apelin concentration toward the values observed in younger adults. Conversely, minocycline treatment (inhibiting microglial metabolism did not affect plasma vasopressin concentration, but increased plasma apelin concentration toward control values for younger adults. This study is the first to demonstrate dual vasopressin/apelin adaptation mediated by inflammatory molecules and neuronal Trpv2, during aging.

  18. 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.

  19. Weak 24-h periodicity of body temperature and increased plasma vasopressin in melancholic depression.

    NARCIS (Netherlands)

    van Londen, L.; Goekoop, J.G.; Kerkhof, G.A.; Zwindeman, K.H.; Wiegant, V.M.; de Wied, D.

    2001-01-01

    Earlier work has shown that plasma vasopressin levels of depressed patients were higher than those of healthy controls. The aim of the present study was to determine whether plasma vasopressin levels were correlated to parameters of the circadian rhythm. 41 patients with major depression (aged 22-77

  20. Hypothalamic dysfunction following whole-brain irradiation

    International Nuclear Information System (INIS)

    Mechanick, J.I.; Hochberg, F.H.; LaRocque, A.

    1986-01-01

    The authors describe 15 cases with evidence of hypothalamic dysfunction 2 to 9 years following megavoltage whole-brain x-irradiation for primary glial neoplasm. The patients received 4000 to 5000 rads in 180- to 200-rad fractions. Dysfunction occurred in the absence of computerized tomography-delineated radiation necrosis or hypothalamic invasion by tumor, and antedated the onset of dementia. Fourteen patients displayed symptoms reflecting disturbances of personality, libido, thirst, appetite, or sleep. Hyperprolactinemia (with prolactin levels up to 70 ng/ml) was present in all of the nine patients so tested. Of seven patients tested with thyrotropin-releasing hormone, one demonstrated an abnormal pituitary gland response consistent with a hypothalamic disorder. Seven patients developed cognitive abnormalities. Computerized tomography scans performed a median of 4 years after tumor diagnosis revealed no hypothalamic tumor or diminished density of the hypothalamus. Cortical atrophy was present in 50% of cases and third ventricular dilatation in 58%. Hypothalamic dysfunction, heralded by endocrine, behavioral, and cognitive impairment, represents a common, subtle form of radiation damage

  1. Dehydration-induced modulation of κ-opioid inhibition of vasopressin neurone activity

    Science.gov (United States)

    Scott, Victoria; Bishop, Valerie R; Leng, Gareth; Brown, Colin H

    2009-01-01

    Dehydration increases vasopressin (antidiuretic hormone) secretion from the posterior pituitary gland to reduce water loss in the urine. Vasopressin secretion is determined by action potential firing in vasopressin neurones, which can exhibit continuous, phasic (alternating periods of activity and silence), or irregular activity. Autocrine κ-opioid inhibition contributes to the generation of activity patterning of vasopressin neurones under basal conditions and so we used in vivo extracellular single unit recording to test the hypothesis that changes in autocrine κ-opioid inhibition drive changes in activity patterning of vasopressin neurones during dehydration. Dehydration increased the firing rate of rat vasopressin neurones displaying continuous activity (from 7.1 ± 0.5 to 9.0 ± 0.6 spikes s−1) and phasic activity (from 4.2 ± 0.7 to 7.8 ± 0.9 spikes s−1), but not those displaying irregular activity. The dehydration-induced increase in phasic activity was via an increase in intraburst firing rate. The selective κ-opioid receptor antagonist nor-binaltorphimine increased the firing rate of phasic neurones in non-dehydrated rats (from 3.4 ± 0.8 to 5.3 ± 0.6 spikes s−1) and dehydrated rats (from 6.4 ± 0.5 to 9.1 ± 1.2 spikes s−1), indicating that κ-opioid feedback inhibition of phasic bursts is maintained during dehydration. In a separate series of experiments, prodynorphin mRNA expression was increased in vasopressin neurones of hyperosmotic rats, compared to hypo-osmotic rats. Hence, it appears that dynorphin expression in vasopressin neurones undergoes dynamic changes in proportion to the required secretion of vasopressin so that, even under stimulated conditions, autocrine feedback inhibition of vasopressin neurones prevents over-excitation. PMID:19822541

  2. Sexual arousal and rhythmic synchronization: A possible effect of vasopressin

    DEFF Research Database (Denmark)

    Miani, Alessandro

    2016-01-01

    Music is ubiquitous. Yet, its biological relevance is still an ongoing debate. Supporting the view that music had an ancestral role in courtship displays, a pilot study presented here provides preliminary evidence on the link between music and sexual selection. The underlying hypothesis is based...... by vasopressin and its genes. Hence, to test this hypothesis, a rhythmic synchronization task was employed here on one male subject during sexual arousal. Results revealed a significant effect of sexual arousal on rhythm synchronization. This is the first report that empirically supports the hypothesis...

  3. A novel splicing mutation in the V2 vasopressin receptor

    DEFF Research Database (Denmark)

    Kamperis, Konstantinos; Siggaard, C; Herlin, Troels

    2000-01-01

    as clinical investigations comprising a fluid deprivation test and a 1-deamino-8-D-arginine-vasopressin (dDAVP) infusion test in the study subject and his mother. We found a highly unusual, novel, de novo 1447A-->C point mutation (gDNA), involving the invariable splice acceptor of the second intron...... of the gene in both the affected male (hemizygous) and his mother (heterozygous). This mutation is likely to cause aberrant splicing of the terminal intron of the gene, leading to a non-functional AVP receptor. The clinical studies were consistent with such a hypothesis, as the affected subject had a severe...

  4. Efferent connections from the lateral hypothalamic region and the lateral preoptic area to the hypothalamic paraventricular nucleus of the rat

    DEFF Research Database (Denmark)

    Larsen, P J; Hay-Schmidt, Anders; Mikkelsen, J D

    1994-01-01

    , iontophoretic injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin were delivered into distinct areas of the lateral hypothalamic region. Neurons of the intermediate hypothalamic area projected mainly to the PVN subnuclei, which contained parvicellular neuroendocrine cells. In contrast...

  5. Effects of arginine vasopressin on musical working memory.

    Science.gov (United States)

    Granot, Roni Y; Uzefovsky, Florina; Bogopolsky, Helena; Ebstein, Richard P

    2013-01-01

    Previous genetic studies showed an association between variations in the gene coding for the 1a receptor of the neuro-hormone arginine vasopressin (AVP) and musical working memory (WM). The current study set out to test the influence of intranasal administration (INA) of AVP on musical as compared to verbal WM using a double blind crossover (AVP-placebo) design. Two groups of 25 males were exposed to 20 IU of AVP in one session, and 20 IU of saline water (placebo) in a second session, 1 week apart. In each session subjects completed the tonal subtest from Gordon's "Musical Aptitude Profile," the interval subtest from the "Montreal Battery for Evaluation of Amusias (MBEA)," and the forward and backward digit span tests. Scores in the digit span tests were not influenced by AVP. In contrast, in the music tests there was an AVP effect. In the MBEA test, scores for the group receiving placebo in the first session (PV) were higher than for the group receiving vasopressin in the first session (VP) (p music test these scores were significantly correlated with memory scores. Together the results reflect a complex interaction between AVP, musical memory, arousal, and contextual effects such as session, and base levels of memory. The results are interpreted in light of music's universal use as a means to modulate arousal on the one hand, and AVP's influence on mood, arousal, and social interactions on the other.

  6. Role of developmental factors in hypothalamic function

    Directory of Open Access Journals (Sweden)

    Jakob eBiran

    2015-04-01

    Full Text Available The hypothalamus is a brain region which regulates homeostasis by mediating endocrine, autonomic and behavioral functions. It is comprised of several nuclei containing distinct neuronal populations producing neuropeptides and neurotransmitters that regulate fundamental body functions including temperature and metabolic rate, thirst and hunger, sexual behavior and reproduction, circadian rhythm, and emotional responses. The identity, number and connectivity of these neuronal populations are established during the organism’s development and are of crucial importance for normal hypothalamic function. Studies have suggested that developmental abnormalities in specific hypothalamic circuits can lead to obesity, sleep disorders, anxiety, depression and autism. At the molecular level, the development of the hypothalamus is regulated by transcription factors, secreted growth factors, neuropeptides and their receptors. Recent studies in zebrafish and mouse have demonstrated that some of these molecules maintain their expression in the adult brain and subsequently play a role in the physiological functions that are regulated by hypothalamic neurons. Here, we summarize the involvement of some of the key developmental factors in hypothalamic development and function by focusing on the mouse and zebrafish genetic model organisms.

  7. Sexual behavior reduces hypothalamic androgen receptor immunoreactivity

    NARCIS (Netherlands)

    Fernandez-Guasti, Alonso; Swaab, Dick; Rodríguez-Manzo, Gabriela

    2003-01-01

    Male sexual behavior is regulated by limbic areas like the medial preoptic nucleus (MPN), the bed nucleus of the stria terminalis (BST), the nucleus accumbens (nAcc) and the ventromedial hypothalamic nucleus (VMN). Neurons in these brain areas are rich in androgen receptors (AR) and express

  8. Hypothalamic functions in patients with pituitary insufficiency

    NARCIS (Netherlands)

    Borgers, A.J.F.

    2013-01-01

    The main objective of this thesis is to increase our understanding of hypothalamic (dys)function in patients with pituitary insufficiency. This goal is driven by the clinical experience of persisting symptoms in patients adequately treated for pituitary insufficiency. We focus primarily on patients

  9. Evolution of Gelastic Epilepsy with Hypothalamic Hamartoma

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-11-01

    Full Text Available The patterns of clinical presentation, evolution of the epilepsy, and electoclinical diagnostic features of hypothalamic hamartoma (HH in 19 patients (8 children and 11 adults, seen between 1991 and 2001, were evaluated at Kings College Hospital and the Institute of Epileptology, London, UK.

  10. Dietary sugars, not lipids, drive hypothalamic inflammation

    NARCIS (Netherlands)

    Gao, Yuanqing; Bielohuby, Maximilian; Fleming, Thomas; Grabner, Gernot F; Foppen, Ewout; Bernhard, Wagner; Guzmán-Ruiz, Mara; Layritz, Clarita; Legutko, Beata; Zinser, Erwin; García-Cáceres, Cristina; Buijs, Ruud M; Woods, Stephen C; Kalsbeek, A.; Seeley, Randy J; Nawroth, Peter P; Bidlingmaier, Martin; Tschöp, Matthias H; Yi, Chun-Xia

    OBJECTIVE: The hypothalamus of hypercaloric diet-induced obese animals is featured by a significant increase of microglial reactivity and its associated cytokine production. However, the role of dietary components, in particular fat and carbohydrate, with respect to the hypothalamic inflammatory

  11. Dietary sugars, not lipids, drive hypothalamic inflammation

    NARCIS (Netherlands)

    Gao, Yuanqing; Bielohuby, Maximilian; Fleming, Thomas; Grabner, Gernot F.; Foppen, Ewout; Bernhard, Wagner; Guzmán-Ruiz, Mara; Layritz, Clarita; Legutko, Beata; Zinser, Erwin; García-Cáceres, Cristina; Buijs, Ruud M.; Woods, Stephen C.; Kalsbeek, Andries; Seeley, Randy J.; Nawroth, Peter P.; Bidlingmaier, Martin; Tschöp, Matthias H.; Yi, Chun-Xia

    2017-01-01

    Objective: The hypothalamus of hypercaloric diet-induced obese animals is featured by a significant increase of microglial reactivity and its associated cytokine production. However, the role of dietary components, in particular fat and carbohydrate, with respect to the hypothalamic inflammatory

  12. Flatfish metamorphosis: a hypothalamic independent process?

    Science.gov (United States)

    Campinho, Marco A; Silva, Nadia; Roman-Padilla, Javier; Ponce, Marian; Manchado, Manuel; Power, Deborah M

    2015-03-15

    Anuran and flatfish metamorphosis are tightly regulated by thyroid hormones that are the necessary and sufficient factors that drive this developmental event. In the present study whole mount in situ hybridization (WISH) and quantitative PCR in sole are used to explore the central regulation of flatfish metamorphosis. Central regulation of the thyroid in vertebrates is mediated by the hypothalamus-pituitary-thyroid (HPT) axis. Teleosts diverge from other vertebrates as hypothalamic regulation in the HPT axis is proposed to be through hypothalamic inhibition although the regulatory factor remains enigmatic. The dynamics of the HPT axis during sole metamorphosis revealed integration between the activity of the thyrotrophes in the pituitary and the thyroid follicles. No evidence was found supporting a role for thyroid releasing hormone (trh) or corticotrophin releasing hormone (crh) in hypothalamic control of TH production during sole metamorphosis. Intriguingly the results of the present study suggest that neither hypothalamic trh nor crh expression changes during sole metamorphosis and raises questions about the role of these factors and the hypothalamus in regulation of thyrotrophs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Hyperprolactinemia from radiation-induced hypothalamic hypopituitarism

    International Nuclear Information System (INIS)

    Corkill, G.; Hanson, F.W.; Gold, E.M.; White, V.A.

    1980-01-01

    In 1975 Samaan et al., described the effects of radiation damage of the hypothalamus in 15 patients with head and neck cancer. Shalet et al., in 1977 described endocrine morbidity in adults who as children had been irradiated for brain tumors. This report describes instances of hyperprolactinemia and associated hypothalamic, pituitary, and thyroid dysfunction following irradiation of a young adult female for brain neoplasia

  14. Sex Differences in the Regulation of Offensive Aggression and Dominance by Arginine-Vasopressin

    Directory of Open Access Journals (Sweden)

    Joseph I. Terranova

    2017-11-01

    Full Text Available Arginine-vasopressin (AVP plays a critical role in the regulation of offensive aggression and social status in mammals. AVP is found in an extensive neural network in the brain. Here, we discuss the role of AVP in the regulation of aggression in the limbic system with an emphasis on the critical role of hypothalamic AVP in the control of aggression. In males, activation of AVP V1a receptors (V1aRs in the hypothalamus stimulates offensive aggression, while in females activation of V1aRs inhibits aggression. Serotonin (5-HT also acts within the hypothalamus to modulate the effects of AVP on aggression in a sex-dependent manner. Activation of 5-HT1a receptors (5-HT1aRs inhibits aggression in males and stimulates aggression in females. There are also striking sex differences in the mechanisms underlying the acquisition of dominance. In males, the acquisition of dominance is associated with the activation of AVP-containing neurons in the hypothalamus. By contrast, in females, the acquisition of dominance is associated with the activation of 5-HT-containing neurons in the dorsal raphe. AVP and 5-HT also play critical roles in the regulation of a form of social communication that is important for the maintenance of dominance relationships. In both male and female hamsters, AVP acts via V1aRs in the hypothalamus, as well as in other limbic structures, to communicate social status through the stimulation of a form of scent marking called flank marking. 5-HT acts on 5-HT1aRs as well as other 5-HT receptors within the hypothalamus to inhibit flank marking induced by AVP in both males and females. Interestingly, while AVP and 5-HT influence the expression of aggression in opposite ways in males and females, there are no sex differences in the effects of AVP and 5-HT on the expression of social communication. Given the profound sex differences in the incidence of many psychiatric disorders and the increasing evidence for a relationship between aggressiveness

  15. Stress responsiveness of the hypothalamic-pituitary-adrenal axis: age-related features of the vasopressinergic regulation

    Directory of Open Access Journals (Sweden)

    Nadezhda Dmitrievna Goncharova

    2013-03-01

    Full Text Available The hypothalamic-pituitary-adrenal (HPA axis plays a key role in adaptation to environmental stresses. Parvicellular neurons of the hypothalamic paraventricular nucleus secrete corticotrophin releasing hormone (CRH and arginine vasopressin (AVP into pituitary portal system; CRH and AVP stimulate ACTH release through specific G protein-coupled membrane receptors on pituitary corticotrophs, CRH1 for CRH and V1b for AVP; the adrenal gland cortex secretes glucocorticoids in response ACTH. The glucocorticoids activate specific receptors in brain and peripheral tissues thereby triggering the necessary metabolic, immune, neuromodulatory and behavioral changes to resist stress. While importance of CRH, as a key hypothalamic factor of HPA axis regulation in basal and stress conditions in most species, is generally recognized, role of AVP remains to be clarified. This review focuses on the role of AVP in the regulation of stress responsiveness of the HPA axis with emphasis on the effects of aging on vasopressinergic regulation of HPA axis stress responsiveness. Under most of the known stressors, AVP is necessary for acute ACTH secretion but in a context-specific manner. The current data on the AVP role in regulation of HPA responsiveness to chronic stress in adulthood are rather contradictory. The importance of the vasopressinergic regulation of the HPA stress responsiveness is greatest during fetal development, in neonatal period, and in the lactating adult. Aging associated with increased variability in several parameters of HPA function including basal state, responsiveness to stressors, and special testing. Reports on the possible role of the AVP/V1b receptor system in the increase of HPA axis hyperactivity with aging are contradictory and requires further research. Many contradictory results may be due to age and species differences in the HPA function of rodents and primates.

  16. Hypothalamic-pituitary-adrenal axis activity in patients with pathological gambling and internet use disorder.

    Science.gov (United States)

    Geisel, Olga; Panneck, Patricia; Hellweg, Rainer; Wiedemann, Klaus; Müller, Christian A

    2015-03-30

    Alterations in secretion of stress hormones within the hypothalamic-pituitary-adrenal (HPA) axis have repeatedly been found in substance-related addictive disorders. It has been suggested that glucocorticoids might contribute to the development and maintenance of substance use disorders by facilitatory effects on behavioral responses to substances of abuse. The objective of this pilot study was to investigate HPA axis activity in patients with non-substance-related addictive disorders, i.e. pathological gambling and internet use disorder. We measured plasma levels of copeptin, a vasopressin surrogate marker, adrenocorticotropic hormone (ACTH) and cortisol in male patients with pathological gambling (n=14), internet use disorder (n=11) and matched healthy controls for pathological gambling (n=13) and internet use disorder (n=10). Plasma levels of copeptin, ACTH and cortisol in patients with pathological gambling or internet use disorder did not differ among groups. However, cortisol plasma levels correlated negatively with the severity of pathological gambling as measured by the PG-YBOCS. Together with our findings of increased serum levels of brain-derived neurotrophic factor (BDNF) in pathological gambling but not internet use disorder, these results suggest that the pathophysiology of pathological gambling shares some characteristics with substance-related addictive disorders on a neuroendocrinological level, whereas those similarities could not be observed in internet use disorder. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Paraneoplastic limbic encephalitis with associated hypothalamitis mimicking a hyperdense hypothalamic tumor: a case report

    International Nuclear Information System (INIS)

    Bataduwaarachchi, Vipula R.; Tissera, Nirmali

    2016-01-01

    Paraneoplastic limbic encephalitis is an uncommon association of common malignancies such as small cell lung carcinoma, testicular teratoma, and breast carcinoma. The nonspecific nature of the clinical presentation, lack of freely available diagnostic markers, and requirement for advanced imaging techniques pose a great challenge in the diagnosis of this disease in resource-poor settings. A 64-year-old previously healthy Sri Lankan man was admitted to the general medical unit with subacute memory impairment regarding recent events that had occurred during the previous 3 weeks. Initial noncontrast computed tomography of the brain revealed a hyperdensity in the hypothalamic region surrounded by hypodensities extending toward the bilateral temporal lobes; these findings were consistent with a possible hypothalamic tumor with perilesional edema. The patient later developed cranial diabetes insipidus, which was further suggestive of hypothalamic disease. Interestingly, gadolinium-enhanced magnetic resonance imaging of the brain showed no such lesions; instead, it showed prominent T2-weighted signals in the inner mesial region, characteristic of encephalitis. The possibility of tuberculosis and viral encephalitis was excluded based on cerebrospinal fluid analysis results. Limbic encephalitis with predominant hypothalamitis was suspected based on the radiological pattern. Subsequent screening for underlying malignancy revealed a mass lesion in the right hilum on chest radiographs. Histological examination of the lesion showed small cell lung cancer of the “oat cell” variety. We suggest that the initial appearance of a hyperdensity in the hypothalamus region on noncontrast computed tomography is probably due to hyperemia caused by hypothalamitis. If hypothalamitis is predominant in a patient with paraneoplastic limbic encephalitis, magnetic resonance imaging will help to differentiate it from a hypothalamic secondary deposit. Limbic encephalitis should be considered in

  18. Improved method and its clinical application of a radioimmunoassay of arginine vasopressin in human serum

    International Nuclear Information System (INIS)

    Wagner, H.; Maier, V.; Franz, H.W.; Ulm Univ.; Ulm Univ.

    1977-01-01

    A sensitive and specific double-antibody radioimmunoassay for measuring circulating levels of arginine vasopressin in human serum is described. It is possible to detect arginine vasopressin levels of 1 μU/ml serum without extraction procedure. Normal subjects were found to have 5.7 +- 4.4 μU/ml after a dehydration period of 12 hours. Water loading diminished arginine vasopressin concentrations while dehydration incrased it. Application of furosemide over a period of 14 days brought forth constant but not significant decreases. Subjects suffering from psychogenic polydipsia showed normal levels in spite of drinking 8-12 liters of water per day. Patients suffering from liver cirrhosis with ascites showed significantly higher arginine vasopressin levels, approaching normal values when ascites was under control. (orig.) [de

  19. A non-equilibrium 24-hour vasopressin radioimmunoassay: development and basal levels in the rat brain

    International Nuclear Information System (INIS)

    Brinton, R.E.; Deshmukh, P.P.; Chen, A.; Davis, T.P.; Hsiao, S.; Yamamura, H.I.

    1983-01-01

    In this paper the authors report a highly-sensitive non-equilibrium RIA which can be performed within 24 h. To demonstrate the sensitivity of this RIA, brain regions from rat were examined for vasopressin content. (Auth.)

  20. Vasopressin Gene-Related Products in the Management of Breast Cancer

    National Research Council Canada - National Science Library

    North, William

    1999-01-01

    ...), and this information coupled with an absence of vasopressin gene-related products from fibrocystic disease potentially provides us with a new screening test for distinguishing both breast cancer...

  1. Oxytocin and vasopressin neural networks: Implications for social behavioral diversity and translational neuroscience.

    Science.gov (United States)

    Johnson, Zachary V; Young, Larry J

    2017-05-01

    Oxytocin- and vasopressin-related systems are present in invertebrate and vertebrate bilaterian animals, including humans, and exhibit conserved neuroanatomical and functional properties. In vertebrates, these systems innervate conserved neural networks that regulate social learning and behavior, including conspecific recognition, social attachment, and parental behavior. Individual and species-level variation in central organization of oxytocin and vasopressin systems has been linked to individual and species variation in social learning and behavior. In humans, genetic polymorphisms in the genes encoding oxytocin and vasopressin peptides and/or their respective target receptors have been associated with individual variation in social recognition, social attachment phenotypes, parental behavior, and psychiatric phenotypes such as autism. Here we describe both conserved and variable features of central oxytocin and vasopressin systems in the context of social behavioral diversity, with a particular focus on neural networks that modulate social learning, behavior, and salience of sociosensory stimuli during species-typical social contexts. Published by Elsevier Ltd.

  2. Improved method and its clinical application of a radioimmunoassay of arginine vasopressin in human serum

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, H; Maier, V; Franz, H W [Ulm Univ. (Germany, F.R.). Abt. Endokrinologie und Stoffwechsel; Ulm Univ. (Germany, F.R.). Zentrum fuer Innere Medizin und Kinderheilkunde; Ulm Univ. (Germany, F.R.). Sektion Nephrologie)

    1977-05-01

    A sensitive and specific double-antibody radioimmunoassay for measuring circulating levels of arginine vasopressin in human serum is described. It is possible to detect arginine vasopressin levels of 1 ..mu..U/ml serum without extraction procedure. Normal subjects were found to have 5.7 +- 4.4 ..mu..U/ml after a dehydration period of 12 hours. Water loading diminished arginine vasopressin concentrations while dehydration incrased it. Application of furosemide over a period of 14 days brought forth constant but not significant decreases. Subjects suffering from psychogenic polydipsia showed normal levels in spite of drinking 8-12 liters of water per day. Patients suffering from liver cirrhosis with ascites showed significantly higher arginine vasopressin levels, approaching normal values when ascites was under control.

  3. Radioimmunoassay for human plasma 8-arginine-vasopressin

    International Nuclear Information System (INIS)

    Conte-Devolx, B.; Rougon-Rapuzzi, G.; Millet, Y.

    1977-01-01

    A radioimmunoassay for human plasma vasopressin (AVP) which permits the estimation of antidiuretic hormone (ADH) level as low as 0.8pg/ml, was developed. The average plasma level of AVP after overnight water restriction was found to be 14.3pg/ml (sd=4.4pg/ml) in normal subjects. They provoked a hypersecretion of ADH by the intravenous injection of 1-2mg of nicotine. In 11 volunteer normal subjects this stimulation by nicotine provoked ADH hypersecretion which reached a maximum between 2nd and 15th minutes after injection. In 3 cases of diabetes insipidus, nicotine injection did not induce ADH hypersecretion: in 1 case of potomania this response was weak; in 2 cases of syndrome of inappropriate ADH secretion, AVP plasma levels were elevated and the response after nicotine stimulation was exaggerated [fr

  4. Radioimmunoassay for human plasma 8-arginine-vasopressin

    Energy Technology Data Exchange (ETDEWEB)

    Conte-Devolx, B [Hopital de la Conception, 13 - Marseille (France); Rougon-Rapuzzi, G [Centre National de la Recherche Scientifique, 13 - Marseille (France); Millet, Y [Aix-Marseille-2 Univ., 13 - Marseille (France)

    1977-01-01

    A radioimmunoassay for human plasma vasopressin (AVP) which permits the estimation of antidiuretic hormone (ADH) level as low as 0.8pg/ml, was developed. The average plasma level of AVP after overnight water restriction was found to be 14.3pg/ml (sd=4.4pg/ml) in normal subjects. They provoked a hypersecretion of ADH by the intravenous injection of 1-2mg of nicotine. In 11 volunteer normal subjects this stimulation by nicotine provoked ADH hypersecretion which reached a maximum between 2nd and 15th minutes after injection. In 3 cases of diabetes insipidus, nicotine injection did not induce ADH hypersecretion: in 1 case of potomania this response was weak; in 2 cases of syndrome of inappropriate ADH secretion, AVP plasma levels were elevated and the response after nicotine stimulation was exaggerated.

  5. Reliability of basal plasma vasopressin concentrations in healthy male adults.

    Science.gov (United States)

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

    2017-10-01

    The neuropeptides oxytocin (OT) and arginine vasopressin (AVP) play important and interrelated roles in modulating mammalian social behaviour. While the OT system has received considerable research attention for its potential to treat psychiatric symptoms, comparatively little is known about the role of the AVP system in human social behaviour. To better understand the intraindividual stability of basal AVP, the present study assessed the reproducibility of basal plasma AVP concentrations. Basal plasma AVP was assessed at four sampling points separated by 8 days, on average, in 16 healthy adult males. Only one out of six comparisons revealed strong evidence for reproducibility of basal AVP concentrations (visit 2 vs. visit 4: r=0.8, p0.1). The concordance correlation coefficient [0.15, 95% CI (-0.55, 0.73)] also revealed poor overall reproducibility. Poor reliability of basal AVP concentrations suggests future work covarying AVP with trait markers should proceed with careful consideration of intraindividual fluctuations.

  6. The Septic Shock 3.0 Definition and Trials: A Vasopressin and Septic Shock Trial Experience.

    Science.gov (United States)

    Russell, James A; Lee, Terry; Singer, Joel; Boyd, John H; Walley, Keith R

    2017-06-01

    The Septic Shock 3.0 definition could alter treatment comparisons in randomized controlled trials in septic shock. Our first hypothesis was that the vasopressin versus norepinephrine comparison and 28-day mortality of patients with Septic Shock 3.0 definition (lactate > 2 mmol/L) differ from vasopressin versus norepinephrine and mortality in Vasopressin and Septic Shock Trial. Our second hypothesis was that there are differences in plasma cytokine levels in Vasopressin and Septic Shock Trial for lactate less than or equal to 2 versus greater than 2 mmol/L. Retrospective analysis of randomized controlled trial. Multicenter ICUs. We compared vasopressin-to-norepinephrine group 28- and 90-day mortality in Vasopressin and Septic Shock Trial in lactate subgroups. We measured 39 cytokines to compare patients with lactate less than or equal to 2 versus greater than 2 mmol/L. Patients with septic shock with lactate greater than 2 mmol/L or less than or equal to 2 mmol/L, randomized to vasopressin or norepinephrine. Concealed vasopressin (0.03 U/min.) or norepinephrine infusions. The Septic Shock 3.0 definition would have decreased sample size by about half. The 28- and 90-day mortality rates were 10-12 % higher than the original Vasopressin and Septic Shock Trial mortality. There was a significantly (p = 0.028) lower mortality with vasopressin versus norepinephrine in lactate less than or equal to 2 mmol/L but no difference between treatment groups in lactate greater than 2 mmol/L. Nearly all cytokine levels were significantly higher in patients with lactate greater than 2 versus less than or equal to 2 mmol/L. The Septic Shock 3.0 definition decreased sample size by half and increased 28-day mortality rates by about 10%. Vasopressin lowered mortality versus norepinephrine if lactate was less than or equal to 2 mmol/L. Patients had higher plasma cytokines in lactate greater than 2 versus less than or equal to 2 mmol/L, a brisker cytokine response to infection. The Septic

  7. Effects of Arginine Vasopressin on musical short-term memory

    Directory of Open Access Journals (Sweden)

    Roni Y. Granot

    2013-10-01

    Full Text Available Previous genetic studies showed an association between variations in the gene coding for the 1a receptor of the neuro-hormone arginine vasopressin (AVP and musical working memory (WM. The current study set out to test the influence of intranasal administration (INA of AVP on musical as compared to verbal WM using a double blind crossover (AVP – placebo design. Two groups of 25 males were exposed to 20 IU of AVP in one session, and 20 IU of saline water (placebo in a second session, one week apart. In each session subjects completed the tonal subtest from Gordon's Musical Aptitude Profile, the interval subtest from the Montreal Battery for Evaluation of Amusias (MBEA, and the forward and backward digit span tests. Scores in the digit span tests were not influenced by AVP. In contrast, in the music tests there was an AVP effect. In the MBEA test, scores for the group receiving placebo in the first session (PV were higher than for the group receiving vasopressin in the first session (VP (p < .05 with no main Session effect nor Group * Session interaction. In the Gordon test there was a main Session effect (p < .05 with scores higher in the second as compared to the first session, a marginal main Group effect (p = .093 and a marginal Group X Session interaction (p = 0.88. In addition we found that the group that received AVP in the first session scored higher on scales indicative of happiness, and alertness on the Positive and Negative Affect Scale, (PANAS. Only in this group and only in the music test these scores were significantly correlated with memory scores. Together the results reflect a complex interaction between AVP, musical memory, arousal, and contextual effects such as session, and base levels of memory. The results are interpreted in light of music's universal use as a means to modulate arousal on the one hand, and AVP's influence on mood, arousal, and social interactions on the other.

  8. Magnetic resonance imaging of hypothalamic hamartoma

    Energy Technology Data Exchange (ETDEWEB)

    Kanazawa, Junichi; Uozumi, Tohru; Sakoda, Katsuaki; Yamanaka, Masami; Kihara, Mikio; Nishi, Yoshikazu; Kagawa, Yoshihiro; Kajima, Toshio.

    1988-05-01

    Magnetic resonance (MR) findings of two patients with a hypothalamic hamartoma are discussed. The two girls showed clinical symptoms and endocrinological signs of precocious puberty. MR imaging was of diagnostic value superior to that of CT in the demonstration of the characteristic location of this tumor and relationships to the neighboring structures because of its multi-dimensional utility. Although it has been reported that CT showed this lesion as isodense to the grey matter with and without injection of contrast medium, MR imaging depicted the lesion as a high signal intensity area on T2-weighted images in both patients. MR imaging is a useful method for the evaluation of the hypothalamic hamartoma.

  9. Lymphocytic hypophysitis and hypothalamitis - a case report

    International Nuclear Information System (INIS)

    Stelmachowska, M.; Bolko, P.; Wasko, R.; Sowinski, J.; Kosinski, D.; Towpik, I.

    2006-01-01

    Lymphocytic hypophysitis is an unusual disorder that nearly exclusively affects women. We present a case of 69 year-old female patient who developed the symptoms of diabetes insipidus and partial insufficiency of the anterior pituitary gland. Magnetic resonance imaging of the brain revealed a mass involving the sella and suprasellar region. After exclusion of other causes of infiltrate in this region and due to evident reaction to glucocorticoid treatment the diagnosis of lymphocytic hypophisitis and hypothalamitis was established. (author)

  10. Protein synthesis inhibitors attenuate water flow in vasopressin-stimulated toad urinary bladder

    International Nuclear Information System (INIS)

    Hoch, B.S.; Ast, M.B.; Fusco, M.J.; Jacoby, M.; Levine, S.D.

    1988-01-01

    Vasopressin stimulates the introduction of aggregated particles, which may represent pathways for water flow, into the luminal membrane of toad urinary bladder. It is not known whether water transport pathways are degraded on removal from membrane or whether they are recycled. The authors examined the effect of the protein synthesis inhibitors cycloheximide and puromycin using repeated 30-min cycles of vasopressin followed by washout of vasopressin, all in the presence of an osmotic gradient, a protocol that maximizes aggregate turnover. High dose cycloheximide inhibited flow immediately. Low dose cycloheximide did not affect initial flow. In the absence of vasopressin, inhibition did not develop. Despite the inhibition of flow in vasopressin-treated tissues, the cAMP-dependent protein kinase ratio was elevated in cycloheximide-treated tissues, suggesting modulation at a distal site in the stimulatory cascade. [ 14 C]urea permeability was not inhibited by cycloheximide. Puromycin also inhibited water flow by the fourth challenge with vasopressin. The data suggest that protein synthesis inhibitors attenuate flow at a site that is distal to cAMP-dependent protein kinase. However, the reversal of inhibition in MIX-treated tissues suggests that the water pathway can be fully manifested given suitable stimulation. They conclude that either large stores of the transport system are available or that the transport system is extensively recycled on retrieval from the membrane

  11. Vasopressin facilitates excitatory transmission in slices of the rat dorso-lateral septum.

    Science.gov (United States)

    Van den Hooff, P; Urban, I J

    1990-01-01

    The effect of vasopressin on neurons of the rat dorso-lateral septum (DLS) was studied in brain slices with intracellular microelectrodes. Two out of 13 neurons showed a small depolarization, spontaneous activity, and increased input resistances following a 15 min exposure to 10(-6) to 10(-8) M vasopressin (VP). These membrane effects disappeared completely within 3-5 min after the application. The remaining DLS neurons treated with these vasopressin concentrations showed an increase in glutamate-mediated excitatory postsynaptic potentials (EPSPs), evoked by stimulation of the fimbria fibers. As little as 10(-12) MVP increased these EPSPs markedly in nearly 80% of the cells studied. This increase in most of the cells disappeared within 15 min after the application period, whereas the increase in EPSPs induced by 10(-10) M VP outlasted the peptide application period for more than 30 min. Neither the blockade of GABA-ergic synaptic inhibition nor the pre-treatment of the neurons with d(CH2)5-Tyr(Me)-arginine vasopressin or 2-amino-5-phosphonovaleric acid (2-APV), antagonists for the V1 type of vasopressin receptor and NMDA receptors, respectively, interfered with the EPSPs potentiating effect of the peptide. It is concluded that a type of vasopressin receptor other then the V1 type is involved in the long-lasting potentiation of the primarily non-NMDA receptor mediated transmission in DLS neurons.

  12. Changes in social functioning and circulating oxytocin and vasopressin following the migration to a new country.

    Science.gov (United States)

    Gouin, Jean-Philippe; Pournajafi-Nazarloo, Hossein; Carter, C Sue

    2015-02-01

    Prior studies have reported associations between plasma oxytocin and vasopressin and markers of social functioning. However, because most human studies have used cross-sectional designs, it is unclear whether plasma oxytocin and vasopressin influences social functioning or whether social functioning modulates the production and peripheral release of these peptides. In order to address this question, we followed individuals who experienced major changes in social functioning subsequent to the migration to a new country. In this study, 59 new international students were recruited shortly after arrival in the host country and reassessed 2 and 5 months later. At each assessment participants provided information on their current social functioning and blood samples for oxytocin and vasopressin analysis. Results indicated that changes in social functioning were not related to changes in plasma oxytocin. Instead, baseline oxytocin predicted changes in social relationship satisfaction, social support, and loneliness over time. In contrast, plasma vasopressin changed as a function of social integration. Baseline vasopressin was not related to changes in social functioning over time. These results emphasize the different roles of plasma oxytocin and vasopressin in responses to changes in social functioning in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Plasma volume, osmolality, vasopressin, and renin activity during graded exercise in man

    Science.gov (United States)

    Convertino, V. A.; Keil, L. C.; Bernauer, E. M.; Greenleaf, J. E.

    1981-01-01

    The influence of work intensity on plasma volume, osmolality, vasopressin and renin activity and the interrelationships between these responses are investigated. Plasma volume, renin activity and osmotic, sodium and arginine vasopressin concentrations were measured in venous blood samples taken from 15 healthy male subjects before and after six minutes of bicycle ergometer exercise at 100, 175 and 225 W. Plasma volume is found to decrease significantly with increasing work intensity, while increases in Na(+) concentration, osmolality and vasopressin are only observed to be significant when the work intensity exceeds 40% maximal aerobic capacity and plasma resin activity increased linearly at all work levels. In addition, significant correlations are observed between plasma volume and osmolality and sodium changes, and between vasopressin and osmolality and sodium content changes. Data thus support the hypotheses that (1) vasopressin may be the primary controlling endocrine for fluid and electrolyte levels following exercise; (2) an exercise intensity greater than 40% maximal aerobic capacity is required to stimulate vasopressin release through changes in plasma osmolality; and (3) the stimulation of the renin-angiotensin system is a more general stress response.

  14. Effect of the addition of vasopressin or vasopressin plus nitroglycerin to epinephrine on arterial blood pressure during cardiopulmonary resuscitation in humans.

    Science.gov (United States)

    Ducros, Laurent; Vicaut, Eric; Soleil, Christian; Le Guen, Morgan; Gueye, Papa; Poussant, Thomas; Mebazaa, Alexandre; Payen, Didier; Plaisance, Patrick

    2011-11-01

    Infusion of a vasopressor during cardiopulmonary resuscitation (CPR) in humans increases end decompression (diastolic) arterial blood pressure, and consequently increases vital organ perfusion pressure and survival. Several vasoactive drugs have been tested alone or in combination, but their hemodynamic effects have not been investigated clinically in humans. We tested the hypothesis that epinephrine (1 mg) co-administered with vasopressin (40 IU) ± nitroglycerin (300 μg) results in higher diastolic blood pressure than epinephrine alone. A prospective, randomized, double-blinded controlled trial in the prehospital setting. The study included 48 patients with witnessed cardiac arrest. Patients received either epinephrine alone (E alone) or epinephrine plus vasopressin (E+V) or epinephrine plus vasopressin plus nitroglycerin (E+V+N). A femoral arterial catheter was inserted for arterial pressure measurement. The primary end point was diastolic blood pressure during CPR, 15 min after the first drug administration (T = 15 min). After exclusions, a total of 44 patients were enrolled. Diastolic blood pressures (mm Hg) at T = 15 min were not statistically different between groups (median [interquartile range]: 20 [10], 15 [6], and 15 [13] for E alone, E+V, and E+V+N, respectively. The rate of return of spontaneous circulation was 63% (n = 10) in the epinephrine group, 43% (n = 6) in the epinephrine plus vasopressin group, and 36% (n = 5) in the triple therapy group (NS). Addition of vasopressin or vasopressin plus nitroglycerin to epinephrine did not increase perfusion blood pressure compared to epinephrine alone in humans in cardiac arrest, suggesting the absence of benefit in using these drug combination(s). Copyright © 2011 Elsevier Inc. All rights reserved.

  15. The role of hypothalamic inflammation, the hypothalamic-pituitary-adrenal axis and serotonin in the cancer anorexia-cachexia syndrome.

    Science.gov (United States)

    van Norren, Klaske; Dwarkasing, Jvalini T; Witkamp, Renger F

    2017-09-01

    In cancer patients, the development of cachexia (muscle wasting) is frequently aggravated by anorexia (loss of appetite). Their concurrence is often referred to as anorexia-cachexia syndrome. This review focusses on the recent evidence underlining hypothalamic inflammation as key driver of these processes. Special attention is given to the involvement of hypothalamic serotonin. The anorexia-cachexia syndrome is directly associated with higher mortality in cancer patients. Recent reports confirm its severe impact on the quality of life of patients and their families.Hypothalamic inflammation has been shown to contribute to muscle and adipose tissue loss in cancer via central hypothalamic interleukine (IL)1β-induced activation of the hypothalamic-pituitary-adrenal axis. The resulting release of glucocorticoids directly stimulates catabolic processes in these tissues via activation of the ubiquitin-proteosome pathway. Next to this, hypothalamic inflammation has been shown to reduce food intake in cancer by triggering changes in orexigenic and anorexigenic responses via upregulation of serotonin availability and stimulation of its signalling pathways in hypothalamic tissues. This combination of reduced food intake and stimulation of tissue catabolism represents a dual mechanism by which hypothalamic inflammation contributes to the development and maintenance of anorexia and cachexia in cancer. Hypothalamic inflammation is a driving force in the development of the anorexia-cachexia syndrome via hypothalamic-pituitary-adrenal axis and serotonin pathway activation.

  16. Exposure to chronic isolation modulates receptors mRNAs for oxytocin and vasopressin in the hypothalamus and heart.

    Science.gov (United States)

    Pournajafi-Nazarloo, Hossein; Kenkel, William; Mohsenpour, Seyed Ramezan; Sanzenbacher, Lisa; Saadat, Habibollah; Partoo, Leila; Yee, Jason; Azizi, Fereidoun; Carter, C Sue

    2013-05-01

    The goal of our study was to explore the effect of social isolation stress of varying durations on the plasma oxytocin (OT), messenger ribonucleic acid (mRNA) for oxytocin receptor (OTR), plasma arginine vasopressin (AVP) and mRNA for V1a receptor of AVP (V1aR) expression in the hypothalamus and heart of socially monogamous female and male prairie voles (Microtus ochrogaster). Continuous isolation for 4 weeks (chronic isolation) increased plasma OT level in females, but not in males. One hour of isolation every day for 4 weeks (repeated isolation) was followed by a significant increase in plasma AVP level. Chronic isolation, but not repeated isolation, significantly decreased OTR mRNA in the hypothalamus and heart in both sexes. Chronic isolation significantly decreased cardiac V1aR mRNA, but no effect on hypothalamic V1aR mRNA expression. We did not find a gender difference within repeated social isolation groups. The results of the present study reveal that although chronic social isolation can down-regulate gene expression for the OTR in both sexes, the release of the OT peptide was increased after chronic isolation only in females, possibly somewhat protecting females from the negative consequences of isolation. In both sexes repeated, but not chronic, isolation increased plasma AVP, which could be permissive for mobilization and thus adaptive in response to a repeated stressor. The differential effects of isolation on OT and AVP systems may help in understanding mechanisms through social interactions can be protective against emotional and cardiovascular disorders. Published by Elsevier Inc.

  17. Arginine vasopressin neuronal loss results from autophagy-associated cell death in a mouse model for familial neurohypophysial diabetes insipidus

    Science.gov (United States)

    Hagiwara, D; Arima, H; Morishita, Y; Wenjun, L; Azuma, Y; Ito, Y; Suga, H; Goto, M; Banno, R; Sugimura, Y; Shiota, A; Asai, N; Takahashi, M; Oiso, Y

    2014-01-01

    Familial neurohypophysial diabetes insipidus (FNDI) characterized by progressive polyuria is mostly caused by mutations in the gene encoding neurophysin II (NPII), which is the carrier protein of the antidiuretic hormone, arginine vasopressin (AVP). Although accumulation of mutant NPII in the endoplasmic reticulum (ER) could be toxic for AVP neurons, the precise mechanisms of cell death of AVP neurons, reported in autopsy studies, remain unclear. Here, we subjected FNDI model mice to intermittent water deprivation (WD) in order to promote the phenotypes. Electron microscopic analyses demonstrated that, while aggregates are confined to a certain compartment of the ER in the AVP neurons of FNDI mice with water access ad libitum, they were scattered throughout the dilated ER lumen in the FNDI mice subjected to WD for 4 weeks. It is also demonstrated that phagophores, the autophagosome precursors, emerged in the vicinity of aggregates and engulfed the ER containing scattered aggregates. Immunohistochemical analyses revealed that expression of p62, an adapter protein between ubiquitin and autophagosome, was elicited on autophagosomal membranes in the AVP neurons, suggesting selective autophagy induction at this time point. Treatment of hypothalamic explants of green fluorescent protein (GFP)-microtubule-associated protein 1 light chain 3 (LC3) transgenic mice with an ER stressor thapsigargin increased the number of GFP-LC3 puncta, suggesting that ER stress could induce autophagosome formation in the hypothalamus of wild-type mice as well. The cytoplasm of AVP neurons in FNDI mice was occupied with vacuoles in the mice subjected to WD for 12 weeks, when 30–40% of AVP neurons are lost. Our data thus demonstrated that autophagy was induced in the AVP neurons subjected to ER stress in FNDI mice. Although autophagy should primarily be protective for neurons, it is suggested that the organelles including ER were lost over time through autophagy, leading to autophagy

  18. Vasopressin and nitroglycerin decrease portal and hepatic venous pressure and hepato-splanchnic blood flow.

    Science.gov (United States)

    Wisén, E; Svennerholm, K; Bown, L S; Houltz, E; Rizell, M; Lundin, S; Ricksten, S-E

    2018-03-26

    Various methods are used to reduce venous blood pressure in the hepato-splanchnic circulation, and hence minimise blood loss during liver surgery. Previous studies show that combination of vasopressin and nitroglycerin reduces portal pressure and flow in patients with portal hypertension, and in this study we investigated this combination in patients with normal portal pressure. In all, 13 patients were studied. Measurements were made twice to confirm baseline (C1 and BL), during vasopressin infusion 4.8 U/h (V), and during vasopressin infusion combined with nitroglycerin infusion (V + N). Portal venous pressure (PVP), hepatic venous pressure (HVP), central haemodynamics and arterial and venous blood gases were obtained at each measuring point, and portal (splanchnic) and hepato-splanchnic blood flow changes were calculated. Vasopressin alone did not affect PVP, whereas HVP increased slightly. In combination with nitroglycerin, PVP decreased from 10.1 ± 1.6 to 8.9 ± 1.3 mmHg (P HVP decreased from 7.9 ± 1.9 to 6.2 ± 1.3 mmHg (P = 0.001). Vasopressin reduced portal blood flow by 47 ± 19% and hepatic venous flow by 11 ± 18%, respectively. Addition of nitroglycerin further reduced portal- and hepatic flow by 55 ± 13% and 30 ± 13%, respectively. Vasopressin alone had minor effects on central haemodynamics, whereas addition of nitroglycerin reduced cardiac index (3.2 ± 0.7 to 2.7 ± 0.5; P < 0.0001). The arterial-portal vein lactate gradient was unaffected. The combination of vasopressin and nitroglycerin decreases portal pressure and hepato-splanchnic blood flow, and could be a potential treatment to reduce bleeding in liver resection surgery. © 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  19. Hypothalamic glucose sensing: making ends meet

    Directory of Open Access Journals (Sweden)

    Vanessa eRouth

    2014-12-01

    Full Text Available The neuroendocrine system governs essential survival and homeostatic functions. For example, growth is needed for development. Thermoregulation maintains optimal core temperature in a changing environment. Reproduction ensures species survival. Stress and immune responses enable an organism to overcome external and internal threats. The circadian system regulates arousal and sleep such that vegetative and active functions do not overlap. All of these functions require a significant portion of the body’s energy. As the integrator of the neuroendocrine system, the hypothalamus carefully assesses the energy status of the body in order to appropriately partition resources to provide for each system without compromising the others. While doing so the hypothalamus must ensure that adequate glucose levels are preserved for brain function since glucose is the primary fuel of the brain. To this end, the hypothalamus contains specialized glucose sensing neurons which are scattered throughout the nuclei controlling distinct neuroendocrine functions. We hypothesize that these neurons play a key role in enabling the hypothalamus to partition energy to meet these peripheral survival needs without endangering the brain’s glucose supply. The goal of this review is to describe the varied mechanisms underlying glucose sensing in neurons within discrete hypothalamic nuclei. We will then evaluate the way in which peripheral energy status regulates glucose sensitivity. For example, during energy deficit such as fasting specific hypothalamic glucose sensing neurons become sensitized to decreased glucose. This increases the gain of the information relay when glucose availability is a greater concern for the brain. Finally, changes in glucose sensitivity under pathological conditions (e.g., recurrent insulin-hypoglycemia, diabetes will be addressed. The overall goal of this review is to place glucose sensing neurons within the context of hypothalamic control of

  20. Hypothalamic control of energy and glucose metabolism.

    Science.gov (United States)

    Sisley, Stephanie; Sandoval, Darleen

    2011-09-01

    The central nervous system (CNS), generally accepted to regulate energy homeostasis, has been implicated in the metabolic perturbations that either cause or are associated with obesity. Normally, the CNS receives hormonal, metabolic, and neuronal input to assure adequate energy levels and maintain stable energy homeostasis. Recent evidence also supports that the CNS uses these same inputs to regulate glucose homeostasis and this aspect of CNS regulation also becomes impaired in the face of dietary-induced obesity. This review focuses on the literature surrounding hypothalamic regulation of energy and glucose homeostasis and discusses how dysregulation of this system may contribute to obesity and T2DM.

  1. Plasma arginine vasopressin response to water load during labour

    International Nuclear Information System (INIS)

    Singhi, Sunit; Parshad, Omkar

    1985-01-01

    To find out whether plasma vasopressin (Psub(AVP)) response to a water load during pregnancy is inappropriately high, as had been speculated, we measured Psub(AVP)by radioimmunoassay in 30 women at the time of delivery. Ten women had received infusion of aqueous glucose solution during labour for hydration (GW group); another ten received infusion of glucose solution as a vehicle for oxytocin (IOT group), and ten women did not receive any intrapartum intravenous fluid therapy (controls). Serum sodium and osmolality were also determined in all the subjects. Psub(AVP) levels were significantly lower in GW (0.70 +- 0.4 pg/ml) and OT groups (0.7 +- 0.6 pg/ml) (P<0.05). Significant negative correlation was seen between the amount of glucose solution infused and levels of Psub(AVP) (r = -0.66; P<0.01), while a significant positive correlation was seen between Psub(AVP) and serum sodium (r = 0.61; P<0.01). These findings suggest that during labour, the physiological relationship between serum osmolality and Psub(AVP) in intact, and the infusion of a water load in the form of aqueous glucose solution is attended by an expected lowering of Psub(AVP). We infer that inappropriate ADH response is not the cause of water retention and hyponatremia often seen in women receiving aqueous glucose solution during labor. (author)

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

    DEFF Research Database (Denmark)

    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....

  3. Plasma arginine vasopressin response to water load during labour

    Energy Technology Data Exchange (ETDEWEB)

    Singhi, S. (West Indies Univ., Mona (Jamaica). Dept. of Child Health); Parshad, O. (West Indies Univ., Mona (Jamaica). Dept. of Physiology)

    1985-02-01

    To find out whether plasma vasopressin (Psub(AVP)) response to a water load during pregnancy is inappropriately high, as had been speculated, we measured Psub(AVP)by radioimmunoassay in 30 women at the time of delivery. Ten women had received infusion of aqueous glucose solution during labour for hydration (GW group); another ten received infusion of glucose solution as a vehicle for oxytocin (IOT group), and ten women did not receive any intrapartum intravenous fluid therapy (controls). Serum sodium and osmolality were also determined in all the subjects. Psub(AVP) levels were significantly lower in GW (0.70 +- 0.4 pg/ml) and OT groups (0.7 +- 0.6 pg/ml) (P < 0.05). Significant negative correlation was seen between the amount of glucose solution infused and levels of Psub(AVP) (r = -0.66; P < 0.01), while a significant positive correlation was seen between Psub(AVP) and serum sodium (r = 0.61; P < 0.01). These findings suggest that during labour, the physiological relationship between serum osmolality and Psub(AVP) in intact, and the infusion of a water load in the form of aqueous glucose solution is attended by an expected lowering of Psub(AVP). We infer that inappropriate ADH response is not the cause of water retention and hyponatremia often seen in women receiving aqueous glucose solution during labor.

  4. Cerebral glucose utilization after vasopressin barrel rotation or bicuculline seizures

    International Nuclear Information System (INIS)

    Wurpel, J.; Dundore, R.; Bryan, R.; Keil, L.; Severs, W.B.

    1986-01-01

    Intraventricular (ivt) arginine vasopressin (AVP) causes a violent motor behavior termed barrel rotation (BR). AVP-BR is affected by visual/vestibular sensory input and may be related to other CNS motor disorders (seizures). Local cerebral glucose utilization (LCGU) was compared in SD rats during AVP-BR and bicuculline (BIC) seizures. Three groups were used: saline-ivt; AVP-ivt 0.5 μg; BIC-5.5 mg/kg,sc. 14 C-glucose (40 μCI iv) was injected 15 sec. after ivt-saline or AVP or onset of BIC seizures. Rats were decapitated 10 min. after 14 C-glucose. Brains were removed and dissected into 19 regions which were digested and glucose uptake quantified by liquid scintillation counting. LCGU was significantly increased in all CNS areas during BIC seizures vs controls (21-92%; p < 0.05 ANOVA). LCGU exhibits variable (upward arrow, downward arrow) changes in discrete areas during AVP-BR (p < .05). Glucose uptake increased in: cortex-olfactory (21%), sensory (9%), motor (8%) cerebellum-rt (13%) and 1t (17%) hemispheres, vermis (6%); pyramidal tract (6%); mesencephalon (5%); and pons (8%). Two areas decreased LCGU during AVP-BR: auditory cortex (-8%) and hippocampus (-11%). AVP-BR exhibits distinct changes in LCGU vs BIC seizures

  5. Supraoptic oxytocin and vasopressin neurons function as glucose and metabolic sensors.

    Science.gov (United States)

    Song, Zhilin; Levin, Barry E; Stevens, Wanida; Sladek, Celia D

    2014-04-01

    Neurons in the supraoptic nuclei (SON) produce oxytocin and vasopressin and express insulin receptors (InsR) and glucokinase. Since oxytocin is an anorexigenic agent and glucokinase and InsR are hallmarks of cells that function as glucose and/or metabolic sensors, we evaluated the effect of glucose, insulin, and their downstream effector ATP-sensitive potassium (KATP) channels on calcium signaling in SON neurons and on oxytocin and vasopressin release from explants of the rat hypothalamo-neurohypophyseal system. We also evaluated the effect of blocking glucokinase and phosphatidylinositol 3 kinase (PI3K; mediates insulin-induced mobilization of glucose transporter, GLUT4) on responses to glucose and insulin. Glucose and insulin increased intracellular calcium ([Ca(2+)]i). The responses were glucokinase and PI3K dependent, respectively. Insulin and glucose alone increased vasopressin release (P glucose in the presence of insulin. The oxytocin (OT) and vasopressin (VP) responses to insulin+glucose were blocked by the glucokinase inhibitor alloxan (4 mM; P ≤ 0.002) and the PI3K inhibitor wortmannin (50 nM; OT: P = 0.03; VP: P ≤ 0.002). Inactivating K ATP channels with 200 nM glibenclamide increased oxytocin and vasopressin release (OT: P neurons functioning as glucose and "metabolic" sensors to participate in appetite regulation.

  6. Supraoptic oxytocin and vasopressin neurons function as glucose and metabolic sensors

    Science.gov (United States)

    Song, Zhilin; Levin, Barry E.; Stevens, Wanida

    2014-01-01

    Neurons in the supraoptic nuclei (SON) produce oxytocin and vasopressin and express insulin receptors (InsR) and glucokinase. Since oxytocin is an anorexigenic agent and glucokinase and InsR are hallmarks of cells that function as glucose and/or metabolic sensors, we evaluated the effect of glucose, insulin, and their downstream effector ATP-sensitive potassium (KATP) channels on calcium signaling in SON neurons and on oxytocin and vasopressin release from explants of the rat hypothalamo-neurohypophyseal system. We also evaluated the effect of blocking glucokinase and phosphatidylinositol 3 kinase (PI3K; mediates insulin-induced mobilization of glucose transporter, GLUT4) on responses to glucose and insulin. Glucose and insulin increased intracellular calcium ([Ca2+]i). The responses were glucokinase and PI3K dependent, respectively. Insulin and glucose alone increased vasopressin release (P glucose in the presence of insulin. The oxytocin (OT) and vasopressin (VP) responses to insulin+glucose were blocked by the glucokinase inhibitor alloxan (4 mM; P ≤ 0.002) and the PI3K inhibitor wortmannin (50 nM; OT: P = 0.03; VP: P ≤ 0.002). Inactivating KATP channels with 200 nM glibenclamide increased oxytocin and vasopressin release (OT: P neurons functioning as glucose and “metabolic” sensors to participate in appetite regulation. PMID:24477542

  7. Radiation and the hypothalamic-pituitary axis

    International Nuclear Information System (INIS)

    Littley, M.D.; Shalet, S.M.; Beardwell, C.G.

    1991-01-01

    This paper reports on radiation therapy which is an essential treatment in the management of many conditions. It is important to appreciate the high incidence of subsequent endocrine morbidity, however, if the hypothalamic pituitary region is within the radiation fields. This is very much more common with external radiation therapy than with other forms of radiation treatment. The dose and fractional of administered radiation are important determinants of the endocrine deficits, their time on onset, and severity. Irradiation of large volumes of brain and hypothalamus may increase the risk of hormonal abnormalities as may preceding surgery in the treatment of pituitary disease. The phenomena observed in children and adults illustrate that there may be damage to pituitary, hypothalamus, and higher centers. In patients who have received a significant radiation dose to the hypothalamic-pituitary region, regular follow-up is mandatory. In adults, surveillance will include pituitary function testing on an annual basis for at least 10 years. In children careful monitoring of growth and pubertal development and early treatment of radiation-induced GH deficiency are vital

  8. Functional variation in the arginine vasopressin 2 receptor as a modifier of human plasma von Willebrand factor levels

    DEFF Research Database (Denmark)

    Nossent, Anne Yaël; Robben, J H; Deen, P M T

    2010-01-01

    SUMMARY OBJECTIVES: Stimulation of arginine vasopressin 2 receptor (V2R) with arginine vasopressin (AVP) results in a rise in von Willebrand factor (VWF) and factor VIII plasma levels. We hypothesized that gain-of-function variations in the V2R gene (AVPR2) would lead to higher plasma levels of V...

  9. Plasma vasopressin levels in patients with right-sided heart dysfunction and chronic thromboembolic pulmonary hypertension (CTEPH).

    Science.gov (United States)

    Nguyen, Liem; Banks, Dalia; Manecke, Gerard; Shurter, Jesse; Schilling, Jan M; Patel, Hemal H; Madani, Michael M; Roth, David M

    2014-06-01

    Patients with left-sided heart dysfunction and volume overload often have associated elevations in vasopressin from neuroendocrine activation. The authors investigated perioperative levels of vasopressin in patients with isolated right-sided heart dysfunction from chronic thromboembolic pulmonary hypertension. Prospective, observational study. Single center, tertiary hospital. Patients with chronic thromboembolic pulmonary hypertension undergoing pulmonary thromboendarterectomy. Vasopressin levels were measured in 22 patients during the perioperative period. Vasopressin was undetectable in 8/22 patients at baseline. As a group, vasopressin levels at baseline and after induction of anesthesia were 0.8 pg/mL (median; 0.5-1.5, interquartile range of 25% and 75%) and 0.7 pg/mL (median; 0.5-1.4, interquartile range of 25% and 75%), respectively. During cardiopulmonary bypass (CPB), vasopressin increased to 13.9 pg/mL (median; 6.7-19.9, interquartile range of 25% and 75%). Vasopressin remained elevated after deep hypothermic circulatory arrest (DHCA) at 10.5 pg/mL (median; 6.5-19.9 interquartile range of 25% and 75%) and after CPB at 19.9 pg/mL (median; 11.1-19.9 interquartile range of 25% and 75%). Vasopressin levels in PTE patients are in the low-to-normal range at baseline and may be a clinically relevant issue in the hemodynamic management of PTE. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. An ultrastructural analysis of the effects of ethanol self-administration on the hypothalamic paraventricular nucleus in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Vanessa Anne Jimenez

    2015-07-01

    Full Text Available A bidirectional relationship between stress and alcohol exists whereby stressful events are comorbid with problematic alcohol use and prolonged alcohol exposure results in adaptations of the physiological stress response. Endocrine response to stress is initiated in the hypothalamic paraventricular nucleus (PVN with the synthesis and release of corticotropin-releasing hormone (CRH and arginine-vasopressin (AVP. Alterations in CRH and AVP following long-term alcohol exposure in rodents is well demonstrated, however little is known about the response to alcohol in primates or the mechanisms of adaptation. We hypothesized that long-term alcohol self-administration in nonhuman primates would lead to ultrastructural changes in the PVN underlying adaptation to chronic alcohol. Double-label immunogold electron microscopy was used to measure presynaptic GABA and glutamate density within synaptic terminals contacting CRH- and AVP-immunoreactive dendrites. Additionally, pituitary-adrenal hormones (ACTH, cortisol, DHEA-s and aldosterone under two conditions (low and mild stress were compared before and after self-administration. All hormones were elevated in response to the mild stressor independent of alcohol consumption. The presynaptic glutamate density in recurrent (i.e., intra-hypothalamic CRH terminals was highly related to alcohol intake, and may be a permissive factor in increased drinking due to stress. Conversely, glutamate density within recurrent AVP terminals showed a trend-level increase following alcohol, but was not related to average daily consumption. Glutamate density in non-recurrent AVP terminals was related to aldosterone under the low stress condition while GABAergic density in this terminal population was related to water consumption. The results reveal distinct populations of presynaptic terminals whose glutamatergic or GABAergic density were uniquely related to water and alcohol consumption and circulating hormones.

  11. High salt intake enhances swim stress-induced PVN vasopressin cell activation and active stress coping.

    Science.gov (United States)

    Mitchell, N C; Gilman, T L; Daws, L C; Toney, G M

    2018-07-01

    Stress contributes to many psychiatric disorders; however, responsivity to stressors can vary depending on previous or current stress exposure. Relatively innocuous heterotypic (differing in type) stressors can summate to result in exaggerated neuronal and behavioral responses. Here we investigated the ability of prior high dietary sodium chloride (salt) intake, a dehydrating osmotic stressor, to enhance neuronal and behavioral responses of mice to an acute psychogenic swim stress (SS). Further, we evaluated the contribution of the osmo-regulatory stress-related neuropeptide arginine vasopressin (VP) in the hypothalamic paraventricular nucleus (PVN), one of only a few brain regions that synthesize VP. The purpose of this study was to determine the impact of high dietary salt intake on responsivity to heterotypic stress and the potential contribution of VPergic-mediated neuronal activity on high salt-induced stress modulation, thereby providing insight into how dietary (homeostatic) and environmental (psychogenic) stressors might interact to facilitate psychiatric disorder vulnerability. Salt loading (SL) with 4% saline for 7 days was used to dehydrate and osmotically stress mice prior to exposure to an acute SS. Fluid intake and hematological measurements were taken to quantify osmotic dehydration, and serum corticosterone levels were measured to index stress axis activation. Immunohistochemistry (IHC) was used to stain for the immediate early gene product c-Fos to quantify effects of SL on SS-induced activation of neurons in the PVN and extended amygdala - brain regions that are synaptically connected and implicated in responding to osmotic stress and in modulation of SS behavior, respectively. Lastly, the role of VPergic PVN neurons and VP type 1 receptor (V1R) activity in the amygdala in mediating effects of SL on SS behavior was evaluated by quantifying c-Fos activation of VPergic PVN neurons and, in functional experiments, by nano-injecting the V1R selective

  12. The relationship of radioimmunoassay to bioassay: In vitro studies with synthetic lysine vasopressin in aqueous solution inactivated by heat

    International Nuclear Information System (INIS)

    Loeve Lemboel, H.

    1978-01-01

    The relationship of radioimmunoassay to pressor assay and antidiuretic assay was investigated in a simple in vitro system of synthetic lysine vasopressin in aqueous solution inactivated by heating at 100 deg C for 9, 18, 27, 36, 54 and 72 h. An apparent dissociation between radioimmunoassay and bioassay was demonstrated, with biological activity being lost more rapidly than immunological activity. The half-times were 32 h for radioimmunoassay, 23 h for antidiuretic assay and 22 h for pressor assay. However, ion-exchange chromatography showed immunological heterogeneity but biological homogeneity of the lysine vasopressin used, and indicated that the presence of impurities in the vasopressin might to some extent explain the discrepancy between assay results. Synthetic arginine vasopressin and arginine vasopressin of pituitary origin showed a similar immunological heterogeneity by ion-exchange chromatography. (author)

  13. The hypothalamic-pituitary-adrenal axis: what can it tell us about stressors?

    Science.gov (United States)

    Armario, Antonio

    2006-10-01

    The hypothalamic-pituitary-adrenal (HPA) axis is an extremely sensitive physiological system whose activation, with the consequent release of ACTH and glucocorticoids, is triggered by a wide range of psychological experiences and physiological perturbations (stressors). The HPA axis is also activated by a high number of pharmacological agents that markedly differ in structure and function, although the precise mechanisms remain in most cases unknown. Activation of the HPA axis is the consequence of the convergence of stimulatory inputs from different brain regions into the paraventricular nucleus of the hypothalamus (PVN), where the most important ACTH secretagogues (corticotrophin releasing factor, CRF, and arginin-vasopressin, AVP) are formed. Plasma levels of ACTH and corticosterone (the latter under more restricted conditions), are considered as good markers of stress for three main reasons: (a) their plasma levels are proportional to the intensity of emotional and systemic stressors, (b) daily repeated exposure to a stressor usually resulted in reduced ACTH response to the same stressor, that is termed adaptation or habituation; and (c) chronic exposure to stressful situations results in tonic changes in the HPA axis that can be used as indices of the accumulative impact of these situations. These changes can be evaluated under resting conditions (i.e. adrenal weight, CRF and AVP gene expression in the PVN) or after some challenges (administration of CRF, ACTH or dexamethasone) that are classical endocrinological tests. There is also evidence that the activation of the HPA axis may also reflect subtle changes in the characteristics of the stressful situations (unpredictability, lack of control, omission of expected rewards, presence of conspecifics), although this is a topic that requires further studies.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Radioimmunoassay of plasma vasopressin. Technique and applicaton to some clinical cases

    International Nuclear Information System (INIS)

    Granier, Francoise.

    1978-01-01

    The object of this work was to develop a sensitive and reliable radioimmunological determination of plasma vasopressin for routine use. Part one is devoted to an outline of the physiological aspects of antidiuretic hormone with emphasis on the vasopressin regulation and secretion mechanisms, especially osmotic regulation. Part two describes our analysis technique by successive stages and gives, for each point considered, a comparative review of the methods described in the literature. Part three reports our results obtained on normal subjects during dehydration tests and in some pathological cases. Our radioimmunoassay is similar to that of Robertson. In 2 observations of diabetes insipidus no detectable amount of vasopressin was measured in contradiction with the results obtained by most authors. On the whole our purpose has been fulfilled. However this work contains inadequacies which are underlined and will have to be corrected in later studies [fr

  16. Vasopressin-induced changes in splanchnic blood flow and hepatic and portal venous pressures in liver resection.

    Science.gov (United States)

    Bown, L Sand; Ricksten, S-E; Houltz, E; Einarsson, H; Söndergaard, S; Rizell, M; Lundin, S

    2016-05-01

    To minimize blood loss during hepatic surgery, various methods are used to reduce pressure and flow within the hepato-splanchnic circulation. In this study, the effect of low- to moderate doses of vasopressin, a potent splanchnic vasoconstrictor, on changes in portal and hepatic venous pressures and splanchnic and hepato-splanchnic blood flows were assessed in elective liver resection surgery. Twelve patients were studied. Cardiac output (CO), stroke volume (SV), mean arterial (MAP), central venous (CVP), portal venous (PVP) and hepatic venous pressures (HVP) were measured, intraoperatively, at baseline and during vasopressin infusion at two infusion rates (2.4 and 4.8 U/h). From arterial and venous blood gases, the portal (splanchnic) and hepato-splanchnic blood flow changes were calculated, using Fick's equation. CO, SV, MAP and CVP increased slightly, but significantly, while systemic vascular resistance and heart rate remained unchanged at the highest infusion rate of vasopressin. PVP was not affected by vasopressin, while HVP increased slightly. Vasopressin infusion at 2.4 and 4.8 U/h reduced portal blood flow (-26% and -37%, respectively) and to a lesser extent hepato-splanchnic blood flow (-9% and -14%, respectively). The arterial-portal vein lactate gradient was not significantly affected by vasopressin. Postoperative serum creatinine was not affected by vasopressin. Short-term low to moderate infusion rates of vasopressin induced a splanchnic vasoconstriction without metabolic signs of splanchnic hypoperfusion or subsequent renal impairment. Vasopressin caused a centralization of blood volume and increased cardiac output. Vasopressin does not lower portal or hepatic venous pressures in this clinical setting. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  17. Restoration of peripheral V2 receptor vasopressin signaling fails to correct behavioral changes in Brattleboro rats.

    Science.gov (United States)

    Balázsfi, Diána; Pintér, Ottó; Klausz, Barbara; Kovács, Krisztina B; Fodor, Anna; Török, Bibiána; Engelmann, Mario; Zelena, Dóra

    2015-01-01

    Beside its hormonal function in salt and water homeostasis, vasopressin released into distinct brain areas plays a crucial role in stress-related behavior resulting in the enhancement of an anxious/depressive-like state. We aimed to investigate whether correction of the peripheral symptoms of congenital absence of AVP also corrects the behavioral alterations in AVP-deficient Brattleboro rats. Wild type (WT) and vasopressin-deficient (KO) male Brattleboro rats were tested. Half of the KO animals were treated by desmopressin (V2-receptor agonist) via osmotic minipump (subcutaneous) to eliminate the peripheral symptoms of vasopressin-deficiency. Anxiety was studied by elevated plus maze (EPM), defensive withdrawal (DW) and marble burying (MB) tests, while depressive-like changes were monitored in forced swimming (FS) and anhedonia by sucrose preference test. Cell activity was examined in septum and amygdala by c-Fos immunohistochemistry after 10 min FS. KO rats spent more time in the open arm of the EPM, spent less time at the periphery of DW and showed less burying behavior in MB suggesting a reduced anxiety state. KO animals showed less floating behavior during FS revealing a less depressive phenotype. Desmopressin treatment compensated the peripheral effects of vasopressin-deficiency without a significant influence on the behavior. The FS-induced c-Fos immunoreactivity in the medial amygdala was different in WT and KO rats, with almost identical levels in KO and desmopressin treated animals. There were no differences in central and basolateral amygdala as well as in lateral septum. Our data confirmed the role of vasopressin in the development of affective disorders through central mechanisms. The involvement of the medial amygdala in the behavioral alterations of vasopressin deficient animals deserves further attention. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Neural injury after use of vasopressin and adrenaline during porcine cardiopulmonary resuscitation.

    Science.gov (United States)

    Halvorsen, Peter; Sharma, Hari Shanker; Basu, Samar; Wiklund, Lars

    2015-03-01

    Our aim was to investigate cerebral and cardiac tissue injury subsequent to use of vasopressin and adrenaline in combination compared with vasopressin alone during cardiopulmonary resuscitation (CPR). In a randomized, prospective, laboratory animal study 28 anesthetized piglets were subject to a 12-min untreated cardiac arrest and subsequent CPR. After 1 min of CPR, 10 of the piglets received 0.4 U/kg of arg(8)-vasopressin (V group), and 10 piglets received 0.4 U/kg of arg(8)-vasopressin, 1 min later followed by 20 µg/kg body weight of adrenaline, and another 1 min later continuous administration (10 µg/kg/min) of adrenaline (VA group). After 8 min of CPR, the piglets were defibrillated and monitored for another 3 h. Then they were killed and the brain immediately removed pending histological analysis. During CPR, the VA group had higher mean blood pressure and cerebral cortical blood flow (CCBF) but similar coronary perfusion pressure. After restoration of spontaneous circulation there was no difference in the pressure variables, but CCBF tended to be (36% ± 16%) higher in the V group. Neuronal injury and signs of a disrupted blood-brain barrier (BBB) were greater, 20% ± 4% and 21% ± 4%, respectively, in the VA group. In a background study of repeated single doses of adrenaline every third minute after 5 min arrest but otherwise the same protocol, histological measurements showed even worse neural injury and disruption of the BBB. Combined use of vasopressin and adrenaline caused greater signs of cerebral and cardiac injury than use of vasopressin alone during experimental cardiopulmonary resuscitation.

  19. Attenuated stress response to acute restraint and forced swimming stress in arginine vasopressin 1b receptor subtype (Avpr1b) receptor knockout mice and wild-type mice treated with a novel Avpr1b receptor antagonist.

    Science.gov (United States)

    Roper, J A; Craighead, M; O'Carroll, A-M; Lolait, S J

    2010-11-01

    Arginine vasopressin (AVP) synthesised in the parvocellular region of the hypothalamic paraventricular nucleus and released into the pituitary portal vessels acts on the 1b receptor subtype (Avpr1b) present in anterior pituitary corticotrophs to modulate the release of adrenocorticotrophic hormone (ACTH). Corticotrophin-releasing hormone is considered the major drive behind ACTH release; however, its action is augmented synergistically by AVP. To determine the extent of vasopressinergic influence in the hypothalamic-pituitary-adrenal axis response to restraint and forced swimming stress, we compared the stress hormone levels [plasma ACTH in both stressors and corticosterone (CORT) in restraint stress only] following acute stress in mutant Avpr1b knockout (KO) mice compared to their wild-type controls following the administration of a novel Avpr1b antagonist. Restraint and forced swimming stress-induced increases in plasma ACTH were significantly diminished in mice lacking a functional Avpr1b and in wild-type mice that had been pre-treated with Avpr1b antagonist. A corresponding decrease in plasma CORT levels was also observed in acute restraint-stressed knockout male mice, and in Avpr1b-antagonist-treated male wild-type mice. By contrast, plasma CORT levels were not reduced in acutely restraint-stressed female knockout animals, or in female wild-type animals pre-treated with Avpr1b antagonist. These results demonstrate that pharmacological antagonism or inactivation of Avpr1b causes a reduction in the hypothalamic-pituitary-adrenal (HPA) axis response, particularly ACTH, to acute restraint and forced swimming stress, and show that Avpr1b knockout mice constitute a model by which to study the contribution of Avpr1b to the HPA axis response to acute stressors. © 2010 The Authors. Journal of Neuroendocrinology © 2010 Blackwell Publishing Ltd.

  20. Central vasopressin V1a receptors modulate neural processing in mothers facing intruder threat to pups

    OpenAIRE

    Caffrey, Martha K.; Nephew, Benjamin C.; Febo, Marcelo

    2009-01-01

    Vasopressin V1a receptors in the rat brain have been studied for their role in modulating aggression and anxiety. In the current study blood-oxygen-level-dependent (BOLD) functional MRI was used to test whether V1a receptors modulate neural processing in the maternal brain when dams are exposed to a male intruder. Primiparous females were given an intracerebroventricular (ICV) injection of vehicle or V1a receptor antagonist ([deamino-Pen1, O-Me-Try, Arg8]-Vasopressin, 125 ng/10 μL) 90-120 min...

  1. Arginine vasopressin stimulates phosphoinositide turnover in an enriched rat Leydig cell preparation

    DEFF Research Database (Denmark)

    Nielsen, J.R.; Hansen, Harald S.; Jensen, B.

    1989-01-01

    An enriched rat Leydig cell preparation was preincubated with [C]arachidonic acid. Stimulation of the cells with arginine vasopressin (AVP) (1 µM) for 2 min caused a significant increase in labelled phosphatidic acid and a significant fall in radioactivity in phosphatidylinositol and phosphatidyl......An enriched rat Leydig cell preparation was preincubated with [C]arachidonic acid. Stimulation of the cells with arginine vasopressin (AVP) (1 µM) for 2 min caused a significant increase in labelled phosphatidic acid and a significant fall in radioactivity in phosphatidylinositol...

  2. Endogenous Oxytocin, Vasopressin, and Aggression in Domestic Dogs

    Directory of Open Access Journals (Sweden)

    Evan L. MacLean

    2017-09-01

    Full Text Available Aggressive behavior in dogs poses public health and animal welfare concerns, however the biological mechanisms regulating dog aggression are not well understood. We investigated the relationships between endogenous plasma oxytocin (OT and vasopressin (AVP—neuropeptides that have been linked to affiliative and aggressive behavior in other mammalian species—and aggression in domestic dogs. We first validated enzyme-linked immunosorbent assays (ELISAs for the measurement of free (unbound and total (free + bound OT and AVP in dog plasma. In Experiment 1 we evaluated behavioral and neuroendocrine differences between a population of pet dogs with a history of chronic aggression toward conspecifics and a matched control group. Dogs with a history of aggression exhibited more aggressive behavior during simulated encounters with conspecifics, and had lower free, but higher total plasma AVP than matched controls, but there were no group differences for OT. In Experiment 2 we compared OT and AVP concentrations between pet dogs and a population of assistance dogs that have been bred for affiliative and non-aggressive temperaments, and investigated neuroendocrine predictors of individual differences in social behavior within the assistance dog population. Compared to pet dogs, assistance dogs had higher free and total OT, but there were no differences in either measure for AVP. Within the assistance dog population, dogs who behaved more aggressively toward a threatening stranger had higher total AVP than dogs who did not. Collectively these data suggest that endogenous OT and AVP may play critical roles in shaping dog social behavior, including aspects of both affiliation and aggression.

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

    Science.gov (United States)

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

    2016-05-20

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

  4. Hypothalamic inflammation: a double-edged sword to nutritional diseases

    Science.gov (United States)

    Cai, Dongsheng; Liu, Tiewen

    2015-01-01

    The hypothalamus is one of the master regulators of various physiological processes, including energy balance and nutrient metabolism. These regulatory functions are mediated by discrete hypothalamic regions that integrate metabolic sensing with neuroendocrine and neural controls of systemic physiology. Neurons and non-neuronal cells in these hypothalamic regions act supportively to execute metabolic regulations. Under conditions of brain and hypothalamic inflammation, which may result from overnutrition-induced intracellular stresses or disease-associated systemic inflammatory factors, extracellular and intracellular environments of hypothalamic cells are disrupted, leading to central metabolic dysregulations and various diseases. Recent research has begun to elucidate the effects of hypothalamic inflammation in causing diverse components of metabolic syndrome leading to diabetes and cardiovascular disease. These new understandings have provocatively expanded previous knowledge on the cachectic roles of brain inflammatory response in diseases, such as infections and cancers. This review describes the molecular and cellular characteristics of hypothalamic inflammation in metabolic syndrome and related diseases as opposed to cachectic diseases, and also discusses concepts and potential applications of inhibiting central/hypothalamic inflammation to treat nutritional diseases. PMID:22417140

  5. Hypothalamic hamartoma: is the epileptogenic zone always hypothalamic? Arguments for independent (third stage) secondary epileptogenesis.

    Science.gov (United States)

    Scholly, Julia; Valenti, Maria-Paola; Staack, Anke M; Strobl, Karl; Bast, Thomas; Kehrli, Pierre; Steinhoff, Bernhard J; Hirsch, Edouard

    2013-12-01

    Gelastic seizures associated with hypothalamic hamartomas (HHs) are a clinicoradiologic syndrome presenting with a variety of symptoms, including pharmacoresistant epilepsy with multiple seizure types, electroencephalography (EEG) abnormalities, precocious puberty, behavioral disturbances, and progressive cognitive deterioration. Surgery in adults provides seizure freedom in only one third of patients. The poor results of epilepsy surgery could be explained by an extrahypothalamic epileptogenic zone. The existence of an independent, secondary epileptogenic area with persistent seizures after resection of the presumably primary lesion supports the concept of a "hypothalamic plus" epilepsy. "Hypothalamic plus" epilepsy could be related to either an extrahypothalamic structural lesion (visible on magnetic resonance imaging [MRI] or on neuropathology) or if the former is absent, to a functional alteration with enhanced epileptogenic properties due to a process termed secondary epileptogenesis. We report two patients with gelastic seizures with HH (gelastic seizures isolated or associated with dyscognitive seizures of temporal origin). Both patients underwent two-step surgery: first an endoscopic resection of the HH, followed at a later time by temporal lobectomy. Both patients became seizure-free only after the temporal lobectomy. In both cases, neuropathology failed to demonstrate a significant structural lesion in the temporal lobe. To our knowledge, for the first time, these two cases suggest the existence of independent secondary epileptogenesis in humans. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  6. Risk factors for mortality caused by hypothalamic obesity in children with hypothalamic tumours.

    Science.gov (United States)

    Haliloglu, B; Atay, Z; Guran, T; Abalı, S; Bas, S; Turan, S; Bereket, A

    2016-10-01

    Hypothalamic obesity (HyOb) is a common complication of childhood hypothalamic tumours. Patients with HyOb probably have a higher mortality rate than those with other types of obesity due in many cases to obstructive sleep apnoea/hypoventilation. To identify predictive factors for mortality caused by HyOb in children. Twenty children with HyOb secondary to hypothalamic tumours that were followed-up for ≥3 years and aged 6 years at diagnosis (3.71 ± 1.96 vs. 0.83 ± 0.73, P  1 SDS after 6 months of therapy (RR: 8.4, P obesity-related mortality rates were higher in the patients aged  0.05). The mortality rate was also 3.7-fold higher in the patients with a maximum BMI SDS ≥ 3 at any time during the first 3 years after therapy(P > 0.05). An increase in BMI SDS after 6 months of therapy was observed to be a risk factor for mortality caused by HyOb. In addition, age obesity is required. © 2015 World Obesity.

  7. Effects of experimentally induced hyperthyroidism on central hypothalamic-pituitary-adrenal axis function in rats: in vitro and in situ studies.

    Science.gov (United States)

    Johnson, Elizabeth O; Calogero, Aldo E; Konstandi, Maria; Kamilaris, Themis C; La Vignera, Sandro; Vignera, Sandro La; Chrousos, George P

    2013-06-01

    Hyperthyroidism is associated with hypercorticosteronemia, although the locus that is principally responsible for the hypercorticosteronism remains unclear. The purpose of this study was to assess the effects of hyperthyroidism on the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis, to identify the locus in the HPA axis that is principally affected, and address the time-dependent effects of alterations in thyroid status. The functional integrity of each component of the HPA axis was examined in vitro and in situ in sham-thyroidectomized male Sprague-Dawley rats given placebo or in thyroidectomized rats given pharmacological dose (50 μg) of thyroxin for 7 or 60 days. Basal plasma corticosterone and corticosterone binding globulin (CBG) concentrations were significantly increased in short- and long-term hyperthyroid rats, and by 60 days. Basal plasma ACTH levels were similar to controls. Both hypothalamic CRH content and the magnitude of KCL- and arginine vasopressin (AVP)-induced CRH release from hypothalamic culture were increased in long-term hyperthyroid rats. There was a significant increase in the content of both ACTH and β-endorphin in the anterior pituitaries of both short- and long-term hyperthyroid animals. Short-term hyperthyroid rats showed a significant increase in basal POMC mRNA expression in the anterior pituitary, and chronically hyperthyroid animals showed increased stress-induced POMC mRNA expression. Adrenal cultures taken from short-term hyperthyroid rats responded to exogenous ACTH with an exaggerated corticosterone response, while those taken from 60-day hyperthyroid animals showed responses similar to controls. The findings show that hyperthyroidism is associated with hypercorticosteronemia and HPA axis dysfunction that becomes more pronounced as the duration of hyperthyroidism increases. The evidence suggests that experimentally induced hyperthyroidism is associated with central hyperactivity of the HPA axis.

  8. Treatment of functional hypothalamic amenorrhea with hypnotherapy.

    Science.gov (United States)

    Tschugguel, Walter; Berga, Sarah L

    2003-10-01

    To determine the effects of hypnotherapy on resumption of menstruation in patients with functional hypothalamic amenorrhea (FHA). Uncontrolled clinical study. Academic clinical care center. Twelve consecutive women with FHA were selected. A single 45- to 70-minute session of hypnotherapy was administered, and patients were observed for 12 weeks. Patients were asked whether or not menstruation resumed and whether or not well-being and self-confidence changed. Within 12 weeks, 9 out of 12 patients (75%) resumed menstruation. All of the patients, including those who did not menstruate, reported several beneficial side effects such as increased general well-being and increased self-confidence. Hypnotherapy could be an efficacious and time-saving treatment option that also avoids the pitfalls of pharmacological modalities for women with FHA.

  9. Use of cognitive behavior therapy for functional hypothalamic amenorrhea.

    Science.gov (United States)

    Berga, Sarah L; Loucks, Tammy L

    2006-12-01

    Behaviors that chronically activate the hypothalamic-pituitary-adrenal (HPA) axis and/or suppress the hypothalamic-pituitary-thyroidal (HPT) axis disrupt the hypothalamic-pituitary-gonadal axis in women and men. Individuals with functional hypothalamic hypogonadism typically engage in a combination of behaviors that concomitantly heighten psychogenic stress and increase energy demand. Although it is not widely recognized clinically, functional forms of hypothalamic hypogonadism are more than an isolated disruption of gonadotropin-releasing hormone (GnRH) drive and reproductive compromise. Indeed, women with functional hypothalamic amenorrhea display a constellation of neuroendocrine aberrations that reflect allostatic adjustments to chronic stress. Given these considerations, we have suggested that complete neuroendocrine recovery would involve more than reproductive recovery. Hormone replacement strategies have limited benefit because they do not ameliorate allostatic endocrine adjustments, particularly the activation of the adrenal and the suppression of the thyroidal axes. Indeed, the rationale for the use of sex steroid replacement is based on the erroneous assumption that functional forms of hypothalamic hypogonadism represent only or primarily an alteration in the hypothalamic-pituitary-gonadal axis. Potential health consequences of functional hypothalamic amenorrhea, often termed stress-induced anovulation, may include an increased risk of cardiovascular disease, osteoporosis, depression, other psychiatric conditions, and dementia. Although fertility can be restored with exogenous administration of gonadotropins or pulsatile GnRH, fertility management alone will not permit recovery of the adrenal and thyroidal axes. Initiating pregnancy with exogenous means without reversing the hormonal milieu induced by chronic stress may increase the likelihood of poor obstetrical, fetal, or neonatal outcomes. In contrast, behavioral and psychological interventions that

  10. Hypothalamic hamartoma associated with precocious puberty: Case report

    International Nuclear Information System (INIS)

    Bae, Won Kyong; Kim, Pyo Nuyn; Kim, Il Young; Lee, Byoung Ho; Lee, Kyeong Seok; Bae, Hack Gun; Yun, Il Gyu

    1989-01-01

    Hamartoma of the hypothalamic area is a well recognized cause of central precocious puberty. We report a case of histologically proven hypothalamic hamartoma in a 8 year old girl with precocious puberty. The CT showed an isodense, nonenhancing mass in suprasellar area, measuring 4.2 X 3.1 cm, which, to our knowledge, seems to be the largest one of the published cases. On MR imaging, the signal intensity of the mass was homogeneous and isointense relative to gray matter on T1-, and hyperintense on T2-weighted images. The clinical and radiologic findings of the published cases of hypothalamic hamartoma are reviewed

  11. Hypothalamic hamartoma associated with precocious puberty: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Won Kyong; Kim, Pyo Nuyn; Kim, Il Young; Lee, Byoung Ho; Lee, Kyeong Seok; Bae, Hack Gun; Yun, Il Gyu [Soonchunhyang University, Chonan Hospital, Chonan (Korea, Republic of)

    1989-12-15

    Hamartoma of the hypothalamic area is a well recognized cause of central precocious puberty. We report a case of histologically proven hypothalamic hamartoma in a 8 year old girl with precocious puberty. The CT showed an isodense, nonenhancing mass in suprasellar area, measuring 4.2 X 3.1 cm, which, to our knowledge, seems to be the largest one of the published cases. On MR imaging, the signal intensity of the mass was homogeneous and isointense relative to gray matter on T1-, and hyperintense on T2-weighted images. The clinical and radiologic findings of the published cases of hypothalamic hamartoma are reviewed.

  12. Indirect evidence for decreased hypothalamic somatostatinergic tone in anorexia nervosa

    DEFF Research Database (Denmark)

    Støving, R K; Andersen, M; Flyvbjerg, A

    2002-01-01

    in the central feeding mechanism in anorexia nervosa (AN). Peripheral administration of pyridostigmine (PD) minimizes the release of hypothalamic SRIH. DESIGN: To study the influence of hypothalamic somatostatinergic inhibition on the exaggerated somatotroph responsiveness to GHRH in patients with severe AN, two...... indirectly to greater SRIH withdrawal and greater GHRH release in anorexia nervosa. Moreover, hypothalamic SRIH activity seems to be inversely related to cortisol levels, indirectly supporting the hypothesis that SRIH and CRH neuronal activity are inversely related in anorexia nervosa. Leptin, which...... is believed to act on hypothalamic feeding mechanisms, seems to be positively related to SRIH activity. Finally, the present data demonstrate that the potentiating effect of pyridostigmine in anorexia nervosa is related to body mass index and increases upon weight gain, suggesting that the low...

  13. Delineating the regulation of energy homeostasis using hypothalamic cell models.

    Science.gov (United States)

    Wellhauser, Leigh; Gojska, Nicole M; Belsham, Denise D

    2015-01-01

    Attesting to its intimate peripheral connections, hypothalamic neurons integrate nutritional and hormonal cues to effectively manage energy homeostasis according to the overall status of the system. Extensive progress in the identification of essential transcriptional and post-translational mechanisms regulating the controlled expression and actions of hypothalamic neuropeptides has been identified through the use of animal and cell models. This review will introduce the basic techniques of hypothalamic investigation both in vivo and in vitro and will briefly highlight the key advantages and challenges of their use. Further emphasis will be place on the use of immortalized models of hypothalamic neurons for in vitro study of feeding regulation, with a particular focus on cell lines proving themselves most fruitful in deciphering fundamental basics of NPY/AgRP, Proglucagon, and POMC neuropeptide function. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Course and forecast of the hypothalamic pubertal syndrome

    International Nuclear Information System (INIS)

    Kayusheva, I.V.

    1987-01-01

    A total of 223 patients with the hypothalamic pubertal syndrome (HPS) were followed up for 1 to 22 years. The course of HPS was regressive, stable , recurrent or progressive and dependent on the initial depth and spread of hypothalamic lesion, repeated unfavourable hypothalamic exposures, and timely and regular treatment. HPS outcomes were followed up in 190 cases. The recovery was complete in 21.05%, obesity alone persisted in 10.53%, vegetovascular dystonia was persistent in 7.36%, and polycystic ovaries in 5.79%. Neuroendocrine hypothalamic syndrome was the most common (50.53%) HPS outcome. Hormone levels in blood were investigated using radioimmunoassay in patients with neuroendocrine form of HPS

  15. Amniotic oxytocin and vasopressin in relation to human fetal development and labour

    NARCIS (Netherlands)

    Oosterbaan, H. P.; Swaab, D. F.

    1989-01-01

    Previous experiments in rats revealed increased amniotic oxytocin (OXT) levels in the course of normal development and increased vasopressin (AVP) levels in retarded fetal growth. In order to see whether similar changes would also occur in human, OXT and AVP levels were determined in amniotic fluid,

  16. Diagnostic and Predictive Values of Thirst, Angiotensin II, and Vasopressin During Trauma Resuscitation

    Science.gov (United States)

    2010-09-01

    and plasma AVP and AT2 levels across a broader spectrum of hemorrhagic shock severity may be warranted. The authors wish to thank the medical, nursing ...301. 2. Olsson K. Central control of vasopressin release and thirst. Acta Paediatr Scand Suppl. 1983;305:36–9. Pr eh os p E m er g C ar e D ow nl oa

  17. Lateral septal vasopressin in rats : Role in social and object recognition?

    NARCIS (Netherlands)

    Everts, H.G J; Koolhaas, J.M.

    1997-01-01

    The capacity of male rats to remember familiar conspecifics is called social recognition. It is a form of short-term memory modulated by lateral septal (LS) vasopressin (VP). The specificity of this phenomenon was studied by examining whether recognition of previously investigated objects is also

  18. Salivary Oxytocin and Vasopressin Levels in Police Officers With and Without Post-Traumatic Stress Disorder

    NARCIS (Netherlands)

    Frijling, J. L.; van Zuiden, M.; Nawijn, L.; Koch, S. B. J.; Neumann, I. D.; Veltman, D. J.; Olff, M.

    2015-01-01

    Post-traumatic stress disorder (PTSD) is characterised by symptoms associated with maladaptive fear and stress responses, as well as with social detachment. The neuropeptides oxytocin (OT) and arginine vasopressin (AVP) have been associated with both regulating fear and neuroendocrine stress

  19. Urinary concentration does not exclusively rely on plasma vasopressin. A study between genders

    DEFF Research Database (Denmark)

    Graugaard-Jensen, Charlotte; Hvistendahl, Gitte M; Frøkiaer, Jørgen

    2014-01-01

    AimWe investigated the influence of gender on the diurnal regulation of urine production with special focus on vasopressin, oxytocin and prostaglandin E2. MethodsFifteen young women in mid-follicular phase and 22 young men (20-33years) were included. All participants underwent a 24-h circadian in...

  20. Decrease of extracellular taurine in the rat dorsal hippocampus after central nervous administration of vasopressin

    DEFF Research Database (Denmark)

    Brust, P; Christensen, Thomas; Diemer, Nils Henrik

    1992-01-01

    of the composition of the extracellular fluid. The concentrations of 16 amino acids were measured by HPLC in the perfusate samples. The level of taurine declined 20% in the right hippocampus during perfusion with vasopressin, whereas o-phosphoethanolamine decreased in both sides, the left 20% and the right 24...

  1. Arginine-vasopressin stimulates the formation of phosphatidic acid in rat Leydig cells

    DEFF Research Database (Denmark)

    Nielsen, J.R.; Hansen, Harald S.; Jensen, B.

    1987-01-01

    Arginine-vasopressin (AVP) stimulated the formation of labelled phosphatidic acid (PA) in [C]arachidonic acid-prelabelled rat Leydig cells. After addition of 10 M AVP [C]arachidonoylphosphatidic acid reached a maximum within 2 min. The increase was dose-dependent (10-10 M). No change in labelling...

  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. Mechanisms of inhibition of vasopressin release during moderate antiorthostatic posture change in humans

    DEFF Research Database (Denmark)

    Pump, B.; Gabrielsen, A.; Christensen, N.J.

    1999-01-01

    The hypothesis was tested that the carotid baroreceptor stimulation caused by a posture change from upright seated with legs horizontal (Seat) to supine (Sup) participates in the suppression of arginine vasopressin (AVP) release. Ten healthy males underwent this posture change for 30 min without...... decreased from 0.9 +/- 0.2 to 0.5 +/- 0.1 pg/ml (P posture...

  4. Oxytocin/vasopressin-like immunoreactivity is present in the nervous system of hydra

    DEFF Research Database (Denmark)

    Grimmelikhuijzen, C J; Dierickx, K; Boer, G J

    1982-01-01

    Nerve cells have been found in hydra, which react with antisera to oxytocin, vasopressin and mesotocin. These nerve cells have a high density in the ectoderm of basal disk and tentacles and lower density in the ectoderm of peduncle, gastric region and hypostome. A very small number of nerve cells...

  5. Purification and characterization of the V1 vasopressin receptor from rat liver

    International Nuclear Information System (INIS)

    Fishman, J.B.; Dickey, B.F.; Attisano, C.; Fine, R.E.

    1987-01-01

    The rat liver V1 vasopressin receptor was purified approximately 21,000-fold from rat liver microsomes. The receptor was solubilized from membranes using the zwitterionic detergent CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate). Since the V1 receptor loses its ability to bind ligand when solubilized, the authors devised a liposome reconstitution system to assay vasopressin binding activity during purification. The purified receptor exhibits a K/sub d/ of 6 nm, when, prior to solubilization, the membranes were exposed to 1 μm vasopressin. This resulted in the association of a pertussis-toxin insensitive guanine-nucleotide binding protein with the receptor during most of the purification procedure. The authors are further characterizing the V1-associated G-proteins. In the absence of this association, the receptor has a K/sub d/ of 30 nM. Crosslinking of 125 I-vasopressin to a partially purified preparation of receptor demonstrated that the receptor had a molecular weight of approximately 68,000 under reducing conditions, and 58,000 under non-reducing conditions. The purification procedure may prove useful in purifying a number of small peptide hormone receptors (e.g., bradykinin, angiotensin II) and perhaps their associated G-proteins as well

  6. Leptin is an effective treatment for hypothalamic amenorrhea

    OpenAIRE

    Chou, Sharon H.; Chamberland, John P.; Liu, Xiaowen; Matarese, Giuseppe; Gao, Chuanyun; Stefanakis, Rianna; Brinkoetter, Mary T.; Gong, Huizhi; Arampatzi, Kalliopi; Mantzoros, Christos S.

    2011-01-01

    Hypothalamic amenorrhea (HA) is associated with dysfunction of the hypothalamic-pituitary-peripheral endocrine axes, leading to infertility and bone loss, and usually is caused by chronic energy deficiency secondary to strenuous exercise and/or decreased food intake. Energy deficiency also leads to hypoleptinemia, which has been proposed, on the basis of observational studies as well as an open-label study, to mediate the neuroendocrine abnormalities associated with this condition. To prove d...

  7. Bilateral LMAN lesions cancel differences in HVC neuronal recruitment induced by unilateral syringeal denervation. Lateral magnocellular nucleus of the anterior neostriatum.

    Science.gov (United States)

    Wilbrecht, L; Petersen, T; Nottebohm, F

    2002-12-01

    Twenty-six-day-old male zebra finches received (1) unilateral section of their tracheosyringeal nerve, (2) bilateral lesions of the lateral magnocellular nucleus of the anterior neostriatum (LMAN), and (3) both operations. All birds were kept with an adult, singing male as a tutor until day 65. Tracheo-syringeal nerve-cut birds were able to imitate this model, but LMAN-lesioned birds were not. Bromodeoxyuridine, a marker of cell division, was injected intramuscularly during post-hatching days 61-65 and all birds were killed at 91 days of age. The number of bromodeoxyuridine+ neurons in the high vocal center of the tracheosyringeal-cut birds was twice as high in the intact as in the nerve cut side. This asymmetry disappeared when nerve section was combined with bilateral LMAN lesions. The latter operation, by itself, had no effect on new neuron counts. We suggest that the single nerve cut produced a hemispheric asymmetry in learning, reflected in new neuron recruitment, which disappeared when LMAN lesions blocked learning.

  8. [Influence of preventive use of vasopressin tannate on diabetes insipidus and serum sodium at the early postoperation of craniopharyngioma].

    Science.gov (United States)

    Xiong, Tao; Wanggou, Siyi; Li, Xuejun; Liu, Qing; Jiang, Xingjun; Peng, Zefeng; Yuan, Xianrui

    2016-10-28

    To explore the influence of preventive use of vasopressin tannate on diabetes insipidus and serum sodium at the early postoperation of craniopharyngioma.
 Methods: The data of 83 patients, who underwent unilateral sub-frontal approach resection of craniopharyngioma between 2010 and 2014 by the same senior neurosurgeon, were retrospectively analyzed. The patients were divided into a vasopressin tannate group (used group) and a control group. The diabetes insipidus and serum sodium changes were compared between the two groups.
 Results: Compared with the control group, the incidence of diabetes insipidus decreased at the early postoperation in the vasopressin tannate group (Pcraniopharyngioma.

  9. Functional hypothalamic amenorrhea: hypoleptinemia and disordered eating.

    Science.gov (United States)

    Warren, M P; Voussoughian, F; Geer, E B; Hyle, E P; Adberg, C L; Ramos, R H

    1999-03-01

    Because the exact etiology of functional, or idiopathic, hypothalamic amenorrhea (FHA) is still unknown, FHA remains a diagnosis of exclusion. The disorder may be stress induced. However, mounting evidence points to a metabolic/nutritional insult that may be the primary causal factor. We explored the thyroid, hormonal, dietary, behavior, and leptin changes that occur in FHA, as they provide a clue to the etiology of this disorder. Fourteen cycling control and amenorrheic nonathletic subjects were matched for age, weight, and height. The amenorrheic subjects denied eating disorders; only after further, detailed questioning did we uncover a higher incidence of anorexia and bulimia in this group. The amenorrheic subjects demonstrated scores of abnormal eating twice those found in normal subjects (P < 0.05), particularly bulimic type behavior (P < 0.01). They also expended more calories in aerobic activity per day and had higher fiber intakes (P < 0.05); lower body fat percentage (P < 0.05); and reduced levels of free T4 (P < 0.05), free T3 (P < 0.05), and total T4 (P < 0.05), without a significant change in rT3 or TSH. Cortisol averaged higher in the amenorrheics, but not significantly, whereas leptin values were significantly lower (P < 0.05). Bone mineral density was significantly lower in the wrist (P < 0.05), with a trend to lower BMD in the spine (P < 0.08). Scores of emotional distress and depression did not differ between groups. The alterations in eating patterns, leptin levels, and thyroid function present in subjects with FHA suggest altered nutritional status and the suppression of the hypothalamic-pituitary-thyroid axis or the alteration of feedback set-points in women with FHA. Both lower leptin and thyroid levels parallel changes seen with caloric restriction. Nutritional issues, particularly dysfunctional eating patterns and changes in thyroid metabolism, and/or leptin effects may also have a role in the metabolic signals suppressing GnRH secretion and

  10. Hypothalamic Circuits for Predation and Evasion.

    Science.gov (United States)

    Li, Yi; Zeng, Jiawei; Zhang, Juen; Yue, Chenyu; Zhong, Weixin; Liu, Zhixiang; Feng, Qiru; Luo, Minmin

    2018-02-21

    The interactions between predator and prey represent some of the most dramatic events in nature and constitute a matter of life and death for both sides. The hypothalamus has been implicated in driving predation and evasion; however, the exact hypothalamic neural circuits underlying these behaviors remain poorly defined. Here, we demonstrate that inhibitory and excitatory projections from the mouse lateral hypothalamus (LH) to the periaqueductal gray (PAG) in the midbrain drive, respectively, predation and evasion. LH GABA neurons were activated during predation. Optogenetically stimulating PAG-projecting LH GABA neurons drove strong predatory attack, and inhibiting these cells reversibly blocked predation. In contrast, LH glutamate neurons were activated during evasion. Stimulating PAG-projecting LH glutamate neurons drove evasion and inhibiting them impeded predictive evasion. Therefore, the seemingly opposite behaviors of predation and evasion are tightly regulated by two dissociable modular command systems within a single neural projection from the LH to the PAG. VIDEO ABSTRACT. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Hypothalamic digoxin, hemispheric chemical dominance, and creativity.

    Science.gov (United States)

    Kurup, Ravi Kumar; Kurup, Parameswara Achutha

    2003-04-01

    The human hypothalamus produces an endogenous membrane Na(+)-K+ ATPase inhibitor, digoxin, which regulates neuronal transmission. The digoxin status and neurotransmitter patterns were studied in creative and non-creative individuals, as well as in individuals with differing hemispheric dominance, in order to find out the role of cerebral dominance in this respect. The activity of HMG CoA reductase and serum levels of digoxin, magnesium, tryptophan catabolites, and tyrosine catabolites were measured in creative/non-creative individuals, and in individuals with differing hemispheric dominance. In creative individuals there was increased digoxin synthesis, decreased membrane Na(+)-K+ ATPase activity, increased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and decreased tyrosine catabolites (dopamine, noradrenaline, and morphine). The pattern in creative individuals correlated with right hemispheric dominance. In non-creative individuals there was decreased digoxin synthesis, increased membrane Na(+)-K+ ATPase activity, decreased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and increased tyrosine catabolites (dopamine, noradrenaline, and morphine). This pattern in non-creative individuals correlated with that obtained in left hemispheric chemical dominance. Hemispheric chemical dominance and hypothalamic digoxin could regulate the predisposition to creative tendency.

  12. Hypothalamic digoxin, hemispheric chemical dominance, and sleep.

    Science.gov (United States)

    Kurup, Ravi Kumar; Kurup, Parameswara Achutha

    2003-04-01

    The isoprenoid path way produces endogenous digoxin, a substance that can regulate neurotransmitter and amino acid transport. Digoxin synthesis and neurotransmitter patterns were assessed in individuals with chronic insomnia. The patterns were compared in those with right hemispheric and left hemispheric dominance. The activity of HMG GoA reductase and serum levels of digoxin, magnesium, tryptophan catabolites, and tyrosine catabolites were measured in individuals with chronic insomnia and in individuals with differing hemispheric dominance. Digoxin synthesis was increased with upregulated tryptophan catabolism (increased levels of serotonin, strychnine, and nicotine), and downregulated tyrosine catabolism (decreased levels of dopamine, noradrenaline, and morphine) in those with chronic insomnia and right hemispheric chemical dominance. Digoxin synthesis was reduced with downregulated tryptophan catabolism (decreased levels of serotonin, strychnine, and nicotine) and upregulated tyrosine catabolism (increased levels of dopamine, noradrenaline, and morphine) in those with normal sleep patterns and left hemispheric chemical dominance. Hypothalamic digoxin plays a central role in the regulation of sleep behavior. Hemispheric chemical dominance in relation to digoxin status is also crucial.

  13. Anomalous hypothalamic responses to humor in cataplexy.

    Directory of Open Access Journals (Sweden)

    Allan L Reiss

    2008-05-01

    Full Text Available Cataplexy is observed in a subset of patients with narcolepsy and affects approximately 1 in 2,000 persons. Cataplexy is most often triggered by strong emotions such as laughter, which can result in transient, yet debilitating, muscle atonia. The objective of this study was to examine the neural systems underlying humor processing in individuals with cataplexy.While undergoing functional Magnetic Resonance Imaging (fMRI, we showed ten narcolepsy-cataplexy patients and ten healthy controls humorous cartoons. In addition, we examined the brain activity of one subject while in a full-blown cataplectic attack. Behavioral results showed that participants with cataplexy rated significantly fewer humorous cartoons as funny compared to controls. Concurrent fMRI showed that patients, when compared to controls and in the absence of overt cataplexy symptoms, showed pronounced activity in the emotional network including the ventral striatum and hypothalamus while viewing humorous versus non-humorous cartoons. Increased activity was also observed in the right inferior frontal gyri--a core component of the inhibitory circuitry. In comparison, the one subject who experienced a cataplectic attack showed dramatic reductions in hypothalamic activity.These findings suggest an overdrive of the emotional circuitry and possible compensatory suppression by cortical inhibitory regions in cataplexy. Moreover, during cataplectic attacks, the hypothalamus is characterized by a marked decrease in activity similar to that observed during sleep. One possible explanation for these findings is an initial overdrive and compensatory shutdown of the hypothalamus resulting in full cataplectic symptoms.

  14. Diagnostic and therapeutic approach to hypothalamic amenorrhea.

    Science.gov (United States)

    Genazzani, Alessandro D; Ricchieri, Federica; Lanzoni, Chiara; Strucchi, Claudia; Jasonni, Valerio M

    2006-12-01

    Hypothalamic amenorrhea (HA) is a secondary amenorrhea with no evidence of endocrine/systemic causal factors, mainly related to various stressors affecting neuroendocrine control of the reproductive axis. In clinical practice, HA is mainly associated with metabolic, physical, or psychological stress. Stress is the adaptive response of our body through all its homeostatic systems, to external and/or internal stimuli that activate specific and nonspecific physiological pathways. HA occurs generally after severe stress conditions/situations such as dieting, heavy training, or intense emotional events, all situations that can induce amenorrhea with or without body weight loss and HA is a secondary amenorrhea with a diagnosis of exclusion. In fact, the diagnosis is essentially based on a good anamnestic investigation. It has to be investigated using the clinical history of the patient: occurrence of menarche, menstrual cyclicity, time and modality of amenorrhea, and it has to be exclude any endocrine disease or any metabolic (i.e., diabetes) and systemic disorders. It is necessary to identify any stress situation induced by loss, family or working problems, weight loss or eating disorders, or physical training or agonist activity. Peculiar, though not specific, endocrine investigations might be proposed but no absolute parameter can be proposed since HA is greatly dependent from individual response to stressors and/or the adaptive response to stress. This article tries to give insights into diagnosis and putative therapeutic strategies.

  15. Psychological correlates of functional hypothalamic amenorrhea.

    Science.gov (United States)

    Marcus, M D; Loucks, T L; Berga, S L

    2001-08-01

    To determine whether mood, attitudes, or symptoms of disordered eating discriminated women with functional hypothalamic amenorrhea (FHA) from those with organic causes of amenorrhea and eumenorrhea. Cross-sectional comparison of women with FHA, women with organic amenorrhea, and eumenorrheic control women. Clinical research center in an academic medical institution. Seventy-seven women > or =18 years old with time since menarche > or =5 and < or =25 years were recruited by advertisement. Ovulation was confirmed in eumenorrheic control women. Causes of anovulation were carefully documented in amenorrheic participants and LH pulse profiles were obtained to document the diagnosis of FHA. All participants were interviewed and completed questionnaires. Self-report measures of dysfunctional attitudes, coping styles, and symptoms of depression and eating disorders. Women with FHA reported more depressive symptoms and dysfunctional attitudes than did eumenorrheic women, but not significantly more than women with organic amenorrhea. However, women with FHA reported significantly more symptoms of disordered eating than did either anovulatory or ovulatory women. The findings are consistent with the hypothesis that FHA is precipitated by a combination of psychosocial stressors and metabolic challenge.

  16. Hypothalamic amenorrhea: from diagnosis to therapeutical approach.

    Science.gov (United States)

    Genazzani, A D; Chierchia, E; Santagni, S; Rattighieri, E; Farinetti, A; Lanzoni, C

    2010-05-01

    Among secondary amenorrheas, hypothalamic amenorrhea (HA) is the one with no evidence of endocrine/systemic causal factors. HA is mainly related to various stressors affecting neuroendocrine control of the reproductive axis. In clinical practice, HA is mainly associated with metabolic, physical, or psychological stress. Stress is the adaptive response of our body through all its homeostatic systems, to external and/or internal stimuli that activate specific and nonspecific physiological pathways. HA occurs generally after severe stressed conditions/situations such as dieting, heavy training, or intense emotional events, all situations that can induce amenorrhea with or without body weight loss and HA is a secondary amenorrhea with a diagnosis of exclusion. In fact, the diagnosis is essentially based on a good anamnestic investigation. It has to be investigated using the clinical history of the patient: occurrence of menarche, menstrual cyclicity, time and modality of amenorrhea, and it has to be excluded any endocrine disease or any metabolic (i.e., diabetes) and systemic disorders. It is necessary to identify any stressed situation induced by loss, family or working problems, weight loss or eating disorders, or physical training or agonist activity. Peculiar, though not specific, endocrine investigations might be proposed but no absolute parameter can be proposed since HA is greatly dependent from individual response to stressors and/or the adaptive response to stress. This chapter aims to give insights into diagnosis and putative therapeutic strategies. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  17. Hypothalamic digoxin, hemispheric chemical dominance, and spirituality.

    Science.gov (United States)

    Kurup, Ravi Kumar; Kurup, Parameswara Achutha

    2003-03-01

    The isoprenoid pathway was assessed in atheistic and spiritually inclined individuals. The pathway was also assessed in individuals with differing hemispheric dominance to assess whether hemispheric dominance has a correlation with spiritual and atheistic tendency. HMG CoA reductase activity, serum digoxin, RBC membrane Na(+)-K+ ATPase activity, serum magnesium, and tyrosine/tryptophan catabolic patterns were assessed in spiritual/atheistic individuals and in those differing hemispheric dominance. In spiritually-inclined individuals, there was increased digoxin synthesis, decreased membrane Na(+)-K+ ATPase activity, increased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and decreased tyrosine catabolites (dopamine, noradrenaline, and morphine). The pattern in spiritually-inclined individuals correlated with right hemispheric chemical dominance. In atheistic individuals there was decreased digoxin synthesis, increased membrane Na(+)-K+ ATPase activity, decreased tryptophan catabolities (serotonin, quinolinic acid, and nicotine), and increased tyrosine catabolites (dopamine, noradrenaline, and morphine). This pattern in atheistic individuals correlated with that obtained in left hemispheric chemical dominance. Hemispheric chemical dominance and hypothalamic digoxin could regulate the predisposition to spirituality or atheism.

  18. Regulation of hypothalamic NPY by diet and smoking.

    Science.gov (United States)

    Chen, Hui; Hansen, Michelle J; Jones, Jessica E; Vlahos, Ross; Bozinovski, Steve; Anderson, Gary P; Morris, Margaret J

    2007-02-01

    Appetite is regulated by a number of hypothalamic neuropeptides including neuropeptide Y (NPY), a powerful feeding stimulator that responds to feeding status, and drugs such as nicotine and cannabis. There is debate regarding the extent of the influence of obesity on hypothalamic NPY. We measured hypothalamic NPY in male Sprague-Dawley rats after short or long term exposure to cafeteria-style high fat diet (32% energy as fat) or laboratory chow (12% fat). Caloric intake and body weight were increased in the high fat diet group, and brown fat and white fat masses were significantly increased after 2 weeks. Hypothalamic NPY concentration was only significantly decreased after long term consumption of the high fat diet. Nicotine decreases food intake and body weight, with conflicting effects on hypothalamic NPY reported. Body weight, plasma hormones and brain NPY were investigated in male Balb/c mice exposed to cigarette smoke for 4 days, 4 and 12 weeks. Food intake was significantly decreased by smoke exposure (2.32+/-0.03g/24h versus 2.71+/-0.04g/24h in control mice (non-smoke exposed) at 12 weeks). Relative to control mice, smoke exposure led to greater weight loss, while pair-feeding the equivalent amount of chow caused an intermediate weight loss. Chronic smoke exposure, but not pair-feeding, was associated with decreased hypothalamic NPY concentration, suggesting an inhibitory effect of cigarette smoking on brain NPY levels. Thus, consumption of a high fat diet and smoke exposure reprogram hypothalamic NPY. Reduced NPY may contribute to the anorexic effect of smoke exposure.

  19. Hemodynamic Effects of Phenylephrine, Vasopressin, and Epinephrine in Children With Pulmonary Hypertension: A Pilot Study.

    Science.gov (United States)

    Siehr, Stephanie L; Feinstein, Jeffrey A; Yang, Weiguang; Peng, Lynn F; Ogawa, Michelle T; Ramamoorthy, Chandra

    2016-05-01

    During a pulmonary hypertensive crisis, the marked increase in pulmonary vascular resistance can result in acute right ventricular failure and death. Currently, there are no therapeutic guidelines for managing an acute crisis. This pilot study examined the hemodynamic effects of phenylephrine, arginine vasopressin, and epinephrine in pediatric patients with pulmonary hypertension. In this prospective, open-label, nonrandomized pilot study, we enrolled pediatric patients previously diagnosed with pulmonary hypertensive who were scheduled electively for cardiac catheterization. Primary outcome was a change in the ratio of pulmonary-to-systemic vascular resistance. Baseline hemodynamic data were collected before and after the study drug was administered. Eleven of 15 participants were women, median age was 9.2 years (range, 1.7-14.9 yr), and median weight was 26.8 kg (range, 8.5-55.2 kg). Baseline mean pulmonary artery pressure was 49 ± 19 mm Hg, and mean indexed pulmonary vascular resistance was 10 ± 5.4 Wood units. Etiology of pulmonary hypertensive varied, and all were on systemic pulmonary hypertensive medications. Patients 1-5 received phenylephrine 1 μg/kg; patients 6-10 received arginine vasopressin 0.03 U/kg; and patients 11-15 received epinephrine 1 μg/kg. Hemodynamics was measured continuously for up to 10 minutes following study drug administration. After study drug administration, the ratio of pulmonary-to-systemic vascular resistance decreased in three of five patients receiving phenylephrine, five of five patients receiving arginine vasopressin, and three of five patients receiving epinephrine. Although all three medications resulted in an increase in aortic pressure, only arginine vasopressin consistently resulted in a decrease in the ratio of systolic pulmonary artery-to-aortic pressure. This prospective pilot study of phenylephrine, arginine vasopressin, and epinephrine in pediatric patients with pulmonary hypertensive showed an increase in aortic

  20. The effect of vasopressin on hormone secretion and blood flow from the thyroid vein in sheep with exteriorized thyroids.

    Science.gov (United States)

    Falconer, I R

    1968-12-01

    1. Vasopressin has been shown to activate the thyroid in some species, and also to be released into the bloodstream after emotional and other stresses.2. Emotional stimuli applied to sheep have previously been shown to increase thyroid secretion and the possible influence of vasopressin in this process has been investigated. Sheep bearing exteriorized thyroid glands were used, so that thyroid vein blood could be collected in undisturbed conscious animals.3. (125)I or (131)I (50 muc) was injected I.M. into the sheep; 4-7 days later, samples of thyroid vein blood were collected at 10 min intervals for 4 hr, and the concentration of total and protein bound (125)I or (131)I was measured. Intravenous infusions of 0.3, 3.0 or 31 m-u./min arginine or lysine vasopressin, or close arterial infusions of 3.0 or 31 m-u./min arginine vasopressin were administered 1.5 hr after commencement of blood sampling. Blood flow from the thyroid was measured by a plethysmographic technique during similar experiments.4. No significant changes in thyroid hormone secretion were observed as a result of vasopressin infusion, and it was concluded that vasopressin release does not play a part in the activation of the thyroid resulting from emotional stimulus in the sheep.

  1. Biological half-lives and organ distribution of tritiated 8-lysine-vasopressin and 1-deamino-8-D-arginine-vasopressin in Brattleboro rats

    International Nuclear Information System (INIS)

    Janaky, T.; Laczi, F.; Laszlo, F.A.

    1982-01-01

    The biological half-lives and organ distribution of tritiated 8-lysine-vasopressin and 1-deamino-8-D-arginine-vasopressin were determined in R-Amsterdam rats and in homozygous and heterozygous Brattleboro rats with hereditary central diabetes insipidus. It was found that the biological half-lives of [ 3 H]LVP and [ 3 H]dDAVP in the Brattleboro rats did not differ significantly from that found in the control R-Amsterdam rats. The half-life of [ 3 H]dDAVP proved longer than that of [ 3 H]LVP in all three groups of animals. In the case of [ 3 H]LVP the highest radioactivities were observed in the neurohypophyses, adenohypophyses, and kidneys of both the R-Amsterdam and Brattleboro rats. The accumulation of tritiated material was higher in the small intestine of the Brattleboro rats than in that of the R-Amsterdam animals. In all three groups of rats, [ 3 H]dDAVP was accumulated to the greatest extent in the kidney and the small intestine. The kidney and small intestine contained less radioactivity in homozygous Brattleboro rats than in the controls. There was only a slight radioactivity accumulation in the adenohypophysis and neurohypophysis. From the results it was concluded that the decrease in the rate of enzymatic decomposition may play a role in the increased duration of antidiuretic action of dDAVP. The results have led to the conclusion that the accelerated elimination of vasopressin and its pathologic organ accumulation are probably not involved in the water metabolism disturbance of Brattleboro rats with hereditary diabetes insipidus

  2. Surgical therapy of lesions within the hypothalamic region

    International Nuclear Information System (INIS)

    Fahlbusch, R.; Schrell, U.

    1985-01-01

    On one hand pituitary microadenomas with autonomous character and those, which had been influenced by hypothalamic disorders, are summarized and discussed. On the other hand, the neurosurgical management of tumours, adjacent to our involved with the hypothalamus, are described. Endocrinologically active pituitary adenomas are characterized by their hormone excess of ACTH, GH, and prolactin. In Cushing's disease endocrine and clinical remission occurred in 74%. 3 patients out of this group showed a reincrease of ACTH after a period of remission, indicating a possible hypothalamic influence. In acromegaly the hypothalamic influence is also discussed. One patient with an ectopic GRF-producing tumour showing a reincrease of GH levels after successful transsphenoidal adenomectomy has been described. In microprolactinomas, 7 patients out of 45 showed a reincrease of prolactin-levels after a period of normalization, we also discussed hypothalamic disorders. Tumours with suprasellar extension such as macroadenomas without endocrine activity and meningiomas are removed nowadays with minimal risk for the life of the patients. In craniopharyngiomas radical excision is accompanied by a high risk of hypothalamic defects caused by mechanical lesions and possible secondary vasospasm. Finally the excision of a hamartoma growing from the floor of the third ventricle into the interpeduncular cistern is discussed. Up to now the successful excision could be documented by endocrinological data, which give no sign of further growth of the hamartoma. (Author)

  3. Surgical therapy of lesions within the hypothalamic region

    Energy Technology Data Exchange (ETDEWEB)

    Fahlbusch, R.; Schrell, U. (Erlangen-Nuernberg Univ., Erlangen (Germany, F.R.))

    1985-01-01

    On one hand pituitary microadenomas with autonomous character and those, which had been influenced by hypothalamic disorders, are summarized and discussed. On the other hand, the neurosurgical management of tumours, adjacent to or involved with the hypothalamus, are described. Endocrinologically active pituitary adenomas are characterized by their hormone excess of ACTH, GH, and prolactin. In Cushing's disease endocrine and clinical remission occurred in 74%. 3 patients out of this group showed a reincrease of ACTH after a period of remission, indicating a possible hypothalamic influence. In acromegaly the hypothalamic influence is also discussed. One patient with an ectopic GRF-producing tumour showing a reincrease of GH levels after successful transsphenoidal adenomectomy has been described. In microprolactinomas, 7 patients out of 45 showed a reincrease of prolactin-levels after a period of normalization, we also discussed hypothalamic disorders. Tumours with suprasellar extension such as macroadenomas without endocrine activity and meningiomas are removed nowadays with minimal risk for the life of the patients. In craniopharyngiomas radical excision is accompanied by a high risk of hypothalamic defects caused by mechanical lesions and possible secondary vasospasm. Finally the excision of a hamartoma growing from the floor of the third ventricle into the interpeduncular cistern is discussed. Up to now the successful excision could be documented by endocrinological data, which give no sign of further growth of the hamartoma.

  4. New immunogenic form for vasopressin: production of high-affinity antiserum and RIA for plasmatic AVP

    International Nuclear Information System (INIS)

    Rougon-Rappuzi, G.; Delaage, M.A.; Conte-Devolx, B.; Millet, Y.

    1977-01-01

    A highly sensitive and specific radioimmunoassay (RIA) for arginine-vasopressin (AVP) was developped and applied to the measurement of AVP in human plasma. High-affinity antivasopressin antibodies with limited association constant heterogeneity have been induced by immunizing rabbits with Lysine-vasopressine (LVP) coupled to a human immunoglobulin (IgA). Replacing air drying of acetone-petroleum ether extracts by lyophilisation increased significantly the yields of AVP. Equilibrium dialysis was used for separating bound and free antigen, thus reducing the total time required for the assay to 48 hours. Only 1 ml of plasma was required for routine determinations due to a sensitivity threshold better than 0.5 pg/ml. Plasma AVP levels of normal subjects and of patients with inappropriate ADH secretion (SIADH) were determined during different hydratation states and following nicotin of ethanol infusions. (orig.) [de

  5. New benzylureas as a novel series of potent, nonpeptidic vasopressin V2 receptor agonists.

    Science.gov (United States)

    Yea, Christopher M; Allan, Christine E; Ashworth, Doreen M; Barnett, James; Baxter, Andy J; Broadbridge, Janice D; Franklin, Richard J; Hampton, Sally L; Hudson, Peter; Horton, John A; Jenkins, Paul D; Penson, Andy M; Pitt, Gary R W; Rivière, Pierre; Robson, Peter A; Rooker, David P; Semple, Graeme; Sheppard, Andy; Haigh, Robert M; Roe, Michael B

    2008-12-25

    Vasopressin (AVP) is a hormone that stimulates an increase in water permeability through activation of V2 receptors in the kidney. The analogue of AVP, desmopressin, has proven an effective drug for diseases where a reduction of urine output is desired. However, its peptidic nature limits its bioavailability. We report herein the discovery of potent, nonpeptidic, benzylurea derived agonists of the vasopressin V2 receptor. We describe substitutions on the benzyl group to give improvements in potency and subsequent modifications to the urea end group to provide improvements in solubility and increased oral efficacy in a rat model of diuresis. The lead compound 20e (VA106483) is reported for the first time and has been selected for clinical development.

  6. Controlled long-term release of small peptide hormones using a new microporous polypropylene polymer: its application for vasopressin in the Brattleboro rat and potential perinatal use

    International Nuclear Information System (INIS)

    Kruisbrink, J.; Boer, G.J.

    1984-01-01

    Based on drug release by microporous hollow fibers and the recent introduction of microporous polymers, a new technique was developed for controlled delivery of peptides. Small-diameter microporous polypropylene tubing, lumen-loaded with microgram quantities of vasopressin, and coated with collodion, releases vasopressin after in vitro immersion slowly (1-100 ng/d) and constantly for months. The mechanism of pseudo-zero-order delivery is based on high adsorption of vasopressin, keeping the void volume concentration of dissolved vasopressin constant, which is consequently a constant driving force of outward diffusion. The collodion coating prevents the entry of proteinaceous compounds which would result in rapid desorption of vasopressin. The present delivery module provides a lasting release for other peptides as well (lysine-vasopressin, oxytocin, alpha-melanocyte-stimulating hormone and, to a lesser extent, Met-enkephalin). The microporous polymer-collodion device is biocompatible and, loaded with vasopressin, successfully alleviates the diabetes insipidus of Brattleboro rats deficient for vasopressin. Subcutaneous implantation normalized diuresis for a period of 60 d and constant urine vasopressin excretion is observed. When the commercially available osmotic minipump is too large for implantation, the small size of the present controlled-delivery system allows peptide treatment of young and immature laboratory rats, even if located in utero

  7. Hypothalamic Obesity in Craniopharyngioma Patients: Disturbed Energy Homeostasis Related to Extent of Hypothalamic Damage and Its Implication for Obesity Intervention

    Directory of Open Access Journals (Sweden)

    Christian L. Roth

    2015-09-01

    Full Text Available Hypothalamic obesity (HO occurs in patients with tumors and lesions in the medial hypothalamic region. Hypothalamic dysfunction can lead to hyperinsulinemia and leptin resistance. This review is focused on HO caused by craniopharyngiomas (CP, which are the most common childhood brain tumors of nonglial origin. Despite excellent overall survival rates, CP patients have substantially reduced quality of life because of significant long-term sequelae, notably severe obesity in about 50% of patients, leading to a high rate of cardiovascular mortality. Recent studies reported that both hyperphagia and decreased energy expenditure can contribute to severe obesity in HO patients. Recognized risk factors for severe obesity include large hypothalamic tumors or lesions affecting several medial and posterior hypothalamic nuclei that impact satiety signaling pathways. Structural damage in these nuclei often lead to hyperphagia, rapid weight gain, central insulin and leptin resistance, decreased sympathetic activity, low energy expenditure, and increased energy storage in adipose tissue. To date, most efforts to treat HO have shown disappointing long-term success rates. However, treatments based on the distinct pathophysiology of disturbed energy homeostasis related to CP may offer options for successful interventions in the future.

  8. Hypothalamic BOLD response to glucose intake and hypothalamic volume are similar in anorexia nervosa and healthy control subjects

    Directory of Open Access Journals (Sweden)

    Anna M Van Opstal

    2015-05-01

    Full Text Available Background. Inconsistent findings about the neurobiology of Anorexia Nervosa (AN hinder the development of effective treatments for this severe mental disorder. Therefore the need arises for elucidation of neurobiological factors involved in the pathophysiology of AN. The hypothalamus plays a key role in the neurobiological processes that govern food intake and energy homeostasis, processes that are disturbed in anorexia nervosa (AN. The present study will assess the hypothalamic response to energy intake and the hypothalamic structure in patients with AN and healthy controls. Methods. 10 women aged 18-30 years diagnosed with AN and 11 healthy, lean (BMI <23 kg/m2 women in the same age range were recruited. We used functional magnetic resonance imaging (MRI to determine function of the hypothalamus in response to glucose. Structural MRI was used to determine differences in hypothalamic volume and local grey volume using manual segmentation and voxel-based morphometry.Results. No differences were found in hypothalamic volume and neuronal activity in response to a glucose load between the patients and controls. Whole brain structural analysis showed a significant decrease in grey matter volume in the cingulate cortex in the AN patients, bilaterally.Conclusions. We argue that in spite of various known changes in the hypothalamus the direct hypothalamic response to glucose intake is similar in AN patients and healthy controls.

  9. A Rare Cause of Hypothalamic Obesity, Rohhad Syndrome: 2 Cases.

    Science.gov (United States)

    Şiraz, Ülkü Gül; Okdemir, Deniz; Direk, Gül; Akın, Leyla; Hatipoğlu, Nihal; Kendırcı, Mustafa; Kurtoğlu, Selim

    2018-03-19

    Rapid-onset obesity with hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) syndrome is a rare disease that is difficult to diagnosis and distinguish from genetic obesity syndromes. The underlying causes of the disease has not been fully explained. Hypothalamic dysfunction causes endocrine problems, respiratory dysfunction and autonomic alterations. There are around 80 reported patients due to lack of recognition. We present two female patient suspected of ROHHAD due to weight gain since early childhood. The presented symptoms, respiratory and circulatory dysfunction, hypothalamic hypernatremia, hypothalamo-pituitary hormonal disorders such as santral hypothyrodism, hyperprolactinemia and santral early puberty are completely matched the criteria of ROHHAD syndrome. ROHHAD syndrome should be considered in differential diagnosis since it is difficult to distinguish from causes of monogenic obesity. Early identification of the disease reduces morbidity of the syndrome and patients require regular follow-up by a multidisciplinary approach.

  10. Hypothalamic mTOR signaling regulates food intake.

    Science.gov (United States)

    Cota, Daniela; Proulx, Karine; Smith, Kathi A Blake; Kozma, Sara C; Thomas, George; Woods, Stephen C; Seeley, Randy J

    2006-05-12

    The mammalian Target of Rapamycin (mTOR) protein is a serine-threonine kinase that regulates cell-cycle progression and growth by sensing changes in energy status. We demonstrated that mTOR signaling plays a role in the brain mechanisms that respond to nutrient availability, regulating energy balance. In the rat, mTOR signaling is controlled by energy status in specific regions of the hypothalamus and colocalizes with neuropeptide Y and proopiomelanocortin neurons in the arcuate nucleus. Central administration of leucine increases hypothalamic mTOR signaling and decreases food intake and body weight. The hormone leptin increases hypothalamic mTOR activity, and the inhibition of mTOR signaling blunts leptin's anorectic effect. Thus, mTOR is a cellular fuel sensor whose hypothalamic activity is directly tied to the regulation of energy intake.

  11. Bone metabolism in anorexia nervosa and hypothalamic amenorrhea.

    Science.gov (United States)

    Chou, Sharon H; Mantzoros, Christos

    2018-03-01

    Anorexia nervosa (AN) and hypothalamic amenorrhea (HA) are states of chronic energy deprivation associated with severely compromised bone health. Poor bone accrual during adolescence followed by increased bone loss results in lifelong low bone density, degraded bone architecture, and higher risk of fractures, despite recovery from AN/HA. Amenorrhea is only one of several compensatory responses to the negative energy balance. Other hypothalamic-pituitary hormones are affected and contribute to bone deficits, including activation of hypothalamic-pituitary-adrenal axis and growth hormone resistance. Adipokines, particularly leptin, provide information on fat/energy stores, and gut hormones play a role in the regulation of appetite and food intake. Alterations in all these hormones influence bone metabolism. Restricted in scope, current pharmacologic approaches to improve bone health have had overall limited success. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Delayed nootropic effects of arginine vasopressin after early postnatal chronic administration to albino rat pups.

    Science.gov (United States)

    Kim, P A; Voskresenskaya, O G; Kamensky, A A

    2009-06-01

    Intranasal administration of arginine vasopressin (10 microg/kg) to albino rat pups had a strong nootropic effect during training with positive and negative reinforcement. This effect was different in animals of various age groups: training with positive reinforcement was improved in "adolescent" rats and pubertal animals, while during training with negative reinforcement, the nootropic effect of the peptide was more prolonged and persisted also in adult animals.

  13. Association of arginine vasopressin receptor 1a gene polymorphisms with hepatorenal syndrome

    International Nuclear Information System (INIS)

    Wang, C.; Luo, X.; Ye, J.; Liu, S.; Miu, L.; Bao, J.; Wang, F.; Yu, Z.

    2017-01-01

    To assess the association of arginine vasopressin receptor 1a gene single nucleotide polymorphisms with type I hepatorenal syndrome. Methods: The case-control study was conducted at the Hangzhou City Xixi Hospital, Hangzhou, China, from January 2012 to June 2014, and comprised patients with type I hepatorenal syndrome and individuals with cirrhosis who acted as the control group. Arginine vasopressin receptor 1a gene rs113481894 locus single nucleotide polymorphisms were analysed by high-resolution melting methods. Statistical analysis was performed using SPSS 17. Results: Of the 60 participants, 28(46.7%) were in the hepatorenal syndrome group and 32(53.3%) were controls. The mean age was 42.21+-11.30years in the hepatorenal syndrome group and 43.69+-12.60 in the control group (p=0.64). Mean total bilirubin, albumin and prothrombin activity levels were 154.76+-51.58, 49.30+-24.67 and 33.42+-3.69 in the hepatorenal syndrome group compared to 181.26+-64.46, 41.78+-17.52 and 32.98+-4.81 among controls (p=0.09, p=0.18 and p=0.70). Statistically significant differences were found in the distributions of arginine vasopressin receptor 1a gene rs113481894 locus T allele between type I hepatorenal syndrome patients and the control group (odds ratio= 2.230; p= 0.040). Conclusion: T allele located at arginine vasopressin receptor 1a receptor promoter rs113481894 locus may be associated with the pathogenesis of type I hepatorenal syndrome. (author)

  14. Involvement of arginine-vasopressin in the diuretic and hypotensive effects of Pereskia grandifolia Haw. (Cactaceae).

    Science.gov (United States)

    Kazama, Caroline Calixto; Uchida, Denise Thiemi; Canzi, Karina Natally; de Souza, Priscila; Crestani, Sandra; Gasparotto, Arquimedes; Laverde, Antonio

    2012-10-31

    Pereskia grandifolia Haw. (Cactaceae), popularly known as "ora-pro-nobis" is well recognized in Brazilian traditional medicine as a diuretic agent, although no scientific data have been published to support this effect. The aim of this work is to evaluate the diuretic and hypotensive activities of the infusion (INFPG) and the ethanol extract (HEPG) of Pereskia grandifolia and possible mechanism of action. The infusions (2.5-10%) and the HEPG (3-100 mg/kg) were orally administered in a single dose or daily (for seven days) to rats. The urine excretion rate, pH, density, conductivity and content of Na(+), K(+), Cl(-) and HCO(3)(-) were measured in the urine of saline-loaded animals. In collected serum samples the concentration of electrolytes, urea, creatinine, aldosterone, vasopressin and angiotensin converting enzyme (ACE) activity were evaluated. The involvement of V(2) vasopressin receptor in the diuretic activity and the hypotensive effect of HEPG were also determined. Water excretion rate was significantly increased by HEPG, while the urinary K(+) and Cl(-) excretion was significantly reduced in acute and prolonged treatment. The oral administration of the HEPG (30mg/kg) significantly reduced serum levels of vasopressin and the mean arterial pressure (MAP) in normotensive rats. All other evaluated parameters have not been affected by any treatment. The results showed that HEPG could present compound(s) responsible for aquaretic activities with no signs of toxicity, and this effect could involve a reduction in the arginine-vasopressin release. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. Deficiency of leptin receptor in myeloid cells disrupts hypothalamic metabolic circuits and causes body weight increase

    Directory of Open Access Journals (Sweden)

    Yuanqing Gao

    2018-01-01

    Conclusions: Myeloid cell leptin receptor deficient mice partially replicate the db/db phenotype. Leptin signaling in hypothalamic microglia is important for microglial function and a correct formation of the hypothalamic neuronal circuit regulating metabolism.

  16. Hypocretin/orexin loss changes the hypothalamic immune response.

    Science.gov (United States)

    Tanaka, Susumu; Takizawa, Nae; Honda, Yoshiko; Koike, Taro; Oe, Souichi; Toyoda, Hiromi; Kodama, Tohru; Yamada, Hisao

    2016-10-01

    Hypocretin, also known as orexin, maintains the vigilance state and regulates various physiological processes, such as arousal, sleep, food intake, energy expenditure, and reward. Previously, we found that when wild-type mice and hypocretin/ataxin-3 littermates (which are depleted of hypothalamic hypocretin-expressing neurons postnatally) were administered lipopolysaccharide (LPS), the two genotypes exhibited significant differences in their sleep/wake cycle, including differences in the degree of increase in sleep periods and in recovery from sickness behaviour. In the present study, we examined changes in the hypothalamic vigilance system and in the hypothalamic expression of inflammatory factors in response to LPS in hypocretin/ataxin-3 mice. Peripheral immune challenge with LPS affected the hypothalamic immune response and vigilance states. This response was altered by the loss of hypocretin. Hypocretin expression was inhibited after LPS injection in both hypocretin/ataxin-3 mice and their wild-type littermates, but expression was completely abolished only in hypocretin/ataxin-3 mice. Increases in the number of histidine decarboxylase (HDC)-positive cells and in Hdc mRNA expression were found in hypocretin/ataxin-3 mice, and this increase was suppressed by LPS. Hypocretin loss did not impact the change in expression of hypothalamic inflammatory factors in response to LPS, except for interferon gamma and colony stimulating factor 3. The number of c-Fos-positive/HDC-positive cells in hypocretin/ataxin-3 mice administered LPS injections was elevated, even during the rest period, in all areas, suggesting that there is an increase in the activity of histaminergic neurons in hypocretin/ataxin-3 mice following LPS injection. Taken together, our results suggest a novel role for hypocretin in the hypothalamic response to peripheral immune challenge. Our findings contribute to the understanding of the pathophysiology of narcolepsy. Copyright © 2016 Elsevier Inc. All

  17. Hypothalamic involvement in stress-induced hypocalcemia in rats.

    Science.gov (United States)

    Aou, S; Ma, J; Hori, T

    1993-08-20

    Although hormonal regulation of blood calcium homeostasis has been intensively investigated in the peripheral organs, the involvement of the central nervous system in calcium regulation is still poorly understood. In the present study, we found that (1) bilateral lesions of the ventromedial nucleus of the hypothalamus (VMH), but not those of the paraventricular hypothalamic nucleus or the lateral hypothalamic area, eliminated immobilization (IMB)-induced hypocalcemia, and (2) electrical stimulation of the VMH decreased the blood calcium level. The results suggest that the VMH has a hypocalcemic function and plays a role in IMB-induced hypocalcemia.

  18. Hypothalamic obesity after treatment for craniopharyngioma: the importance of the home environment

    NARCIS (Netherlands)

    Meijneke, Ruud W. H.; Schouten-van Meeteren, Antoinette Y. N.; de Boer, Nienke Y.; van Zundert, Suzanne; van Trotsenburg, Paul A. S.; Stoelinga, Femke; van Santen, Hanneke M.

    2015-01-01

    Abstract Hypothalamic obesity after treatment for craniopharyngioma is a well-recognized, severe problem. Treatment of hypothalamic obesity is difficult and often frustrating for the patient, the parents and the professional care-giver. Because hypothalamic obesity is caused by an underlying medical

  19. Increased hypothalamic serotonin turnover in inflammation-induced anorexia

    NARCIS (Netherlands)

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

    2016-01-01

    Background: Anorexia can occur as a serious complication of disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections

  20. Hypothalamic leptin action is mediated by histone deacetylase 5

    DEFF Research Database (Denmark)

    Kabra, Dhiraj G; Pfuhlmann, Katrin; García-Cáceres, Cristina

    2016-01-01

    Hypothalamic leptin signalling has a key role in food intake and energy-balance control and is often impaired in obese individuals. Here we identify histone deacetylase 5 (HDAC5) as a regulator of leptin signalling and organismal energy balance. Global HDAC5 KO mice have increased food intake and...

  1. Early life stress experience may blunt hypothalamic leptin signalling

    Indian Academy of Sciences (India)

    2016-12-21

    Dec 21, 2016 ... membrane-filtered purified water were available ad libi- tum. Animals were cared for according ... Care and Use of Laboratory Animals, revised 1996. All .... section was blind-counted by hand, and STAT3 auto- counted, after ..... the hypothalamic 5-HT concentration and increases plasma lep- tin in rats. Eur.

  2. Functional MRI of human hypothalamic responses following glucose ingestion

    NARCIS (Netherlands)

    Smeets, P.A.M.; Graaf, C. de; Stafleu, A.; Osch, M.J.P. van; Grond, J. van der

    2005-01-01

    The hypothalamus is intimately involved in the regulation of food intake, integrating multiple neural and hormonal signals. Several hypothalamic nuclei contain glucose-sensitive neurons, which play a crucial role in energy homeostasis. Although a few functional magnetic resonance imaging (fMRI)

  3. Hypothalamic control of energy metabolism via the autonomic nervous system

    NARCIS (Netherlands)

    Kalsbeek, A.; Bruinstroop, E.; Yi, C. X.; Klieverik, L. P.; La Fleur, S. E.; Fliers, E.

    2010-01-01

    The hypothalamic control of hepatic glucose production is an evident aspect of energy homeostasis. In addition to the control of glucose metabolism by the circadian timing system, the hypothalamus also serves as a key relay center for (humoral) feedback information from the periphery, with the

  4. In vitro binding and receptor-mediated activity of terlipressin at vasopressin receptors V1 and V2.

    Science.gov (United States)

    Jamil, Khurram; Pappas, Stephen Chris; Devarakonda, Krishna R

    2018-01-01

    Terlipressin, a synthetic, systemic vasoconstrictor with selective activity at vasopressin-1 (V 1 ) receptors, is a pro-drug for the endogenous/natural porcine hormone [Lys 8 ]-vasopressin (LVP). We investigated binding and receptor-mediated cellular activities of terlipressin, LVP, and endogenous human hormone [Arg 8 ]-vasopressin (AVP) at V 1 and vasopressin-2 (V 2 ) receptors. Cell membrane homogenates of Chinese hamster ovary cells expressing human V 1 and V 2 receptors were used in competitive binding assays to measure receptor-binding activity. These cells were used in functional assays to measure receptor-mediated cellular activity of terlipressin, LVP, and AVP. Binding was measured by [ 3 H]AVP counts, and the activity was measured by fluorometric detection of intracellular calcium mobilization (V 1 ) and cyclic adenosine monophosphate (V 2 ). Binding potency at V 1 and V 2 was AVP>LVP>terlipressin. LVP and terlipressin had approximately sixfold higher affinity for V 1 than for V 2 . Cellular activity potency was also AVP>LVP>terlipressin. Terlipressin was a partial agonist at V 1 and a full agonist at V 2 ; LVP was a full agonist at both V 1 and V 2 . The in vivo response to terlipressin is likely due to the partial V 1 agonist activity of terlipressin and full V 1 agonist activity of its metabolite, LVP. These results provide supportive evidence for previous findings and further establish terlipressin pharmacology for vasopressin receptors.

  5. Differential effects of vasopressin and phenylephrine on protein kinase C-mediated protein phosphorylations in isolated hepatocytes

    International Nuclear Information System (INIS)

    Cooper, R.H.; Johanson, R.A.; Wiliamson, J.R.

    1986-01-01

    Receptor-mediated breakdown of inositol lipids produces two intracellular signals, diacylglycerol, which activates protein kinase C, and inositol trisphosphate, which causes release of intracellular vesicular Ca 2+ . This study examined the effects of Ca 2+ -ionophores, vasopressin, phenylephrine, and phorbol ester (PMA) on hepatocyte protein phosphorylations. [ 32 P] Phosphoproteins from hepatocytes prelabeled with 32 P were resolved by 2-dimensional SDS-PAGE and corresponding autoradiographs were quantitated by densitometric analysis. The phosphorylation of five proteins, a plasma membrane bound 16 kDa protein with pI 6.4, a cytosolic 16 kDa protein with pI 5.8, and proteins with Mr's of 36 kDa, 52 kDa, and 68 kDa, could be attributed to phosphorylation by protein kinase C since the phosphorylation was stimulated by PMA. When the vasopressin concentration was varied, low vasopressin stimulated the phosphorylation of only the membrane bound 16 kDa protein of the above set of proteins, while higher vasopressin concentrations were required to stimulate the phosphorylation of all five proteins. Phenylephrine, even at supramaximal concentrations, stimulated the phosphorylation of only the membrane bound 16 kDa protein. These results suggest that phenylephrine is a less potent activator of protein kinase C than vasopressin by virtue of limited or localized diacylglycerol production

  6. Increased expression of tyrosine hydroxylase immunoreactivity in paraventricular and supraoptic neurons in illnesses with prolonged osmotic or nonosmotic stimulation of vasopressin release

    NARCIS (Netherlands)

    Panayotacopoulou, Maria T.; Malidelis, Yiannis I.; Fliers, Eric; Bouras, Constantin; Ravid, Rivka; Swaab, Dick F.

    2002-01-01

    Our previous studies indicated that in the human para-ventricular (PVN) and supraoptic (SON) nuclei, tyrosine hydroxylase (TH) - the first and rate-limiting enzyme in catecholamine synthesis - is localized mainly in magnocellular neurons and that antemortem factors regulate its expression. The

  7. Selepressin, a novel selective vasopressin V1A agonist, is an effective substitute for norepinephrine in a phase IIa randomized, placebo-controlled trial in septic shock patients

    DEFF Research Database (Denmark)

    Russell, James A; Vincent, Jean-Louis; Kjølbye, Anne Louise

    2017-01-01

    BACKGROUND: Vasopressin is widely used for vasopressor support in septic shock patients, but experimental evidence suggests that selective V1A agonists are superior. The initial pharmacodynamic effects, pharmacokinetics, and safety of selepressin, a novel V1A-selective vasopressin analogue, was e...

  8. Craniopharyngioma and hypothalamic injury: latest insights into consequent eating disorders and obesity

    Science.gov (United States)

    Müller, Hermann L.

    2016-01-01

    Purpose of review Hypothalamic alterations, pathological or treatment induced, have major impact on prognosis in craniopharyngioma patients mainly because of consequent hypothalamic obesity. Recent insight in molecular genetics, treatment strategies, risk factors and outcomes associated with hypothalamic obesity provide novel therapeutic perspectives. This review includes relevant publications since 2013. Recent findings Recent findings confirm that alterations in posterior hypothalamic areas because of tumour location and/or treatment-related injuries are associated with severe hypothalamic obesity, reduced overall survival and impaired quality of life in long-term survivors of childhood-onset craniopharyngioma. However, eating disorders are observed because of hypothalamic obesity without clear disease-specific patterns. Treatment options for hypothalamic obesity are very limited. Treatment with invasive, nonreversible bariatric methods such as Roux-en-Y gastric bypass is most efficient in weight reduction, but controversial in the paediatric population because of medical, ethical, and legal considerations. Accordingly, treatment in craniopharyngioma should focus on prevention of (further) hypothalamic injury. Presurgical imaging for grading of hypothalamic involvement should be the basis for hypothalamus-sparing strategies conducted by experienced multidisciplinary teams. Summary Until a nonsurgical therapeutic option for hypothalamic obesity for paediatric patients is found, prevention of hypothalamic injury should be the preferred treatment strategy, conducted exclusively by experienced multidisciplinary teams. PMID:26574645

  9. 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.

  10. Diabetes diminishes the portal-systemic collateral vascular response to vasopressin via vasopressin receptor and Gα proteins regulations in cirrhotic rats.

    Directory of Open Access Journals (Sweden)

    Jing-Yi Lee

    Full Text Available Liver cirrhosis may lead to portal-systemic collateral formation and bleeding. The hemostatic effect is influenced by the response of collateral vessels to vasoconstrictors. Diabetes and glucose also influence vasoresponsiveness, but their net effect on collaterals remains unexplored. This study investigated the impact of diabetes or glucose application on portal-systemic collateral vasoresponsiveness to arginine vasopressin (AVP in cirrhosis. Spraque-Dawley rats with bile duct ligation (BDL-induced cirrhosis received vehicle (citrate buffer or streptozotocin (diabetic, BDL/STZ. The in situ collateral perfusion was done after hemodynamic measurements: Both were perfused with Krebs solution, D-glucose, or D-glucose and NaF, with additional OPC-31260 for the BDL/STZ group. Splenorenal shunt vasopressin receptors and Gα proteins mRNA expressions were evaluated. The survival rate of cirrhotic rats was decreased by STZ injection. The collateral perfusion pressure changes to AVP were lower in STZ-injected groups, which were reversed by OPC-31260 (a V2R antagonist and overcome by NaF (a G protein activator. The splenorenal shunt V2R mRNA expression was increased while Gα proteins mRNA expressions were decreased in BDL/STZ rats compared to BDL rats. The Gαq and Gα11 mRNA expressions also correlated with the maximal perfusion pressure changes to AVP. Diabetes diminished the portal-systemic collateral vascular response to AVP in rats with BDL-induced cirrhosis, probably via V2 receptor up-regulation and Gα proteins down-regulation.

  11. Development of a human vasopressin V1a-receptor antagonist from an evolutionary-related insect neuropeptide

    Science.gov (United States)

    di Giglio, Maria Giulia; Muttenthaler, Markus; Harpsøe, Kasper; Liutkeviciute, Zita; Keov, Peter; Eder, Thomas; Rattei, Thomas; Arrowsmith, Sarah; Wray, Susan; Marek, Ales; Elbert, Tomas; Alewood, Paul F.; Gloriam, David E.; Gruber, Christian W.

    2017-02-01

    Characterisation of G protein-coupled receptors (GPCR) relies on the availability of a toolbox of ligands that selectively modulate different functional states of the receptors. To uncover such molecules, we explored a unique strategy for ligand discovery that takes advantage of the evolutionary conservation of the 600-million-year-old oxytocin/vasopressin signalling system. We isolated the insect oxytocin/vasopressin orthologue inotocin from the black garden ant (Lasius niger), identified and cloned its cognate receptor and determined its pharmacological properties on the insect and human oxytocin/vasopressin receptors. Subsequently, we identified a functional dichotomy: inotocin activated the insect inotocin and the human vasopressin V1b receptors, but inhibited the human V1aR. Replacement of Arg8 of inotocin by D-Arg8 led to a potent, stable and competitive V1aR-antagonist ([D-Arg8]-inotocin) with a 3,000-fold binding selectivity for the human V1aR over the other three subtypes, OTR, V1bR and V2R. The Arg8/D-Arg8 ligand-pair was further investigated to gain novel insights into the oxytocin/vasopressin peptide-receptor interaction, which led to the identification of key residues of the receptors that are important for ligand functionality and selectivity. These observations could play an important role for development of oxytocin/vasopressin receptor modulators that would enable clear distinction of the physiological and pathological responses of the individual receptor subtypes.

  12. Protein- and diabetes-induced glomerular hyperfiltration: role of glucagon, vasopressin, and urea.

    Science.gov (United States)

    Bankir, Lise; Roussel, Ronan; Bouby, Nadine

    2015-07-01

    A single protein-rich meal (or an infusion of amino acids) is known to increase the glomerular filtration rate (GFR) for a few hours, a phenomenon known as "hyperfiltration." It is important to understand the factors that initiate this upregulation because it becomes maladaptive in the long term. Several mediators and paracrine factors have been shown to participate in this upregulation, but they are not directly triggered by protein intake. Here, we explain how a rise in glucagon and in vasopressin secretion, directly induced by protein ingestion, might be the initial factors triggering the hepatic and renal events leading to an increase in the GFR. Their effects include metabolic actions in the liver and stimulation of sodium chloride reabsorption in the thick ascending limb. Glucagon is not only a glucoregulatory hormone. It is also important for the excretion of nitrogen end products by stimulating both urea synthesis in the liver (along with gluconeogenesis from amino acids) and urea excretion by the kidney. Vasopressin allows the concentration of nitrogenous end products (urea, ammonia, etc.) and other protein-associated wastes in a hyperosmotic urine, thus allowing a very significant water economy characteristic of all terrestrial mammals. No hyperfiltration occurs in the absence of one or the other hormone. Experimental results suggest that the combined actions of these two hormones, along with the complex intrarenal handling of urea, lead to alter the composition of the tubular fluid at the macula densa and to reduce the intensity of the signal activating the tubuloglomerular feedback control of GFR, thus allowing GFR to raise. Altogether, glucagon, vasopressin, and urea contribute to set up the best compromise between efficient urea excretion and water economy. Copyright © 2015 the American Physiological Society.

  13. Blockade of central vasopressin receptors reduces the cardiovascular response to acute stress in freely moving rats.

    Science.gov (United States)

    Stojicić, S; Milutinović-Smiljanić, S; Sarenac, O; Milosavljević, S; Paton, J F R; Murphy, D; Japundzić-Zigon, N

    2008-04-01

    To investigate the contribution of central vasopressin receptors to blood pressure (BP) and heart rate (HR) response to stress we injected non-peptide selective V(1a) (SR49059), V(1b) (SSR149415), V(2) (SR121463) receptor antagonists, diazepam or vehicle in the lateral cerebral ventricle of conscious freely moving rats stressed by blowing air on their heads for 2 min. Cardiovascular effects of stress were evaluated by analyzing maximum increase of BP and HR (MAX), latency of maximum response (LAT), integral under BP and HR curve (integral), duration of their recovery and spectral parameters of BP and HR indicative of increased sympathetic outflow (LF(BP) and LF/HF(HR)). Moreover, the increase of serum corticosterone was measured. Exposure to air-jet stress induced simultaneous increase in BP and HR followed by gradual decline during recovery while LF(BP) oscillation remained increased as well as serum corticosterone level. Rats pre-treated with vasopressin receptor antagonists were not sedated while diazepam induced sedation that persisted during exposure to stress. V(1a), V(1b) and V(2) receptor antagonists applied separately did not modify basal values of cardiovascular parameters but prevented the increase in integral(BP). In addition, V(1b) and V(2) receptor antagonists reduced BP(MAX) whereas V(1a), V(1b) antagonist and diazepam reduced HR(MAX) induced by exposure to air-jet stress. All drugs shortened the recovery period, prevented the increase of LF(BP) without affecting the increase in serum corticosterone levels. Results indicate that vasopressin receptors located within the central nervous system mediate, in part, the cardiovascular response to air-jet stress without affecting either the neuroendocrine component or inducing sedation. They support the view that the V(1b) receptor antagonist may be of potential therapeutic value in reducing arterial pressure induced by stress-related disorders.

  14. Phasic firing in vasopressin cells: understanding its functional significance through computational models.

    Directory of Open Access Journals (Sweden)

    Duncan J MacGregor

    Full Text Available Vasopressin neurons, responding to input generated by osmotic pressure, use an intrinsic mechanism to shift from slow irregular firing to a distinct phasic pattern, consisting of long bursts and silences lasting tens of seconds. With increased input, bursts lengthen, eventually shifting to continuous firing. The phasic activity remains asynchronous across the cells and is not reflected in the population output signal. Here we have used a computational vasopressin neuron model to investigate the functional significance of the phasic firing pattern. We generated a concise model of the synaptic input driven spike firing mechanism that gives a close quantitative match to vasopressin neuron spike activity recorded in vivo, tested against endogenous activity and experimental interventions. The integrate-and-fire based model provides a simple physiological explanation of the phasic firing mechanism involving an activity-dependent slow depolarising afterpotential (DAP generated by a calcium-inactivated potassium leak current. This is modulated by the slower, opposing, action of activity-dependent dendritic dynorphin release, which inactivates the DAP, the opposing effects generating successive periods of bursting and silence. Model cells are not spontaneously active, but fire when perturbed by random perturbations mimicking synaptic input. We constructed one population of such phasic neurons, and another population of similar cells but which lacked the ability to fire phasically. We then studied how these two populations differed in the way that they encoded changes in afferent inputs. By comparison with the non-phasic population, the phasic population responds linearly to increases in tonic synaptic input. Non-phasic cells respond to transient elevations in synaptic input in a way that strongly depends on background activity levels, phasic cells in a way that is independent of background levels, and show a similar strong linearization of the response

  15. Combination decongestion therapy in hospitalized heart failure: loop diuretics, mineralocorticoid receptor antagonists and vasopressin antagonists.

    Science.gov (United States)

    Vaduganathan, Muthiah; Mentz, Robert J; Greene, Stephen J; Senni, Michele; Sato, Naoki; Nodari, Savina; Butler, Javed; Gheorghiade, Mihai

    2015-01-01

    Congestion is the most common reason for admissions and readmissions for heart failure (HF). The vast majority of hospitalized HF patients appear to respond readily to loop diuretics, but available data suggest that a significant proportion are being discharged with persistent evidence of congestion. Although novel therapies targeting congestion should continue to be developed, currently available agents may be utilized more optimally to facilitate complete decongestion. The combination of loop diuretics, natriuretic doses of mineralocorticoid receptor antagonists and vasopressin antagonists represents a regimen of currently available therapies that affects early and persistent decongestion, while limiting the associated risks of electrolyte disturbances, hemodynamic fluctuations, renal dysfunction and mortality.

  16. Urinary prostaglandin E and vasopressin excretion in essential fatty acid-deficient rats

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Jensen, B.

    1983-01-01

    excretion of prostaglandin E (PGE), immunoreactive arginine vasopressin (iA VP), and kallikrein were determined. PGE was quantitated with a radioimmunoassay having 4.9% cross-reactivity with prostaglandin E (PGE). After 4 weeks on the diet, water consumption and urinary iAVP excretion increased....... Increased water consumption and increased urinary iAVP excretion seem to be early symptoms (after 4 weeks) of EFA deficiency, whereas decreased urine output and decreased urinary PGE excretion occur much later (after 10 weeks). Two energy% linolenate supplementation to a fat-free diet did not change...

  17. Radio-immunoassay of plasma arginine vasopressin in man. Comparison of two methods of extraction

    International Nuclear Information System (INIS)

    Wolf, J.P.; Dumoulin, G.; Henriet, M.T.; Baulay, A.; Berthelay, S.

    1987-01-01

    Two methods of extraction, prior to radio-immunoassay (RIA) of human plasma arginine vasopressin (AVP) were tested: ethanol extraction (ETH), chromatography with ODS-Silice (ODS-Sil). Recovery of 125 I AVP was higher when using ODS-Sil than when using ETH. Recovery of standard AVP was found to be more efficient and reproducible for ODS-Sil. However, the RIA used, performed after chromatography with ODS-Sil, is not enough sensitive to detect low concentrations but is able to detect high concentrations and physiological variations of plasma AVP [fr

  18. Synthesis of two tritium-labeled derivatives of a vasopressin antagonist peptide

    International Nuclear Information System (INIS)

    Landvatter, S.W.; Heys, J.R.

    1986-01-01

    SK and F 101926, a potent vasopressin antagonist, has been tritium labeled in the tyrosine residue via exchange followed by solid phase coupling to a hexapeptide. The peptide thus obtained was subsequently coupled with a PMP residue, cleaved from the resin with HF, oxidized by ferricyanide and purified by HPLC giving the desired cyclic peptide. Alternatively, a labeled PMP residue can be prepared via reduction starting from phenol. Conversion of the labeled cyclohexanone to PMP followed by solid phase coupling to a heptapeptide can then afford PMP labeled peptide. 3 refs

  19. Effect of the selective vasopressin V2 receptor antagonists in hepatic cirrhosis patients with ascites: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Shao-hui TANG

    2013-07-01

    Full Text Available Objective To evaluate the efficacy and safety of selective vasopressin V2 receptor antagonists in the treatment of hepatic cirrhosis patients with ascites. Methods PubMed, EMBASE, Web of Science, The Cochrane Central Register of Controlled Trials, Database for Chinese Technical Periodical (VIP, Chinese Journal Full-Text Database (CNKI, and Wan Fang Digital Journal Full-text Database were retrieved to collect clinical randomized controlled trials of hepatic cirrhosis with ascites treated by selective vasopressin V2 receptor antagonists. Meta analysis was performed by using Review Manager 5.0. Results Nine randomized controlled trials including 1884 patients met the inclusion criteria. Meta-analysis showed that: 1 The selective vasopressin V2 receptor antagonists were associated with a significant reduction in body weight compared with placebo (WMD=–1.98kg, 95%CI:–3.24-–0.72kg, P=0.002. Treatment with selective vasopressin V2 receptor antagonists was associated with an improvement of low serum sodium concentration compared to placebo (WMD=3.74mmol/L, 95%CI: 0.91-6.58mmol/L, P=0.01. The percentage of patients with worsening ascites was higher in the group of patients treated with placebo (RR=0.51, 95%CI: 0.34-0.77, P=0.001. 2 The amplitude of increased urine volume was obviously higher in selective vasopressin V2 receptor antagonists group than in placebo group (WMD=1437.65ml, 95%CI: 649.01-2226.30ml, P=0.0004. The difference of serum creatinine in the selective vasopressin V2 receptor antagonists group was not statistically significant compared with the control group (WMD=–3.49μmol/L, 95%CI: –12.54¬5.56μmol/L, P=0.45. 3 There was no statistical significance between the two groups in the heart rate, systolic pressure, diastolic pressure and mortality (P>0.05. The rate of other adverse reactions was higher in the selective vasopressin V2 receptor antagonists group compared with that of placebo group (P=0.003. Conclusion

  20. Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes

    Science.gov (United States)

    Fuente-Martín, Esther; García-Cáceres, Cristina; Granado, Miriam; de Ceballos, María L.; Sánchez-Garrido, Miguel Ángel; Sarman, Beatrix; Liu, Zhong-Wu; Dietrich, Marcelo O.; Tena-Sempere, Manuel; Argente-Arizón, Pilar; Díaz, Francisca; Argente, Jesús; Horvath, Tamas L.; Chowen, Julie A.

    2012-01-01

    Glial cells perform critical functions that alter the metabolism and activity of neurons, and there is increasing interest in their role in appetite and energy balance. Leptin, a key regulator of appetite and metabolism, has previously been reported to influence glial structural proteins and morphology. Here, we demonstrate that metabolic status and leptin also modify astrocyte-specific glutamate and glucose transporters, indicating that metabolic signals influence synaptic efficacy and glucose uptake and, ultimately, neuronal function. We found that basal and glucose-stimulated electrical activity of hypothalamic proopiomelanocortin (POMC) neurons in mice were altered in the offspring of mothers fed a high-fat diet. In adulthood, increased body weight and fasting also altered the expression of glucose and glutamate transporters. These results demonstrate that whole-organism metabolism alters hypothalamic glial cell activity and suggest that these cells play an important role in the pathology of obesity. PMID:23064363

  1. Leptin inhibits and ghrelin augments hypothalamic noradrenaline release after stress.

    Science.gov (United States)

    Kawakami, Akio; Okada, Nobukazu; Rokkaku, Kumiko; Honda, Kazufumi; Ishibashi, Shun; Onaka, Tatsushi

    2008-09-01

    Metabolic conditions affect hypothalamo-pituitary-adrenal responses to stressful stimuli. Here we examined effects of food deprivation, leptin and ghrelin upon noradrenaline release in the hypothalamic paraventricular nucleus (PVN) and plasma adrenocorticotropic hormone (ACTH) concentrations after stressful stimuli. Food deprivation augmented both noradrenaline release in the PVN and the increase in plasma ACTH concentration following electrical footshocks (FSs). An intracerebroventricular injection of leptin attenuated the increases in hypothalamic noradrenaline release and plasma ACTH concentrations after FSs, while ghrelin augmented these responses. These data suggest that leptin inhibits and ghrelin facilitates neuroendocrine stress responses via noradrenaline release and indicate that a decrease in leptin and an increase in ghrelin release after food deprivation might contribute to augmentation of stress-induced ACTH release in a fasting state.

  2. Implications of mitochondrial dynamics on neurodegeneration and on hypothalamic dysfunction

    Directory of Open Access Journals (Sweden)

    Antonio eZorzano

    2015-06-01

    Full Text Available Mitochondrial dynamics is a term that encompasses the movement of mitochondria along the cytoskeleton, regulation of their architecture, and connectivity mediated by tethering and fusion/fission. The importance of these events in cell physiology and pathology has been partially unraveled with the identification of the genes responsible for the catalysis of mitochondrial fusion and fission. Mutations in two mitochondrial fusion genes (MFN2 and OPA1 cause neurodegenerative diseases, namely Charcot-Marie Tooth type 2A and autosomal dominant optic atrophy. Alterations in mitochondrial dynamics may be involved in the pathophysiology of prevalent neurodegenerative conditions. Moreover, impairment of the activity of mitochondrial fusion proteins dysregulates the function of hypothalamic neurons, leading to alterations in food intake and in energy homeostasis. Here we review selected findings in the field of mitochondrial dynamics and their relevance for neurodegeneration and hypothalamic dysfunction.

  3. Stochastic modeling of the hypothalamic pulse generator activity.

    Science.gov (United States)

    Camproux, A C; Thalabard, J C; Thomas, G

    1994-11-01

    Luteinizing hormone (LH) is released by the pituitary in discrete pulses. In the monkey, the appearance of LH pulses in the plasma is invariably associated with sharp increases (i.e, volleys) in the frequency of the hypothalamic pulse generator electrical activity, so that continuous monitoring of this activity by telemetry provides a unique means to study the temporal structure of the mechanism generating the pulses. To assess whether the times of occurrence and durations of previous volleys exert significant influence on the timing of the next volley, we used a class of periodic counting process models that specify the stochastic intensity of the process as the product of two factors: 1) a periodic baseline intensity and 2) a stochastic regression function with covariates representing the influence of the past. This approach allows the characterization of circadian modulation and memory range of the process underlying hypothalamic pulse generator activity, as illustrated by fitting the model to experimental data from two ovariectomized rhesus monkeys.

  4. Dissecting the hypothalamic pathways that underlie innate behaviors.

    Science.gov (United States)

    Zha, Xi; Xu, Xiaohong

    2015-12-01

    Many complex behaviors that do not require learning are displayed and are termed innate. Although traditionally the subject matter of ethology, innate behaviors offer a unique entry point for neuroscientists to dissect the physiological mechanisms governing complex behaviors. Since the last century, converging evidence has implicated the hypothalamus as the central brain area that controls innate behaviors. Recent studies using cutting-edge tools have revealed that genetically-defined populations of neurons residing in distinct hypothalamic nuclei and their associated neural pathways regulate the initiation and maintenance of diverse behaviors including feeding, sleep, aggression, and parental care. Here, we review the newly-defined hypothalamic pathways that regulate each innate behavior. In addition, emerging general principles of the neural control of complex behaviors are discussed.

  5. Stress-associated or functional hypothalamic amenorrhea in the adolescent.

    Science.gov (United States)

    Liu, James H; Bill, Arthur H

    2008-01-01

    Stress-associated amenorrhea in the adolescent is likely similar to the disorder found in young reproductive-aged adults and is termed hypothalamic amenorrhea. The key defect is an abnormality in the secretion of gonadotropin-releasing hormone. This review examines the current studies that characterize the disorder and the plausible factor(s) that may account for the disturbances in gonadotropin-releasing hormone, and identifies directions for future research in this group of disorders.

  6. Hypothalamic control of pituitary and adrenal hormones during hypothermia.

    Science.gov (United States)

    Okuda, C; Miyazaki, M; Kuriyama, K

    1986-01-01

    In order to investigate neuroendocrinological mechanisms of hypothermia, we determined the changes in plasma concentrations of corticosterone (CS), prolactin (PRL), and thyrotropin (TSH), and their correlations with alterations in hypothalamic dopamine (DA) and thyrotropin releasing hormone (TRH), in rats restrained and immersed in a water bath at various temperatures. A graded decrease of body temperature induced a progressive increase in the plasma level of CS, whereas that of PRL showed a drastic decrease. The plasma level of TSH also showed an increase during mild hypothermia (about 35 degrees C), but this increase was not evident during profound hypothermia (below 24 degrees C). The changes in these hormones were readily reversed by rewarming animals. Although DA content in the hypothalamus was not affected, its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), showed an increase following the decrease of body temperature. Pretreatment of the animals with sulpiride, a D2-antagonist, prevented the hypothermia-induced inhibition of PRL release. Hypothalamic TRH was significantly decreased during mild hypothermia, and it returned to control levels after rewarming. These results suggest that the decrease in plasma PRL induced by hypothermia may be associated with the activation of hypothalamic DA neurons, whereas the increase in plasma TSH during mild hypothermia seems to be caused by the increased release of TRH in the hypothalamus.

  7. Effect of cancer treatment on hypothalamic-pituitary function.

    Science.gov (United States)

    Crowne, Elizabeth; Gleeson, Helena; Benghiat, Helen; Sanghera, Paul; Toogood, Andrew

    2015-07-01

    The past 30 years have seen a great improvement in survival of children and young adults treated for cancer. Cancer treatment can put patients at risk of health problems that can develop many years later, most commonly affecting the endocrine system. Patients treated with cranial radiotherapy often develop dysfunction of the hypothalamic-pituitary axis. A characteristic pattern of hormone deficiencies develops over several years. Growth hormone is disrupted most often, followed by gonadal, adrenal, and thyroid hormones, leading to abnormal growth and puberty in children, and affecting general wellbeing and fertility in adults. The severity and rate of development of hypopituitarism is determined by the dose of radiotherapy delivered to the hypothalamic-pituitary axis. Individual growth hormone deficiencies can develop after a dose as low as 10 Gy, whereas multiple hormone deficiencies are common after 60 Gy. New techniques in radiotherapy aim to reduce the effect on the hypothalamic-pituitary axis by minimising the dose received. Patients taking cytotoxic drugs do not often develop overt hypopituitarism, although the effect of radiotherapy might be enhanced. The exception is adrenal insufficiency caused by glucocorticosteroids which, although transient, can be life-threatening. New biological drugs to treat cancer can cause autoimmune hypophysitis and hypopituitarism; therefore, oncologists and endocrinologists should be vigilant and work together to optimise patient outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Hypothalamic Projections to the Optic Tectum in Larval Zebrafish

    Science.gov (United States)

    Heap, Lucy A.; Vanwalleghem, Gilles C.; Thompson, Andrew W.; Favre-Bulle, Itia; Rubinsztein-Dunlop, Halina; Scott, Ethan K.

    2018-01-01

    The optic tectum of larval zebrafish is an important model for understanding visual processing in vertebrates. The tectum has been traditionally viewed as dominantly visual, with a majority of studies focusing on the processes by which tectal circuits receive and process retinally-derived visual information. Recently, a handful of studies have shown a much more complex role for the optic tectum in larval zebrafish, and anatomical and functional data from these studies suggest that this role extends beyond the visual system, and beyond the processing of exclusively retinal inputs. Consistent with this evolving view of the tectum, we have used a Gal4 enhancer trap line to identify direct projections from rostral hypothalamus (RH) to the tectal neuropil of larval zebrafish. These projections ramify within the deepest laminae of the tectal neuropil, the stratum album centrale (SAC)/stratum griseum periventriculare (SPV), and also innervate strata distinct from those innervated by retinal projections. Using optogenetic stimulation of the hypothalamic projection neurons paired with calcium imaging in the tectum, we find rebound firing in tectal neurons consistent with hypothalamic inhibitory input. Our results suggest that tectal processing in larval zebrafish is modulated by hypothalamic inhibitory inputs to the deep tectal neuropil. PMID:29403362

  9. Effects of sugar solutions on hypothalamic appetite regulation.

    Science.gov (United States)

    Colley, Danielle L; Castonguay, Thomas W

    2015-02-01

    Several hypotheses for the causes of the obesity epidemic in the US have been proposed. One such hypothesis is that dietary intake patterns have significantly shifted to include unprecedented amounts of refined sugar. We set out to determine if different sugars might promote changes in the hypothalamic mechanisms controlling food intake by measuring several hypothalamic peptides subsequent to overnight access to dilute glucose, sucrose, high fructose corn syrup, or fructose solutions. Rats were given access to food, water and a sugar solution for 24h, after which blood and tissues were collected. Fructose access (as opposed to other sugars that were tested) resulted in a doubling of circulating triglycerides. Glucose consumption resulted in upregulation of 7 satiety-related hypothalamic peptides whereas changes in gene expression were mixed for remaining sugars. Also, following multiple verification assays, 6 satiety related peptides were verified as being affected by sugar intake. These data provide evidence that not all sugars are equally effective in affecting the control of intake. Copyright © 2014. Published by Elsevier Inc.

  10. Hypothalamic Projections to the Optic Tectum in Larval Zebrafish

    Directory of Open Access Journals (Sweden)

    Lucy A. Heap

    2018-01-01

    Full Text Available The optic tectum of larval zebrafish is an important model for understanding visual processing in vertebrates. The tectum has been traditionally viewed as dominantly visual, with a majority of studies focusing on the processes by which tectal circuits receive and process retinally-derived visual information. Recently, a handful of studies have shown a much more complex role for the optic tectum in larval zebrafish, and anatomical and functional data from these studies suggest that this role extends beyond the visual system, and beyond the processing of exclusively retinal inputs. Consistent with this evolving view of the tectum, we have used a Gal4 enhancer trap line to identify direct projections from rostral hypothalamus (RH to the tectal neuropil of larval zebrafish. These projections ramify within the deepest laminae of the tectal neuropil, the stratum album centrale (SAC/stratum griseum periventriculare (SPV, and also innervate strata distinct from those innervated by retinal projections. Using optogenetic stimulation of the hypothalamic projection neurons paired with calcium imaging in the tectum, we find rebound firing in tectal neurons consistent with hypothalamic inhibitory input. Our results suggest that tectal processing in larval zebrafish is modulated by hypothalamic inhibitory inputs to the deep tectal neuropil.

  11. Synthesis of specific deuterium labeled tyrosine and phenylalanine derivatives and their use in the total synthesis of [8-arginine]vasopressin derivatives: the separation of diastereomeric [8-arginine]vasopressin derivatives by partition chromatography

    International Nuclear Information System (INIS)

    Yamamoto, D.M.; Upson, D.A.; Linn, D.K.; Hruby, V.J.

    1977-01-01

    Derivatives of tyrosine specifically deuterated at the α carbon ([α- 2 H 1 ]tyrosine) and at both the α and β carbons ([α,β,β- 2 H 3 ]tyrosine) and a derivative of phenylalanine specifically deuterated at the α carbon ([α- 2 H 1 ]phenylalanine) have been synthesized in high yield. These labeled compounds have been resolved enzymatically, and the enantiomers and racemates have been converted to N-tert-butyloxycarbonyl derivatives. The deuterium labels were not exchanged under the conditions of the syntheses. The protected derivatives as well as specifically deuterated derivatives of S-benzylcysteine and of glycine were used to prepare specifically deuterated analogues of [8-arginine] vasopressin using solid phase peptide procedures. The use of improved synthetic procedures resulted in considerable improvements in the yields of [8-arginine]vasopressin compared with previous reports. In addition, new solvent systems for partition chromatography purification of [8-arginine]vasopressin on Sephadex were developed which allowed a facile one-step separation of diastereomers of [8-arginine]vasopressin containing a racemic amino acid at either the 1-hemicystine or the 2-tyrosine positions of the hormone

  12. Pseudoaneurysm embolization and vasopressin infusion for lower gastrointestinal bleeding due to recurrence of urinary bladder carcinoma.

    Science.gov (United States)

    Kakizawa, Hideaki; Toyota, Naoyuki; Mita, Koji; Fujimura, Yoshio; Hieda, Masashi; Hirai, Nobuhiko; Tachikake, Toshihiro; Ito, Katsuhide

    2006-05-01

    We report a case that was successfully treated for massive lower gastrointestinal (LGI) bleeding due to a recurrent urinary bladder carcinoma. Treatment consisted of combination therapy including embolization of an inferior gluteal artery (IGA) pseudoaneurysm and low-dose arterial vasopressin infusion via a sigmoid artery (SA). A 57-year-old man presented with life-threatening sudden, massive LGI bleeding due to an obturator lymph node (LN) metastasis from a urinary bladder carcinoma. Computed tomography showed that the LN recurrence had invaded all the way to the sigmoid colon, and there was a pseudoaneurysm with extravasation inside the recurrence. An angiogram revealed a left IGA pseudoaneurysm. We therefore excluded the pseudoaneurysm by embolization with microcoils. Following this treatment the bleeding decreased, but intermittent LGI bleeding continued. Endoscopic examination showed the tumor with a huge ulcer inside the colonic lumen, and continuous oozing was confirmed. A second angiogram showed no recurrence of the IGA pseudoaneurysm and no apparent findings of bleeding. Then a 3F microcatheter was placed in the SA selectively using a coaxial catheter system, and vasopressin was infused at a rate 0.05 U/min for 12 h. Bleeding completely ceased 2 days later. There were no signs of ischemic gastrointestinal complications. Massive LGI bleeding has not recurred in 5 months.

  13. Modulation of mouse Leydig cell steroidogenesis through a specific arginine-vasopressin receptor

    International Nuclear Information System (INIS)

    Tahri-Joutei, A.; Pointis, G.

    1988-01-01

    Characterization of specific vasopressin binding sites was investigated in purified mouse Leydig cells using tritiated arginine-vasopressin. Binding of radioligand was saturable, time- and temperature-dependent and reversible. ( 3 H)-AVP was found to bind to a single class of sites with high affinity and low capacity. Binding displacements with specific selection analogs of AVP indicated the presence of V 1 subtype receptors on Leydig cells. The ability of AVP to displace ( 3 H)-AVP binding was greater than LVP and oxytocin. The unrelated peptides, somatostatin and substance P, were less potent, while neurotensin and LHRH did not displace ( 3 H)-AVP binding. The time-course effects of AVP-pretreatment on basal and hCG-stimulated testosterone and cAMP accumulations were studied in primary culture of Leydig cells. Basal testosterone accumulation was significantly increased by a 24 h AVP-pretreatment of Leydig cells. This effect was potentiated by the phosphodiesterase inhibitor (MIX) and was concomitantly accompanied by a slight but significant increase in cAMP accumulation. AVP-pretreatment of the cells for 72 h had no effect on basal testosterone accumulation, but exerted a marked inhibitory effect on the hCG-stimulated testosterone accumulation. This reduction of testosterone accumulation occurred even in the presence of MIX and was not accompanied by any significant change of cAMP levels

  14. Pharmacokinetics of the vasopressin antagonist, SK and F 101926, a synthetic octapeptide, in the rat

    International Nuclear Information System (INIS)

    Lynn, R.K.; Straub, K.M.; Landvatter, S.W.; Garvie, C.T.

    1986-01-01

    SK and F 101926 is a synthetic analogue of vasopressin which antagonizes vasopressin induced antidiuresis. Radiolabeled SK and F 101926 ( 3 H-3,3-D-TYR) was administered i.v. as a single bolus to male Sprague Dawley rats. Serial plasma samples were analyzed for SK and F 101926 by HPLC/LSC. The plasma concentration time curve for SK and F 101926 displayed three disposition phases. However, 80% of the total area under the curve was represented in one phase which displayed a half-life (t 1/2) of 20 min. The total systematic clearance (Cl) and the steady state volume of distribution (Vdss) were 15 ml/min/kg and 450 ml/kg, respectively. The t 1/2, Cl and Vdss were identical following doses of 10 and 100 μg/kg. 3 H-SK and F 101926 accounted for > 80% of the plasma radiolabel 0-30 min after dosing. However, by 12 hr, 3 H-SK and F 101926 represented only 6% of the plasma radiolabel. Following oral administration of 3 H-SK and F 101926, < 5% of the administered radiolabel reached the systematic circulation; however, no parent compound was detectable in plasma. These studies demonstrate that although SK and F 101926 has a relatively low systematic clearance, it also displays a relatively small volume of distribution which together result in a moderate beta elimination half-life

  15. Vasopressin-induced constriction of the isolated rat occipital artery is segment dependent.

    Science.gov (United States)

    Chelko, Stephen P; Schmiedt, Chad W; Lewis, Tristan H; Lewis, Stephen J; Robertson, Tom P

    2013-01-01

    Circulating factors delivered to the nodose ganglion (NG) by the occipital artery (OA) have been shown to affect vagal afferent activity, and thus the contractile state of the OA may influence blood flow to the NG. OA were isolated and bisected into proximal and distal segments relative to the external carotid artery. Bisection highlighted stark differences between maximal contractile responses and OA sensitivity. Specifically, maximum responses to vasopressin and the V1 receptor agonist were significantly higher in distal than proximal segments. Distal segments were significantly more sensitive to 5-hydroxytryptamine (5-HT) and the 5-HT2 receptor agonist than proximal segments. Angiotensin II (AT)2, V2 and 5-HT(1B/1D) receptor agonists did not elicit vascular responses. Additionally, AT1 receptor agonists elicited mild, yet not significantly different maximal responses between segments. The results of this study are consistent with contractile properties of rat OA being mediated via AT1, V1 and 5-HT2 receptors and dependent upon the OA segment. Furthermore, vasopressin-induced constriction of the OA, regardless of a bolus dose or a first and second concentration-response curve, retained this unique segmental difference. We hypothesize that these segmental differences may be important in the regulation of blood flow through the OA in health and disease. © 2013 S. Karger AG, Basel.

  16. Vasopressin-induced constriction of the isolated rat occipital artery is segment-dependent

    Science.gov (United States)

    Chelko, Stephen P.; Schmiedt, Chad W.; Lewis, Tristan H.; Lewis, Stephen J.; Robertson, Tom P.

    2014-01-01

    Background Circulating factors delivered to the nodose ganglion (NG) by the occipital artery (OA) have shown to affect vagal afferent activity, and thus the contractile state of the OA may influence blood flow to the NG. Methods OA were isolated and bisected into proximal and distal segments, relative to the external carotid artery. Results Bisection, highlighted stark differences between maximal contractile responses and OA sensitivity. Specifically, maximum responses to vasopressin and the V1 receptor agonist, were significantly higher in distal than proximal segments. Distal segments were significantly more sensitive to 5-HT and the 5-HT2 receptor agonist than proximal segments. AT2, V2 and 5-HT1B/1D receptor agonists did not elicit vascular responses. Additionally, AT1 receptor agonists elicited mild, yet not significantly different maximal responses between segments. Conclusion The results of this study are consistent with contractile properties of rat OA being mediated via AT1, V1 and 5-HT2 receptors, and are dependent upon the OA segment. Furthermore, vasopressin-induced constriction of the OA, regardless of a bolus dose or a first and second concentration response curve retained this unique segmental difference and therefore we hypothesize this may be a pathophysiological response in the regulation of blood flow through the OA. PMID:24192548

  17. A novel polymorphism in the coding region of the vasopressin type 2 receptor gene

    Directory of Open Access Journals (Sweden)

    J.L. Rocha

    1997-04-01

    Full Text Available Nephrogenic diabetes insipidus (NDI is a rare disease characterized by renal inability to respond properly to arginine vasopressin due to mutations in the vasopressin type 2 receptor (V2(R gene in affected kindreds. In most kindreds thus far reported, the mode of inheritance follows an X chromosome-linked recessive pattern although autosomal-dominant and autosomal-recessive modes of inheritance have also been described. Studies demonstrating mutations in the V2(R gene in affected kindreds that modify the receptor structure, resulting in a dys- or nonfunctional receptor have been described, but phenotypically indistinguishable NDI patients with a structurally normal V2(R gene have also been reported. In the present study, we analyzed exon 3 of the V2(R gene in 20 unrelated individuals by direct sequencing. A C®T alteration in the third position of codon 331 (AGC®AGT, which did not alter the encoded amino acid, was found in nine individuals, including two unrelated patients with NDI. Taken together, these observations emphasize the molecular heterogeneity of a phenotypically homogeneous syndrome

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

    Science.gov (United States)

    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.

  19. Postnatal Expression of V2 Vasopressin Receptor Splice Variants in the Rat Cerebellum

    Science.gov (United States)

    Vargas, Karina J.; Sarmiento, José M.; Ehrenfeld, Pamela; Añazco, Carolina C.; Villanueva, Carolina I.; Carmona, Pamela L.; Brenet, Marianne; Navarro, Javier; Müller-Esterl, Werner; Figueroa, Carlos D.; González, Carlos B.

    2010-01-01

    The V2 vasopressin receptor gene contains an alternative splice site in exon-3, which leads to the generation of two splice variants (V2a and V2b) first identified in the kidney. The open reading frame of the alternatively spliced V2b transcripten codes a truncated receptor, showing the same amino acid sequence as the canonical V2a receptor up to the 6th transmembrane segment, but displaying a distinct sequence to the corresponding 7th transmembrane segment and C-terminal domain relative to the V2a receptor. Here, we demonstrate the postnatal expression of V2a and V2b variants in the rat cerebellum. Most importantly, we showed by in situ hybridization and immunocytochemistry that both V2 splice variants were preferentially expressed in Purkinje cells, from early to late postnatal development. In addition, both variants were transiently expressed in the neuroblastic external granule cells and Bergmann fibers. These results indicate that the cellular distributions of both splice variants are developmentally regulated, and suggest that the transient expression of the V2 receptor is involved in the mechanisms of cerebellar cytodifferentiation by AVP. Finally, transfected CHO-K1 .expressing similar amounts of both V2 splice variants, as that found in the cerebellum, showed a significant reduction in the surface expression of V2a receptors, suggesting that the differential expression of the V2 splice variants regulate the vasopressin signaling in the cerebellum. PMID:19281786

  20. 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.

  1. Oxytocin and Vasopressin: Linking Pituitary Neuropeptides and their Receptors to Social Neurocircuits

    Directory of Open Access Journals (Sweden)

    Danielle Andrea Baribeau

    2015-09-01

    Full Text Available Oxytocin and vasopressin are pituitary neuropeptides that have been shown to affect social processes in mammals. There is growing interest in these molecules and their receptors as potential precipitants of, and/or treatments for, social deficits in neurodevelopmental disorders, including autism spectrum disorder. Numerous behavioral-genetic studies suggest that there is an association between these peptides and individual social abilities; however, an explanatory model that links hormonal activity at the receptor level to complex human behavior remains elusive. The following review summarizes the known associations between the oxytocin and vasopressin neuropeptide systems and social neurocircuits in the brain. Following a micro- to macro- level trajectory, current literature on the synthesis and secretion of these peptides, and the structure, function and distribution of their respective receptors is first surveyed. Next, current models regarding the mechanism of action of these peptides on microcircuitry and other neurotransmitter systems are discussed. Functional neuroimaging evidence on the acute effects of exogenous administration of these peptides on brain activity is then reviewed. Overall, a model in which the local neuromodulatory effects of pituitary neuropeptides on brainstem and basal forebrain regions strengthen signaling within social neurocircuits proves appealing. However, these findings are derived from animal models; more research is needed to clarify the relevance of these mechanisms to human behavior and treatment of social deficits in neuropsychiatric disorders.

  2. 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.

  3. Studies of GI bleeding with scintigraphy and the influence of vasopressin

    International Nuclear Information System (INIS)

    Alavi, A.; McLean, G.K.

    1981-01-01

    The management of patients with gastrointestinal (GI) bleeding depends on accurate localization of the site of hemorrhage. Endoscopy and arteriography, although successful in achieving this goal in the majority of patients, are invasive and have other shortcomings. The introduction of the 99mTc-sulfur colloid technique has greatly simplified the evaluation and management of these patients. This test is useful in detecting and localizing the bleeding site in the lower GI tract. Scintigraphy is now used as the initial study of choice in patients with rectal bleeding. Advances made in angiography and nuclear medicine techniques also have resulted in improved management of patients. Conservative approaches succeed in controlling hemorrhage in most patients. Vasopressin is the most widely tested agent and has been adopted by many as the preferred preparation for this purpose. Before the introduction of the 99mTc-sulfur colloid technique, angiography was used to monitor the effectiveness of this drug, whether administered intravenously or intraarterially. With the use of scintigraphy and intravenous administration of vasopressin, these patients now can be managed noninvasively. Only when the intravenous Pitressin infusion fails to stop hemorrhage, is the intraarterial approach considered. Surgery is used as a last resort when these measures fail to stop the bleeding

  4. Personality is Tightly Coupled to Vasopressin-Oxytocin Neuron Activity in a Gregarious Finch

    Directory of Open Access Journals (Sweden)

    Aubrey M Kelly

    2014-02-01

    Full Text Available Nonapeptides of the vasopressin-oxytocin family modulate social processes differentially in relation to sex, species, behavioral phenotype, and human personality. However, the mechanistic bases for these differences are not well understood, in part because multidimensional personality structures remain to be described for common laboratory animals. Based upon principal components (PC analysis of extensive behavioral measures in social and nonsocial contexts, we now describe three complex dimensions of phenotype (personality for the zebra finch, a species that exhibits a human-like social organization that is based upon biparental nuclear families embedded within larger social groups. These dimensions can be characterized as Social competence/dominance, Gregariousness, and Anxiety. We further demonstrate that the phasic Fos response of nonapeptide neurons in the paraventricular nucleus of the hypothalamus and medial bed nucleus of the stria terminalis are significantly predicted by personality, sex, social context, and their interactions. Furthermore the behavioral PCs are each associated with a distinct suite of neural PCs that incorporate both peptide cell numbers and their phasic Fos responses, indicating that personality is reflected in complex patterns of neuromodulation arising from multiple peptide cell groups. These findings provide novel insights into the mechanisms underlying sex- and phenotype-specific modulation of behavior, and should be broadly relevant, given that vasopressin-oxytocin systems are strongly conserved across vertebrates.

  5. Hypothalamic obesity in patients with craniopharyngioma: Profound changes of several weight regulatory circuits

    Directory of Open Access Journals (Sweden)

    Christian eRoth

    2011-10-01

    Full Text Available One of the most striking examples of dysfunctional hypothalamic signaling of energy homeostasis is observed in patients with hypothalamic lesions leading to hypothalamic obesity (HO. This drastic condition is frequently seen in patients with craniopharyngioma (CP, an embryological tumor located in the hypothalamic and/or pituitary region, frequently causing not only hypopituitarism, but also leading to damage of medial hypothalamic nuclei due to the tumor and its treatment. HO syndrome in CP patients is characterized by fatigue, decreased physical activity, uncontrolled appetite, and morbid obesity, and is associated with insulin and leptin resistance. Mechanisms leading to the profoundly disturbed energy homeostasis are complex. This review summarizes different aspects of important clinical studies as well as data obtained in rodent studies. In addition a model is provided describing how medial hypothalamic lesion can interact simultaneously with several weight regulating circuitries.

  6. Differential modulation of lateral septal vasopressin receptor blockade in spatial learning, social recognition, and anxiety-related behaviors in rats

    NARCIS (Netherlands)

    Everts, HGJ; Koolhaas, JM

    1999-01-01

    The role of lateral septal vasopressin (VP) in the modulation of spatial memory, social memory, and anxiety-related behavior was studied in adult, male Wistar rats. Animals were equipped with osmotic minipumps delivering the VP-antagonist d(CH2)5-D-Tyr(Et)VAVP (1 ng/0.5 mu l per h) bilaterally into

  7. Response of arginine vasopressin-enhanced green fluorescent protein fusion gene in the hypothalamus of adjuvant-induced arthritic rats

    Czech Academy of Sciences Publication Activity Database

    Suzuki, H.; Onaka, T.; Kasai, M.; Kawasaki, M.; Ohnishi, H.; Otsubo, H.; Saito, T.; Hashimoto, H.; Yokoyama, T.; Fujihara, H.; Dayanithi, Govindan; Murphy, D.; Nakamura, T.; Ueta, Y.

    2009-01-01

    Roč. 21, č. 3 (2009), s. 183-190 ISSN 0953-8194 Institutional research plan: CEZ:AV0Z50390512 Keywords : arginine vasopressin * Corticotrophin-releasing hormone * GFP Subject RIV: FH - Neurology Impact factor: 3.700, year: 2009

  8. Familial neurohypophyseal diabetes insipidus due to a novel mutation in the arginine vasopressin-neurophysin II gene

    NARCIS (Netherlands)

    de Fost, M.; van Trotsenburg, A. S. P.; van Santen, H. M.; Endert, E.; van den Elzen, C.; Kamsteeg, E. J.; Swaab, D. F.; Fliers, E.

    2011-01-01

    Familial neurohypophyseal (central) diabetes insipidus (DI) is caused by mutations in the arginine vasopressin-neurophysin II (AVP-NPII) gene. The majority of cases is inherited in an autosomal dominant way. In this study, we present the clinical features of a mother and her son with autosomal

  9. Familial neurohypophyseal diabetes insipidus due to a novel mutation in the arginine vasopressin-neurophysin II gene

    NARCIS (Netherlands)

    Fost, M. de; Trotsenburg, A.S. van; Santen, H.M. van; Endert, E.; Elzen, C. van den; Kamsteeg, E.J.; Swaab, D.F.; Fliers, E.A.

    2011-01-01

    BACKGROUND: Familial neurohypophyseal (central) diabetes insipidus (DI) is caused by mutations in the arginine vasopressin-neurophysin II (AVP-NPII) gene. The majority of cases is inherited in an autosomal dominant way. In this study, we present the clinical features of a mother and her son with

  10. Copeptin, a surrogate marker for arginine vasopressin, is associated with declining glomerular filtration in patients with diabetes mellitus (ZODIAC-33)

    NARCIS (Netherlands)

    Boertien, W. E.; Riphagen, I. J.; Drion, I.; Alkhalaf, A.; Bakker, S. J. L.; Groenier, K. H.; Struck, J.; de Jong, P. E.; Bilo, H. J. G.; Kleefstra, N.; Gansevoort, R. T.

    Arginine vasopressin (AVP), the hormone important for maintaining fluid balance, has been shown to cause kidney damage in rodent models of diabetes. We investigated the potential role of AVP in the natural course of kidney function decline in diabetes in an epidemiological study. Plasma copeptin, a

  11. Vasopressin immunoreactivity and release in the suprachiasmatic nucleus of wild-type and tau mutant Syrian hamsters

    NARCIS (Netherlands)

    Van der Zee, EA; Oklejewicz, M; Jansen, K; Daan, S; Gerkema, MP

    2002-01-01

    Despite the prominent role of the Syrian hamster (Mesocricetus auratus) in studies of circadian rhythms, there are no data available on the temporal dynamics of the neuropeptide vasopressin (AVP), a major output system of the suprachiasmatic nucleus (SCN). We studied the hamster SCN-AVP system in

  12. Analogues of arginine vasopressin modified in the N-terminal part of the molecule with pipecolic acid isomers

    Czech Academy of Sciences Publication Activity Database

    Sobolewski, D.; Prahl, A.; Slaninová, Jiřina; Lammek, B.

    2009-01-01

    Roč. 611, - (2009), s. 501-502 ISSN 0065-2598. [American Peptide Society Symposium /20./. 26.06.2007-30.06.2007, Montreal] Institutional research plan: CEZ:AV0Z40550506 Keywords : vasopressin * pipecolic acid * biological activity Subject RIV: CC - Organic Chemistry

  13. Analogues of arginine vasopressin modified at position 2 with proline derivatives: selective antagonists of oxytocin in vitro

    Czech Academy of Sciences Publication Activity Database

    Sobolewski, D.; Prahl, A.; Slaninová, Jiřina; Lammek, B.

    2009-01-01

    Roč. 611, - (2009), s. 503-504 ISSN 0065-2598. [American Peptide Society Symposium /20./. 26.06.2007-30.06.2007, Montreal] Institutional research plan: CEZ:AV0Z40550506 Keywords : vasopressin * proline derivatives * oxytocin antagonists Subject RIV: CC - Organic Chemistry

  14. Sociality and oxytocin and vasopressin in the brain of male and female dominant and subordinate mandarin voles.

    Science.gov (United States)

    Qiao, Xufeng; Yan, Yating; Wu, Ruiyong; Tai, Fadao; Hao, Ping; Cao, Yan; Wang, Jianli

    2014-02-01

    The dominant-subordinate hierarchy in animals often needs to be established via agonistic encounters and consequently affects reproduction and survival. Differences in brain neuropeptides and sociality among dominant and subordinate males and females remain poorly understood. Here we explore neuropeptide levels and sociality during agonistic encounter tests in mandarin voles. We found that dominant mandarin voles engaged in higher levels of approaching, investigating, self-grooming and exploring behavior than subordinates. Dominant males habituated better to a stimulus vole than dominant females. Dominant males displayed significantly less oxytocin-immunoreactive neurons in the paraventricular nuclei and more vasopressin-immunoreactive neurons in the paraventricular nuclei, supraoptic nuclei, and the lateral and anterior hypothalamus than subordinates. Dominant females displayed significantly more vasopressin-immunoreactive neurons in the lateral hypothalamus and anterior hypothalamus than subordinates. Sex differences were found in the level of oxytocin and vasopressin. These results indicate that distinct parameters related to central nervous oxytocin and vasopressin are associated with behaviors during agonistic encounters in a sex-specific manner in mandarin voles.

  15. Polyuria due to vasopressin V2 receptor antagonism is not associated with increased ureter diameter in ADPKD patients

    NARCIS (Netherlands)

    Casteleijn, Niek F.; Messchendorp, A. Lianne; Bae, Kyong T.; Higashihara, Eiji; Kappert, Peter; Torres, Vicente; Meijer, Esther; Leliveld, Anna M.

    Tolvaptan, a vasopressin V2 receptor antagonist, has been shown to reduce the rates of growth in total kidney volume (TKV) and renal function loss in ADPKD patients, but also leads to polyuria because of its aquaretic effect. Prolonged polyuria can result in ureter dilatation with consequently renal

  16. Vasopressin increases S261 phosphorylation in AQP2-P262L, a mutant in recessive nephrogenic diabetes insipidus

    NARCIS (Netherlands)

    Trimpert, C.; van den Berg, D.T.; Fenton, R.A.; Klussmann, E.; Deen, P.M.T.

    2012-01-01

    Background Mutations in the aquaporin-2 (AQP2) gene cause nephrogenic diabetes insipidus (NDI), a renal disorder characterized by polyuria due to a lacking antidiuretic response to vasopressin. While most AQP2 mutants in recessive NDI are misfolded and retained in the endoplasmic reticulum,

  17. Dialysis Hypotension : A Role for Inadequate Increase in Arginine Vasopressin Levels? A Systematic Literature Review and Meta-Analysis

    NARCIS (Netherlands)

    Ettema, Esmee M.; Zittema, Debbie; Kuipers, Johanna; Gansevoort, Ron T.; Vart, Priya; de Jong, Paul E.; Westerhuis, Ralf; Franssen, Casper F. M.

    2014-01-01

    Background: Intradialytic hypotension is a common complication of hemodialysis (HD). Some studies have suggested that inadequate arginine vasopressin (AVP) increase could play a role in the pathogenesis of intradialytic hypotension. However, AVP levels during HD and its relation to hypotension has

  18. Analogues of arginine vasopressin (AVP) modified inthe N-terminal part of the molecule with stereoisomers of 4-aminopyroglutamic acid

    Czech Academy of Sciences Publication Activity Database

    Sobolewski, D.; Kowalczyk, W.; Derdowska, I.; Slaninová, Jiřina; Zabrocki, J.; Lammek, B.

    2005-01-01

    Roč. 79, č. 4 (2005), 731-737 ISSN 0137- 5083 Grant - others:PSCSR(PL) KBN6P05F01021; PSCSR(PL) BW8000-5-0222-3 Institutional research plan: CEZ:AV0Z40550506 Keywords : arginine vasopressin (AVP) * oxytocin * 4-aminopyroglutamic acid Subject RIV: CE - Biochemistry Impact factor: 0.513, year: 2005

  19. Analogues of arginine vasopressin (AVP) modified in the N-terminal part of the molecule with N-benzylglycine

    Czech Academy of Sciences Publication Activity Database

    Jastrzebska, B.; Derdowska, I.; Kunčarová, Pavla; Slaninová, Jiřina; Lammek, B.; Olejniczak, B.; Zabrocki, J.

    2002-01-01

    Roč. 76, - (2002), s. 823-830 ISSN 0137- 5083 Grant - others:PSCSR(PL) 6PO5F01021; PSCSR(PL) BW8000-5-0171-1 Institutional research plan: CEZ:AV0Z4055905 Keywords : arginine vasopressin (AVP) Subject RIV: CC - Organic Chemistry Impact factor: 0.528, year: 2002

  20. Increased plasma concentrations of vasopressin, oxytocin, cortisol and the prostaglandin F2alpha metabolite during labour in the dog.

    Science.gov (United States)

    Olsson, K; Bergström, A; Kindahl, H; Lagerstedt, A-S

    2003-11-01

    This study investigated if the plasma vasopressin concentration increases during labour in the dog and whether the change in vasopressin correlates with that of oxytocin, 15-ketodihydro-PGF2alpha and cortisol. Five beagle dogs each delivered three to seven puppies. Blood samples were taken from a catheter inserted into the cephalic vein during labour and by venepuncture during the other periods. Vasopressin concentration increased from 2 +/- 0 pmol L-1 (anoestrus) to 26 +/- 11 pmol L-1 at the birth of the first puppy, remained high at the birth of the second puppy and then decreased. Oxytocin increased from 63 +/- 5 pmol L-1 (anoestrus) to 166 +/- 19 pmol L-1 at the birth of the first puppy and remained elevated throughout labour. The PGF2alpha metabolite concentration increased from 0.2 +/- 0.0 nmol L-1 (anoestrus) to 66 +/- 17 nmol L-1 at the birth of the first puppy and remained elevated 1 h after the completion of parturition. The cortisol concentration increased from 49 +/- 9 nmol L-1 (anoestrus) to 242 +/- 35 nmol L-1 at the birth of the first puppy, remained high during the birth of the second puppy and then declined. The plasma level of vasopressin was strongly correlated with that of cortisol but less with that of the PGF2alpha metabolite, and not significantly with the concentration of oxytocin. This indicates that the four hormones play different roles during labour in the dog.

  1. Endogenous vasopressin, innate anxiety, and the emission of pro-social 50-kHz ultrasonic vocalizations during social play behavior in juvenile rats.

    Science.gov (United States)

    Lukas, Michael; Wöhr, Markus

    2015-06-01

    Although the involvement of the neuropeptide arginine vasopressin (AVP) in rodent social interaction is already extensively characterized, little is known about its role in social communication. Rats communicate in the ultrasonic range by means of ultrasonic vocalizations (USV). Depending on developmental stage and affective state, rats emit various distinct types of USV, with appetitive 50-kHz USV being induced by positive social interactions, like juvenile social play, probably serving an affiliative communicative function, namely to (re)establish or induce social proximity. In rats and mice selectively bred for low (LAB) and high (HAB) anxiety-related behavior, the emission of isolation-induced distress USV during maternal deprivation as pups correlates with innate high levels of hypothalamic AVP availability. Moreover, male LAB and HAB rats express deficits in social approach towards conspecifics, together with high and/or abnormal forms of aggression when confronted with harmless opponents, possibly due to a lack of social communication skills. The aim of this study was therefore (1) to investigate and characterize social play behavior and concomitant pro-social 50-kHz USV emission in male and female, juvenile LAB and HAB rats and to compare them to non-selected Wistar (NAB) rats; and (2) to link these findings pharmacologically to the central AVP system via applying an AVP 1a receptor (V1aR) antagonist (0.75 μg; Manning compound) or synthetic AVP (1 ng) into the lateral ventricle of male juvenile NAB rats. Our results show that reduced social play behavior in highly anxious male and female, juvenile HAB rats is accompanied by low amounts of pro-social 50-kHz USV, as compared to respective LAB and NAB rats, possibly reflecting a lack of positive affective states in expectation of or following social interactions in these individuals. Secondly, although synthetic AVP did not alter social play behavior and pro-social 50-kHz USV, we demonstrated for the first

  2. Correlation between neurohypophyseal vasopressin content and signal intensity on T{sub 1}-weighted magnetic resonance images. An experimental study of vasopressin depletion model using dehydrated rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Kurokawa, Hiroaki; Nakano, Yoshihisa; Ikeda, Koshi; Tanaka, Yoshimasa [Kansai Medical Univ., Moriguchi, Osaka (Japan); Fujisawa, Ichiro

    1998-06-01

    We investigated the correlation between the signal intensity on T{sub 1}-weighted MR images and vasopressin (VP) content in the posterior pituitary lobe. Fourteen rabbits were studied. There were 12 water-deprived rabbits (48, 72, 96, 120, 144 and 168 hours: 2 each) and 2 controls. Sagittal T{sub 1}-weighted SE (spin-echo) MR images were obtained before and after dehydration. The signal intensity ratio of the posterior pituitary lobe to the pons was correlated with the VP content in the posterior lobe as measured by radioimmunoassay. Before water deprivation, high signal intensity in the posterior lobe was demonstrated clearly in all 14 rabbits. After water deprivation, the hyperintense signal gradually decreased and became indistinguishable from anterior lobe in four animals. The mean signal intensity ratio before water deprivation was 1.55{+-}0.12 (mean{+-}SD) and after water deprivation, gradually decreased over time and reached to 1.19 after 168 hours of water deprivation. Pituitary VP content and concentration decreased in parallel with the signal intensity ratio of the posterior pituitary. Significantly correlation was observed between the signal intensity ratio and VP concentration of posterior pituitary (r=0.809, p<0.001) . In conclusion, the results indicate that the signal intensity ratio on T{sub 1}-weighted image may reflect a indicator of pituitary VP content and thus may enable evaluation of disorders of water metabolism. (author)

  3. Correlation between neurohypophyseal vasopressin content and signal intensity on T1-weighted magnetic resonance images. An experimental study of vasopressin depletion model using dehydrated rabbits

    International Nuclear Information System (INIS)

    Kurokawa, Hiroaki; Nakano, Yoshihisa; Ikeda, Koshi; Tanaka, Yoshimasa; Fujisawa, Ichiro

    1998-01-01

    We investigated the correlation between the signal intensity on T 1 -weighted MR images and vasopressin (VP) content in the posterior pituitary lobe. Fourteen rabbits were studied. There were 12 water-deprived rabbits (48, 72, 96, 120, 144 and 168 hours: 2 each) and 2 controls. Sagittal T 1 -weighted SE (spin-echo) MR images were obtained before and after dehydration. The signal intensity ratio of the posterior pituitary lobe to the pons was correlated with the VP content in the posterior lobe as measured by radioimmunoassay. Before water deprivation, high signal intensity in the posterior lobe was demonstrated clearly in all 14 rabbits. After water deprivation, the hyperintense signal gradually decreased and became indistinguishable from anterior lobe in four animals. The mean signal intensity ratio before water deprivation was 1.55±0.12 (mean±SD) and after water deprivation, gradually decreased over time and reached to 1.19 after 168 hours of water deprivation. Pituitary VP content and concentration decreased in parallel with the signal intensity ratio of the posterior pituitary. Significantly correlation was observed between the signal intensity ratio and VP concentration of posterior pituitary (r=0.809, p 1 -weighted image may reflect a indicator of pituitary VP content and thus may enable evaluation of disorders of water metabolism. (author)

  4. Effects of Intraosseous Tibial vs. Intravenous Vasopressin in a Hypovolemic Cardiac Arrest Model

    Directory of Open Access Journals (Sweden)

    Justin Fulkerson, MSN

    2016-03-01

    Full Text Available Introduction: This study compared the effects of vasopressin via tibial intraosseous (IO and intravenous (IV routes on maximum plasma concentration (Cmax, the time to maximum concentration (Tmax, return of spontaneous circulation (ROSC, and time to ROSC in a hypovolemic cardiac arrest model. Methods: This study was a randomized prospective, between-subjects experimental design. A computer program randomly assigned 28 Yorkshire swine to one of four groups: IV (n=7, IO tibia (n=7, cardiopulmonary resuscitation (CPR + defibrillation (n=7, and a control group that received just CPR (n=7. Ventricular fibrillation was induced, and subjects remained in arrest for two minutes. CPR was initiated and 40 units of vasopressin were administered via IO or IV routes. Blood samples were collected at 0.5, 1, 1.5, 2, 2.5, 3, and 4 minutes. CPR and defibrillation were initiated for 20 minutes or until ROSC was achieved. We measured vasopressin concentrations using highperformance liquid chromatography. Results: There was no significant difference between the IO and IV groups relative to achieving ROSC (p=1.0 but a significant difference between the IV compared to the CPR+ defibrillation group (p=0.031 and IV compared to the CPR-only group (p=0.001. There was a significant difference between the IO group compared to the CPR+ defibrillation group (p=0.031 and IO compared to the CPR-only group (p=0.001. There was no significant difference between the CPR + defibrillation group and the CPR group (p=0.127. There was no significant difference in Cmax between the IO and IV groups (p=0.079. The mean ± standard deviation of Cmax of the IO group was 58,709±25,463pg/mL compared to the IV group, which was 106,198±62,135pg/mL. There was no significant difference in mean Tmax between the groups (p=0.084. There were no significant differences in odds of ROSC between the tibial IO and IV groups. Conclusion: Prompt access to the vascular system using the IO route can circumvent

  5. Estrogens modulate ventrolateral ventromedial hypothalamic glucose-inhibited neurons

    Directory of Open Access Journals (Sweden)

    Ammy M. Santiago

    2016-10-01

    Full Text Available Objective: Brain regulation of glucose homeostasis is sexually dimorphic; however, the impact sex hormones have on specific neuronal populations within the ventromedial hypothalamic nucleus (VMN, a metabolically sensitive brain region, has yet to be fully characterized. Glucose-excited (GE and -inhibited (GI neurons are located throughout the VMN and may play a critical role in glucose and energy homeostasis. Within the ventrolateral portion of the VMN (VL-VMN, glucose sensing neurons and estrogen receptor (ER distributions overlap. We therefore tested the hypothesis that VL-VMN glucose sensing neurons were sexually dimorphic and regulated by 17β-estradiol (17βE. Methods: Electrophysiological recordings of VL-VMN glucose sensing neurons in brain slices isolated from age- and weight-matched female and male mice were performed in the presence and absence of 17βE. Results: We found a new class of VL-VMN GI neurons whose response to low glucose was transient despite continued exposure to low glucose. Heretofore, we refer to these newly identified VL-VMN GI neurons as ‘adapting’ or AdGI neurons. We found a sexual dimorphic response to low glucose, with male nonadapting GI neurons, but not AdGI neurons, responding more robustly to low glucose than those from females. 17βE blunted the response of both nonadapting GI and AdGI neurons to low glucose in both males and females, which was mediated by activation of estrogen receptor β and inhibition of AMP-activated kinase. In contrast, 17βE had no impact on GE or non-glucose sensing neurons in either sex. Conclusion: These data suggest sex differences and estrogenic regulation of VMN hypothalamic glucose sensing may contribute to the sexual dimorphism in glucose homeostasis. Author Video: Author Video Watch what authors say about their articles Keywords: 17β-estradiol, AMP-activated kinase, Glucose excited neurons, Glucose inhibited neurons, Ventromedial hypothalamic nucleus, Sexual dimorphism

  6. Alterations in the hypothalamic melanocortin pathway in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Vercruysse, Pauline; Sinniger, Jérôme; El Oussini, Hajer; Scekic-Zahirovic, Jelena; Dieterlé, Stéphane; Dengler, Reinhard; Meyer, Thomas; Zierz, Stephan; Kassubek, Jan; Fischer, Wilhelm; Dreyhaupt, Jens; Grehl, Torsten; Hermann, Andreas; Grosskreutz, Julian; Witting, Anke; Van Den Bosch, Ludo; Spreux-Varoquaux, Odile; Ludolph, Albert C; Dupuis, Luc

    2016-04-01

    Amyotrophic lateral sclerosis, the most common adult-onset motor neuron disease, leads to death within 3 to 5 years after onset. Beyond progressive motor impairment, patients with amyotrophic lateral sclerosis suffer from major defects in energy metabolism, such as weight loss, which are well correlated with survival. Indeed, nutritional intervention targeting weight loss might improve survival of patients. However, the neural mechanisms underlying metabolic impairment in patients with amyotrophic lateral sclerosis remain elusive, in particular due to the lack of longitudinal studies. Here we took advantage of samples collected during the clinical trial of pioglitazone (GERP-ALS), and characterized longitudinally energy metabolism of patients with amyotrophic lateral sclerosis in response to pioglitazone, a drug with well-characterized metabolic effects. As expected, pioglitazone decreased glycaemia, decreased liver enzymes and increased circulating adiponectin in patients with amyotrophic lateral sclerosis, showing its efficacy in the periphery. However, pioglitazone did not increase body weight of patients with amyotrophic lateral sclerosis independently of bulbar involvement. As pioglitazone increases body weight through a direct inhibition of the hypothalamic melanocortin system, we studied hypothalamic neurons producing proopiomelanocortin (POMC) and the endogenous melanocortin inhibitor agouti-related peptide (AGRP), in mice expressing amyotrophic lateral sclerosis-linked mutant SOD1(G86R). We observed lower Pomc but higher Agrp mRNA levels in the hypothalamus of presymptomatic SOD1(G86R) mice. Consistently, numbers of POMC-positive neurons were decreased, whereas AGRP fibre density was elevated in the hypothalamic arcuate nucleus of SOD1(G86R) mice. Consistent with a defect in the hypothalamic melanocortin system, food intake after short term fasting was increased in SOD1(G86R) mice. Importantly, these findings were replicated in two other amyotrophic

  7. Hypothalamic amenorrhea in young women with underlying polycystic ovary syndrome.

    Science.gov (United States)

    Sum, Melissa; Warren, Michelle P

    2009-12-01

    The purpose of this study was to compare the hormonal/clinical profiles and markers of bone health of women with hypothalamic amenorrhea (HA) to women with suspected HA and underlying polycystic ovary syndrome (PCOS). The results indicate that compared to women with HA, women with HA and underlying PCOS exhibit higher body mass index (BMI), bone mineral densities, and incidence of hyperandrogenism, that they may exhibit increased hyperandrogenism and irregular menses with weight gain, and that they remain at similar risk for osteopenia and osteoporosis.

  8. Conception, synthesis and evaluation of fluorescent probes and PET radioligands for the oxytocin and vasopressin receptors

    International Nuclear Information System (INIS)

    Karpenko, Iuliia

    2014-01-01

    In order to better understand the role of OTR and AVPR in ASD, to reveal new features in its pharmacology and signaling and to establish high-throughput screening method on wild-type G protein-coupled receptors, we developed imaging probes for the oxytocin-vasopressin receptors family, namely radiotracers for positron emission tomography and optical probes for fluorescence detection and imaging. The fluorescent ligands have been used to establish TR-FRET binding assay for OTR and to initiate the development the screening assay for the wild-type oxytocin receptor. The PET radiotracers will be shortly tested in mice and monkeys to evaluate their potency in detecting the central oxytocin receptors. (author)

  9. Vasopressin-dependent short-term regulation of aquaporin 4 expressed in Xenopus oocytes

    DEFF Research Database (Denmark)

    Moeller, H B; Fenton, R A; Zeuthen, T

    2009-01-01

    Aquaporin 4 (AQP4) is abundantly expressed in the perivascular glial endfeet in the central nervous system (CNS), where it is involved in the exchange of fluids between blood and brain. At this location, AQP4 contributes to the formation and/or the absorption of the brain edema that may arise...... following pathologies such as brain injuries, brain tumours, and cerebral ischemia. As vasopressin and its G-protein-coupled receptor (V1(a)R) have been shown to affect the outcome of brain edema, we have investigated the regulatory interaction between AQP4 and V1(a)R by heterologous expression in Xenopus......)R may prove to be a potential therapeutic target in the prevention and treatment of brain edema....

  10. Phylogenetic study of the arginine-vasotocin/arginine-vasopressin-like immunoreactive system in invertebrates.

    Science.gov (United States)

    Mizuno, J; Takeda, N

    1988-01-01

    1. A phylogenetic study of arg-vasotocin (AVT)/arg-vasopressin (AVP)-like immunoreactive cells was performed by the PAP method in the central nervous system of invertebrates. 2. The immunoreactivity was detected in the nerve cells of Hydra magnipapillata of the Coelenterata; Neanthes japonica and Pheretima communissima of the Annelida; Pomacea canaliculata, Aplysia kurodai, Oncidium verrucosum, Bradybaena similaris, Achatina fulica, Limax marginatus and Meretrix lamarckii of the Mollusca; Gnorimosphaeroma rayi, Hemigrapsus sanguineus, Gryllus bimaculatus and Baratha brassicae of the Arthropoda; Asterina pectinifera of the Echinodermata; and Halocynthia roretzi of the Protochordata. 3. No immunoreactivity was detected in Bipalium sp. of the Platyhelminthes, or in Procambarus clarkii and Helice tridens of the Arthropoda. 4. From these results, it appears that AVT/AVP is a phylogenetically ancient peptide which is present in a wide variety of invertebrates. 5. The actions of AVT/AVP and its presence in invertebrates are discussed.

  11. Polarized expression of the GFP-tagged rat V(1a) vasopressin receptor.

    Science.gov (United States)

    Campos, D M; Reyes, C E; Sarmiento, J; Navarro, J; González, C B

    2001-11-30

    We investigated the targeting of the V(1a) receptor fused with the green fluorescence protein (V(1a)R-GFP) in polarized MDCK cells. Cells expressing V(1a)R-GFP displayed binding to vasopressin (AVP) and AVP-induced calcium responses, similar to cells expressing the wild-type V1a receptor. Interestingly, as with the wild-type V(1a)R, V(1a)R-GFP is preferentially distributed in the basolateral side of MDCK cells as monitored by confocal microscopy. Furthermore, AVP induced internalization of GFP-tagged receptors. Therefore, the GFP-tagged V(1a) receptor retains all the sorting signals of the wild-type receptor and offers an excellent system to elucidate the mechanisms of cell trafficking of V(1a) receptors.

  12. Increased concentration of vasopressin in plasma of essential fatty acid-deficient rats

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Jensen, B.; Warberg, J.

    1985-01-01

    The effect of essential fatty acid deficiency (EFA-D) on the plasma concentration of arginine-vasopressin (AVP) and the urinary AVP excretion was investigated. Weanling rats were fed a fat-free diet (FF-rats). Control rats received the same diet in which 6% by wt. of sucrose was replaced by arachis...... oil. After 4-6 weeks of feeding, urine and plasma were analysed for AVP, osmolality, sodium and potassium. When compared to control rats FF-rats had decreased urine volume (6.0 ± 1.6 ml/24 hr versus 11.7 ± 3.2 ml/24 hr), increased urine osmolality (2409 ± 691 mOsm/kg versus 1260 ± 434 m...

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

    Science.gov (United States)

    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.

  14. Effect of arginine vasopressin in the nucleus raphe magnus on antinociception in the rat.

    Science.gov (United States)

    Yang, Jun; Chen, Jian-Min; Liu, Wen-Yan; Song, Cao-You; Wang, Cheng-Hai; Lin, Bao-Cheng

    2006-09-01

    Previous work has shown that arginine vasopressin (AVP) regulates antinociception through brain nuclei rather than the spinal cord and peripheral organs. The present study investigated the nociceptive effect of AVP in the nucleus raphe magnus (NRM) of the rat. Microinjection of AVP into the NRM increased pain threshold in a dose-dependent manner, while local administration of AVP-receptor antagonist-d(CH2)5Tyr(Et)DAVP decreased the pain threshold. Pain stimulation elevated AVP concentration in the NRM perfuse liquid. NRM pretreatment with AVP-receptor antagonist completely reversed AVP's effect on pain threshold in the NRM. The data suggest that AVP in the NRM is involved in antinociception.

  15. Radioimmunoassay of arginine-vasopressin in human urine and its use in physiological and pathological states

    International Nuclear Information System (INIS)

    Khokhar, A.M.; Ramaga, C.M.; Slater, J.D.H.

    1978-01-01

    A highly specific radioimmunoassay for arginine-vasopressin (AVP) in human urine has been developed with a detection limit of 2.2 fmol/ml. The mean recovery of added AVP was 99.5 +- 3.1 (S.D.) % when correction was made for the fact that an inverse relationship was observed between the recovery of AVP and the osmolarity of the urine. The intra- and interassay coefficients of variation were 3.5 - 7 and 2.5 - 10% respectively. Arginine-vasopressin remains stable in urine after repeated freezing and thawing after storage at 4 or 20 0 C for up to 7 days and at 20 0 C for more than 3 months. During unrestricted fluid intake in normal people, the mean rate of renal excretion of AVP was 95 +- 68 (SD) fmol/min. An osmotic reduction of 9% in the plasma volume increased the excretion of AVP to 259 +- 147 (SD) fmol/min. Fluid deprivation for 18 h produced a moderate but significant increase in mean excretion of AVP, to a value of 116 +- 67 (SD) fmol/min. Patients with compulsive water drinking showed a normal relationship between urine osmolarity and the rate of excretion of AVP. In pituitary diabetes insipidus, AVP was undetectable, whereas in hereditary nephrogenic diabetes insipidus a progressive increase in the rate of excretion was observed in response to dehydration. There was a wide variation in the rate of excretion of AVP (range 126 - 8704 fmol/min) in patients with unexplained hyponatraemia, presumed to be due to an inappropriate secretion of antidiuretic hormone. Despite this variation, the relationship between urine osmolarity and the rate of excretion of AVP differed from that observed in normal people. (author)

  16. Relationships among estrogen receptor, oxytocin and vasopressin gene expression and social interaction in male mice.

    Science.gov (United States)

    Murakami, G; Hunter, R G; Fontaine, C; Ribeiro, A; Pfaff, D

    2011-08-01

    The incidence of social disorders such as autism and schizophrenia is significantly higher in males, and the presentation more severe, than in females. This suggests the possible contribution of sex hormones to the development of these psychiatric disorders. There is also evidence that these disorders are highly heritable. To contribute toward our understanding of the mechanisms underlying social behaviors, particularly social interaction, we assessed the relationship of social interaction with gene expression for two neuropeptides, oxytocin (OT) and arginine vasopressin (AVP), using adult male mice. Social interaction was positively correlated with: oxytocin receptor (OTR) and vasopressin receptor (V1aR) mRNA expression in the medial amygdala; and OT and AVP mRNA expression in the paraventricular nucleus of the hypothalamus (PVN). When mice representing extremes of social interaction were compared, all of these mRNAs were more highly expressed in high social interaction mice than in low social interaction mice. OTR and V1aR mRNAs were highly correlated with estrogen receptor α (ERα) mRNA in the medial amygdala, and OT and AVP mRNAs with estrogen receptor β (ERβ) mRNA in the PVN, indicating that OT and AVP systems are tightly regulated by estrogen receptors. A significant difference in the level of ERα mRNA in the medial amygdala between high and low social interaction mice was also observed. These results support the hypothesis that variations of estrogen receptor levels are associated with differences in social interaction through the OT and AVP systems, by upregulating gene expression for those peptides and their receptors. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  17. Diagnostic accuracy and comparison of BIPSS in response to lysine vasopressin and hCRH

    Directory of Open Access Journals (Sweden)

    Kush Dev Singh Jarial

    2018-03-01

    Full Text Available Context: Bilateral inferior petrosal sinus sampling (BIPSS using hCRH is currently considered the ‘gold standard’ test for the differential diagnosis of ACTH-dependent Cushing’s syndrome (CS. Vasopressin is more potent than CRH to stimulate ACTH secretion as shown in animal studies; however, no comparative data of its use are available during BIPSS. Objective: To study the diagnostic accuracy and comparison of hCRH and lysine vasopressin (LVP stimulation during BIPSS. Patients and methods: 29 patients (27-Cushing’s disease, 2-ectopic CS; confirmed on histopathology underwent BIPSS and were included for the study. Patients were randomized to receive hCRH, 5 U LVP or 10 U LVP during BIPSS for ACTH stimulation. BIPSS and contrast-enhanced magnetic resonance imaging (CEMRI were compared with intra-operative findings of trans-sphenoidal surgery (TSS for localization and lateralization of the ACTH source. Results: BIPSS correctly localized the source of ACTH excess in 29/29 of the patients with accuracy of 26/26 patients, using any of the agent, whereas sensitivity and PPV for lateralization with hCRH, 5 U LVP and 10 U LVP was seen in 10/10, 6/10; 10/10,8/10 and 7/7,6/7 patients respectively. Concordance of BIPSS with TSS was seen in 20/27, CEMRI with BIPSS in 16/24 and CEMRI with TSS in 18/24 of patients for lateralizing the adenoma. Most of the side effects were transient and were comparable in all the three groups. Conclusion: BIPSS using either hCRH or LVP (5 U or 10 U confirmed the source of ACTH excess in all the patients, while 10 U LVP correctly lateralized the pituitary adenoma in three fourth of the patients.

  18. Functionality of promoter microsatellites of arginine vasopressin receptor 1A (AVPR1A): implications for autism

    LENUS (Irish Health Repository)

    Tansey, Katherine E

    2011-03-31

    Abstract Background Arginine vasopressin (AVP) has been hypothesized to play a role in aetiology of autism based on a demonstrated involvement in the regulation of social behaviours. The arginine vasopressin receptor 1A gene (AVPR1A) is widely expressed in the brain and is considered to be a key receptor for regulation of social behaviour. Moreover, genetic variation at AVPR1A has been reported to be associated with autism. Evidence from non-human mammals implicates variation in the 5\\'-flanking region of AVPR1A in variable gene expression and social behaviour. Methods We examined four tagging single nucleotide polymorphisms (SNPs) (rs3803107, rs1042615, rs3741865, rs11174815) and three microsatellites (RS3, RS1 and AVR) at the AVPR1A gene for association in an autism cohort from Ireland. Two 5\\'-flanking region polymorphisms in the human AVPR1A, RS3 and RS1, were also tested for their effect on relative promoter activity. Results The short alleles of RS1 and the SNP rs11174815 show weak association with autism in the Irish population (P = 0.036 and P = 0.008, respectively). Both RS1 and RS3 showed differences in relative promoter activity by length. Shorter repeat alleles of RS1 and RS3 decreased relative promoter activity in the human neuroblastoma cell line SH-SY5Y. Conclusions These aligning results can be interpreted as a functional route for this association, namely that shorter alleles of RS1 lead to decreased AVPR1A transcription, which may proffer increased susceptibility to the autism phenotype.

  19. Hepatic vagotomy alters limbic and hypothalamic neuropeptide responses to insulin-dependent diabetes and voluntary lard ingestion

    NARCIS (Netherlands)

    la Fleur, Susanne E.; Manalo, Sotara L.; Roy, Monica; Houshyar, Hani; Dallman, Mary F.

    2005-01-01

    Hypothalamic anorexigenic [corticotropin-releasing factor (CRF) and proopiomelanocortin] peptides decrease and the orexigen, neuropeptide Y, increases with diabetic hyperphagia. However, when diabetic rats are allowed to eat lard (saturated fat) as well as chow, both caloric intake and hypothalamic

  20. A randomised, double-blind, multi-centre trial comparing vasopressin and adrenaline in patients with cardiac arrest presenting to or in the Emergency Department.

    Science.gov (United States)

    Ong, Marcus Eng Hock; Tiah, Ling; Leong, Benjamin Sieu-Hon; Tan, Elaine Ching Ching; Ong, Victor Yeok Kein; Tan, Elizabeth Ai Theng; Poh, Bee Yen; Pek, Pin Pin; Chen, Yuming

    2012-08-01

    To compare vasopressin and adrenaline in the treatment of patients with cardiac arrest presenting to or in the Emergency Department (ED). A randomised, double-blind, multi-centre, parallel-design clinical trial in four adult hospitals. Eligible cardiac arrest patients (confirmed by the absence of pulse, unresponsiveness and apnea) aged >16 (aged>21 for one hospital) were randomly assigned to intravenous adrenaline (1mg) or vasopressin (40 IU) at ED. Patients with traumatic cardiac arrest or contraindication for cardiopulmonary resuscitation (CPR) were excluded. Patients received additional open label doses of adrenaline as per current guidelines. Primary outcome was survival to hospital discharge (defined as participant discharged alive or survival to 30 days post-arrest). The study recruited 727 participants (adrenaline = 353; vasopressin = 374). Baseline characteristics of the two groups were comparable. Eight participants (2.3%) from adrenaline and 11 (2.9%) from vasopressin group survived to hospital discharge with no significant difference between groups (p = 0.27, RR = 1.72, 95% CI = 0.65-4.51). After adjustment for race, medical history, bystander CPR and prior adrenaline given, more participants survived to hospital admission with vasopressin (22.2%) than with adrenaline (16.7%) (p = 0.05, RR = 1.43, 95% CI = 1.02-2.04). Sub-group analysis suggested improved outcomes for vasopressin in participants with prolonged arrest times. Combination of vasopressin and adrenaline did not improve long term survival but seemed to improve survival to admission in patients with prolonged cardiac arrest. Further studies on the effect of vasopressin combined with therapeutic hypothermia on patients with prolonged cardiac arrest are needed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  1. Oral glucose intake inhibits hypothalamic neuronal activity more effectively than glucose infusion

    NARCIS (Netherlands)

    Smeets, P.A.M.; Vidarsdottir, S.; Graaf, de C.; Stafleu, A.; Osch, M.J.P.; Viergever, M.A.; Pijl, H.; Grond, van der J.

    2007-01-01

    Oral glucose intake inhibits hypothalamic neuronal activity more effectively than glucose infusion. Am J Physiol Endocrinol Metab 293: E754-E758, 2007. First published June 12, 2007; doi:10.1152/ajpendo.00231.2007. - We previously showed that hypothalamic neuronal activity, as measured by the blood

  2. Oral glucose intake inhibits hypothalamic neuronal activity more effectively than glucose infusion

    NARCIS (Netherlands)

    Smeets, P.A.M.; Vidarsdottir, S.; Graaf, C. de; Stafleu, A.; Osch, M.J.P. van; Viergever, M.A.; Pijl, H.; Grond, J. van der

    2007-01-01

    We previously showed that hypothalamic neuronal activity, as measured by the blood oxygen level-dependent (BOLD) functional MRI signal, declines in response to oral glucose intake. To further explore the mechanism driving changes in hypothalamic neuronal activity in response to an oral glucose load,

  3. Vasopressin-dependent flank marking in golden hamsters is suppressed by drugs used in the treatment of obsessive-compulsive disorder

    Directory of Open Access Journals (Sweden)

    Messenger Tara

    2001-08-01

    Full Text Available Abstract Background Alterations in arginine vasopressin regulation and secretion have been proposed as one possible biochemical abnormality in patients with obsessive-compulsive disorder. In golden hamsters, arginine vasopressin microinjections into the anterior hypothalamus trigger robust grooming and flank marking, a stereotyped scent marking behaviors. The intensity and repetition of the behaviors induced by arginine vasopressin is somewhat reminiscent of Obsessive Compulsive Disorder in humans. The present experiments were carried out to test whether pharmacological agents used to alleviate obsessive compulsive disorder could inhibit arginine vasopressin-induced flank marking and grooming. Results Male golden hamsters were treated daily for two weeks with either vehicle, fluoxetine, clomipramine, or desipramine (an ineffective drug, before being tested for arginine vasopressin-induced flank marking and grooming. Flank marking was significantly inhibited in animals treated with fluoxetine or clomipramine but unaffected by treatment with desipramine. Grooming behavior was not affected by any treatment. Conclusion These data suggest that arginine vasopressin-induced flank marking may serve as an animal model for screening drugs used in the control of Obsessive Compulsive Disorder.

  4. Hypophysitis, Panhypopituitarism, and Hypothalamitis in a Scottish Terrier Dog.

    Science.gov (United States)

    Polledo, L; Oliveira, M; Adamany, J; Graham, P; Baiker, K

    2017-09-01

    A 6-year old male neutered Scottish Terrier was referred with a 1 week history of progressive lethargy and anorexia. Neurological examination localized a lesion to the forebrain and hormonal testing showed panhypopituitarism. Magnetic resonance imaging (MRI) of the brain revealed a rounded, well-defined, suprasellar central mass. The mass was slightly hyperintense to the cortical grey matter on T2-weighted (T2W), hypointense on T1-weighted (T1W) images and without T2* signal void. There was a central fusiform enhancement of the mass after contrast administration which raised the suspicion of a pituitary neoplasm. Rapid deterioration of the dog prevented further clinical investigations. Histopathologic examination revealed a lymphocytic panhypophysitis of unknown origin suspected autoimmune involving the hypothalamus (hypothalamitis). This is a unique case report of a dog presenting with inflammatory hypophysitis and hypothalamitis of suspected autoimmune origin with detailed clinical, MRI, histology and immunohistochemistry findings. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  5. Hypothalamic growth hormone releasing factor deficiency following cranial irradiation

    International Nuclear Information System (INIS)

    Ahmed, S.R.; Shalet, S.M.

    1984-01-01

    The effect of synthetic human pancreatic tumour GH releasing factor (hp GRF1-44) on GH release has been studied in 10 patients with radiation-induced GH deficiency and four normal subjects. All 10 patients showed subnormal GH responses to both an ITT (median peak GH 3.2 mU/1) and to arginine stimulation (median peak GH 2.9 mU/1), although the remainder of pituitary function was intact. Following an acute intravenous bolus (100 μg) of hp GRF1-44, there was no GH response in two patients and a subnormal but definite GH response in a further four. The remaining four patients showed a significant GH response (median peak GH level 29 mU/1; range 22-57 mU/1) to hp GRF1-44, similar in magnitude and timing to that seen in th four normals. This strongly suggests that in these four subjects, the discrepancy in GH responses to hp GRF1-44, ITT and to arginine was a result of radiation-induced hypothalamic damage leading to a deficiency of endogenous GRF. The availability of synthetic hp GRF capable of stimulating GH secretion means that the distinction between hypothalamic and pituitary causes of GH deficiency will be of considerable therapeutic importance in the future. (author)

  6. Hypothalamic and pituitary clusterin modulates neurohormonal responses to stress.

    Science.gov (United States)

    Shin, Mi-Seon; Chang, Hyukki; Namkoong, Churl; Kang, Gil Myoung; Kim, Hyun-Kyong; Gil, So Young; Yu, Ji Hee; Park, Kyeong Han; Kim, Min-Seon

    2013-01-01

    Clusterin is a sulfated glycoprotein abundantly expressed in the pituitary gland and hypothalamus of mammals. However, its physiological role in neuroendocrine function is largely unknown. In the present study, we investigated the effects of intracerebroventricular (ICV) administration of clusterin on plasma pituitary hormone levels in normal rats. Single ICV injection of clusterin provoked neurohormonal changes seen under acute stress condition: increased plasma adrenocorticotropic hormone (ACTH), corticosterone, GH and prolactin levels and decreased LH and FSH levels. Consistently, hypothalamic and pituitary clusterin expression levels were upregulated following a restraint stress, suggesting an involvement of endogenous clusterin in stress-induced neurohormonal changes. In the pituitary intermediate lobe, clusterin was coexpressed with proopiomelanocortin (POMC), a precursor of ACTH. Treatment of clusterin in POMC expressing AtT-20 pituitary cells increased basal and corticotropin-releasing hormone (CRH)-stimulated POMC promoter activities and intracellular cAMP levels. Furthermore, clusterin treatment triggered ACTH secretion from AtT-20 cells in a CRH-dependent manner, indicating that increased clusterin under stressful conditions may augment CRH-stimulated ACTH production and release. In summary, hypothalamic and pituitary clusterin may function as a modulator of neurohormonal responses under stressful conditions. © 2013 S. Karger AG, Basel.

  7. Early effects of cranial irradiation on hypothalamic-pituitary function

    International Nuclear Information System (INIS)

    Lam, K.S.; Tse, V.K.; Wang, C.; Yeung, R.T.; Ma, J.T.; Ho, J.H.

    1987-01-01

    Hypothalamic-pituitary function was studied in 31 patients before and after cranial irradiation for nasopharyngeal carcinoma. The estimated radiotherapy (RT) doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 centiGrays, respectively. All patients had normal pituitary function before RT. One year after RT, there was a significant decrease in the integrated serum GH response to insulin-induced hypoglycemia. In the male patients, basal serum FSH significantly increased, while basal serum LH and testosterone did not change. Moreover, in response to LHRH, the integrated FSH response was increased while that of LH was decreased. Such discordant changes in FSH and LH may be explained by a defect in LHRH pulsatile release involving predominantly a decrease in pulse frequency. The peak serum TSH response to TRH became delayed in 28 patients, suggesting a defect in TRH release. Twenty-one patients were reassessed 2 yr after RT. Their mean basal serum T4 and plasma cortisol levels had significantly decreased. Hyperprolactinemia associated with oligomenorrhoea was found in 3 women. Further impairment in the secretion of GH, FSH, LH, TSH, and ACTH had occurred, and 4 patients had hypopituitarism. Thus, progressive impairment in hypothalamic-pituitary function occurs after cranial irradiation and can be demonstrated as early as 1 yr after RT

  8. MRI of the hypothalamic-pituitary axis in children

    International Nuclear Information System (INIS)

    Argyropoulou, Maria I.; Kiortsis, Dimitrios Nikiforos

    2005-01-01

    In childhood, the MR characteristics of the normal pituitary gland are well established. During the first 2 months of life the adenohypophysis demonstrates high signal. Pituitary gland height (PGH) decreases during the 1st year of life and then increases, reaching a plateau after puberty. The magnetization transfer ratio (MTR) increases in both sexes up to the age of 20 years. On dynamic contrast-enhanced studies, the posterior pituitary lobe enhances simultaneously with the straight sinus, and the adenohypophysis later, but within 30 s. In genetically determined dysfunctional states, the adenohypophysis may be normal, hypoplastic, or enlarged. Pituitary enlargement, observed in Prop 1 gene mutations, is characterized by a mass interposed between the anterior and posterior lobes. An ectopic posterior lobe (EPP), associated with a hypoplastic or absent pituitary stalk, may be observed in patients with hypopituitarism. Tumors of the hypothalamic-pituitary (HP) axis may be the origin of adenohypophyseal deficiencies. A small hypointense adenohypophysis is found in iron overload states and is often associated with hypogonadotrophic hypogonadism. Absence of the posterior lobe bright signal, with or without a thick pituitary stalk or a mass at any site from the median eminence to the posterior pituitary lobe, may be found in diabetes insipidus. Hydrocephalus, suprasellar arachnoid cysts, hypothalamic hamartomas and craniopharyngiomas may result in central precocious puberty (CPP). Increased PGH in girls with idiopathic CPP is useful for its differential diagnosis from premature thelarche (PT). Pituitary adenomas, observed mainly in adolescents, present the same MR characteristics as those in adults. (orig.)

  9. MRI of the hypothalamic-pituitary axis in children

    Energy Technology Data Exchange (ETDEWEB)

    Argyropoulou, Maria I. [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); Kiortsis, Dimitrios Nikiforos [University of Ioannina, Department of Physiology, Medical School, Ioannina (Greece)

    2005-11-01

    In childhood, the MR characteristics of the normal pituitary gland are well established. During the first 2 months of life the adenohypophysis demonstrates high signal. Pituitary gland height (PGH) decreases during the 1st year of life and then increases, reaching a plateau after puberty. The magnetization transfer ratio (MTR) increases in both sexes up to the age of 20 years. On dynamic contrast-enhanced studies, the posterior pituitary lobe enhances simultaneously with the straight sinus, and the adenohypophysis later, but within 30 s. In genetically determined dysfunctional states, the adenohypophysis may be normal, hypoplastic, or enlarged. Pituitary enlargement, observed in Prop 1 gene mutations, is characterized by a mass interposed between the anterior and posterior lobes. An ectopic posterior lobe (EPP), associated with a hypoplastic or absent pituitary stalk, may be observed in patients with hypopituitarism. Tumors of the hypothalamic-pituitary (HP) axis may be the origin of adenohypophyseal deficiencies. A small hypointense adenohypophysis is found in iron overload states and is often associated with hypogonadotrophic hypogonadism. Absence of the posterior lobe bright signal, with or without a thick pituitary stalk or a mass at any site from the median eminence to the posterior pituitary lobe, may be found in diabetes insipidus. Hydrocephalus, suprasellar arachnoid cysts, hypothalamic hamartomas and craniopharyngiomas may result in central precocious puberty (CPP). Increased PGH in girls with idiopathic CPP is useful for its differential diagnosis from premature thelarche (PT). Pituitary adenomas, observed mainly in adolescents, present the same MR characteristics as those in adults. (orig.)

  10. Functional hypothalamic amenorrhea and its influence on women's health.

    Science.gov (United States)

    Meczekalski, B; Katulski, K; Czyzyk, A; Podfigurna-Stopa, A; Maciejewska-Jeske, M

    2014-11-01

    Functional hypothalamic amenorrhea (FHA) is one of the most common causes of secondary amenorrhea. There are three types of FHA: weight loss-related, stress-related, and exercise-related amenorrhea. FHA results from the aberrations in pulsatile gonadotropin-releasing hormone (GnRH) secretion, which in turn causes impairment of the gonadotropins (follicle-stimulating hormone and luteinizing hormone). The final consequences are complex hormonal changes manifested by profound hypoestrogenism. Additionally, these patients present mild hypercortisolemia, low serum insulin levels, low insulin-like growth factor 1 (IGF-1) and low total triiodothyronine. The aim of this work is to review the available data concerning the effects of FHA on different aspects of women's health. Functional hypothalamic amenorrhea is related to profound impairment of reproductive functions including anovulation and infertility. Women's health in this disorder is disturbed in several aspects including the skeletal system, cardiovascular system, and mental problems. Patients manifest a decrease in bone mass density, which is related to an increase in fracture risk. Therefore, osteopenia and osteoporosis are the main long-term complications of FHA. Cardiovascular complications include endothelial dysfunction and abnormal changes in the lipid profile. FHA patients present significantly higher depression and anxiety and also sexual problems compared to healthy subjects. FHA patients should be carefully diagnosed and properly managed to prevent both short- and long-term medical consequences.

  11. Leptin is an effective treatment for hypothalamic amenorrhea.

    Science.gov (United States)

    Chou, Sharon H; Chamberland, John P; Liu, Xiaowen; Matarese, Giuseppe; Gao, Chuanyun; Stefanakis, Rianna; Brinkoetter, Mary T; Gong, Huizhi; Arampatzi, Kalliopi; Mantzoros, Christos S

    2011-04-19

    Hypothalamic amenorrhea (HA) is associated with dysfunction of the hypothalamic-pituitary-peripheral endocrine axes, leading to infertility and bone loss, and usually is caused by chronic energy deficiency secondary to strenuous exercise and/or decreased food intake. Energy deficiency also leads to hypoleptinemia, which has been proposed, on the basis of observational studies as well as an open-label study, to mediate the neuroendocrine abnormalities associated with this condition. To prove definitively a causal role of leptin in the pathogenesis of HA, we performed a randomized, double-blinded, placebo-controlled trial of human recombinant leptin (metreleptin) in replacement doses over 36 wk in women with HA. We assessed its effects on reproductive outcomes, neuroendocrine function, and bone metabolism. Leptin replacement resulted in recovery of menstruation and corrected the abnormalities in the gonadal, thyroid, growth hormone, and adrenal axes. We also demonstrated changes in markers of bone metabolism suggestive of bone formation, but no changes in bone mineral density were detected over the short duration of this study. If these data are confirmed, metreleptin administration in replacement doses to normalize circulating leptin levels may prove to be a safe and effective therapy for women with HA.

  12. Glutamate and GABA as rapid effectors of hypothalamic peptidergic neurons

    Directory of Open Access Journals (Sweden)

    Cornelia eSchöne

    2012-11-01

    Full Text Available Vital hypothalamic neurons regulating hunger, wakefulness, reward-seeking, and body weight are often defined by unique expression of hypothalamus-specific neuropeptides. Gene-ablation studies show that some of these peptides, notably orexin/hypocretin (hcrt/orx, are themselves critical for stable states of consciousness and metabolic health. However, neuron-ablation studies often reveal more severe phenotypes, suggesting key roles for co-expressed transmitters. Indeed, most hypothalamic neurons, including hcrt/orx cells, contain fast transmitters glutamate and GABA, as well as several neuropeptides. What are the roles and relations between different transmitters expressed by the same neuron? Here, we consider signaling codes for releasing different transmitters in relation to transmitter and receptor diversity in behaviorally-defined, widely-projecting peptidergic neurons, such as hcrt/orx cells. We then discuss latest optogenetic studies of endogenous transmitter release from defined sets of axons in situ, which suggest that recently-characterized vital peptidergic neurons (e.g. hcrt/orx, proopiomelanocortin , and agouti-related peptide cells, as well as classical modulatory neurons (e.g. dopamine and acetylcholine cells, all use fast transmitters to control their postsynaptic targets. These optogenetic insights are complemented by recent observations of behavioral deficiencies caused by genetic ablation of fast transmission from specific neuropeptidergic and aminergic neurons. Powerful and fast (millisecond-scale GABAergic and glutamatergic signaling from neurons previously considered to be primarily modulatory raises new questions about the roles of slower co-transmitters they co-express.

  13. Elevated hypothalamic TCPTP in obesity contributes to cellular leptin resistance

    Science.gov (United States)

    Loh, Kim; Fukushima, Atsushi; Zhang, Xinmei; Galic, Sandra; Briggs, Dana; Enriori, Pablo J.; Simonds, Stephanie; Wiede, Florian; Reichenbach, Alexander; Hauser, Christine; Sims, Natalie A.; Bence, Kendra K.; Zhang, Sheng; Zhang, Zhong-Yin; Kahn, Barbara B.; Neel, Benjamin G.; Andrews, Zane B.; Cowley, Michael A.; Tiganis, Tony

    2011-01-01

    SUMMARY In obesity, anorectic responses to leptin are diminished, giving rise to the concept of ‘leptin resistance’. Increased expression of protein tyrosine phosphatase 1B (PTP1B) has been associated with the attenuation of leptin signaling and development of cellular leptin resistance. Here we report that hypothalamic levels of the tyrosine phosphatase TCPTP are also elevated in obesity to attenuate the leptin response. We show that mice that lack TCPTP in neuronal cells have enhanced leptin sensitivity and are resistant to high fat diet-induced weight gain and the development of leptin resistance. Also, intracerebroventricular administration of a TCPTP inhibitor enhances leptin signaling and responses in mice. Moreover, the combined deletion of TCPTP and PTP1B in neuronal cells has additive effects in the prevention of diet-induced obesity. Our results identify TCPTP as a critical negative regulator of hypothalamic leptin signaling and causally link elevated TCPTP to the development of cellular leptin resistance in obesity. PMID:22000926

  14. A treasure trove of hypothalamic neurocircuitries governing body weight homeostasis.

    Science.gov (United States)

    Vianna, Claudia R; Coppari, Roberto

    2011-01-01

    Changes in physical activities and feeding habits have transformed the historically rare disease of obesity into a modern metabolic pandemic. Obesity occurs when energy intake exceeds energy expenditure over time. This energy imbalance significantly increases the risk for cardiovascular disease and type 2 diabetes mellitus and as such represents an enormous socioeconomic burden and health threat. To combat obesity, a better understanding of the molecular mechanisms and neurocircuitries underlying normal body weight homeostasis is required. In the 1940s, pioneering lesion experiments unveiled the importance of medial and lateral hypothalamic structures. In the 1980s and 1990s, several neuropeptides and peripheral hormones critical for appropriate feeding behavior, energy expenditure, and hence body weight homeostasis were identified. In the 2000s, results from metabolic analyses of genetically engineered mice bearing mutations only in selected neuronal groups greatly advanced our knowledge of the peripheral/brain feedback-loop modalities by which central neurons control energy balance. In this review, we will summarize these recent progresses with particular emphasis on the biochemical identities of hypothalamic neurons and molecular components underlying normal appetite, energy expenditure, and body weight homeostasis. We will also parse which of those neurons and molecules are critical components of homeostatic adaptive pathways against obesity induced by hypercaloric feeding.

  15. Hypothalamic-Pituitary Autoimmunity and Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Federica Guaraldi

    2015-05-01

    Full Text Available Background: Traumatic brain injury (TBI is a leading cause of secondary hypopituitarism in children and adults, and is responsible for impaired quality of life, disabilities and compromised development. Alterations of pituitary function can occur at any time after the traumatic event, presenting in various ways and evolving during time, so they require appropriate screening for early detection and treatment. Although the exact pathophysiology is unknown, several mechanisms have been hypothesized, including hypothalamic-pituitary autoimmunity (HP-A. The aim of this study was to systematically review literature on the association between HP-A and TBI-induced hypopituitarism. Major pitfalls related to the HP-A investigation were also discussed. Methods: The PubMed database was searched with a string developed for this purpose, without temporal or language limits, for original articles assessing the association of HP-A and TBI-induced hypopituitarism. Results: Three articles from the same group met the inclusion criteria. Anti-pituitary and anti-hypothalamic antibodies were detected using indirect immunofluorescence in a significant number of patients with acute and chronic TBI. Elevated antibody titer was associated with an increased risk of persistent hypopituitarism, especially somatotroph and gonadotroph deficiency, while no correlations were found with clinical parameters. Conclusion: HPA seems to contribute to TBI-induced pituitary damage, although major methodological issues need to be overcome and larger studies are warranted to confirm these preliminary data.

  16. Glucose and hypothalamic astrocytes: More than a fueling role?

    Science.gov (United States)

    Leloup, C; Allard, C; Carneiro, L; Fioramonti, X; Collins, S; Pénicaud, L

    2016-05-26

    Brain plays a central role in energy homeostasis continuously integrating numerous peripheral signals such as circulating nutrients, and in particular blood glucose level, a variable that must be highly regulated. Then, the brain orchestrates adaptive responses to modulate food intake and peripheral organs activity in order to achieve the fine tuning of glycemia. More than fifty years ago, the presence of glucose-sensitive neurons was discovered in the hypothalamus, but what makes them specific and identifiable still remains disconnected from their electrophysiological signature. On the other hand, astrocytes represent the major class of macroglial cells and are now recognized to support an increasing number of neuronal functions. One of these functions consists in the regulation of energy homeostasis through neuronal fueling and nutrient sensing. Twenty years ago, we discovered that the glucose transporter GLUT2, the canonical "glucosensor" of the pancreatic beta-cell together with the glucokinase, was also present in astrocytes and participated in hypothalamic glucose sensing. Since then, many studies have identified other actors and emphasized the astroglial participation in this mechanism. Growing evidence suggest that astrocytes form a complex network and have to be considered as spatially coordinated and regulated metabolic units. In this review we aim to provide an updated view of the molecular and respective cellular pathways involved in hypothalamic glucose sensing, and their relevance in physiological and pathological states. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. A single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin that produces reduced food and water intake induces long-lasting expression of corticotropin-releasing factor, arginine vasopressin, and proopiomelanocortin in rat brain

    International Nuclear Information System (INIS)

    Moon, Bo-Hyun; Hong, Chang Gwun; Kim, Soo-Young; Kim, Hyun-Ju; Shin, Seung Keon; Kang, Seungwoo; Lee, Kuem-Ju; Kim, Yong-Ku; Lee, Min-Soo; Shin, Kyung-Ho

    2008-01-01

    The mechanism by which a single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduces food and water intake is unclear. We examined whether such a food and water intake-reducing single administration of TCDD induced changes in corticotropin-releasing factor (CRF), arginine vasopressin (AVP), and proopiomelanocortin (POMC) expression in rat brain. To observe time-dependent changes in these neuropeptides, male Sprague-Dawley rats were given TCDD (50 μg/kg) and terminated 1, 2, 4, or 7 days later. In addition, to observe dose-dependent changes in feeding and neuropeptides, rats were also given a range of TCDD doses (12.5, 25, or 50 μg/kg) and terminated 14 days later. TCDD suppressed food and water intake over 14 days in a dose-dependent manner. TCDD treatment also increased CRF and POMC mRNA levels in the hypothalamic paraventricular nucleus (PVN) and arcuate nucleus, respectively, in a dose- and time-dependent manner. These increases were related to decreased food intake following TCDD administration. TCDD treatment increased AVP and CRF mRNA levels in the PVN, and these increases were related to decreased water intake. Interestingly, the increases in CRF, AVP and POMC expression were observed 7 to 14 days after TCDD administration. These results suggest that a single administration of TCDD induced long-lasting increases in CRF, AVP, and POMC mRNA levels in the hypothalamus and that these changes are related to reduced food and water intake 7 to 14 days after TCDD administration

  18. Association of Variants of Arginine Vasopressin and Arginine Vasopressin Receptor 1A With Severe Acetaminophen Liver InjurySummary

    Directory of Open Access Journals (Sweden)

    Matthew Randesi

    2017-05-01

    Full Text Available Background & Aims: Acetaminophen-related acute liver injury and liver failure (ALF result from ingestion of supratherapeutic quantities of this analgesic, frequently in association with other forms of substance abuse including alcohol, opioids, and cocaine. Thus, overdosing represents a unique high-risk behavior associated with other forms of drug use disorder. Methods: We examined a series of 21 single nucleotide polymorphisms (SNPs in 9 genes related to impulsivity and/or stress responsivity that may modify response to stress. Study subjects were 229 white patients admitted to tertiary care liver centers for ALF that was determined to be due to acetaminophen toxicity after careful review of historical and biochemical data. Identification of relevant SNPs used Sanger sequencing, TaqMan, or custom microarray. Association tests were carried out to compare genotype frequencies between patients and healthy white controls. Results: The mean age was 37 years, and 75.6% were female, with similar numbers classified as intentional overdose or unintentional (without suicidal intent, occurring for a period of several days, usually due to pain. There was concomitant alcohol abuse in 30%, opioid use in 33.6%, and use of other drugs of abuse in 30.6%. The genotype frequencies of 2 SNPs were found to be significantly different between the cases and controls, specifically SNP rs2282018 in the arginine vasopressin gene (AVP, odds ratio 1.64 and SNP rs11174811 in the AVP receptor 1A gene (AVPR1A, odds ratio 1.89, both of which have been previously linked to a drug use disorder diagnosis. Conclusions: Patients who develop acetaminophen-related ALF have increased frequency of gene variants that may cause altered stress responsivity, which has been shown to be associated with other unrelated substance use disorders. Keywords: Impulsivity, Stress Responsivity, Pituitary-Adrenal Axis, Overdose

  19. Variation in the ovine cortisol response to systemic bacterial endotoxin challenge is predominantly determined by signalling within the hypothalamic-pituitary-adrenal axis

    International Nuclear Information System (INIS)

    You Qiumei; Karrow, Niel A.; Cao Honghe; Rodriguez, Alexander; Mallard, Bonnie A.; Boermans, Herman J.

    2008-01-01

    Bi-directional communication between the neuroendocrine and immune systems is designed, in part, to maintain or restore homeostasis during physiological stress. Exposure to endotoxin during Gram-negative bacterial infection for example, elicits the release of pro-inflammatory cytokines that activate the hypothalamic-pituitary-adrenal axis (HPAA). The secretion of adrenal glucocorticoids subsequently down regulates the host inflammatory response, minimizing potential tissue damage. Sequence and epigenetic variants in genes involved in regulating the neuroendocrine and immune systems are likely to contribute to individual differences in the HPAA response, and this may influence the host anti-inflammatory response to toxin exposure and susceptibility to inflammatory disease. In this study, high (HCR) and low (LCR) cortisol responders were selected from a normal population of 110 female sheep challenged iv with Escherichia coli endotoxin (400 ng/kg) to identify potential determinants that contribute to variation in the cortisol response phenotype. This phenotype was stable over several years in the HCR and LCR animals, and did not appear to be attributed to differences in expression of hepatic immune-related genes or systemic pro-inflammatory cytokine concentrations. Mechanistic studies using corticotrophin-releasing factor (0.5 μg/kg body weight), arginine vasopressin (0.5 μg/kg), and adrenocorticotropic hormone (0.5 μg/kg) administered iv demonstrated that variation in this phenotype is largely determined by signalling within the HPAA. Future studies will use this ovine HCR/LCR model to investigate potential genetic and epigenetic variants that may contribute to variation in cortisol responsiveness to bacterial endotoxin

  20. Damage Control Resuscitation Supplemented with Vasopressin in a Severe Polytrauma Model with Traumatic Brain Injury and Uncontrolled Internal Hemorrhage.

    Science.gov (United States)

    Dickson, J Michael; Wang, Xu; St John, Alexander E; Lim, Esther B; Stern, Susan A; White, Nathan J

    2018-03-14

    Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of traumatic death worldwide and particularly on the battlefield. They are especially challenging when present simultaneously (polytrauma), and clear blood pressure end points during fluid resuscitation are not well described for this situation. The goal of this study is to evaluate for any benefit of increasing blood pressure using a vasopressor on brain blood flow during initial fluid resuscitation in a swine polytrauma model. We used a swine polytrauma model with simultaneous TBI, femur fracture, and HS with uncontrolled noncompressible internal bleeding from an aortic tear injury. Five animals were assigned to each of three experimental groups (hydroxyethyl starch only [HES], HES + 0.4 U/kg vasopressin, and no fluid resuscitation [No Fluids]). Fluids were given as two 10 mL/kg boluses according to tactical field care guidelines. Primary outcomes were mean arterial blood pressure (MAP) and brain blood flow at 60 min. Secondary outcomes were blood flows in the heart, intestine, and kidney; arterial blood lactate level; and survival at 6 hr. Organ blood flow was measured using injection of colored microspheres. Five animals were tested in each of the three groups. There was a statistically significant increase in MAP with vasopressin compared with other experimental groups, but no significant increase in brain blood flow during the first 60 min of resuscitation. The vasopressin group also exhibited greater total internal hemorrhage volume and rate. There was no difference in survival at 6 hours. In this experimental swine polytrauma model, increasing blood pressure with vasopressin did not improve brain perfusion, likely due to increased internal hemorrhage. Effective hemostasis should remain the top priority for field treatment of the polytrauma casualty with TBI.

  1. The bidirectional phase-shifting effects of melatonin on the arginine vasopressin secretion rhythm in rat suprachiasmatic nuclei in vitro

    Czech Academy of Sciences Publication Activity Database

    Svobodová, Irena; Vaněček, Jiří; Zemková, Hana

    2003-01-01

    Roč. 116, 1-2 (2003), s. 80-85 ISSN 0169-328X R&D Projects: GA ČR GA309/02/1519; GA ČR GA309/02/1479; GA AV ČR IAA5011103; GA AV ČR IAA5011105 Institutional research plan: CEZ:AV0Z5011922 Keywords : melatonin * arginine vasopressin * circadian rhythm Subject RIV: ED - Physiology Impact factor: 2.107, year: 2003

  2. 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...

  3. [Vasopressin V2 receptor-related pathologies: congenital nephrogenic diabetes insipidus and nephrogenic syndrome of inappropiate antidiuresis].

    Science.gov (United States)

    Morin, Denis

    2014-12-01

    Congenital nephrogenic diabetes insipidus is a rare hereditary disease with mainly an X-linked inheritance (90% of the cases) but there are also autosomal recessive and dominant forms. Congenital nephrogenic diabetes insipidus is characterized by a resistance of the renal collecting duct to the action of the arginine vasopressin hormone responsible for the inability of the kidney to concentrate urine. The X-linked form is due to inactivating mutations of the vasopressin 2 receptor gene leading to a loss of function of the mutated receptors. Affected males are often symptomatic in the neonatal period with a lack of weight gain, dehydration and hypernatremia but mild phenotypes may also occur. Females carrying the mutation may be asymptomatic but, sometimes, severe polyuria is found due to the random X chromosome inactivation. The autosomal recessive and dominant forms, occurring in both genders, are linked to mutations in the aquaporin-2 gene. The treatment remains difficult, especially in infants, and is based on a low osmotic diet with increased water intake and the use of thiazides and indomethacin. The main goal is to avoid hypernatremic episodes and maintain a good hydration state. Potentially, specific treatment, in some cases of X-linked congenital nephrogenic diabetes insipidus, with pharmacological chaperones such as non-peptide vasopressin-2 receptor antagonists will be available in the future. Conversely, the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is linked to a constitutive activation of the V(2)-receptor due to activating mutations with clinical and biological features of inappropriate antidiuresis but with low or undetectable plasma arginine vasopressin hormone levels. Copyright © 2014 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  4. Effect of vasopressin on rabbit hepatic energy metabolism evaluated using in vivo P-31 magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Ono, Shigeki; Moriyasu, Fuminori; Tamada, Takashi

    1989-01-01

    Changes in metabolic state of rabbit livers after administration of vasopressin (10 mU/kg/min d.i.v.) were evaluated using in vivo P-31 magnetic resonance (MR) spectroscopy. Targets were nine normal control rabbits and eight with chronically carbontetrachloride-damaged livers. A 2.0 Tesla whole-body MR imager was used for measurement. After administration of vasopressin, liver spectroscopy showed a mild ischemic pattern. The inorganic phosphate peak increased statistically significantly (p<0.05) both in the normal control group and in the damaged-liver group (20% and 16% above base line value respectively). In the normal control group, there was a statistically significant decrease (p<0.05) in the ATP peak to 18% below the base line value while the PME (phosphomonoester) peak increased slightly (about 10%); there was little change in the damaged-liver group. It was thought that the difference between the two groups was due to differences in blood flow mechanism and liver metabolism. Magnetic resonance spectroscopy was considered to be useful in studying the detailed changes in metabolic state of rabbit liver after administration of vasopressin. (author)

  5. Genetic forms of nephrogenic diabetes insipidus (NDI): Vasopressin receptor defect (X-linked) and aquaporin defect (autosomal recessive and dominant).

    Science.gov (United States)

    Bichet, Daniel G; Bockenhauer, Detlef

    2016-03-01

    Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). Polyuria with hyposthenuria and polydipsia are the cardinal clinical manifestations of the disease. About 90% of patients with congenital NDI are males with X-linked NDI who have mutations in the vasopressin V2 receptor (AVPR2) gene encoding the vasopressin V2 receptor. In less than 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance with mutations in the aquaporin-2 (AQP2) gene. When studied in vitro, most AVPR2 and AQP2 mutations lead to proteins trapped in the endoplasmic reticulum and are unable to reach the plasma membrane. Prior knowledge of AVPR2 or AQP2 mutations in NDI families and perinatal mutation testing is of direct clinical value and can avert the physical and mental retardation associated with repeated episodes of dehydration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Sweet taste signaling functions as a hypothalamic glucose sensor

    Directory of Open Access Journals (Sweden)

    Xueying Ren

    2009-06-01

    Full Text Available Brain glucosensing is essential for normal body glucose homeostasis and neuronal function. However, the exact signaling mechanisms involved in the neuronal sensing of extracellular glucose levels remain poorly understood. Of particular interest is the identification of candidate membrane molecular sensors allowing neurons to change firing rates independently of intracellular glucose metabolism. Here we describe for the first time the expression of the taste receptor genes Tas1r1, Tas1r2 and Tas1r3, and their associated G-protein genes, in the mammalian brain. Neuronal expression of taste genes was detected in different nutrient-sensing forebrain regions, including the paraventricular and arcuate nuclei of the hypothalamus, the CA fields and dentate gyrus of the hippocampus, the habenula, and cortex. Expression was also observed in the intra-ventricular epithelial cells of the choroid plexus. These same regions were found to express the corresponding gene products that form the heterodimeric T1R2/T1R3 and T1R1/T1R3 sweet and L-amino acid taste G-protein coupled receptors, respectively. These regions were also found to express the taste G-protein α-Gustducin. Moreover, in vivo studies in mice demonstrate that the hypothalamic expression of taste-related genes is regulated by the nutritional state of the animal, with food deprivation significantly increasing expression levels of Tas1r1 and Tas1r2 in hypothalamus, but not in cortex. Furthermore, exposing mouse hypothalamic cells to a low-glucose medium, while maintaining normal L-amino acid concentrations, specifically resulted in higher expression levels of the sweet-associated gene Tas1r2. This latter effect was reversed by adding the non-metabolizable artificial sweetener sucralose to the low-glucose medium, indicating that taste-like signaling in hypothalamic neurons does not require intracellular glucose oxidation. Our findings suggest that the G-protein coupled sweet receptor T1R2/T1R3 is a

  7. Hypothalamic stem cells control ageing speed partly through exosomal miRNAs.

    Science.gov (United States)

    Zhang, Yalin; Kim, Min Soo; Jia, Baosen; Yan, Jingqi; Zuniga-Hertz, Juan Pablo; Han, Cheng; Cai, Dongsheng

    2017-08-03

    It has been proposed that the hypothalamus helps to control ageing, but the mechanisms responsible remain unclear. Here we develop several mouse models in which hypothalamic stem/progenitor cells that co-express Sox2 and Bmi1 are ablated, as we observed that ageing in mice started with a substantial loss of these hypothalamic cells. Each mouse model consistently displayed acceleration of ageing-like physiological changes or a shortened lifespan. Conversely, ageing retardation and lifespan extension were achieved in mid-aged mice that were locally implanted with healthy hypothalamic stem/progenitor cells that had been genetically engineered to survive in the ageing-related hypothalamic inflammatory microenvironment. Mechanistically, hypothalamic stem/progenitor cells contributed greatly to exosomal microRNAs (miRNAs) in the cerebrospinal fluid, and these exosomal miRNAs declined during ageing, whereas central treatment with healthy hypothalamic stem/progenitor cell-secreted exosomes led to the slowing of ageing. In conclusion, ageing speed is substantially controlled by hypothalamic stem cells, partially through the release of exosomal miRNAs.

  8. Pathophysiology and clinical characteristics of hypothalamic obesity in children and adolescents

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    Ja Hye Kim

    2013-12-01

    Full Text Available The hypothalamus plays a key role in the regulation of body weight by balancing the intake of food, energy expenditure, and body fat stores, as evidenced by the fact that most monogenic syndromes of morbid obesity result from mutations in genes expressed in the hypothalamus. Hypothalamic obesity is a result of impairment in the hypothalamic regulatory centers of body weight and energy expenditure, and is caused by structural damage to the hypothalamus, radiotherapy, Prader-Willi syndrome, and mutations in the LEP, LEPR, POMC, MC4R and CART genes. The pathophysiology includes loss of sensitivity to afferent peripheral humoral signals, such as leptin, dysregulated insulin secretion, and impaired activity of the sympathetic nervous system. Dysregulation of 11β-hydroxysteroid dehydrogenase 1 activity and melatonin may also have a role in the development of hypothalamic obesity. Intervention of this complex entity requires simultaneous targeting of several mechanisms that are deranged in patients with hypothalamic obesity. Despite a great deal of theoretical understanding, effective treatment for hypothalamic obesity has not yet been developed. Therefore, understanding the mechanisms that control food intake and energy homeostasis and pathophysiology of hypothalamic obesity can be the cornerstone of the development of new treatments options. Early identification of patients at-risk can relieve the severity of weight gain by the provision of dietary and behavioral modification, and antiobesity medication. This review summarizes recent advances of the pathophysiology, endocrine characteristics, and treatment strategies of hypothalamic obesity.

  9. Desipramine inhibits histamine H1 receptor-induced Ca2+ signaling in rat hypothalamic cells.

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    Ji-Ah Kang

    Full Text Available The hypothalamus in the brain is the main center for appetite control and integrates signals from adipose tissue and the gastrointestinal tract. Antidepressants are known to modulate the activities of hypothalamic neurons and affect food intake, but the cellular and molecular mechanisms by which antidepressants modulate hypothalamic function remain unclear. Here we have investigated how hypothalamic neurons respond to treatment with antidepressants, including desipramine and sibutramine. In primary cultured rat hypothalamic cells, desipramine markedly suppressed the elevation of intracellular Ca(2+ evoked by histamine H1 receptor activation. Desipramine also inhibited the histamine-induced Ca(2+ increase and the expression of corticotrophin-releasing hormone in hypothalamic GT1-1 cells. The effect of desipramine was not affected by pretreatment with prazosin or propranolol, excluding catecholamine reuptake activity of desipramine as an underlying mechanism. Sibutramine which is also an antidepressant but decreases food intake, had little effect on the histamine-induced Ca(2+ increase or AMP-activated protein kinase activity. Our results reveal that desipramine and sibutramine have different effects on histamine H1 receptor signaling in hypothalamic cells and suggest that distinct regulation of hypothalamic histamine signaling might underlie the differential regulation of food intake between antidepressants.

  10. [Patients with functional hypothalamic amenorrhea are characterized by low serum inhibin B concentrations].

    Science.gov (United States)

    Podfigurna-Stopa, Agnieszka; Luisi, Stefano; Lazzeri, Lucia; Ciani, Valentina; Meczekalski, Błazej; Petraglia, Felice

    2010-05-01

    Functional hypothalamic disturbances may be the cause of secondary amenorrhea and are related to aberration in both the pattern of pulsatility and amplitude in the release of gonadotropin-releasing hormone (GnRH) in hypothalamus. Inhibin B, as an ovarian peptide plays a crucial role in reproduction function throughout regulation of folliculotropin (FSH) pituitary production and inhibiting GnRH secretion during the menstrual cycle. To measure and estimate serum inhibin B concentration in patients with functional hypothalamic amenorrhea. Material and methods. The study included 41 women suffering from functional hypothalamic amenorrhea. Secondary amenorrhea was defined as the lack of menstruation lasting at least 90 days not due to pregnancy, characterized by low serum concentrations of lutropin (LH < 5 mIU/ml)) and typical for functional hypothalamic disturbances anamnestic investigation. The control group consists of 40 healthy women with normal menstrual cycles and Body Mass Index (BMI between 18.5- 24.9 kg/m2). Medical history, examination and laboratory analysis of LH, FSH, estradiol (E), prolactin, testosterone and inhibin B were performed (ELISA--enzyme-linked immunosorbent assay). There are statistically lower serum inhibin B, FSH, LH, estradiol and prolactin concentrations in patients with functional hypothalamic amenorrhea in comparison to healthy women. Positive correlation between serum concentration of inhibin B and estradiol concentration was found in patients with functional hypothalamic amenorrhea. Patients with functional hypothalamic amenorrhea are characterized by statistical significant decrease in serum inhibin B concentration in comparison to the control group.

  11. Maternal neglect with reduced depressive-like behavior and blunted c-fos activation in Brattleboro mothers, the role of central vasopressin.

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    Fodor, Anna; Klausz, Barbara; Pintér, Ottó; Daviu, Nuria; Rabasa, Cristina; Rotllant, David; Balazsfi, Diana; Kovacs, Krisztina B; Nadal, Roser; Zelena, Dóra

    2012-09-01

    Early mother-infant relationships exert important long-term effects in offspring and are disturbed by factors such as postpartum depression. We aimed to clarify if lack of vasopressin influences maternal behavior paralleled by the development of a depressive-like phenotype. We compared vasopressin-deficient Brattleboro mothers with heterozygous and homozygous normal ones. The following parameters were measured: maternal behavior (undisturbed and separation-induced); anxiety by the elevated plus maze; sucrose and saccharin preference and forced swim behavior. Underlying brain areas were examined by c-fos immunocytochemistry among rest and after swim-stress. In another group of rats, vasopressin 2 receptor agonist was used peripherally to exclude secondary changes due to diabetes insipidus. Results showed that vasopressin-deficient rats spend less time licking-grooming their pups through a centrally driven mechanism. There was no difference between genotypes during the pup retrieval test. Vasopressin-deficient mothers tended to explore more the open arms of the plus maze, showed more preference for sucrose and saccharin and struggled more in the forced swim test, suggesting that they act as less depressive. Under basal conditions, vasopressin-deficient mothers had more c-fos expression in the medial preoptic area, shell of nucleus accumbens, paraventricular nucleus of the hypothalamus and amygdala, but not in other structures. In these areas the swim-stress-induced activation was smaller. In conclusion, vasopressin-deficiency resulted in maternal neglect due to a central effect and was protective against depressive-like behavior probably as a consequence of reduced activation of some stress-related brain structures. The conflicting behavioral data underscores the need for more sex specific studies. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Hypothalamic digoxin, hemispheric dominance, and neurobiology of love and affection.

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    Kurup, Ravi Kumar; Kurup, Parameswara Achutha

    2003-05-01

    The human hypothalamus produces an endogenous membrane Na+-K+ ATPase inhibitor, digoxin, which can regulate neuronal transmission. The digoxin status and neurotransmitter patterns were studied in individuals with a predilection to fall in love. It was also studied in individuals with differing hemispheric dominance to find out the role of cerebral dominance in this respect. In individuals with a predilection to fall in love there was decreased digoxin synthesis, increased membrane Na+-K+ ATPase activity, decreased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and increased tyrosine catabolites (dopamine, noradrenaline, and morphine). This pattern correlated with that obtained in left hemispheric chemical dominance. Hemispheric dominance and hypothalamic digoxin could regulate the predisposition to fall in love.

  13. Hypothalamic obesity after craniopharyngioma: mechanisms, diagnosis, and treatment

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    Robert H. Lustig

    2011-11-01

    Full Text Available Obesity is a common complication after craniopharyngioma therapy, occurring in up to 75% of survivors. Its weight gain is unlike that of normal obesity, in that it occurs even with caloric restriction, and attempts at lifestyle modification are useless to prevent or treat the obesity. The pathogenesis of this condition involves the inability to transduce afferent hormonal signals of adiposity, in effect mimicking a state of CNS starvation. Efferent sympathetic activity drops, resulting in malaise and reduced energy expenditure, and vagal activity increases, resulting in increased insulin secretion and adipogenesis. Lifestyle intervention is essentially useless in this syndrome, termed hypothalamic obesity. Pharmacologic treatment is also difficult, consisting of adrenergics to mimic sympathetic activity, or suppression of insulin secretion with octreotide, or both. Recently, bariatric surgery (Roux-en-Y gastric bypass, laparoscopic gastric banding, truncal vagotomy have also been attempted with variable results. Early and intensive management is required to mitigate the obesity and its negative consequences.

  14. The complex relationship between hypothalamic amenorrhea and polycystic ovary syndrome.

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    Wang, Jeff G; Lobo, Rogerio A

    2008-04-01

    Polycystic ovarian morphology (PCOM) is occasionally observed in women with hypothalamic amenorrhea (HA). Although these women with HA/PCOM meet two of the Rotterdam criteria, they are excluded from the diagnosis of polycystic ovary syndrome (PCOS) by having HA. We explored the coexistence of these two disorders in women with HA/PCOM by analyzing their androgen response to gonadotropins and by following their clinical characteristics over time. Baseline and dynamic endocrine profiles during controlled ovarian hyperstimulation for women with HA/PCOM [n = 6, median (interquartile range) age 30 yr (28-31), body mass index (BMI) 19.2 kg/m(2) (18.0-19.2)] were retrospectively compared with those of women with PCOS [n = 10, age 33 (31-34), BMI 24.8 (23.2-27.6)] and normoovulatory controls [n = 20, age 33 (31-35), BMI 21.5(20.3-23.1)]. Long-term outcomes for five women with HA/PCOM were followed during their spontaneous recovery from HA. With the exception of decreased LH [0.7 (0.3-0.8) vs. 6.0 IU/liter (4.8-7.4); P = 0.003], FSH [3.9 (2.5-5.7) vs. 7.5 IU/liter (5.3-9.5); P < 0.025], and estradiol [20 (14-24) vs. 32 pg/ml (20-39); P < 0.027], baseline endocrine profiles of women with HA/PCOM did not differ significantly from those of normoovulatory controls in terms of 17alpha-hydroxyprogesterone, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androstenedione, and total testosterone. However, controlled ovarian hyperstimulation with similar doses of gonadotropins resulted in an excess of androgen production compared with the controls [Deltaandrostenedione per dominant follicle 0.30 (0.23-0.37) vs. 0.10 ng/ml (0.05-0.18), P = 0.005; Deltatestosterone per dominant follicle 16 (7-24) vs. 6 ng/dl (2-12), P = 0.04], and these levels were comparable to those of women with PCOS. Recovery from HA/PCOM in some patients was associated with the development of oligomenorrhea and symptoms of androgen excess. Women with HA/PCOM may have inherently hyperandrogenic ovaries but

  15. Bilateral descending hypothalamic projections to the spinal trigeminal nucleus caudalis in rats.

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    Khaled Abdallah

    Full Text Available Several lines of evidence suggest that the hypothalamus is involved in trigeminal pain processing. However, the organization of descending hypothalamic projections to the spinal trigeminal nucleus caudalis (Sp5C remains poorly understood. Microinjections of the retrograde tracer, fluorogold (FG, into the Sp5C, in rats, reveal that five hypothalamic nuclei project to the Sp5C: the paraventricular nucleus, the lateral hypothalamic area, the perifornical hypothalamic area, the A11 nucleus and the retrochiasmatic area. Descending hypothalamic projections to the Sp5C are bilateral, except those from the paraventricular nucleus which exhibit a clear ipsilateral predominance. Moreover, the density of retrogradely FG-labeled neurons in the hypothalamus varies according to the dorso-ventral localization of the Sp5C injection site. There are much more labeled neurons after injections into the ventrolateral part of the Sp5C (where ophthalmic afferents project than after injections into its dorsomedial or intermediate parts (where mandibular and maxillary afferents, respectively, project. These results demonstrate that the organization of descending hypothalamic projections to the spinal dorsal horn and Sp5C are different. Whereas the former are ipsilateral, the latter are bilateral. Moreover, hypothalamic projections to the Sp5C display somatotopy, suggesting that these projections are preferentially involved in the processing of meningeal and cutaneous inputs from the ophthalmic branch of the trigeminal nerve in rats. Therefore, our results suggest that the control of trigeminal and spinal dorsal horn processing of nociceptive information by hypothalamic neurons is different and raise the question of the role of bilateral, rather than unilateral, hypothalamic control.

  16. Thiamine Deficiency Induces Anorexia by Inhibiting Hypothalamic AMPK

    Science.gov (United States)

    Liu, Mei; Alimov, Alexander; Wang, Haiping; Frank, Jacqueline A.; Katz, Wendy; Xu, Mei; Ke, Zun-Ji; Luo, Jia

    2014-01-01

    Obesity and eating disorders are prevailing health concerns worldwide. It is important to understand the regulation of food intake and energy metabolism. Thiamine (vitamin B1) is an essential nutrient. Thiamine deficiency (TD) can cause a number of disorders in humans, such as Beriberi and Wernicke-Korsakoff syndrome. We demonstrated here that TD caused anorexia in C57BL/6 mice. After feeding a TD diet for 16 days, the mice displayed a significant decrease in food intake and an increase in resting energy expenditure (REE), which resulted in a severe weight loss. At the 22nd day, the food intake was reduced by 69% and 74% for male and female mice, respectively in TD group. The REE increased by 9 folds in TD group. The loss of body weight (17–24%) was similar between male and female animals and mainly resulted from the reduction of fat mass (49% decrease). Re-supplementation of thiamine (benfotiamine) restored animal's appetite, leading to a total recovery of body weight. The hypothalamic AMPK is a critical regulator of food intake. TD inhibited the phosphorylation of AMPK in the arcuate nucleus (ARN) and paraventricular nucleus (PVN) of the hypothalamus without affecting its expression. TD-induced inhibition of AMPK phosphorylation was reversed once thiamine was re-supplemented. In contrast, TD increased AMPK phosphorylation in the skeletal muscle and upregulated the uncoupling protein (UCP)-1 in brown adipose tissues which was consistent with increased basal energy expenditure. Re-administration of thiamine stabilized AMPK phosphorylation in the skeletal muscle as well as energy expenditure. Taken together, TD may induce anorexia by inhibiting hypothalamic AMPK activity. With a simultaneous increase in energy expenditure, TD caused an overall body weight loss. The results suggest that the status of thiamine levels in the body may affect food intake and body weight. PMID:24607345

  17. Effect of hemorrhage on cardiac output, vasopressin, aldosterone, and diuresis during immersion in men

    Science.gov (United States)

    Greenleaf, J. E.; Simanonok, K.; Bernauer, E. M.; Wade, C. E.; Keil, L. C.

    1992-01-01

    The purpose of this research was to test the hypotesis that a reduction in blood volume would attenuate or eliminate immersion-induced increases in cardiac output (Q(sub co)) and urine excretion, and to investigate accompanying vasoactive and fluid-electrolyte hormonal responses. Eight men (19-23 yr) were supine during a 2-hr control period in air, and then sat for 5-hr test periods in air at 20 C (dry control, DC); water at 34.5 C (wet control, WC); and water (34.5 C) after hemorrhage (WH) of 14.8 plus or minus 0.3 percent of their blood volume. Blood volume was -11.6 plus or minus 0.6 percent at immersion (time 0). Mean (bar-X hrs 1-5) Q(sub co) was unchanged in WC (5.3 plus or minus 0.01 l/min) and in WH (4.5 plus or minus 0.1 l/min), but decreased (P less than 0.05) in DC to 3.6 plus or minus 0.1 l/min. Mean urine excretion rates were 1.0 plus or minus 0.2 ml/min for DC and 1.1 plus or minus 0.2 ml/min for WH; both were lower (P less than 0.05) than that for WC of 2.0 plus or minus 0.4 ml/min. Plasma (Na+) and (Osm) were unchanged in all experiments. Mean plasma vasopressin (PVP) (bar-X hrs 1-5) was 1.1 plus or minus 0.1 pg/ml in WC, and higher (P less than 0.05) in DC (2.1 plus or minus 0.2 pg/ml)and WH (2.1 plus or minus 0.1 pg/ml); it was unchanged during air and water test periods. Thus, hemorrhage attenuated the immersion-induced increase in Q(sub co), eliminated the WC diuresis, maintained plasma renin activity and PVP at DC levels and did not change immersion-induced aldosterone suppression; the osmotic diuresis during control immersion is apparently not due to either aldosterone suppression or vasopressin suppression.

  18. Heightened cortisol response to exercise challenge in women with functional hypothalamic amenorrhea.

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    Sanders, Kristen M; Kawwass, Jennifer F; Loucks, Tammy; Berga, Sarah L

    2018-02-01

    Functional hypothalamic amenorrhea is characterized by anovulation caused by reduced gonadotropin-releasing hormone drive and is associated with hypercortisolemia that has been linked to heightened hypothalamic-pituitary-adrenal reactivity to common psychological and metabolic challenges. We hypothesized that women with functional hypothalamic amenorrhea would display greater cortisol responses to exercise challenge than ovulatory women with eumenorrhea. We completed a cross-sectional comparison of 9 women with functional hypothalamic amenorrhea and 11 women with eumenorrhea who were of reproductive age, who weighed 90-110% ideal body weight, who did not exercise excessively, and who had no formal psychiatric diagnosis. Subjects completed a 20-minute submaximal exercise challenge using a cycle ergometer in a research exercise laboratory. Heart rate and circulatory cortisol, glucose, and lactate were measured at 10-minute intervals before, during, and after the exercise challenge. Baseline (t= -10 minutes) cortisol, glucose, lactate, and heart rate were comparable between groups. Glucose levels rose modestly during exercise by 2.9% in women with eumenorrhea (P=.4) but declined by 10.6% in functional hypothalamic amenorrhea (P<.03). The nadir in glucose levels in functional hypothalamic amenorrhea occurred at the end of the 20-minute exercise challenge (t= +20 min). Lactate levels rose comparably in both groups (P<.01). Heart rate increased significantly with exercise in both groups (P<.01), but the increase was smaller in subjects with functional hypothalamic amenorrhea (P<.01). Cortisol levels increased during the exercise challenge in both groups (P<.01) and peaked 10 minutes after the exercise ended (t= +30 min). At peak, subjects with functional hypothalamic amenorrhea displayed higher cortisol levels (147±22 [standard error of the mean] ng/mL) than women with eumenorrhea (96±12 ng/mL; P=.05). The mean percent increase over baseline was 62% in women with

  19. Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity.

    Science.gov (United States)

    Oyola, Mario G; Handa, Robert J

    2017-09-01

    Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic-pituitary-adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism's response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic-pituitary-gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life.

  20. Cardiovascular responses to chemical stimulation of the hypothalamic arcuate nucleus in the rat: role of the hypothalamic paraventricular nucleus.

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    Tetsuya Kawabe

    Full Text Available The mechanism of cardiovascular responses to chemical stimulation of the hypothalamic arcuate nucleus (ARCN was studied in urethane-anesthetized adult male Wistar rats. At the baseline mean arterial pressure (BLMAP close to normal, ARCN stimulation elicited decreases in MAP and sympathetic nerve activity (SNA. The decreases in MAP elicited by ARCN stimulation were attenuated by either gamma-aminobutyric acid (GABA, neuropeptide Y (NPY, or beta-endorphin receptor blockade in the ipsilateral hypothalamic paraventricular nucleus (PVN. Combined blockade of GABA-A, NPY1 and opioid receptors in the ipsilateral PVN converted the decreases in MAP and SNA to increases in these variables. Conversion of inhibitory effects on the MAP and SNA to excitatory effects following ARCN stimulation was also observed when the BLMAP was decreased to below normal levels by an infusion of sodium nitroprusside. The pressor and tachycardic responses to ARCN stimulation at below normal BLMAP were attenuated by blockade of melanocortin 3/4 (MC3/4 receptors in the ipsilateral PVN. Unilateral blockade of GABA-A receptors in the ARCN increased the BLMAP and heart rate (HR revealing tonic inhibition of the excitatory neurons in the ARCN. ARCN stimulation elicited tachycardia regardless of the level of BLMAP. ARCN neurons projecting to the PVN were immunoreactive for glutamic acid decarboxylase 67 (GAD67, NPY, and beta-endorphin. These results indicated that: 1 at normal BLMAP, decreases in MAP and SNA induced by ARCN stimulation were mediated via GABA-A, NPY1 and opioid receptors in the PVN, 2 lowering of BLMAP converted decreases in MAP following ARCN stimulation to increases in MAP, and 3 at below normal BLMAP, increases in MAP and HR induced by ARCN stimulation were mediated via MC3/4 receptors in the PVN. These results provide a base for future studies to explore the role of ARCN in cardiovascular diseases.

  1. Interplay of oxytocin, vasopressin, and sex hormones in the regulation of social recognition.

    Science.gov (United States)

    Gabor, Christopher S; Phan, Anna; Clipperton-Allen, Amy E; Kavaliers, Martin; Choleris, Elena

    2012-02-01

    Social Recognition is a fundamental skill that forms the basis of behaviors essential to the proper functioning of pair or group living in most social species. We review here various neurobiological and genetic studies that point to an interplay of oxytocin (OT), arginine-vasopressin (AVP), and the gonadal hormones, estrogens and testosterone, in the mediation of social recognition. Results of a number of studies have shown that OT and its actions at the medial amygdala seem to be essential for social recognition in both sexes. Estrogens facilitate social recognition, possibly by regulating OT production in the hypothalamus and the OT receptors at the medial amygdala. Estrogens also affect social recognition on a rapid time scale, likely through nongenomic actions. The mechanisms of these rapid effects are currently unknown but available evidence points at the hippocampus as the possible site of action. Male rodents seem to be more dependent on AVP acting at the level of the lateral septum for social recognition than female rodents. Results of various studies suggest that testosterone and its metabolites (including estradiol) influence social recognition in males primarily through the AVP V1a receptor. Overall, it appears that gonadal hormone modulation of OT and AVP regulates and fine tunes social recognition and those behaviors that depend upon it (e.g., social bonds, social hierarchies) in a sex specific manner. This points at an important role for these neuroendocrine systems in the regulation of the sex differences that are evident in social behavior and of sociality as a whole.

  2. Oxytocin, vasopressin and estrogen receptor gene expression in relation to social recognition in female mice.

    Science.gov (United States)

    Clipperton-Allen, Amy E; Lee, Anna W; Reyes, Anny; Devidze, Nino; Phan, Anna; Pfaff, Donald W; Choleris, Elena

    2012-02-28

    Inter- and intra-species differences in social behavior and recognition-related hormones and receptors suggest that different distribution and/or expression patterns may relate to social recognition. We used qRT-PCR to investigate naturally occurring differences in expression of estrogen receptor-alpha (ERα), ER-beta (ERβ), progesterone receptor (PR), oxytocin (OT) and receptor, and vasopressin (AVP) and receptors in proestrous female mice. Following four 5 min exposures to the same two conspecifics, one was replaced with a novel mouse in the final trial (T5). Gene expression was examined in mice showing high (85-100%) and low (40-60%) social recognition scores (i.e., preferential novel mouse investigation in T5) in eight socially-relevant brain regions. Results supported OT and AVP involvement in social recognition, and suggest that in the medial preoptic area, increased OT and AVP mRNA, together with ERα and ERβ gene activation, relate to improved social recognition. Initial social investigation correlated with ERs, PR and OTR in the dorsolateral septum, suggesting that these receptors may modulate social interest without affecting social recognition. Finally, increased lateral amygdala gene activation in the LR mice may be associated with general learning impairments, while decreased lateral amygdala activity may indicate more efficient cognitive mechanisms in the HR mice. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. A V1-vascular vasopressin antagonist suitable for radioiodination and photoaffinity labeling

    International Nuclear Information System (INIS)

    Thibonnier, M.; Chehade, N.; Hinko, A.

    1990-01-01

    We have previously characterized the V1-vascular arginine vasopressin (AVP) receptors of human platelets. We now report on a radiomonoiodinated and photoreactive V1-vascular AVP antagonist (V1-ag) to be used for the purification of human V1-vascular AVP receptors. The V1-ag, d(CH2)5Tyr(Me)Tyr(NH2)AVP was modified by radiomonoiodination of d(CH2)5-Tyr(Me)Tyr(NH2)AVP with the Iodogen technique, and derivatization of d(CH2)5Tyr(Me)Tyr[125I](NH2)-AVP with the photoreactive crosslinker, N-hydroxysuccinimidyl-4-azidobenzoate (HSAB) (each step included HPLC purification). In competition experiments, the affinity of these V1-ag for the human platelet AVP receptors remained excellent. Irreversible photoaffinity labeling of the platelet V1-vascular AVP receptor was successfully achieved by UV lamp exposure (365 nm, 20 min). Thus, AzBz-d(CH2)5Tyr(Me)Tyr[125I](NH2)AVP is a promising tool to use for the purification of human V1-vascular AVP receptors

  4. Early life manipulations of vasopressin-family peptides alter vocal learning.

    Science.gov (United States)

    Baran, Nicole M; Peck, Samantha C; Kim, Tabitha H; Goldstein, Michael H; Adkins-Regan, Elizabeth

    2017-07-26

    Vocal learning from social partners is crucial for the successful development of communication in a wide range of species. Social interactions organize attention and enhance motivation to learn species-typical behaviour. However, the neurobiological mechanisms connecting social motivation and vocal learning are unknown. Using zebra finches ( Taeniopygia guttata ), a ubiquitous model for vocal learning, we show that manipulations of nonapeptide hormones in the vasopressin family (arginine vasotocin, AVT) early in development can promote or disrupt both song and social motivation. Young male zebra finches, like human infants, are socially gregarious and require interactive feedback from adult tutors to learn mature vocal forms. To investigate the role of social motivational mechanisms in song learning, in two studies, we injected hatchling males with AVT or Manning compound (MC, a nonapeptide receptor antagonist) on days 2-8 post-hatching and recorded song at maturity. In both studies, MC males produced a worse match to tutor song than controls. In study 2, which experimentally controlled for tutor and genetic factors, AVT males also learned song significantly better compared with controls. Furthermore, song similarity correlated with several measures of social motivation throughout development. These findings provide the first evidence that nonapeptides are critical to the development of vocal learning. © 2017 The Author(s).

  5. Oroxylin A, but Not Vasopressin, Ameliorates Cardiac Dysfunction of Endotoxemic Rats

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    Chin-Hung Liu

    2012-01-01

    Full Text Available The mortality in septic patients with myocardial dysfunction is higher than those without it. Beneficial effects of flavonoid oroxylin A (Oro-A on endotoxemic hearts were evaluated and compared with that of arginine vasopressin (AVP which is used to reverse hypotension in septic patients. Endotoxemia in rats was induced by one-injection of lipopolysaccharides (LPS, 10 mg/kg, i.p., and hearts were isolated 5-hrs or 16-hrs later. Isolated hearts with constant-pressure or constant-flow mode were examined by Langendorff technique. Rate and force of contractions of isolated atrial and ventricular strips were examined by tissue myography. Isolated endotoxemic hearts were characterized by decreased or increased coronary flow (CF in LPS-treated-for-5hr and LPS-treated-for-16-hr groups, respectively, with decreased inotropy in both groups. Oro-A-perfusion ameliorated while AVP-perfusion worsened the decreased CF and inotropy in both preparations. Oro-A and AVP, however, did not affect diminished force or rate of contraction of atrial and ventricular strips of endotoxemic hearts. Oro-A-induced CF increase was not affected following coronary endothelium-denudation with saponin. These results suggest that Oro-A ameliorates LPS-depressed cardiac functions by increasing CF, leading to positive inotropy. In contrast, AVP aggravates cardiac dysfunction by decreasing CF. Oro-A is a potentially useful candidate for treating endotoxemia complicated with myocardial dysfunction.

  6. Radioimmunoassay of arginine-vasopressin in human plasma: Development and clinical application

    International Nuclear Information System (INIS)

    Hummerich, W.; Konrads, A.; Roesch, R.; Sofroniew, M.

    1983-01-01

    A sensitive and specific radioimmunoassay for the measurement of arg-vasopressin (AVP) in human plasma is described. Recovery of added AVP from plasma was about 65-70%. An acetone extraction step was necessary to prevent unspecific blank effects. Sensitivity of the assay in 0.5 pg AVP/ml plasma. In normally hydrated subjects AVP-concentration ranged from 0.7 pg/ml to 5.8 pg/ml and showed a good correlation with plasma osmolality. In patients with complete diabetes insipidus (D.i.) AVP-values were below the sensitivity limit of the method and they were subnormal when D.i. was incomplete. There was no increase of AVP-concentration during fluid restriction in patients with complete or incomplete D.i. In subjects with psychogenic polydipsia AVP-values were normal and dehydration produced adequate rises of plasma AVP. In patients with SIADH (Schwartz-Bartter-syndrome) AVP-values were greatly enhanced (> 10 pg/ml) when correlated to plasma osmolality ( 2 O). (orig.)

  7. Radioimmunoassay of arginine-vasopressin in human plasma: Development and clinical application

    Energy Technology Data Exchange (ETDEWEB)

    Hummerich, W.; Konrads, A.; Roesch, R.; Sofroniew, M.

    1983-02-15

    A sensitive and specific radioimmunoassay for the measurement of arg-vasopressin (AVP) in human plasma is described. Recovery of added AVP from plasma was about 65-70%. An acetone extraction step was necessary to prevent unspecific blank effects. Sensitivity of the assay in 0.5 pg AVP/ml plasma. In normally hydrated subjects AVP-concentration ranged from 0.7 pg/ml to 5.8 pg/ml and showed a good correlation with plasma osmolality. In patients with complete diabetes insipidus (D.i.) AVP-values were below the sensitivity limit of the method and they were subnormal when D.i. was incomplete. There was no increase of AVP-concentration during fluid restriction in patients with complete or incomplete D.i. In subjects with psychogenic polydipsia AVP-values were normal and dehydration produced adequate rises of plasma AVP. In patients with SIADH (Schwartz-Bartter-syndrome) AVP-values were greatly enhanced (> 10 pg/ml) when correlated to plasma osmolality (< 170 mosmol/kg H/sub 2/O).

  8. Oxytocin and vasopressin flatten dominance hierarchy and enhance behavioral synchrony in part via anterior cingulate cortex.

    Science.gov (United States)

    Jiang, Yaoguang; Platt, Michael L

    2018-05-29

    The neuropeptides oxytocin (OT) and arginine vasopressin (AVP) influence social functions in many mammals. In humans and rhesus macaques, OT delivered intranasally can promote prosocial behavior in certain contexts. Yet the precise neural mechanisms mediating these behavioral effects remain unclear. Here we show that treating a group of male macaque monkeys intranasally with aerosolized OT relaxes their spontaneous social interactions with other monkeys. OT reduces differences in social behavior between dominant and subordinate monkeys, thereby flattening the status hierarchy. OT also increases behavioral synchrony within a pair. Intranasal delivery of aerosolized AVP reproduces the effects of OT with greater efficacy. Remarkably, all behavioral effects are replicated when OT or AVP is injected focally into the anterior cingulate gyrus (ACCg), a brain area linked to empathy and other-regarding behavior. ACCg lacks OT receptors but is rich in AVP receptors, suggesting exogenous OT may shape social behavior, in part, via nonspecific binding. Notably, OT and AVP alter behaviors of both the treated monkey and his untreated partner, consistent with enhanced feedback through reciprocal social interactions. These findings bear important implications for use of OT in both basic research and as a therapy for social impairments in neurodevelopmental disorders.

  9. Effects of Chronic Central Arginine Vasopressin (AVP) on Maternal Behavior in Chronically Stressed Rat Dams

    Science.gov (United States)

    Coverdill, Alexander J.; McCarthy, Megan; Bridges, Robert S.; Nephew, Benjamin C.

    2012-01-01

    Exposure of mothers to chronic stressors during pregnancy or the postpartum period often leads to the development of depression, anxiety, or other related mood disorders. The adverse effects of mood disorders are often mediated through maternal behavior and recent work has identified arginine vasopressin (AVP) as a key neuropeptide hormone in the expression of maternal behavior in both rats and humans. Using an established rodent model that elicits behavioral and physiological responses similar to human mood disorders, this study tested the effectiveness of chronic AVP infusion as a novel treatment for the adverse effects of exposure to chronic social stress during lactation in rats. During early (day 3) and mid (day 10) lactation, AVP treatment significantly decreased the latency to initiate nursing and time spent retrieving pups, and increased pup grooming and total maternal care (sum of pup grooming and nursing). AVP treatment was also effective in decreasing maternal aggression and the average duration of aggressive bouts on day 3 of lactation. Central AVP may be an effective target for the development of treatments for enhancing maternal behavior in individuals exposed to chronic social stress. PMID:24349762

  10. Copeptin in the diagnosis of vasopressin-dependent disorders of fluid homeostasis.

    Science.gov (United States)

    Christ-Crain, Mirjam; Fenske, Wiebke

    2016-03-01

    Copeptin and arginine vasopressin (AVP) are derived from a common precursor molecule and have equimolar secretion and response to osmotic, haemodynamic and stress-related stimuli. Plasma concentrations of copeptin and AVP in relation to serum osmolality are highly correlated. The physiological functions of AVP with respect to homeostasis of fluid balance, vascular tonus and regulation of the endocrine stress response are well known, but the exact function of copeptin is undetermined. Quantification of AVP can be difficult, but copeptin is stable in plasma and can be easily measured with a sandwich immunoassay. For this reason, copeptin has emerged as a promising marker for the diagnosis of AVP-dependent fluid disorders. Copeptin measurements can enable differentiation between various conditions within the polyuria-polydipsia syndrome. In the absence of prior fluid deprivation, baseline copeptin levels >20 pmol/l identify patients with nephrogenic diabetes insipidus. Conversely, copeptin levels measured upon osmotic stimulation differentiate primary polydipsia from partial central diabetes insipidus. In patients with hyponatraemia, low levels of copeptin together with low urine osmolality identify patients with primary polydipsia, and the ratio of copeptin to urinary sodium can distinguish the syndrome of inappropriate antidiuretic hormone secretion from other AVP-dependent forms of hyponatraemia.

  11. Epigenetic control of vasopressin expression is maintained by steroid hormones in the adult male rat brain

    Science.gov (United States)

    Auger, Catherine J.; Coss, Dylan; Auger, Anthony P.; Forbes-Lorman, Robin M.

    2011-01-01

    Although some DNA methylation patterns are altered by steroid hormone exposure in the developing brain, less is known about how changes in steroid hormone levels influence DNA methylation patterns in the adult brain. Steroid hormones act in the adult brain to regulate gene expression. Specifically, the expression of the socially relevant peptide vasopressin (AVP) within the bed nucleus of the stria terminalis (BST) of adult brain is dependent upon testosterone exposure. Castration dramatically reduces and testosterone replacement restores AVP expression within the BST. As decreases in mRNA expression are associated with increases in DNA promoter methylation, we explored the hypothesis that AVP expression in the adult brain is maintained through sustained epigenetic modifications of the AVP gene promoter. We find that castration of adult male rats resulted in decreased AVP mRNA expression and increased methylation of specific CpG sites within the AVP promoter in the BST. Similarly, castration significantly increased estrogen receptor α (ERα) mRNA expression and decreased ERα promoter methylation within the BST. These changes were prevented by testosterone replacement. This suggests that the DNA promoter methylation status of some steroid responsive genes in the adult brain is actively maintained by the presence of circulating steroid hormones. The maintenance of methylated or demethylated states of some genes in the adult brain by the presence of steroid hormones may play a role in the homeostatic regulation of behaviorally relevant systems. PMID:21368111

  12. Oxytocin and vasopressin enhance responsiveness to infant stimuli in adult marmosets.

    Science.gov (United States)

    Taylor, Jack H; French, Jeffrey A

    2015-09-01

    The neuropeptides oxytocin (OT) and arginine-vasopressin (AVP) have been implicated in modulating sex-specific responses to offspring in a variety of uniparental and biparental rodent species. Despite the large body of research in rodents, the effects of these hormones in biparental primates are less understood. Marmoset monkeys (Callithrix jacchus) belong to a clade of primates with a high incidence of biparental care and also synthesize a structurally distinct variant of OT (proline instead of leucine at the 8th amino acid position; Pro(8)-OT). We examined the roles of the OT and AVP systems in the control of responses to infant stimuli in marmoset monkeys. We administered neuropeptide receptor agonists and antagonists to male and female marmosets, and then exposed them to visual and auditory infant-related and control stimuli. Intranasal Pro(8)-OT decreased latencies to respond to infant stimuli in males, and intranasal AVP decreased latencies to respond to infant stimuli in females. Our study is the first to demonstrate that Pro(8)-OT and AVP alter responsiveness to infant stimuli in a biparental New World monkey. Across species, the effects of OT and AVP on parental behavior appear to vary by species-typical caregiving responsibilities in males and females. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. The role of oxytocin and vasopressin in conditioned mate guarding behavior in the female rat.

    Science.gov (United States)

    Holley, Amanda; Bellevue, Shannon; Vosberg, Daniel; Wenzel, Kerstin; Roorda, Sieger; Pfaus, James G

    2015-05-15

    We have shown previously that female rats given their first copulatory experiences with the same male rat display mate guarding behavior in the presence of that male provided a female competitor is also present. Females given access to the familiar male show more Fos induction within regions of the brain that contain oxytocin (OT) and vasopressin (AVP) cell bodies, notably the supraoptic (SON) and paraventricular nuclei (PVN) relative to females given sexual experience with different males. The present experiments examined whether the Fos induction we previously observed within the SON and PVN occurred within OT and/or AVP neurons, and whether exogenous administration of OT or AVP prior to female rats first sexual experience could potentiate the acquisition of mate guarding behavior. Female rats that display conditioned mate guarding had significantly more double-labeled Fos/OT neurons in both SON and PVN, and significantly more Fos/AVP neurons in the PVN. Peripheral administration of OT or AVP prior to their first sexual experience with the familiar male facilitated different aspects of mate guarding: OT augmented affiliative behaviors and presenting responses whereas AVP augmented interference behavior. These results indicate that female rats' first experiences with sexual reward when paired with the same male induce changes to bonding networks in the brain. Moreover peripheral administration of OT or AVP during their first sexual experience can augment different aspects of mate guarding behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. ER-associated degradation is required for vasopressin prohormone processing and systemic water homeostasis

    Science.gov (United States)

    Somlo, Diane R.M.; Kim, Geun Hyang; Prescianotto-Baschong, Cristina; Sun, Shengyi; Beuret, Nicole; Long, Qiaoming; Rutishauser, Jonas

    2017-01-01

    Peptide hormones are crucial regulators of many aspects of human physiology. Mutations that alter these signaling peptides are associated with physiological imbalances that underlie diseases. However, the conformational maturation of peptide hormone precursors (prohormones) in the ER remains largely unexplored. Here, we report that conformational maturation of proAVP, the precursor for the antidiuretic hormone arginine-vasopressin, within the ER requires the ER-associated degradation (ERAD) activity of the Sel1L-Hrd1 protein complex. Serum hyperosmolality induces expression of both ERAD components and proAVP in AVP-producing neurons. Mice with global or AVP neuron–specific ablation of Se1L-Hrd1 ERAD progressively developed polyuria and polydipsia, characteristics of diabetes insipidus. Mechanistically, we found that ERAD deficiency causes marked ER retention and aggregation of a large proportion of all proAVP protein. Further, we show that proAVP is an endogenous substrate of Sel1L-Hrd1 ERAD. The inability to clear misfolded proAVP with highly reactive cysteine thiols in the absence of Sel1L-Hrd1 ERAD causes proAVP to accumulate and participate in inappropriate intermolecular disulfide–bonded aggregates, promoted by the enzymatic activity of protein disulfide isomerase (PDI). This study highlights a pathway linking ERAD to prohormone conformational maturation in neuroendocrine cells, expanding the role of ERAD in providing a conducive ER environment for nascent proteins to reach proper conformation. PMID:28920920

  15. Progressive polyuria without vasopressin neuron loss in a mouse model for familial neurohypophysial diabetes insipidus.

    Science.gov (United States)

    Hayashi, Masayuki; Arima, Hiroshi; Ozaki, Noriyuki; Morishita, Yoshiaki; Hiroi, Maiko; Ozaki, Nobuaki; Nagasaki, Hiroshi; Kinoshita, Noriaki; Ueda, Masatsugu; Shiota, Akira; Oiso, Yutaka

    2009-05-01

    Familial neurohypophysial diabetes insipidus (FNDI), an autosomal dominant disorder, is mostly caused by mutations in the gene of neurophysin II (NPII), the carrier protein of arginine vasopressin (AVP). Previous studies suggest that loss of AVP neurons might be the cause of polyuria in FNDI. Here we analyzed knockin mice expressing mutant NPII that causes FNDI in humans. The heterozygous mice manifested progressive polyuria as do patients with FNDI. Immunohistochemical analyses revealed that inclusion bodies that were not immunostained with antibodies for mutant NPII, normal NPII, or AVP were present in the AVP cells in the supraoptic nucleus (SON), and that the size of inclusion bodies gradually increased in parallel with the increases in urine volume. Electron microscopic analyses showed that aggregates existed in the endoplasmic reticulum (ER) as well as in the nucleus of AVP neurons in 1-mo-old heterozygous mice. At 12 mo, dilated ER filled with aggregates occupied the cytoplasm of AVP cells, while few aggregates were found in the nucleus. Analyses with in situ hybridization revealed that expression of AVP mRNA was significantly decreased in the SON in the heterozygous mice compared with that in wild-type mice. Counting cells expressing AVP mRNA in the SON indicated that polyuria had progressed substantially in the absence of neuronal loss. These data suggest that cell death is not the primary cause of polyuria in FNDI, and that the aggregates accumulated in the ER might be involved in the dysfunction of AVP neurons that lead to the progressive polyuria.

  16. Effect of naftopidil on brain noradrenaline-induced decrease in arginine-vasopressin secretion in rats

    Directory of Open Access Journals (Sweden)

    Masaki Yamamoto

    2016-09-01

    Full Text Available Naftopidil, an α1-adrenoceptor antagonist, has been shown to inhibit nocturnal polyuria in patients with lower urinary tract symptom. However, it remains unclear how naftopidil decreases nocturnal urine production. Here, we investigated the effects of naftopidil on arginine-vasopressin (AVP plasma level and urine production and osmolality in rats centrally administered with noradrenaline (NA. NA (3 or 30 μg/kg was administered into the left ventricle (i.c.v. of male Wistar rats 3 h after naftopidil pretreatment (10 or 30 mg/kg, i.p.. Blood samples were collected from the inferior vena cava 1 h after NA administration or 4 h after peritoneal administration of naftopidil; plasma levels of AVP were assessed by ELISA. Voiding behaviors of naftopidil (30 mg/kg, i.p.-administered male Wistar rats were observed during separate light- and dark cycles. Administration of NA decreased plasma AVP levels and elevated urine volume, which were suppressed by systemic pretreatment with naftopidil (30 mg/kg, i.p.. Urine osmolality decreased 1 h after NA administration. However, naftopidil by itself had no effect on plasma AVP levels or urodynamic parameters during light- and dark cycles. Our findings suggest that systemic administration of naftopidil could prevent central noradrenergic nervous system-mediated decline in AVP secretion and increase in urine production in rats.

  17. Combined sodium ion sensitivity in agonist binding and internalization of vasopressin V1b receptors.

    Science.gov (United States)

    Koshimizu, Taka-Aki; Kashiwazaki, Aki; Taniguchi, Junichi

    2016-05-03

    Reducing Na(+) in the extracellular environment may lead to two beneficial effects for increasing agonist binding to cell surface G-protein coupled receptors (GPCRs): reduction of Na(+)-mediated binding block and reduce of receptor internalization. However, such combined effects have not been explored. We used Chinese Hamster Ovary cells expressing vasopressin V1b receptors as a model to explore Na(+) sensitivity in agonist binding and receptor internalization. Under basal conditions, a large fraction of V1b receptors is located intracellularly, and a small fraction is in the plasma membrane. Decreases in external Na(+) increased cell surface [(3)H]AVP binding and decreased receptor internalization. Substitution of Na(+) by Cs(+) or NH4(+) inhibited agonist binding. To suppress receptor internalization, the concentration of NaCl, but not of CsCl, had to be less than 50 mM, due to the high sensitivity of the internalization machinery to Na(+) over Cs(+). Iso-osmotic supplementation of glucose or NH4Cl maintained internalization of the V1b receptor, even in a low-NaCl environment. Moreover, iodide ions, which acted as a counter anion, inhibited V1b agonist binding. In summary, we found external ionic conditions that could increase the presence of high-affinity state receptors at the cell surface with minimum internalization during agonist stimulations.

  18. Simultaneous measurement of arginine vasopressin and oxytocin in plasma and neurohypophysis by radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Landgraf, R [Deutsche Hochschule fuer Koerperkultur, Leipzig (German Democratic Republic). Forschungsinstitut Koerperkultur und Sport

    1981-12-01

    Arginine vasopressin (AVP) and oxytocin (OXT) were measured simultaneously in the same sample by specific and sensitive radioimmunoassays (RIAs). The antibodies used did not cross-react to a variety of analogs and related peptides. The extraction procedure using Vycor glass powder resulted in mean recoveries of 84.4% (AVP) and 64.6% (OXT). In both assays, the sensitivity was 1 to 2 pg/ml plasma. A preincubation procedure that depresses plasma levels of both AVP and OXT selectively, provided specific blank values for a given plasma sample. To confirm the validity of the RIAs, dehydration experiments were performed. In rats, the basal levels of plasma AVP and OXT (means: 2,63 pg/ml and 6.80 pg/ml, respectively) are increased significantly after 24 h, 48 h and 72 h of water deprivation. Relationships are presented between both neurohormones in the plasma and neurohypophyses of control and dehydrated animals. As shown in cows, a significant correlation exists between plasma AVP and plasma osmolality but not between plasma OXT and osmolality or plasma AVP and OXT. Basal levels as well as physiological changes in plasma and neurohypophyseal AVP and OXT can be measured by the RIAs described.

  19. Vasopressin activates Akt/mTOR pathway in smooth muscle cells cultured in high glucose concentration

    Energy Technology Data Exchange (ETDEWEB)

    Montes, Daniela K.; Brenet, Marianne; Muñoz, Vanessa C.; Burgos, Patricia V.; Villanueva, Carolina I. [Department of Physiology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); Figueroa, Carlos D. [Department of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); González, Carlos B., E-mail: cbgonzal@uach.cl [Department of Physiology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555 (United States)

    2013-11-29

    Highlights: •AVP induces mTOR phosphorylation in A-10 cells cultured in high glucose concentration. •The mTOR phosphorylation is mediated by the PI3K/Akt pathway activation. •The AVP-induced mTOR phosphorylation inhibited autophagy and stimulated cell proliferation. -- Abstract: Mammalian target of rapamycin (mTOR) complex is a key regulator of autophagy, cell growth and proliferation. Here, we studied the effects of arginine vasopressin (AVP) on mTOR activation in vascular smooth muscle cells cultured in high glucose concentration. AVP induced the mTOR phosphorylation in A-10 cells grown in high glucose, in contrast to cells cultured in normal glucose; wherein, only basal phosphorylation was observed. The AVP-induced mTOR phosphorylation was inhibited by a PI3K inhibitor. Moreover, the AVP-induced mTOR activation inhibited autophagy and increased thymidine incorporation in cells grown in high glucose. This increase was abolished by rapamycin which inhibits the mTORC1 complex formation. Our results suggest that AVP stimulates mTOR phosphorylation by activating the PI3K/Akt signaling pathway and, subsequently, inhibits autophagy and raises cell proliferation in A-10 cells maintained in high glucose concentration.

  20. Individual Differences in Social Behavior and Cortical Vasopressin Receptor: Genetics, Epigenetics, and Evolution

    Directory of Open Access Journals (Sweden)

    Steven M. Phelps

    2017-10-01

    Full Text Available Social behavior is among the most complex and variable of traits. Despite its diversity, we know little about how genetic and developmental factors interact to shape natural variation in social behavior. This review surveys recent work on individual differences in the expression of the vasopressin 1a receptor (V1aR, a major regulator of social behavior, in the neocortex of the socially monogamous prairie vole. V1aR exhibits profound variation in the retrosplenial cortex (RSC, a region critical to spatial and contextual memory. RSC-V1aR abundance is associated with patterns of male space-use and sexual fidelity in the field: males with high RSC-V1aR show high spatial and sexual fidelity to partners, while low RSC-V1aR males are significantly more likely to mate outside the pair-bond. Individual differences in RSC-V1aR are predicted by a set of linked single nucleotide polymorphisms within the avpr1a locus. These alternative alleles have been actively maintained by selection, suggesting that the brain differences represent a balanced polymorphism. Lastly, the alleles occur within regulatory sequences, and result in differential sensitivity to environmental perturbation. Together the data provide insight into how genetic, epigenetic and evolutionary forces interact to shape the social brain.

  1. The Oxytocin–Vasopressin Pathway in the Context of Love and Fear

    Directory of Open Access Journals (Sweden)

    C. Sue Carter

    2017-12-01

    Full Text Available Vasopressin (VP and oxytocin (OT are distinct molecules; these peptides and their receptors [OT receptor (OTR and V1a receptor (V1aR] also are evolved components of an integrated and adaptive system, here described as the OT–VP pathway. The more ancient peptide, VP, and the V1aRs support individual survival and play a role in defensive behaviors, including mobilization and aggression. OT and OTRs have been associated with positive social behaviors and may function as a biological metaphor for social attachment or “love.” However, complex behavioral functions, including selective sexual behaviors, social bonds, and parenting require combined activities of OT and VP. The behavioral effects of OT and VP vary depending on perceived emotional context and the history of the individual. Paradoxical or contextual actions of OT also may reflect differential interactions with the OTR and V1aR. Adding to the complexity of this pathway is the fact that OT and VP receptors are variable, across species, individuals, and brain region, and these receptors are capable of being epigenetically tuned. This variation may help to explain experience-related individual and sex differences in behaviors that are regulated by these peptides, including the capacity to form social attachments and the emotional consequences of these attachments.

  2. Sexually dimorphic role for vasopressin in the development of social play

    Directory of Open Access Journals (Sweden)

    Matthew J. Paul

    2014-02-01

    Full Text Available Despite the well-established role of vasopressin (AVP in adult social behavior, its role in social development is relatively unexplored. In this paper, we focus on the most prominent social behavior of juvenile rats, social play. Previous pharmacological experiments in our laboratory suggested that AVP regulates play in a sex- and brain region-specific manner in juvenile rats. Here we investigate the role of specific AVP systems in the emergence of social play. We first characterize the development of play in male and female Wistar rats and then ask whether the development of AVP mRNA expression correlates with the emergence of play. Unexpectedly, play emerged more rapidly in weanling-aged females than in males, resulting in a sex difference opposite of that typically reported for older, juvenile rats. AVP mRNA and play were correlated in males only, with a negative correlation in the bed nucleus of the stria terminalis and a positive correlation in the paraventricular nucleus of the hypothalamus. These findings support the hypothesis that AVP acts differentially on multiple systems in a sex-specific manner to regulate social play and suggest a role for PVN and BNST AVP systems in the development of play. Differential neuropeptide regulation of male and female social development may underlie well-documented sex differences in incidence, progression, and symptom severity of behavioral disorders during development.

  3. Vasopressin up-regulates the expression of growth-related immediate-early genes via two distinct EGF receptor transactivation pathways

    Science.gov (United States)

    Fuentes, Lida Q.; Reyes, Carlos E.; Sarmiento, José M.; Villanueva, Carolina I.; Figueroa, Carlos D.; Navarro, Javier; González, Carlos B.

    2008-01-01

    Activation of V1a receptor triggers the expression of growth-related immediate-early genes (IEGs), including c-Fos and Egr-1. Here we found that pre-treatment of rat vascular smooth muscle A-10 cell line with the EGF receptor inhibitor AG1478 or the over-expression of an EGFR dominant negative mutant (HEBCD533) blocked the vasopressin-induced expression of IEGs, suggesting that activation of these early genes mediated by V1a receptor is via transactivation of the EGF receptor. Importantly, the inhibition of the metalloproteinases, which catalyzed the shedding of the EGF receptor agonist HB-EGF, selectively blocked the vasopressin-induced expression c-Fos. On the other hand, the inhibition of c-Src selectively blocked the vasopressin-induced expression of Egr-1. Interestingly, in contrast to the expression of c-Fos, the expression of Egr-1 was mediated via the Ras/MEK/MAPK-dependent signalling pathway. Vasopressin-triggered expression of both genes required the release of intracellular calcium, activation of PKC and β-arrestin 2. These findings demonstrated that vasopressin up-regulated the expression of c-Fos and Erg-1 via transactivation of two distinct EGF receptor-dependent signalling pathways. PMID:18571897

  4. HPG-axis hormones during puberty : A study on the association with hypothalamic and pituitary volumes

    NARCIS (Netherlands)

    Peper, Jiska S.; Brouwer, Rachel M.; van Leeuwen, Marieke; Schnack, Hugo G.; Boomsma, Dorret I.; Kahn, Rene S.; Pol, Hilleke E. Hulshoff

    Objective: During puberty, the hypothalamus-pituitary-gonadal (HPG) axis is activated, leading to increases in luteinizing hormone (LH), follicle stimulating hormone (FSH) and sex steroids (testosterone and estradiol) levels. We aimed to study the association between hypothalamic and pituitary

  5. Neonatal GLP1R activation limits adult adiposity by durably altering hypothalamic architecture

    Directory of Open Access Journals (Sweden)

    Andrea V. Rozo

    2017-07-01

    Conclusion: These observations suggest that the acute activation of GLP1R in neonates durably alters hypothalamic architecture to limit adult weight gain and adiposity, identifying GLP1R as a therapeutic target for obesity prevention.

  6. Brain Innate Immunity Regulates Hypothalamic Arcuate Neuronal Activity and Feeding Behavior

    NARCIS (Netherlands)

    Reis, Wagner L.; Yi, Chun-Xia; Gao, Yuanqing; Tschöp, Mathias H.; Stern, Javier E.

    2015-01-01

    Hypothalamic inflammation, involving microglia activation in the arcuate nucleus (ARC), is proposed as a novel underlying mechanism in obesity, insulin and leptin resistance. However, whether activated microglia affects ARC neuronal activity, and consequently basal and hormonal-induced food intake,

  7. Hypopituitarism after external irradiation. Evidence for both hypothalamic and pituitary origin

    International Nuclear Information System (INIS)

    Samaan, N.A.; Bakdash, M.M.; Caderao, J.B.; Cangir, A.; Jesse, R.H. Jr.; Ballantyne, A.J.

    1975-01-01

    Endocrine complications after radiotherapy for tumors of the head and neck are thought to be relatively rare. The availability of synthetic hypothalamic hormones for clinical investigations and the radioimmunoassay of hormones have enabled us to study function of the hypothalamic pituitary axis in 15 patients who had radiotherapy for nasopharyngeal cancer. Fourteen had evidence of endocrine deficiency. Twelve patients had evidence of hypothalamic dysfunction, 7 developed primary pituitary hormone deficiencies, and 3 developed primary hypothyroidism. These results indicate that (1) secondary hypopituitarism due to a hypothalamic lesion after radiotherapy for nasopharyngeal cancer may be more common than suspected in the past; (2) primary hypopituitarism after irradiation of extracranial tumors can occur; and (3) primary hypothyroidism may result from irradiation of regional neck nodes

  8. Reduced α-MSH Underlies Hypothalamic ER-Stress-Induced Hepatic Gluconeogenesis.

    Science.gov (United States)

    Schneeberger, Marc; Gómez-Valadés, Alicia G; Altirriba, Jordi; Sebastián, David; Ramírez, Sara; Garcia, Ainhoa; Esteban, Yaiza; Drougard, Anne; Ferrés-Coy, Albert; Bortolozzi, Analía; Garcia-Roves, Pablo M; Jones, John G; Manadas, Bruno; Zorzano, Antonio; Gomis, Ramon; Claret, Marc

    2015-07-21

    Alterations in ER homeostasis have been implicated in the pathophysiology of obesity and type-2 diabetes (T2D). Acute ER stress induction in the hypothalamus produces glucose metabolism perturbations. However, the neurobiological basis linking hypothalamic ER stress with abnormal glucose metabolism remains unknown. Here, we report that genetic and induced models of hypothalamic ER stress are associated with alterations in systemic glucose homeostasis due to increased gluconeogenesis (GNG) independent of body weight changes. Defective alpha melanocyte-stimulating hormone (α-MSH) production underlies this metabolic phenotype, as pharmacological strategies aimed at rescuing hypothalamic α-MSH content reversed this phenotype at metabolic and molecular level. Collectively, our results posit defective α-MSH processing as a fundamental mediator of enhanced GNG in the context of hypothalamic ER stress and establish α-MSH deficiency in proopiomelanocortin (POMC) neurons as a potential contributor to the pathophysiology of T2D. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Prokineticin 2 Is a Hypothalamic Neuropeptide That Potently Inhibits Food Intake

    OpenAIRE

    Gardiner, JV; Bataveljic, A; Patel, NA; Bewick, GA; Roy, D; Campbell, D; Greenwood, HC; Murphy, KG; Hameed, S; Jethwa, PH; Ebling, FJP; Vickers, SP; Cheetham, S; Ghatei, MA; Bloom, SR

    2009-01-01

    OBJECTIVE Prokineticin 2 (PK2) is a hypothalamic neuropeptide expressed in central nervous system areas known to be involved in food intake. We therefore hypothesized that PK2 plays a role in energy homeostasis. RESEARCH DESIGN AND METHODS We investigated the effect of nutritional status on hypothalamic PK2 expression and effects of PK2 on the regulation of food intake by intracerebroventricular (ICV) injection of PK2 and anti-PK2 antibody. Subsequently, we investigated the potential mechanis...

  10. Hypothalamic 2-arachidonoylglycerol regulates multistage process of high-fat diet preferences.

    Directory of Open Access Journals (Sweden)

    Sei Higuchi

    Full Text Available In this study, we examined alterations in the hypothalamic reward system related to high-fat diet (HFD preferences. We previously reported that hypothalamic 2-arachidonoylglycerol (2-AG and glial fibrillary acid protein (GFAP were increased after conditioning to the rewarding properties of a HFD. Here, we hypothesized that increased 2-AG influences the hypothalamic reward system.The conditioned place preference test (CPP test was used to evaluate HFD preferences. Hypothalamic 2-AG was quantified by gas chromatography-mass spectrometry. The expression of GFAP was examined by immunostaining and western blotting.Consumption of a HFD over either 3 or 7 days increased HFD preferences and transiently increased hypothalamic 2-AG levels. HFD consumption over 14 days similarly increased HFD preferences but elicited a long-lasting increase in hypothalamic 2-AG and GFAP levels. The cannabinoid 1 receptor antagonist O-2050 reduced preferences for HFDs after 3, 7, or 14 days of HFD consumption and reduced expression of GFAP after 14 days of HFD consumption. The astrocyte metabolic inhibitor Fluorocitrate blocked HFD preferences after 14 days of HFD consumption.High levels of 2-AG appear to induce HFD preferences, and activate hypothalamic astrocytes via the cannabinoid system. We propose that there may be two distinct stages in the development of HFD preferences. The induction stage involves a transient increase in 2-AG, whereas the maintenance stage involves a long lasting increase in 2-AG levels and activation of astrocytes. Accordingly, hypothalamic 2-AG may influence the development of HFD preferences.

  11. Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance

    OpenAIRE

    Kaushik, Susmita; Rodriguez-Navarro, Jose Antonio; Arias, Esperanza; Kiffin, Roberta; Sahu, Srabani; Schwartz, Gary J.; Cuervo, Ana Maria; Singh, Rajat

    2011-01-01

    Macroautophagy is a lysosomal degradative pathway that maintains cellular homeostasis by turning over cellular components. Here, we demonstrate a role for autophagy in hypothalamic agouti-related peptide (AgRP) neurons in the regulation of food intake and energy balance. We show that starvation-induced hypothalamic autophagy mobilizes neuron-intrinsic lipids to generate endogenous free fatty acids, which in turn regulate AgRP levels. The functional consequences of inhibiting autophagy are the...

  12. Proliferative hypothalamic neurospheres express NPY, AGRP, POMC, CART and Orexin-A and differentiate to functional neurons.

    Directory of Open Access Journals (Sweden)

    Lígia Sousa-Ferreira

    Full Text Available Some pathological conditions with feeding pattern alterations, including obesity and Huntington disease (HD are associated with hypothalamic dysfunction and neuronal cell death. Additionally, the hypothalamus is a neurogenic region with the constitutive capacity to generate new cells of neuronal lineage, in adult rodents. The aim of the present work was to evaluate the expression of feeding-related neuropeptides in hypothalamic progenitor cells and their capacity to differentiate to functional neurons which have been described to be affected by hypothalamic dysfunction. Our study shows that hypothalamic progenitor cells from rat embryos grow as floating neurospheres and express the feeding-related neuropeptides Neuropeptide Y (NPY, Agouti-related Protein (AGRP, Pro-OpioMelanocortin (POMC, Cocaine-and-Amphetamine Responsive Transcript (CART and Orexin-A/Hypocretin-1. Moreover the relative mRNA expression of NPY and POMC increases during the expansion of hypothalamic neurospheres in proliferative conditions.Mature neurons were obtained from the differentiation of hypothalamic progenitor cells including NPY, AGRP, POMC, CART and Orexin-A positive neurons. Furthermore the relative mRNA expression of NPY, CART and Orexin-A increases after the differentiation of hypothalamic neurospheres. Similarly to the adult hypothalamic neurons the neurospheres-derived neurons express the glutamate transporter EAAT3. The orexigenic and anorexigenic phenotype of these neurons was identified by functional response to ghrelin and leptin hormones, respectively. This work demonstrates the presence of appetite-related neuropeptides in hypothalamic progenitor cells and neurons obtained from the differentiation of hypothalamic neurospheres, including the neuronal phenotypes that have been described by others as being affected by hypothalamic neurodegeneration. These in vitro models can be used to study hypothalamic progenitor cells aiming a therapeutic intervention to

  13. Hypoxia-inducible factor directs POMC gene to mediate hypothalamic glucose sensing and energy balance regulation.

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    Hai Zhang

    2011-07-01

    Full Text Available Hypoxia-inducible factor (HIF is a nuclear transcription factor that responds to environmental and pathological hypoxia to induce metabolic adaptation, vascular growth, and cell survival. Here we found that HIF subunits and HIF2α in particular were normally expressed in the mediobasal hypothalamus of mice. Hypothalamic HIF was up-regulated by glucose to mediate the feeding control of hypothalamic glucose sensing. Two underlying molecular pathways were identified, including suppression of PHDs by glucose metabolites to prevent HIF2α degradation and the recruitment of AMPK and mTOR/S6K to regulate HIF2α protein synthesis. HIF activation was found to directly control the transcription of POMC gene. Genetic approach was then employed to develop conditional knockout mice with HIF inhibition in POMC neurons, revealing that HIF loss-of-function in POMC neurons impaired hypothalamic glucose sensing and caused energy imbalance to promote obesity development. The metabolic effects of HIF in hypothalamic POMC neurons were independent of leptin signaling or pituitary ACTH pathway. Hypothalamic gene delivery of HIF counteracted overeating and obesity under conditions of nutritional excess. In conclusion, HIF controls hypothalamic POMC gene to direct the central nutrient sensing in regulation of energy and body weight balance.

  14. Role of Hypothalamic VGF in Energy Balance and Metabolic Adaption to Environmental Enrichment in Mice

    Science.gov (United States)

    Foglesong, Grant D.; Huang, Wei; Liu, Xianglan; Slater, Andrew M.; Siu, Jason; Yildiz, Vedat; Salton, Stephen R. J.

    2016-01-01

    Environmental enrichment (EE), a housing condition providing complex physical, social, and cognitive stimulation, leads to improved metabolic health and resistance to diet-induced obesity and cancer. One underlying mechanism is the activation of the hypothalamic-sympathoneural-adipocyte axis with hypothalamic brain-derived neurotrophic factor (BDNF) as the key mediator. VGF, a peptide precursor particularly abundant in the hypothalamus, was up-regulated by EE. Overexpressing BDNF or acute injection of BDNF protein to the hypothalamus up-regulated VGF, whereas suppressing BDNF signaling down-regulated VGF expression. Moreover, hypothalamic VGF expression was regulated by leptin, melanocortin receptor agonist, and food deprivation mostly paralleled to BDNF expression. Recombinant adeno-associated virus-mediated gene transfer of Cre recombinase to floxed VGF mice specifically decreased VGF expression in the hypothalamus. In contrast to the lean and hypermetabolic phenotype of homozygous germline VGF knockout mice, specific knockdown of hypothalamic VGF in male adult mice led to increased adiposity, decreased core body temperature, reduced energy expenditure, and impaired glucose tolerance, as well as disturbance of molecular features of brown and white adipose tissues without effects on food intake. However, VGF knockdown failed to block the EE-induced BDNF up-regulation or decrease of adiposity indicating a minor role of VGF in the hypothalamic-sympathoneural-adipocyte axis. Taken together, our results suggest hypothalamic VGF responds to environmental demands and plays an important role in energy balance and glycemic control likely acting in the melanocortin pathway downstream of BDNF. PMID:26730934

  15. Hypoxia-Inducible Factor Directs POMC Gene to Mediate Hypothalamic Glucose Sensing and Energy Balance Regulation

    Science.gov (United States)

    Zhang, Hai; Zhang, Guo; Gonzalez, Frank J.; Park, Sung-min; Cai, Dongsheng

    2011-01-01

    Hypoxia-inducible factor (HIF) is a nuclear transcription factor that responds to environmental and pathological hypoxia to induce metabolic adaptation, vascular growth, and cell survival. Here we found that HIF subunits and HIF2α in particular were normally expressed in the mediobasal hypothalamus of mice. Hypothalamic HIF was up-regulated by glucose to mediate the feeding control of hypothalamic glucose sensing. Two underlying molecular pathways were identified, including suppression of PHDs by glucose metabolites to prevent HIF2α degradation and the recruitment of AMPK and mTOR/S6K to regulate HIF2α protein synthesis. HIF activation was found to directly control the transcription of POMC gene. Genetic approach was then employed to develop conditional knockout mice with HIF inhibition in POMC neurons, revealing that HIF loss-of-function in POMC neurons impaired hypothalamic glucose sensing and caused energy imbalance to promote obesity development. The metabolic effects of HIF in hypothalamic POMC neurons were independent of leptin signaling or pituitary ACTH pathway. Hypothalamic gene delivery of HIF counteracted overeating and obesity under conditions of nutritional excess. In conclusion, HIF controls hypothalamic POMC gene to direct the central nutrient sensing in regulation of energy and body weight balance. PMID:21814490

  16. Gelastic seizures associated with hypothalamic hamartomas. An update in the clinical presentation, diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    José F. Tellez-Zenteno

    2008-10-01

    Full Text Available José F. Tellez-Zenteno1, Cesar Serrano-Almeida2, Farzad Moien-Afshari11Division of Neurology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; 2Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, CanadaAbstract: Gelastic seizures are epileptic events characterized by bouts of laughter. Laughter-like vocalization is usually combined with facial contraction in the form of a smile. Autonomic features such as flushing, tachycardia, and altered respiration are widely recognized. Conscious state may not be impaired, although this is often difficult to asses particularly in young children. Gelastic seizures have been associated classically to hypothalamic hamartomas, although different extrahypothalamic localizations have been described. Hypothalamic hamartomas are rare congenital lesions presenting with the classic triad of gelastic epilepsy, precocious puberty and developmental delay. The clinical course of patients with gelastic seizures associated with hypothalamic hamartomas is progressive, commencing with gelastic seizures in infancy, deteriorating into more complex seizure disorder resulting in intractable epilepsy. Electrophysiological, radiological, and pathophysiological studies have confirmed the intrinsic epileptogenicity of the hypothalamic hamartoma. Currently the most effective surgical approach is the trancallosal anterior interforniceal approach, however newer approaches including the endoscopic and other treatment such as radiosurgery and gamma knife have been used with success. This review focuses on the syndrome of gelastic seizures associated with hypothalamic hamartomas, but it also reviews other concepts such as status gelasticus and some aspects of gelastic seizures in other locations.Keywords: epilepsy, gelastic seizures, epilepsy surgery, hypothalamic hamartoma, intractable epilepsy

  17. Increasing fatty acid oxidation remodels the hypothalamic neurometabolome to mitigate stress and inflammation.

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    Joseph W McFadden

    Full Text Available Modification of hypothalamic fatty acid (FA metabolism can improve energy homeostasis and prevent hyperphagia and excessive weight gain in diet-induced obesity (DIO from a diet high in saturated fatty acids. We have shown previously that C75, a stimulator of carnitine palmitoyl transferase-1 (CPT-1 and fatty acid oxidation (FAOx, exerts at least some of its hypophagic effects via neuronal mechanisms in the hypothalamus. In the present work, we characterized the effects of C75 and another anorexigenic compound, the glycerol-3-phosphate acyltransferase (GPAT inhibitor FSG67, on FA metabolism, metabolomics profiles, and metabolic stress responses in cultured hypothalamic neurons and hypothalamic neuronal cell lines during lipid excess with palmitate. Both compounds enhanced palmitate oxidation, increased ATP, and inactivated AMP-activated protein kinase (AMPK in hypothalamic neurons in vitro. Lipidomics and untargeted metabolomics revealed that enhanced catabolism of FA decreased palmitate availability and prevented the production of fatty acylglycerols, ceramides, and cholesterol esters, lipids that are associated with lipotoxicity-provoked metabolic stress. This improved metabolic signature was accompanied by increased levels of reactive oxygen species (ROS, and yet favorable changes in oxidative stress, overt ER stress, and inflammation. We propose that enhancing FAOx in hypothalamic neurons exposed to excess lipids promotes metabolic remodeling that reduces local inflammatory and cell stress responses. This shift would restore mitochondrial function such that increased FAOx can produce hypothalamic neuronal ATP and lead to decreased food intake and body weight to improve systemic metabolism.

  18. Hypothalamic hamartoma with precocious puberty: a case report.

    Science.gov (United States)

    Amin, M S; Kader, M A; Huq, F I; Khan, N A

    2012-07-01

    Hypothalamic hamartoma (HH) is one of the most important causes of central precocious puberty in male children. Hamartomas are malformations composed of ectopic gonadotropic hormone (GnRH) neurons which secrete pulsatile gonadotropin releasing hormone. They are generally observed in children under 3 years. A case of 11/3 year-old male child presented with premature development of secondary sexual characters i.e., growth of pubic and axillary hair, enlargement of penis and acne over the face for the last 5 months. On physical examination, his height was 1.02 m and his weight 18kg, enlarged penile length of which 58mm; testicles were enlarged in size right one measuring 32X25mm and the left 30X23mm. His hematological and other biochemical investigations revealed no abnormality. Plain radiographic examination revealed radiological bone age of about 8-9 years. Endocrinological findings were as follows: Follicle stimulating hormone (FSH): 1.5mIU/ml, Luteinizing hormone (LH): 9.1mIU/ml, Testosterone: 701ng/dl (Testosterone level less than 30ng/dl in prepubertal age). Thyroid function tests were normal. Patient showed no adrenal pathology on ultrasound and his testicular parenchyma was homogeneous echotexture with the size of 30X22X16mm on the right (volume 5.4ml) and 30X20X15mm on the left (volume 4.6ml). With above physical & endocrinological findings and age of the child, it was suspected as a case of central precocious puberty. Subsequently MR imaging of the brain done & showed an oval non-enhancing pedunculated hypothalamic mass arising from the tubercinereum that was iso to hypointense to brain parenchyma on T1 - and intermediate signal on T2-weighted images, 20X10X10mm in diameter, extending into suprasellar cistern. During follow up after 06 months of starting conservative medication with gonadotropin-releasing hormone (GnRH) analog (Leuprolide acetate), his progression of puberty has been arrested and the testosterone level 18ng/dl, which is normal for his age.

  19. Reproductive performance of male mice after hypothalamic ghrelin administration.

    Science.gov (United States)

    Poretti, Maria Belen; Frautschi, Camila; Luque, Eugenia Mercedes; Bianconi, Santiago; Martini, Ana Carolina; Stutz, Graciela; Vincenti, Laura Maria; Santillán, María Emilia; Ponzio, Marina Flavia; Schiöth, Helgi; Fiol De Cuneo, Marta Haydee; Carlini, Valeria Paola

    2018-05-23

    It has been demonstrated that food intake and reproductive physiology are both simultaneously modulated to optimize reproductive success under fluctuating metabolic conditions. Ghrelin (Ghr) is an orexigenic peptide identified as the endogenous ligand of the growth hormone secretagogue receptor that is being investigated for its potential role on reproduction. Considering that data available so far are still limited and characterization of Ghr action mechanism on the reproductive system has not been fully elucidated, we studied the hypothalamus participation in Ghr effects on sperm functional activity, plasma levels of gonodotropins and histological morphology in mice testes after hypothalamic infusion of 0.3 or 3.0 nmol/day Ghr or artificial cerebrospinal fluid (ACSF) at different treatment periods. We found that Ghr 3.0 nmol/day administration for 42 days significantly reduced sperm concentration (Ghr 3.0 nmol/day=14.05±2.44 x106/ml vs. ACSF=20.33±1.35 x106/ml, p< 0.05) and motility (Ghr 3.0 nmol/day=59.40±4.20% vs. ACSF=75.80±1.40%, p< 0.05). In addition, histological studies showed a significant decrease percentage of spermatogonia (Ghr 3.0 nmol/day=6,76±0,68% vs. ACSF=9,56±0,41%, p< 0.05) and sperm (Ghr 3.0 nmol/day=24,24±1,92% vs. ACSF=31,20±3,06%, p< 0.05). These results were associated with a significant reduction in luteinizing hormone and testosterone plasma levels (p<0.05). As Ghr is an orexigenic peptide, body weight and food intake were measured. Results showed that Ghr increases both parameters; however, the effect did not last beyond the first week of treatment. Results presented in this work confirm that central Ghr administration impairs spermatogenesis and suggest that this effect is mediated by inhibition of hypothalamic-pituitary-gonadal axis.

  20. Radioimmunoassay of 1-Deamino-8-D-Arginine Vasopressin and related peptides with special condsideration to their gastrointestinal absorption

    International Nuclear Information System (INIS)

    Lundin, S.

    1986-01-01

    A sensitive and specific radioimminoassy for 1-deamino-8-D-arginine vasopressin (DDAVP) was developed. Measurements of the analogue in extracted and non-extracted plasma yielded indentical results, the sensitivity was reduced with non-extracted samples. The assay was validated by correlating DDAVP blood levels to a biologic response (antidiuretic). Dilutions of plasma extracts containing DDAVP were parallel with the standard curve. Fractionations of extracted plasma DDAVP samples on HPLC revealed that immunoreactivity eluted as standard DDAVP. Prolonged infusion of DDAVP in rats did not alter pituitary secretion of oxytocin and vasopressin and urine osmolatity and volume changes were modest. DDAVP was absorbed from the gastrointestinal tract of humans, rats, rabbits and dogs in quantities sufficient to induce a biological response. Peak plasma concentrations were reached between 30-90 min after peptide administration. By the use of an in vitro model, the everted rat intestine, the transmucosal passage of a number of vasopressin analogues were tested. There was no clear-cut correlation between hydrophobicity and intestinal transport rates. Metabolic inhibitors and N/sub2/ did not decrease DDAVP transport. No transport maximum could be demonstrated over a 10/sup4/ fold concentration range. The distribution volume of /sup3/H-polyethyleneglycol was greater. then that of DDAVP in mucosal flakes. There was a close correlation between immunoassayable DDAVP levels and those found after HPLC analyses. It is proposed that DDAVP absorption occurs mainly by passive diffusion. The bioavailability of perorally ingested DDAVP in humans was about 1 percent. Minor amounts were excreted in urine

  1. 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.

  2. Amino acid sensing in hypothalamic tanycytes via umami taste receptors.

    Science.gov (United States)

    Lazutkaite, Greta; Soldà, Alice; Lossow, Kristina; Meyerhof, Wolfgang; Dale, Nicholas

    2017-11-01

    Hypothalamic tanycytes are glial cells that line the wall of the third ventricle and contact the cerebrospinal fluid (CSF). While they are known to detect glucose in the CSF we now show that tanycytes also detect amino acids, important nutrients that signal satiety. Ca 2+ imaging and ATP biosensing were used to detect tanycyte responses to l-amino acids. The downstream pathway of the responses was determined using ATP receptor antagonists and channel blockers. The receptors were characterized using mice lacking the Tas1r1 gene, as well as an mGluR4 receptor antagonist. Amino acids such as Arg, Lys, and Ala evoke Ca 2+ signals in tanycytes and evoke the release of ATP via pannexin 1 and CalHM1, which amplifies the signal via a P2 receptor dependent mechanism. Tanycytes from mice lacking the Tas1r1 gene had diminished responses to lysine and arginine but not alanine. Antagonists of mGluR4 greatly reduced the responses to alanine and lysine. Two receptors previously implicated in taste cells, the Tas1r1/Tas1r3 heterodimer and mGluR4, contribute to the detection of a range of amino acids by tanycytes in CSF. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

  3. Hypothalamic digoxin, hemispheric chemical dominance, and eating behavior.

    Science.gov (United States)

    Kurup, Ravi Kumar; Kurup, Parameswara Achutha

    2003-08-01

    The isoprenoid pathway produces an endogenous membrane Na+-K+ ATPase inhibitor, digoxin, which can regulate neurotransmitter and amino acid transport. Digoxin synthesis and neurotransmitter patterns were assessed in eating disorders. The patterns were compared in those with right hemispheric and left hemispheric dominance. The serum HMG CoA reductase activity, RBC membrane Na+-K+ ATPase activity, serum digoxin, magnesium, tryptophan catabolites (serotonin, quinolinic acid, strychnine, and nicotine), and tyrosine catabolites (morphine, dopamine, and noradrenaline) were measured in anorexia nervosa, bulimia nervosa, right hemispheric dominant, left hemispheric dominant, and bihemispheric dominant individuals. Digoxin synthesis was increased with upregulated tryptophan catabolism and downregulated tyrosine catabolism in those with anorexia nervosa and right hemispheric chemical dominance. Digoxin synthesis was reduced with downregulated tryptophan catabolism and upregulated tyrosine catabolism in those with bulimia nervosa and left hemispheric chemical dominance. The membrane Na+-K+ ATPase activity and serum magnesium were decreased in anorexia nervosa and right hemispheric chemical dominance while they were increased in bulimia nervosa and left hemispheric chemical dominance. Hypothalamic digoxin and hemispheric chemical dominance play a central role in the regulation of eating behavior. Anorexia nervosa represents the right hemispheric chemically dominant/hyperdigoxinemic state and bulimia nervosa the left hemispheric chemically dominant/hypodigoxinemic state.

  4. Hypothalamic-pituitary-testicular system following testicular X-irradiation

    International Nuclear Information System (INIS)

    Verjans, H.L.; Eik-Nes, K.B.

    1976-01-01

    Testes of adult, male rats were exposed to a total dose of 1500 R of X-irradiation. Testicular weight decreased from day 8 after X-ray treatment. This decrease was, however, precded by an increment of the testis weight on day 4 following treatment. X-ray treatment of testes was associated with significant increase in serum FSH. Testicular irradiation had, however, no effect on ventral prostate and seminal vesicles weights. Serum testosterone increased only on day 1, 2 and 4 after irradiation, while serum LH levels tended to increase from day 8 post-irradiation. These changes were not significant, however, when compared with non-irradiated controls. At 7, 13 and 20 days following 1500 R of bilateral, testicular X-irradiation, the hypothalamic-pituitary unit was still capable of responding to exogenous gonadotrophin releasing factor. Serum FSH may in male rats be regulated at least partly by circulating steroids of testicular origin and partly by an unknown factor of non-interstitial cell nature. (author)

  5. Hypothalamic-Pituitary Function in Brain Death: A Review.

    Science.gov (United States)

    Nair-Collins, Michael; Northrup, Jesse; Olcese, James

    2016-01-01

    The Uniform Determination of Death Act (UDDA) states that an individual is dead when "all functions of the entire brain" have ceased irreversibly. However, it has been questioned whether some functions of the hypothalamus, particularly osmoregulation, can continue after the clinical diagnosis of brain death (BD). In order to learn whether parts of the hypothalamus can continue to function after the diagnosis of BD, we performed 2 separate systematic searches of the MEDLINE database, corresponding to the functions of the posterior and anterior pituitary. No meta-analysis is possible due to nonuniformity in the clinical literature. However, some modest generalizations can reasonably be drawn from a narrative review and from anatomic considerations that explain why these findings should be expected. We found evidence suggesting the preservation of hypothalamic function, including secretion of hypophysiotropic hormones, responsiveness to anterior pituitary stimulation, and osmoregulation, in a substantial proportion of patients declared dead by neurological criteria. We discuss several possible explanations for these findings. We conclude by suggesting that additional clinical research with strict inclusion criteria is necessary and further that a more nuanced and forthright public dialogue is needed, particularly since standard diagnostic practices and the UDDA may not be entirely in accord. © The Author(s) 2014.

  6. Melatonin controls seasonal breeding by a network of hypothalamic targets

    DEFF Research Database (Denmark)

    Revel, Florent G; Masson-Pévet, Mireille; Pévet, Paul

    2009-01-01

    In seasonal species, the photoperiod (i.e. day length) tightly regulates reproduction to ensure that birth occurs at the most favourable time of year. In mammals, a distinct photoneuroendocrine circuit controls this process via the pineal hormone melatonin. This hormone is responsible for the sea......In seasonal species, the photoperiod (i.e. day length) tightly regulates reproduction to ensure that birth occurs at the most favourable time of year. In mammals, a distinct photoneuroendocrine circuit controls this process via the pineal hormone melatonin. This hormone is responsible...... for the seasonal timing of reproduction, but the anatomical substrates and the cellular mechanisms through which melatonin modulates seasonal functions remain imprecise. Recently, several genes have been identified as being regulated by the photoperiod in the brain of seasonal mammals. These genes are thought....../GPR54 system and to the RFamide-related peptides.Interestingly, these systems involve different hypothalamic nuclei, suggesting that several brain loci may be crucial for melatonin to regulate reproduction, and thus represent key starting points to identify the long-sought-after mode and site...

  7. Ginseng and the hypothalamic-pituitary control of stress.

    Science.gov (United States)

    Fulder, S J

    1981-01-01

    There are a group of so-called tonic remedies in Far Eastern medicine which are traditionally viewed as harmonizing or adjustive. Ginseng and eleutherococcus are the best known, and there is evidence that they increase arousal, stamina and stress resistance. We have attempted to explore the relationship between the behavioral and the stress effects, and to relate this to traditional concepts. In one series of experiments mice were given ginseng throughout their lifespan. At intervals their behavior response to mild stress was examined and found to be exaggerated compared to controls without ginseng. However, normal ambulatory behavior in the absence of stress was unaffected. A second series of experiments indicated that the binding of corticosteroid to certain brain regions was increased in adrenalectomized rats given ginseng saponin, compared to saline treated controls. This can be interpreted as a result of an increase in hypothalamic-pituitary-adrenal sensitivity caused by ginseng saponin. This is in accord with traditional concepts of the use of these remedies.

  8. Hypothalamic eIF2α Signaling Regulates Food Intake

    Directory of Open Access Journals (Sweden)

    Anne-Catherine Maurin

    2014-02-01

    Full Text Available The reversible phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α is a highly conserved signal implicated in the cellular adaptation to numerous stresses such as the one caused by amino acid limitation. In response to dietary amino acid deficiency, the brain-specific activation of the eIF2α kinase GCN2 leads to food intake inhibition. We report here that GCN2 is rapidly activated in the mediobasal hypothalamus (MBH after consumption of a leucine-deficient diet. Furthermore, knockdown of GCN2 in this particular area shows that MBH GCN2 activity controls the onset of the aversive response. Importantly, pharmacological experiments demonstrate that the sole phosphorylation of eIF2α in the MBH is sufficient to regulate food intake. eIF2α signaling being at the crossroad of stress pathways activated in several pathological states, our study indicates that hypothalamic eIF2α phosphorylation could play a critical role in the onset of anorexia associated with certain diseases.

  9. Social behaviour shapes hypothalamic neural ensemble representations of conspecific sex

    Science.gov (United States)

    Remedios, Ryan; Kennedy, Ann; Zelikowsky, Moriel; Grewe, Benjamin F.; Schnitzer, Mark J.; Anderson, David J.

    2017-10-01

    All animals possess a repertoire of innate (or instinctive) behaviours, which can be performed without training. Whether such behaviours are mediated by anatomically distinct and/or genetically specified neural pathways remains unknown. Here we report that neural representations within the mouse hypothalamus, that underlie innate social behaviours, are shaped by social experience. Oestrogen receptor 1-expressing (Esr1+) neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl) control mating and fighting in rodents. We used microendoscopy to image Esr1+ neuronal activity in the VMHvl of male mice engaged in these social behaviours. In sexually and socially experienced adult males, divergent and characteristic neural ensembles represented male versus female conspecifics. However, in inexperienced adult males, male and female intruders activated overlapping neuronal populations. Sex-specific neuronal ensembles gradually separated as the mice acquired social and sexual experience. In mice permitted to investigate but not to mount or attack conspecifics, ensemble divergence did not occur. However, 30 minutes of sexual experience with a female was sufficient to promote the separation of male and female ensembles and to induce an attack response 24 h later. These observations uncover an unexpected social experience-dependent component to the formation of hypothalamic neural assemblies controlling innate social behaviours. More generally, they reveal plasticity and dynamic coding in an evolutionarily ancient deep subcortical structure that is traditionally viewed as a ‘hard-wired’ system.

  10. Neonatal ghrelin programs development of hypothalamic feeding circuits

    Science.gov (United States)

    Steculorum, Sophie M.; Collden, Gustav; Coupe, Berengere; Croizier, Sophie; Lockie, Sarah; Andrews, Zane B.; Jarosch, Florian; Klussmann, Sven; Bouret, Sebastien G.

    2015-01-01

    A complex neural network regulates body weight and energy balance, and dysfunction in the communication between the gut and this neural network is associated with metabolic diseases, such as obesity. The stomach-derived hormone ghrelin stimulates appetite through interactions with neurons in the arcuate nucleus of the hypothalamus (ARH). Here, we evaluated the physiological and neurobiological contribution of ghrelin during development by specifically blocking ghrelin action during early postnatal development in mice. Ghrelin blockade in neonatal mice resulted in enhanced ARH neural projections and long-term metabolic effects, including increased body weight, visceral fat, and blood glucose levels and decreased leptin sensitivity. In addition, chronic administration of ghrelin during postnatal life impaired the normal development of ARH projections and caused metabolic dysfunction. Consistent with these observations, direct exposure of postnatal ARH neuronal explants to ghrelin blunted axonal growth and blocked the neurotrophic effect of the adipocyte-derived hormone leptin. Moreover, chronic ghrelin exposure in neonatal mice also attenuated leptin-induced STAT3 signaling in ARH neurons. Collectively, these data reveal that ghrelin plays an inhibitory role in the development of hypothalamic neural circuits and suggest that proper expression of ghrelin during neonatal life is pivotal for lifelong metabolic regulation. PMID:25607843

  11. Childhood Parental Loss and Adult Hypothalamic-Pituitary-Adrenal Function

    Science.gov (United States)

    Tyrka, Audrey R.; Wier, Lauren; Price, Lawrence H.; Ross, Nicole; Anderson, George M.; Wilkinson, Charles W.; Carpenter, Linda L.

    2009-01-01

    Background Several decades of research link childhood parental loss with risk for major depression and other forms of psychopathology. A large body of preclinical work on maternal separation and some recent studies of humans with childhood parental loss have demonstrated alterations of hypothalamic-pituitary-adrenal (HPA) axis function which could predispose to the development of psychiatric disorders. Methods Eighty-eight healthy adults with no current Axis I psychiatric disorder participated in this study. Forty-four participants experienced parental loss during childhood, including 19 with a history of parental death and 25 with a history of prolonged parental separation. The loss group was compared to a matched group of individuals who reported no history of childhood parental separation or childhood maltreatment. Participants completed diagnostic interviews and questionnaires and the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test. Repeated measures general linear models were used to test the effects of parental loss, a measure of parental care, sex, and age on the hormone responses to the Dex/CRH test. Results Parental loss was associated with increased cortisol responses to the test, particularly in males. The effect of loss was moderated by levels of parental care; participants with parental desertion and very low levels of care had attenuated cortisol responses. ACTH responses to the Dex/CRH test did not differ significantly as a function of parental loss. Conclusions These findings are consistent with the hypothesis that early parental loss induces enduring changes in neuroendocrine function. PMID:18339361

  12. Functional hypothalamic amenorrhea and its psychological correlates: a controlled comparison.

    Science.gov (United States)

    Pentz, Ivana; Nakić Radoš, Sandra

    2017-04-01

    The goal of the study was to examine differences between adolescents and young women with functional hypothalamic amenorrhea (FHA) and control groups in personality traits, eating attitudes and behaviours, and perception of parental behaviour. The FHA is stress-induced anovulation, both related to metabolic challenges, such as excessive exercise and malnutrition, and psychogenic challenges, such as perfectionism and poor coping strategies. Three groups of adolescents and young women participated in the study: the FHA group (N = 25), the organic anovulation group (N = 21) and the eumenorrheic group with regular menstrual cycle (N = 20). Questionnaires on multidimensional perfectionism, self-control methods, eating attitudes and behaviours and perception of parental behaviour were administered. A clinical interview (SCID) was conducted with each participant. The FHA group had higher levels of perfectionism traits, i.e. higher levels of concerns over mistakes and personal standards, compared to control groups. The FHA group did not engage in disordered eating behaviours more often in comparison with control groups, but reported more prevalent history of anorexia nervosa. The FHA group did not differ from controls in perception of parental rejection, emotional warmth or overprotection. The findings suggest that FHA can be characterised by the subtle psychological differences in personality traits, so the patients need to be diagnosed carefully.

  13. Retino-hypothalamic regulation of light-induced murine sleep

    Directory of Open Access Journals (Sweden)

    Fanuel eMuindi

    2014-08-01

    Full Text Available The temporal organization of sleep is regulated by an interaction between the circadian clock and homeostatic processes. Light indirectly modulates sleep through its ability to phase shift and entrain the circadian clock. Light can also exert a direct, circadian-independent effect on sleep. For example, acute exposure to light promotes sleep in nocturnal animals and wake in diurnal animals. The mechanisms whereby light directly influences sleep and arousal are not well understood. In this review, we discuss the direct effect of light on sleep at the level of the retina and hypothalamus in rodents. We review murine data from recent publications showing the roles of rod-, cone- and melanopsin-based photoreception on the initiation and maintenance of light-induced sleep. We also present hypotheses about hypothalamic mechanisms that have been advanced to explain the acute control of sleep by light. Specifically, we review recent studies assessing the roles of the ventrolateral preoptic area and the suprachiasmatic nucleus. We also discuss how light might differentially promote sleep and arousal in nocturnal and diurnal animals respectively. Lastly, we suggest new avenues for research on this topic which is still in its early stages.

  14. Hypothalamic endoplasmic reticulum stress of overtrained mice after recovery

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    Ana P. Pinto

    2017-05-01

    Full Text Available Abstract AIMS knowing the relationship between endoplasmic reticulum (ER stress and inflammation and based on the fact that downhill running-based overtraining (OT model increases hypothalamus levels of some pro-inflammatory cytokines, we verified the effects of three OT protocols on the levels of BiP, pIRE-1 (Ser734, pPERK (Thr981, pelF2alpha (Ser52, ATF-6 and GRP-94 proteins in the mouse hypothalamus after two weeks of recovery. METHODS the mice were randomized into control (CT, overtrained by downhill running (OTR/down, overtrained by uphill running (OTR/up and overtrained by running without inclination (OTR groups. After 2-week total recovery period (i.e., week 10, hypothalamus was removed and used for immunoblotting. RESULTS the OTR/down group exhibited high levels of BiP and ATF6. The other OT protocols showed higher levels of pPERK (Th981 and pelf-2alpha (Ser52 when compared with the CT group. CONCLUSION the current results suggest that after a 2-week total recovery period, the overtrained groups increased partially their ER stress protein levels, but without hypothalamic inflammation, which characterizes a physiological condition related to an adaptation mechanism.

  15. Functional Hypothalamic Amenorrhea: An Endocrine Society Clinical Practice Guideline.

    Science.gov (United States)

    Gordon, Catherine M; Ackerman, Kathryn E; Berga, Sarah L; Kaplan, Jay R; Mastorakos, George; Misra, Madhusmita; Murad, M Hassan; Santoro, Nanette F; Warren, Michelle P

    2017-05-01

    The American Society for Reproductive Medicine, the European Society of Endocrinology, and the Pediatric Endocrine Society. This guideline was funded by the Endocrine Society. To formulate clinical practice guidelines for the diagnosis and treatment of functional hypothalamic amenorrhea (FHA). The participants include an Endocrine Society-appointed task force of eight experts, a methodologist, and a medical writer. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. One group meeting, several conference calls, and e-mail communications enabled consensus. Endocrine Society committees and members and cosponsoring organizations reviewed and commented on preliminary drafts of this guideline. FHA is a form of chronic anovulation, not due to identifiable organic causes, but often associated with stress, weight loss, excessive exercise, or a combination thereof. Investigations should include assessment of systemic and endocrinologic etiologies, as FHA is a diagnosis of exclusion. A multidisciplinary treatment approach is necessary, including medical, dietary, and mental health support. Medical complications include, among others, bone loss and infertility, and appropriate therapies are under debate and investigation. Copyright © 2017 Endocrine Society

  16. [A case of multiple sclerosis with hypothalamic amenorrhea].

    Science.gov (United States)

    Miyamoto, T; Miyamoto, M; Yokota, N; Kubo, J; Hirata, K

    2000-03-01

    We present a 31-year-old woman of multiple sclerosis. At age 28, she was admitted with complaints of echolalia and a gradual onset of weakness affecting the right upper and bilateral lower limbs. Brain MRI showed high intensity areas in the bilateral frontal gyri, lobuli paracentralis, and left anterior thalamus. Although she had been in remission for 3 years, she developed dysesthesia of left upper and lower limbs. Cervical T2 weighted MRI showed a new high signal intensity lesion in the spinal cord from the C2 to C3 level. The combination of the cerebral, thalamic and spinal cord lesions with remission and excerbations allowed the diagnosis of clinically MS to be made. She suffered amenorrhea from the onset of her illness. Serum prolactin was within the normal range. The LH and FSH basal secretions were decreased and there were low delayed secretions of LH and FSH after intravenous injection of 100 micrograms LHRH. We consider that her amenorrhea was caused by the hypothalamic lesion, supported by MR findings of dilatation of the third ventricle.

  17. Functional hypothalamic amenorrhea: current view on neuroendocrine aberrations.

    Science.gov (United States)

    Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Warenik-Szymankiewicz, Alina; Genazzani, Andrea Riccardo

    2008-01-01

    Functional hypothalamic amenorrhea (FHA) is defined as a non-organic and reversible disorder in which the impairment of gonadotropin-releasing hormone (GnRH) pulsatile secretion plays a key role. There are main three types of FHA: stress-related amenorrhea, weight loss-related amenorrhea and exercise-related amenorrhea. The spectrum of GnRH-luteinizing hormone (LH) disturbances in FHA is very broad and includes lower mean frequency of LH pulses, complete absence of LH pulsatility, normal-appearing secretion pattern and higher mean frequency of LH pulses. Precise mechanisms underlying the pathophysiology of FHA are very complex and unclear. Numerous neuropeptides, neurotransmitters and neurosteroids play important roles in the physiological regulation of GnRH pulsatile secretion and there is evidence that different neuropeptides may be involved in the pathophysiology of FHA. Particular attention is paid to such substances as allopregnanolone, neuropeptide Y, corticotropin-releasing hormone, leptin, ghrelin and beta-endorphin. Some studies reveal significant changes in these mentioned substances in patients with FHA. There are also speculations about use some of these substances or their antagonists in the treatment of FHA.

  18. ADHD-like behavior in a patient with hypothalamic hamartoma.

    Science.gov (United States)

    Katayama, Koujyu; Yamashita, Yushiro; Yatsuga, Shuichi; Koga, Yasutoshi; Matsuishi, Toyojiro

    2016-01-01

    We report a male patient with hypothalamic hamartoma (HH) who manifested central precocious puberty (CPP) at 4 years of age. Gonadotropin-releasing hormone (GnRH) analogue treatment was started at 6 years of age and his pubertal signs were suppressed. At 9 years of age, the patient was emotionally unstable, aggressive, and antisocial. He had severe attention deficit hyperactivity disorder (ADHD)-like behavior and conduct disorder. No seizure activity was observed. GnRH analogue treatment was discontinued for 8 months from 9 years and 4 months of age due to his mother's illness. During this period sexual urges were observed. Treatment with daily methylphenidate markedly improved his behavioral problems. However, his sexual urges were not suppressed until 3 months after the GnRH analogue treatment was restarted. The present case is unique because the patient's behavioral problems were observed despite the parahypothalamic type of HH and absence of seizures. This case is also rare because behavioral problems were observed without seizures, and no ADHD cases with hamartoma have been reported previously. Recently, clinical studies have described an association between psychiatric morbidity, including ADHD, and hyperandrogenism disorders. Our patient's ADHD-like symptoms might be due to hyperandrogenism. In such cases, GnRH analogue with methylphenidate could be effective for improving ADHD-like symptoms. Copyright © 2015. Published by Elsevier B.V.

  19. Hypothalamic regulation of brown adipose tissue thermogenesis and energy homeostasis

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    Wei eZhang

    2015-08-01

    Full Text Available Obesity and diabetes are increasing at an alarming rate worldwide, but the strategies for the prevention and treatment of these disorders remain inadequate. Brown adipose tissue (BAT is important for cold protection by producing heat using lipids and glucose as metabolic fuels. This thermogenic action causes increased energy expenditure and significant lipid/glucose disposal. In addition, BAT in white adipose tissue (WAT or beige cells have been found and they also exhibit the thermogenic action similar to BAT. These data provide evidence indicating BAT/beige cells as a potential target for combating obesity and diabetes. Recent discoveries of active BAT and beige cells in adult humans have further highlighted this potential. Growing studies have also shown the importance of central nervous system in the control of BAT thermogenesis and WAT browning using animal models. This review is focused on central neural thermoregulation, particularly addressing our current understanding of the importance of hypothalamic neural signaling in the regulation of BAT/beige thermogenesis and energy homeostasis.

  20. Bradykinin and vasopressin activate phospholipase D in rat Leydig cells by a protein kinase C-dependent mechanism

    DEFF Research Database (Denmark)

    Vinggaard, Anne Marie; Hansen, Harald S.

    1993-01-01

    of PMA and vasopressin (AVP), PMA and bradykinin, or AVP and bradykinin produced no additive phosphatidylethanol or choline response, suggesting that AVP, bradykinin and PMA stimulated phospholipase D catalysed phosphatidylcholine hydrolysis by a similar protein kinase C-dependent mechanism. Furthermore......, LH (10 ng/ml), insulin (500 nmol/l), GH (100 ng/ml), interleukin-1ß (5 U/ml) and platelet-activating factor (200 nmol/l) were found not to activate phospholipase D, whereas the Ca ionophore A23187 (10 µmol/l) stimulated phosphatidylethanol formation, suggesting that Ca might be a regulator...

  1. [Influence, in normal subjects, of an isocaloric hyperprotein diet on cortisol, ACTH, GH and PRL response to lysine-8-vasopressin].

    Science.gov (United States)

    Giovannini, C; Sellini, M; Manzo, G; Barletta, C; Scavo, D

    1981-12-30

    The Lysin-8-Vasopressin test has been experimented in ten healthy subjects during normocaloric balanced diet and after hyperproteic-normocaloric diet. The levels of ACTH, Cortisol and GH are significantly more elevated after hyperproteic-normocaloric diet than in basal conditions. The levels of Prolactin do not show any remarkable change. These results can indicate the increased reactivity of the diencephalon-hypophysis-adrenal axis and of the hormones connected with the mechanisms of homeostasis and stress, probably correlated to more disposable proteic material and to the metabolic effects which follow.

  2. Autosomal dominant familial neurohypophyseal diabetes insipidus caused by a mutation in the arginine-vasopressin II gene in four generations of a Korean family

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    Myo-Jing Kim

    2014-12-01

    Full Text Available Autosomal dominant neurohypophyseal diabetes insipidus is a rare form of central diabetes insipidus that is caused by mutations in the vasopressin-neurophysin II (AVP-NPII gene. It is characterized by persistent polydipsia and polyuria induced by deficient or absent secretion of arginine vasopressin (AVP. Here we report a case of familial neurohypophyseal diabetes insipidus in four generations of a Korean family, caused by heterozygous missense mutation in exon 2 of the AVP-NPII gene (c.286G>T. This is the first report of such a case in Korea.

  3. Angiotensin II AT1 receptor blockade decreases vasopressin-induced water reabsorption and AQP2 levels in NaCl-restricted rats

    DEFF Research Database (Denmark)

    Kwon, Tae-Hwan; Nielsen, Jakob; Knepper, M.A.

    2005-01-01

    Vasopressin and ANG II, which are known to play a major role in renal water and sodium reabsorption, are mainly coupled to the cAMP/PKA and phosphoinositide pathways, respectively. There is evidence for cross talk between these intracellular signaling pathways. We therefore hypothesized that vaso......Vasopressin and ANG II, which are known to play a major role in renal water and sodium reabsorption, are mainly coupled to the cAMP/PKA and phosphoinositide pathways, respectively. There is evidence for cross talk between these intracellular signaling pathways. We therefore hypothesized...

  4. The role of arginine vasopressin in electroacupuncture treatment of primary sciatica in human.

    Science.gov (United States)

    Zhao, Xue-Yan; Zhang, Qi-Shun; Yang, Jun; Sun, Fang-Jie; Wang, Da-Xin; Wang, Chang-Hong; He, Wei-Ya

    2015-08-01

    It has been implicated that electroacupuncture can relieve the symptoms of sciatica with the increase of pain threshold in human, and arginine vasopressin (AVP) in the brain rather than the spinal cord and blood circulation participates in antinociception. Our previous study has proven that AVP in the brain played a role in the process of electroacupuncture analgesia in rat. The goal of the present study was to investigate the role of AVP in electroacupuncture in treating primary sciatica in human. The results showed that (1) AVP concentration of cerebrospinal fluid (CSF) (7.5 ± 2.5 pg/ml), not plasma (13.2 ± 4.2 pg/ml) in primary sciatica patients was lower than that in health volunteers (16.1 ± 3.8 pg/ml and 12.3 ± 3.4 pg/ml), although the osmotic pressure in CSF and plasma did not change; (2) electroacupuncture of the bilateral "Zusanli" points (St. 36) for 60 min relieved the pain sensation in primary sciatica patients; (3) electroacupuncture increased the AVP level of CSF, not plasma in primary sciatica patients; and (4) there was the positive correlation between the effect of electroacupuncture relieving the pain and the AVP level of CSF in the primary sciatica patients. The data suggested that central AVP, not peripheral AVP might improve the effect of electroacupuncture treatment of primary sciatica in human, i.e., central AVP might take part in the electroacupuncture relieving the pain sensation in primary sciatica patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Oxytocin and Vasopressin Receptor Gene Polymorphisms: Role in Social and Psychiatric Traits

    Science.gov (United States)

    Aspé-Sánchez, Mauricio; Moreno, Macarena; Rivera, Maria Ignacia; Rossi, Alejandra; Ewer, John

    2016-01-01

    Oxytocin (OXT) and arginine-vasopressin (AVP) are two phylogenetically conserved neuropeptides that have been implicated in a wide range of social behaviors. Although a large body of research, ranging from rodents to humans, has reported on the effects of OXT and AVP administration on affiliative and trust behaviors, and has highlighted the genetic contributions of OXT and AVP receptor polymorphisms to both social behaviors and to diseases related to social deficits, the consequences of peptide administration on psychiatric symptoms, and the impact of receptor polymorphisms on receptor function, are still unclear. Despite the exciting advances that these reports have brought to social neuroscience, they remain preliminary and suffer from the problems that are inherent to monogenetic linkage and association studies. As an alternative, some studies are using polygenic approaches, and consider the contributions of other genes and pathways, including those involving DA, 5-HT, and reelin, in addition to OXT and AVP; a handful of report are also using genome-wide association studies. This review summarizes findings on the associations between OXT and AVP receptor polymorphism, social behavior, and psychiatric diseases. In addition, we discuss reports on the interactions of OXT and AVP receptor genes and genes involved in other pathways (such as those of dopamine, serotonin, and reelin), as well as research that has shed some light on the impact of gene polymorphisms on the volume, connectivity, and activation of specific neural structures, differential receptor expression, and plasma levels of the OXT and AVP peptides. We hope that this effort will be helpful for understanding the studies performed so far, and for encouraging the inclusion of other candidate genes not explored to date. PMID:26858594

  6. Manipulating the Cellular Circadian Period of Arginine Vasopressin Neurons Alters the Behavioral Circadian Period.

    Science.gov (United States)

    Mieda, Michihiro; Okamoto, Hitoshi; Sakurai, Takeshi

    2016-09-26

    As the central pacemaker in mammals, the circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is a heterogeneous structure consisting of multiple types of GABAergic neurons with distinct chemical identities [1, 2]. Although individual cells have a cellular clock driven by autoregulatory transcriptional/translational feedback loops of clock genes, interneuronal communication among SCN clock neurons is likely essential for the SCN to generate a highly robust, coherent circadian rhythm [1]. However, neuronal mechanisms that determine circadian period length remain unclear. The SCN is composed of two subdivisions: a ventral core region containing vasoactive intestinal peptide (VIP)-producing neurons and a dorsal shell region characterized by arginine vasopressin (AVP)-producing neurons. Here we examined whether AVP neurons act as pacemaker cells that regulate the circadian period of behavior rhythm in mice. The deletion of casein kinase 1 delta (CK1δ) specific to AVP neurons, which was expected to lengthen the period of cellular clocks [3-6], lengthened the free-running period of circadian behavior as well. Conversely, the overexpression of CK1δ specific to SCN AVP neurons shortened the free-running period. PER2::LUC imaging in slices confirmed that cellular circadian periods of the SCN shell were lengthened in mice without CK1δ in AVP neurons. Thus, AVP neurons may be an essential component of circadian pacemaker cells in the SCN. Remarkably, the alteration of the shell-core phase relationship in the SCN of these mice did not impair the generation per se of circadian behavior rhythm, thereby underscoring the robustness of the SCN network. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Arginine Vasopressin Is a Blood-Based Biomarker of Social Functioning in Children with Autism.

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    Dean S Carson

    Full Text Available Brain arginine vasopressin (AVP critically regulates normative social behavior in mammals, and experimental disruption of the AVP signaling pathway produces social impairments in rodent models. We therefore hypothesized that AVP signaling deficits may contribute to social impairments in children with autism spectrum disorder (ASD. Since blood measures (which are far easier to obtain than brain measures of AVP are most meaningful if they are related to brain AVP activity, Study 1 tested the relationship between AVP concentrations in concomitantly collected blood and CSF samples from children and adults (N = 28 undergoing clinical procedures. Study 2 tested whether blood AVP concentrations: 1 differed between children with ASD (N = 57, their ASD discordant siblings (N = 47, and neurotypical controls (N = 55; and 2 predicted social functioning (using the NEPSY-II Theory of Mind and Affect Recognition tasks and the Social Responsiveness Scale in this large, well-characterized child cohort. Blood AVP concentrations significantly and positively predicted CSF AVP concentrations (F1,26 = 7.17, r = 0.46, p = 0.0127 in Study 1. In Study 2, blood AVP concentrations did not differ between groups or by sex, but significantly and positively predicted Theory of Mind performance, specifically in children with ASD, but not in non-ASD children (F1,144 = 5.83, p = 0.017. Blood AVP concentrations can be used: 1 as a surrogate for brain AVP activity in humans; and 2 as a robust biomarker of theory of mind ability in children with ASD. These findings also suggest that AVP biology may be a promising therapeutic target by which to improve social cognition in individuals with ASD.

  8. ACTHsub(1-24) and lysine vasopressin selectively activate dopamine synthesis in frontal cortex

    Energy Technology Data Exchange (ETDEWEB)

    Delanoy, R L; Kramarcy, N R; Dunn, A J [Florida Univ., Gainesville (USA). Coll. of Medicine

    1982-01-07

    The accumulation of (/sup 3/H)catecholamines from (/sup 3/H)tyrosine in frontal cortical, septal, striatal and hippocampal slices was examined following intracerebroventricular (i.c.v.) injections of ACTHsub(1-24), lysine vasopressin (LVP) and saline. Both ACTHsub(1-24) and LVP (1..mu..g) selectively increased the accumulation of (/sup 3/H)dopamine (DA) in frontal cortical slices, but did not affect that of (/sup 3/H)norepinephrine (NE). LVP but not ACTHsub(1-24) also inhibited the accumulation of (/sup 3/H)DA in striatal slices. ACTHsub(1-24) did not alter the accumulation of (/sup 3/H)NE in hippocampal slices, nor did LVP alter the accumulation of either catecholamine (CA) in septal slices. In vitro incubations with ACTH analogs or LVP failed to alter the rate of accumulation of (/sup 3/H)CAs in striatal, substantia nigral and frontal cortical slices, except for an inhibitory effect at high doses. This effect is believed to be an artifact of precursor dilution caused by release of tyrosine following degradation of the peptides. Neither peptide modified the increased (/sup 3/H)CA accumulation stimulated by 26 mM K/sup +/, nor did ACTHsub(1-24) modify the inhibition of (/sup 3/H)CA accumulation caused by 3 X 10/sup -6/ M Haloperidol or 3 X 10/sup -7/ M apomorphine. Selective activation of the mesocortical DA system has also been reported to occur in response to footshock, suggesting the possibility that endogenous ACTH and/or LVP might mediate the stress-induced activation of mesocortical DA synthesis. Alternatively, i.c.v. injections of these peptides may themselves be stressful and thus indirectly elicit the response.

  9. A Volumetric and Functional Connectivity MRI Study of Brain Arginine-Vasopressin Pathways in Autistic Children.

    Science.gov (United States)

    Shou, Xiao-Jing; Xu, Xin-Jie; Zeng, Xiang-Zhu; Liu, Ying; Yuan, Hui-Shu; Xing, Yan; Jia, Mei-Xiang; Wei, Qing-Yun; Han, Song-Ping; Zhang, Rong; Han, Ji-Sheng

    2017-04-01

    Dysfunction of brain-derived arginine-vasopressin (AVP) systems may be involved in the etiology of autism spectrum disorder (ASD). Certain regions such as the hypothalamus, amygdala, and hippocampus are known to contain either AVP neurons or terminals and may play an important role in regulating complex social behaviors. The present study was designed to investigate the concomitant changes in autistic behaviors, circulating AVP levels, and the structure and functional connectivity (FC) of specific brain regions in autistic children compared with typically developing children (TDC) aged from 3 to 5 years. The results showed: (1) children with ASD had a significantly increased volume in the left amygdala and left hippocampus, and a significantly decreased volume in the bilateral hypothalamus compared to TDC, and these were positively correlated with plasma AVP level. (2) Autistic children had a negative FC between the left amygdala and the bilateral supramarginal gyri compared to TDC. The degree of the negative FC between amygdala and supramarginal gyrus was associated with a higher score on the clinical autism behavior checklist. (3) The degree of negative FC between left amygdala and left supramarginal gyrus was associated with a lowering of the circulating AVP concentration in boys with ASD. (4) Autistic children showed a higher FC between left hippocampus and right subcortical area compared to TDC. (5) The circulating AVP was negatively correlated with the visual and listening response score of the childhood autism rating scale. These results strongly suggest that changes in structure and FC in brain regions containing AVP may be involved in the etiology of autism.

  10. Distribution of vasopressin in the brain of the eusocial naked mole-rat.

    Science.gov (United States)

    Rosen, Greta J; De Vries, Geert J; Goldman, Sharry L; Goldman, Bruce D; Forger, Nancy G

    2007-02-20

    Naked mole-rats are eusocial rodents that live in large subterranean colonies in which one queen breeds with one to three males. All other animals are nonbreeding subordinates. The external features of male and female subordinates, including their genitalia, are remarkably monomorphic, as is their behavior. Because vasopressin (VP) is associated with social behaviors and sex differences in other species, its distribution in naked mole-rats was of interest. We used immunohistochemistry to examine VP in the brains of subordinate and breeding naked mole-rats of both sexes. As in other mammals, VP-immunoreactive (-ir) somata were found in the paraventricular (PVN) and supraoptic nuclei (SON) and VP-ir projections from these nuclei ran through the internal and external zone of the median eminence. However, naked mole-rats had very few VP-ir cells in the bed nucleus of the stria terminalis (BST) and none in the suprachiasmatic nucleus (SCN); the extensive network of fine-caliber VP-ir fibers usually seen in projection sites of the BST and SCN were also absent. Equally unexpected was the abundance of large-caliber VP-ir fibers in the dorsomedial septum. VP immunoreactivity was generally similar in all groups, with the exception of VP-ir cell number in the dorsomedial hypothalamus (DMH). Breeders had a population of labeled cells in the DMH that was absent, or nearly absent, in subordinates. Future studies on the function of VP in these areas are needed to determine how the atypical distribution of VP immunoreactivity relates to eusociality and the unusual physiology of naked mole-rats.

  11. Extending the socio-sexual brain: arginine-vasopressin immunoreactive circuits in the telencephalon of mice.

    Science.gov (United States)

    Otero-Garcia, Marcos; Martin-Sanchez, Ana; Fortes-Marco, Lluis; Martínez-Ricós, Joana; Agustin-Pavón, Carmen; Lanuza, Enrique; Martínez-García, Fernando

    2014-05-01

    Quantitative analysis of the immunoreactivity for arginine-vasopressin (AVP-ir) in the telencephalon of male (intact and castrated) and female CD1 mice allows us to precisely locate two sexually dimorphic (more abundant in intact than castrated males and females) AVP-ir cell groups in the posterior bed nucleus of the stria terminalis (BST) and the amygdala. Chemoarchitecture (NADPH diaphorase) reveals that the intraamygdaloid AVP-ir cells are located in the intra-amygdaloid BST (BSTIA) rather than the medial amygdala (Me), as previously thought. Then, we have used for the first time tract tracing (combined with AVP immunofluorescence) and fiber-sparing lesions of the BST to analyze the projections of the telencephalic AVP-ir cell groups. The results demonstrate that the posterior BST originates the sexually dimorphic innervation of the lateral septum, the posterodorsal Me and a substance P-negative area in the medioventral striato-pallidum (mvStP).The BSTIA may also contribute to some of these terminal fields. Our material also reveals non-dimorphic AVP-ir processes in two locations of the amygdala. First, the ventral Me shows dendrite-like AVP-ir processes apparently belonging supraoptic neurons, whose possible functions are discussed. Second, the Ce shows sparse, thick AVP-ir axons with high individual variability in density and distribution, whose possible influence on stress coping in relation to the affiliative or agonistic behaviors mediated by the Me are discussed. Finally, we propose that the region of the mvStP showing sexually dimorphic AVP-ir innervation is part of the brain network for socio-sexual behavior, in which it would mediate motivational aspects of chemosensory-guided social interactions.

  12. Early Intranasal Vasopressin Administration Impairs Partner Preference in Adult Male Prairie Voles (Microtus ochrogaster

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    Trenton C. Simmons

    2017-06-01

    Full Text Available Research supports a modulatory role for arginine vasopressin (AVP in the expression of socially motivated behaviors in mammals. The acute effects of AVP administration are demonstrably pro-social across species, providing the justification for an ever-increasing measure of clinical interest over the last decade. Combining these results with non-invasive intranasal delivery results in an attractive system for offering intranasal AVP (IN-AVP as a therapeutic for the social impairments of children with autism spectrum disorder. But, very little is known about the long-term effects of IN-AVP during early development. In this experiment, we explored whether a single week of early juvenile administration of IN-AVP (low = 0.05 IU/kg, medium = 0.5 IU/kg, high = 5.0 IU/kg could impact behavior across life in prairie voles. We found increases in fecal boli production during open field and novel object recognition testing for the medium dose in both males and females. Medium-dose females also had significantly more play bouts than control when exposed to novel conspecifics during the juvenile period. Following sexual maturity, the medium and high doses of IN-AVP blocked partner preference formation in males, while no such impairment was found for any of the experimental groups in females. Finally, the high-dose selectively increased adult male aggression with novel conspecifics, but only after extended cohabitation with a mate. Our findings confirm that a single week of early IN-AVP treatment can have organizational effects on behavior across life in prairie voles. Specifically, the impairments in pair-bonding behavior experienced by male prairie voles should raise caution when the prosocial effects of acute IN-AVP demonstrated in other studies are extrapolated to long-term treatment.

  13. Dose-Dependent and Lasting Influences of Intranasal Vasopressin on Face Processing in Men

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    Daniel Price

    2017-09-01

    Full Text Available Arginine vasopressin (AVP and related peptides have diverse effects on social behaviors in vertebrates, sometimes promoting affiliative interactions and sometimes aggressive or antisocial responses. The type of influence, in at least some species, depends on social contexts, including the sex of the individuals in the interaction and/or on the levels of peptide within brain circuits that control the behaviors. To determine if AVP promotes different responses to same- and other-sex faces in men, and if those effects are dose dependent, we measured the effects of two doses of AVP on subjective ratings of male and female faces. We also tested if any influences persist beyond the time of drug delivery. When AVP was administered intranasally on an initial test day, 20 IU was associated with decreased social assessments relative to placebo and 40 IU, and some of the effects persisted beyond the initial drug delivery and appeared to generalize to novel faces on subsequent test days. In single men, those influences were most pronounced, but not exclusive, for male faces, whereas in coupled men they were primarily associated with responses to female faces. Similar influences were not observed if AVP was delivered after placebo on a second test day. In a preliminary analysis, the differences in social assessments observed between men who received 20 and 40 IU, which we suggest primarily reflect lowered social assessments induced by the lower dose, appeared most pronounced in subjects who carry what has been identified as a risk allele for the V1a receptor gene. Together, these results suggest that AVP’s effects on face processing, and possibly other social responses, differ according to dose, depend on relationship status, and may be more prolonged than previously recognized.

  14. Intergenerational transmission of alloparental behavior and oxytocin and vasopressin receptor distribution in the prairie vole

    Directory of Open Access Journals (Sweden)

    Allison M Perkeybile

    2015-07-01

    Full Text Available Variation in the early environment has the potential to permanently alter offspring behavior and development. We have previously shown that naturally occurring variation in biparental care of offspring in the prairie vole is related to differences in social behavior of the offspring. It was not, however, clear whether the behavioral differences seen between offspring receiving high compared to low amounts of parental care were the result of different care experiences or were due to shared genetics with their high-contact or low-contact parents. Here we use cross-fostering methods to determine the mode of transmission of alloparental behavior and oxytocin receptor (OTR and vasopressin V1a receptor (V1aR binding from parent to offspring. Offspring were cross-fostered or in-fostered on postnatal day 1 and parental care received was quantified in the first week postpartum. At weaning, offspring underwent an alloparental care test and brains were then collected from all parents and offspring to examine OTR and V1aR binding. Results indicate that alloparental behavior of offspring was predicted by the parental behavior of their rearing parents. Receptor binding for both OTR and V1aR tended to be predicted by the genetic mothers for female offspring and by the genetic fathers for male offspring. These findings suggest a different role of early experience and genetics in shaping behavior compared to receptor distribution and support the notion of sex-dependent outcomes, particularly in the transmission of receptor binding patterns.

  15. Sex differences in associations of arginine vasopressin and oxytocin with resting-state functional brain connectivity.

    Science.gov (United States)

    Rubin, Leah H; Yao, Li; Keedy, Sarah K; Reilly, James L; Bishop, Jeffrey R; Carter, C Sue; Pournajafi-Nazarloo, Hossein; Drogos, Lauren L; Tamminga, Carol A; Pearlson, Godfrey D; Keshavan, Matcheri S; Clementz, Brett A; Hill, Scot K; Liao, Wei; Ji, Gong-Jun; Lui, Su; Sweeney, John A

    2017-01-02

    Oxytocin (OT) and arginine vasopressin (AVP) exert robust and sexually dimorphic influences on cognition and emotion. How these hormones regulate relevant functional brain systems is not well understood. OT and AVP serum concentrations were assayed in 60 healthy individuals (36 women). Brain functional networks assessed with resting-state functional magnetic resonance imaging (rs-fMRI) were constructed with graph theory-based approaches that characterize brain networks as connected nodes. Sex differences were demonstrated in rs-fMRI. Men showed higher nodal degree (connectedness) and efficiency (information propagation capacity) in left inferior frontal gyrus (IFG) and bilateral superior temporal gyrus (STG) and higher nodal degree in left rolandic operculum. Women showed higher nodal betweenness (being part of paths between nodes) in right putamen and left inferior parietal gyrus (IPG). Higher hormone levels were associated with less intrinsic connectivity. In men, higher AVP was associated with lower nodal degree and efficiency in left IFG (pars orbitalis) and left STG and less efficiency in left IFG (pars triangularis). In women, higher AVP was associated with lower betweenness in left IPG, and higher OT was associated with lower nodal degree in left IFG (pars orbitalis). Hormones differentially correlate with brain networks that are important for emotion processing and cognition in men and women. AVP in men and OT in women may regulate orbital frontal cortex connectivity, which is important in emotion processing. Hormone associations with STG and pars triangularis in men and parietal cortex in women may account for well-established sex differences in verbal and visuospatial abilities, respectively. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Should unobstructed gasping be facilitated and confirmed before administering adrenaline, otherwise, give titrated vasopressin?

    Science.gov (United States)

    Rottenberg, Eric M

    2015-02-01

    A recent commentary, "Resuscitation That's (Un)Shockable: Time to Get the Adrenaline Flowing", published in the New England Journal of Medicine Journal Watch called attention to a relatively recent study showing that a large and increasing percentage of patients with in-hospital cardiac arrests exhibit initial nonshockable rhythms (asystole or pulseless electrical activity [PEA]; 82% in 2009 vs 69% in 2000) and a most recent study that concluded that neurologically intact survival to hospital discharge after in-hospital cardiac arrest was significantly more likely after earlier epinephrine administration. It was found that delayed administration of epinephrine was associated significantly with lower chance for survival to hospital discharge, in stepwise fashion (12%, 10%, 8%, and 7% survival, respectively, for patients receiving their first epinephrine dose≤3, 4-6, 7-9, and >9 minutes after arrest). Although early use of epinephrine to manage patients with nonshockable rhythms lacks strong evidence to support efficacy, focus on time to epinephrine administration-in addition to high-quality chest compressions-might be the best early intervention. However, evidence may strongly support the recommendation that adrenaline needs to be used very early because without effective-depth cardiopulmonary resuscitation (CPR) with complete recoil, epinephrine may only be effective when gasping is present, which is a time-limited phenomenon. However, because very few rescuers can perform effective-depth chest compressions with complete recoil, gasping is critically necessary for adequate ventilation and generation of adequate coronary and cerebral perfusion. However, under acidemic conditions and high catecholamine levels and/or absence of gasping, vasopressin should be administered instead. Published by Elsevier Inc.

  17. Chlorpropamide action on renal concentrating mechanism in rats with hypothalamic diabetes insipidus.

    Science.gov (United States)

    Kusano, E; Braun-Werness, J L; Vick, D J; Keller, M J; Dousa, T P

    1983-10-01

    To determine vasopressin (VP)-potentiating effect of chlorpropamide (CPMD), we studied the effect of CPMD in vivo and in vitro in kidneys and in specific tubule segments of rats with hypothalamic diabetes insipidus, homozygotes of the Brattleboro strain (DI rats). Rats on ad lib. water intake were treated with CPMD (20 mg/100 g body wt s.c. daily) for 7 d. While on ad lib. water intake, the urine flow, urine osmolality, urinary excretion of Na +, K +, creatinine, or total solute excretion did not change. However, corticopapillary gradient of solutes was significantly increased in CPMD-treated rats. Higher tissue osmolality was due to significantly increased concentration of Na +, and to a lesser degree urea, in the medulla and papilla of CPMD-treated rats. Consequently, the osmotic gradient between urine and papillary tissue of CPMD-treated rats (delta = 385 +/- 47 mosM) was significantly (P less than 0.001) higher compared with controls (delta = 150 +/- 26 mosM). Minimum urine osmolality after water loading was higher in CPMD-treated DI rats than in controls. Oxidation of [14C]lactate to 14CO2 coupled to NaCl cotransport was measured in thick medullary ascending limb of Henle's loop (MAL) microdissected from control and CPMD-treated rats. The rate of 14CO2 production was higher (delta + 113% +/- 20; P less than 0.01) in CPMD-treated MAL compared with controls, but 14CO2 production in the presence of 10(-3) M furosemide did not differ between MAL from control and from CPMD-treated rats. These observations suggest that CPMD treatment enhances NaCl transport in MAL. Cyclic AMP metabolism was analyzed in microdissected MAL and in medullary collecting tubule (MCT). MCT from control and from CPMD-treated rats did not differ in the basal or VP-stimulated accumulated of cAMP. The increase in cAMP content elicited by 10(-6) M VP in MAL from CPMD-treated rats (delta + 12.0 +/- 1.8 fmol cAMP/mm) was significantly (P less than 0.02) higher compared with MAL from control rats

  18. A longitudinal study of disturbances of the hypothalamic-pituitary-adrenal axis in women with progestin-negative functional hypothalamic amenorrhea.

    Science.gov (United States)

    Kondoh, Y; Uemura, T; Murase, M; Yokoi, N; Ishikawa, M; Hirahara, F

    2001-10-01

    To longitudinally evaluate disturbances of the hypothalamic-pituitary-adrenal (HPA) axis in women with secondary progestin-negative hypothalamic amenorrhea. Retrospective cohort study. Yokohama City University, Yokohama, Japan. Twenty-four women with progestin-negative hypothalamic amenorrhea. Administration of human corticotropin-releasing hormone (hCRH) and treatment with a combination of estrogen and progesterone. Plasma cortisol and ACTH concentrations and period required for recovery from amenorrhea. Plasma ACTH concentrations 30 and 60 minutes after injection of hCRH and the percent maximum increment (%Cmax) of ACTH were significantly lower in the amenorrheic patients compared with the control group patients. The basal cortisol was significantly higher, and the %Cmax of cortisol was significantly lower. In the 16 patients who recovered from amenorrhea, there was a significant positive correlation (Y = 1.93X-10.8, r = 0.629) between the basal cortisol concentrations (X) and the period for recovery (Y). The serum E2 gradually increased before recovery, and this E2 increase was preceded by changes in the plasma cortisol concentration and the %Cmax values of cortisol and ACTH. The CRH test might be useful for evaluating the roles of stress and for estimating the period required for recovery in hypothalamic amenorrhea.

  19. Growth hormone modulates hypothalamic inflammation in long-lived pituitary dwarf mice.

    Science.gov (United States)

    Sadagurski, Marianna; Landeryou, Taylor; Cady, Gillian; Kopchick, John J; List, Edward O; Berryman, Darlene E; Bartke, Andrzej; Miller, Richard A

    2015-12-01

    Mice in which the genes for growth hormone (GH) or GH receptor (GHR(-/-) ) are disrupted from conception are dwarfs, possess low levels of IGF-1 and insulin, have low rates of cancer and diabetes, and are extremely long-lived. Median longevity is also increased in mice with deletion of hypothalamic GH-releasing hormone (GHRH), which leads to isolated GH deficiency. The remarkable extension of longevity in hypopituitary Ames dwarf mice can be reversed by a 6-week course of GH injections started at the age of 2 weeks. Here, we demonstrate that mutations that interfere with GH production or response, in the Snell dwarf, Ames dwarf, or GHR(-/-) mice lead to reduced formation of both orexigenic agouti-related peptide (AgRP) and anorexigenic proopiomelanocortin (POMC) projections to the main hypothalamic projection areas: the arcuate nucleus (ARH), paraventricular nucleus (PVH), and dorsomedial nucleus (DMH). These mutations also reduce hypothalamic inflammation in 18-month-old mice. GH injections, between 2 and 8 weeks of age, reversed both effects in Ames dwarf mice. Disruption of GHR specifically in liver (LiGHRKO), a mutation that reduces circulating IGF-1 but does not lead to lifespan extension, had no effect on hypothalamic projections or inflammation, suggesting an effect of GH, rather than peripheral IGF-1, on hypothalamic development. Hypothalamic leptin signaling, as monitored by induction of pStat3, is not impaired by GHR deficiency. Together, these results suggest that early-life disruption of GH signaling produces long-term hypothalamic changes that may contribute to the longevity of GH-deficient and GH-resistant mice. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  20. Cultured hypothalamic neurons are resistant to inflammation and insulin resistance induced by saturated fatty acids.

    Science.gov (United States)

    Choi, Sun Ju; Kim, Francis; Schwartz, Michael W; Wisse, Brent E

    2010-06-01

    Hypothalamic inflammation induced by high-fat feeding causes insulin and leptin resistance and contributes to the pathogenesis of obesity. Since in vitro exposure to saturated fatty acids causes inflammation and insulin resistance in many cultured cell types, we determined how cultured hypothalamic neurons respond to this stimulus. Two murine hypothalamic neuronal cell cultures, N43/5 and GT1-7, were exposed to escalating concentrations of saturated fatty acids for up to 24 h. Harvested cells were evaluated for activation of inflammation by gene expression and protein content. Insulin-treated cells were evaluated for induction of markers of insulin receptor signaling (p-IRS, p-Akt). In both hypothalamic cell lines, inflammation was induced by prototypical inflammatory mediators LPS and TNFalpha, as judged by induction of IkappaBalpha (3- to 5-fold) and IL-6 (3- to 7-fold) mRNA and p-IkappaBalpha protein, and TNFalpha pretreatment reduced insulin-mediated p-Akt activation by 30% (P fatty acid (100, 250, or 500 microM for neurons, whereas they did in control muscle and endothelial cell lines. Despite the lack of evidence of inflammatory signaling, saturated fatty acid exposure in cultured hypothalamic neurons causes endoplasmic reticulum stress, induces mitogen-activated protein kinase, and causes apoptotic cell death with prolonged exposure. We conclude that saturated fatty acid exposure does not induce inflammatory signaling or insulin resistance in cultured hypothalamic neurons. Therefore, hypothalamic neuronal inflammation in the setting of DIO may involve an indirect mechanism mediated by saturated fatty acids on nonneuronal cells.

  1. Paradoxical effects of oxytocin and vasopressin on basal prolactin secretion and the estrogen-induced prolactin surge

    International Nuclear Information System (INIS)

    Mai, Leemin; Pan, Jenntser

    1990-01-01

    The roles of oxytocin (OT) and vasopressin (AVP) on both basal and estrogen-induced prolactin (PRL) secretion were examined. Adult female Sprague-Dawley rats that were ovariectomized for 3 weeks and received estrogen treatment for 1 week were used. Intravenous administration of hormones and serial blood sampling were accomplished through indwelling intraatrial catheters which were implanted two days before. Plasma PRL levels were measured by radioimmunoassay. Oxytocin at a dose of 20 μg/rat stimulated a moderate PRL release in the morning and lower doses were without effect. Vasopressin was most effective at a dose of 5 μg/rat in stimulating PRL release, while consecutive injections of higher doses were less effective. In contrast, TRH, ranging from 1 to 8 μg/rat, induced a dose-dependent increases in PRL secretion. Using the effective dosages determined from the morning studies, repeated injections of either OT, AVP or their specific antagonists MPOMeOVT were given hourly between 1300 to 1800h and blood samples were obtained hourly from 1100 to 1900h. It was found that either OT or AVP significantly reduced the afternoon PRL surge, while their antagonists were not as effective

  2. The DSA diagnosis, artery embolization combined with low dose of vasopressin infusion treatment for lower digestive tract hemorrhage

    International Nuclear Information System (INIS)

    Huang Guoxin; Dou Yongchong; Zhang Yanfang; Shen Xinying; Xu Jianmin

    2005-01-01

    Objective: To evaluate the clinical value of digital subtraction angiography (DSA) diagnosis and interventional treatment for lower digestive tract hemorrhage of unknown reasons. Methods: DSA was performed in 32 patients with unknown etiologic lower digestive tract hemorrhage. The locations and causes of hemorrhage were determined by angiography according to the demonstration of contrast medium extravasation, abnormal vasculature and tumor staining. Superselective arterial embolization was performed with retaining catheter of low dose vasopressin infusion for 12 hours of hemostasis. Results: Seventy-five percent of the lesions were identified by DSA with 2 cases of intestinal typhoid, 1 intestinal tuberculosis, 14 cases of vascular malformation and 7 cases of tumor. Hemostasis was succeeded in 20 of 24 patients. The rate of success was 83.3%. Conclusions: DSA and interventional therapy are of great value in diagnosing and treating patients with lower digestive tract hemorrhage of unknown reasons and even those undergone unsuccessful conservative treatment. Low dose vasopressin infusion through retained catheter is safe and efficient after superselective arterial embolization. (authors)

  3. Molecular evolution of the neurohypophysial hormone precursors in mammals: Comparative genomics reveals novel mammalian oxytocin and vasopressin analogues.

    Science.gov (United States)

    Wallis, Michael

    2012-11-01

    Among vertebrates the neurohypophysial hormones show considerable variation. However, in eutherian mammals they have been considered rather conserved, with arginine vasopressin (AVP) and oxytocin (OT) in all species except pig and some relatives, where lysine vasopressin replaces AVP. The availability of genomic data for a wide range of mammals makes it possible to assess whether these peptides and their precursors may be more variable in Eutheria than previously suspected. A survey of these data confirms that AVP and OT occur in most eutherians, but with exceptions. In a New-World monkey (marmoset, Callithrix jacchus) and in tree shrew (Tupaia belangeri), Pro(8)OT replaces OT, confirming a recent report for these species. In armadillo (Dasypus novemcinctus) Leu(3)OT replaces OT, while in tenrec (Echinops telfairi) Thr(4)AVP replaces AVP. In these two species there is also evidence for additional genes/pseudogenes, encoding much-modified forms of AVP, but in most other eutherian species there is no evidence for additional neurohypophysial hormone genes. Evolutionary analysis shows that sequences of eutherian neurohypophysial hormone precursors are generally strongly conserved, particularly those regions encoding active peptide and neurophysin. The close association between OT and VP genes has led to frequent gene conversion of sequences encoding neurophysins. A monotreme, platypus (Ornithorhynchus anatinus) has genes for OT and AVP, organized tail-to-tail as in eutherians, but in marsupials 3-4 genes are present for neurohypophysial hormones, organized tail-to-head as in lower vertebrates. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. VMN hypothalamic dopamine and serotonin in anorectic septic rats.

    Science.gov (United States)

    Torelli, G F; Meguid, M M; Miyata, G; Fetissov, S O; Carter, J L; Kim, H J; Muscaritoli, M; Rossi Fanelli, F

    2000-03-01

    During sepsis, catabolism of proteins and associated changes in plasma amino acids occur. Tryptophan and tyrosine, and their derivatives serotonin (5-HT) and dopamine (DA), influence hypothalamic feeding-related areas and are associated with the onset of anorexia. We hypothesized that anorexia of sepsis is associated with changes in serotonin and dopamine in the ventromedial nucleus (VMN) of the hypothalamus. The aim of this study was to test our hypothesis by measuring intra-VMN changes of these two neurotransmitters at the onset of anorexia during sepsis. Fischer 344 male rats had an intracerebral guide cannula stereotaxically implanted into the VMN. Ten days later, in awake, overnight-food-deprived rats, a microdialysis probe was inserted through the in situ VMN cannula. Two hours thereafter, serial baseline serotonin and dopamine concentrations were measured. Then cecal ligation and puncture to induce sepsis or a control laparotomy was performed under isoflurane anesthesia. VMN microdialysis samples were serially collected every 30 min for 8 h after the surgical procedure to determine 5-HT and DA changes in response to sepsis. During the hypermetabolic response to sepsis, a strong association occurred between anorexia and a significant reduction of VMN dopamine concentration (P anorexia of sepsis. Six hours after operation, a single meal was offered for 20 min to assess the response of neurotransmitters to food ingestion. Food intake was minimal in anorectic septic rats (mean size of the after food-deprived meal in the Septic group was 0.03+/-0.01 g, that of the Control group was 1.27+/-0.14 g; P = 0.0001), while Control rats demonstrated anticipated changes in neurotransmitters in response to eating. We conclude that the onset of anorexia in septic rats is associated with a reduction in VMN dopamine.

  5. Characteristics and mechanisms of hypothalamic neuronal fatty acid sensing.

    Science.gov (United States)

    Le Foll, Christelle; Irani, Boman G; Magnan, Christophe; Dunn-Meynell, Ambrose A; Levin, Barry E

    2009-09-01

    We assessed the mechanisms by which specialized hypothalamic ventromedial nucleus (VMN) neurons utilize both glucose and long-chain fatty acids as signaling molecules to alter their activity as a potential means of regulating energy homeostasis. Fura-2 calcium (Ca(2+)) and membrane potential dye imaging, together with pharmacological agents, were used to assess the mechanisms by which oleic acid (OA) alters the activity of dissociated VMN neurons from 3- to 4-wk-old rats. OA excited up to 43% and inhibited up to 29% of all VMN neurons independently of glucose concentrations. In those neurons excited by both 2.5 mM glucose and OA, OA had a concentration-dependent effective excitatory concentration (EC(50)) of 13.1 nM. Neurons inhibited by both 2.5 mM glucose and OA had an effective inhibitory concentration (IC(50)) of 93 nM. At 0.5 mM glucose, OA had markedly different effects on these same neurons. Inhibition of carnitine palmitoyltransferase, reactive oxygen species formation, long-chain acetyl-CoA synthetase and ATP-sensitive K(+) channel activity or activation of uncoupling protein 2 (UCP2) accounted for only approximately 20% of OA's excitatory effects and approximately 40% of its inhibitory effects. Inhibition of CD36, a fatty acid transporter that can alter cell function independently of intracellular fatty acid metabolism, reduced the effects of OA by up to 45%. Thus OA affects VMN neuronal activity through multiple pathways. In glucosensing neurons, its effects are glucose dependent. This glucose-OA interaction provides a potential mechanism whereby such "metabolic sensing" neurons can respond to differences in the metabolic states associated with fasting and feeding.

  6. Rapid dopaminergic modulation of the fish hypothalamic transcriptome and proteome.

    Directory of Open Access Journals (Sweden)

    Jason T Popesku

    2010-08-01

    Full Text Available Dopamine (DA is a major neurotransmitter playing an important role in the regulation of vertebrate reproduction. We developed a novel method for the comparison of transcriptomic and proteomic data obtained from in vivo experiments designed to study the neuroendocrine actions of DA.Female goldfish were injected (i.p. with DA agonists (D1-specific; SKF 38393, or D2-specific; LY 171555 and sacrificed after 5 h. Serum LH levels were reduced by 57% and 75% by SKF 38393 and LY 171555, respectively, indicating that the treatments produced physiologically relevant responses in vivo. Bioinformatic strategies and a ray-finned fish database were established for microarray and iTRAQ proteomic analysis of the hypothalamus, revealing a total of 3088 mRNAs and 42 proteins as being differentially regulated by the treatments. Twenty one proteins and mRNAs corresponding to these proteins appeared on both lists. Many of the mRNAs and proteins affected by the treatments were grouped into the Gene Ontology categorizations of protein complex, signal transduction, response to stimulus, and regulation of cellular processes. There was a 57% and 14% directional agreement between the differentially-regulated mRNAs and proteins for SKF 38393 and LY 171555, respectively.The results demonstrate the applicability of advanced high-throughput genomic and proteomic analyses in an amendable well-studied teleost model species whose genome has yet to be sequenced. We demonstrate that DA rapidly regulates multiple hypothalamic pathways and processes that are also known to be involved in pathologies of the central nervous system.

  7. Management of optic pathway and chiasmatic-hypothalamic gliomas in children with radiation therapy

    International Nuclear Information System (INIS)

    Erkal, Haldun Suekrue; Serin, Meltem; Cakmak, Ahmet

    1997-01-01

    Background and purpose: Optic pathway and chiasmatic-hypothalamic gliomas are rare childhood tumors. This study presents the experience in management of these tumors with radiation therapy. Materials and methods: Thirty-three children with the diagnosis of optic pathway and chiasmatic-hypothalamic gliomas were treated with radiation therapy from 1973 through 1994 in the Department of Radiation Oncology at Ankara University Faculty of Medicine. Twenty-four children had optic pathway gliomas and nine had chiasmatic-hypothalamic gliomas. Evidence of neurofibromatosis was present in six children. Subtotal resection was performed in 22 children and a biopsy in seven. The most common prescription for total tumor dose was 50 Gy, delivered in 2 Gy daily fractions. Follow-up ranged from 0.5 to 16.1 years (mean, 13.6 years). Results: Overall, progression-free and cause-specific survival probabilities for the entire group were 93%, 82% and 93%, respectively, at 5 years and 79%, 77% and 88%, respectively, at 10 years. Differences in overall, progression-free and cause-specific survival probabilities between optic pathway and chiasmatic-hypothalamic gliomas were not statistically significant. Absence of evidence of neurofibromatosis correlated with significantly better progression-free and cause-specific survival probabilities. Conclusion: Radiation therapy is effective in stabilization or improvement of vision and prevention of tumor progression in both optic pathway and chiasmatic-hypothalamic gliomas

  8. Altered hypothalamic protein expression in a rat model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Wei-na Cong

    Full Text Available Huntington's disease (HD is a neurodegenerative disorder, which is characterized by progressive motor impairment and cognitive alterations. Changes in energy metabolism, neuroendocrine function, body weight, euglycemia, appetite function, and circadian rhythm can also occur. It is likely that the locus of these alterations is the hypothalamus. We used the HD transgenic (tg rat model bearing 51 CAG repeats, which exhibits similar HD symptomology as HD patients to investigate hypothalamic function. We conducted detailed hypothalamic proteome analyses and also measured circulating levels of various metabolic hormones and lipids in pre-symptomatic and symptomatic animals. Our results demonstrate that there are significant alterations in HD rat hypothalamic protein expression such as glial fibrillary acidic protein (GFAP, heat shock protein-70, the oxidative damage protein glutathione peroxidase (Gpx4, glycogen synthase1 (Gys1 and the lipid synthesis enzyme acylglycerol-3-phosphate O-acyltransferase 1 (Agpat1. In addition, there are significant alterations in various circulating metabolic hormones and lipids in pre-symptomatic animals including, insulin, leptin, triglycerides and HDL, before any motor or cognitive alterations are apparent. These early metabolic and lipid alterations are likely prodromal signs of hypothalamic dysfunction. Gaining a greater understanding of the hypothalamic and metabolic alterations that occur in HD, could lead to the development of novel therapeutics for early interventional treatment of HD.

  9. Epigenetic changes in fetal hypothalamic energy regulating pathways are associated with maternal undernutrition and twinning.

    Science.gov (United States)

    Begum, Ghazala; Stevens, Adam; Smith, Emma Bolton; Connor, Kristin; Challis, John R G; Bloomfield, Frank; White, Anne

    2012-04-01

    Undernutrition during pregnancy is implicated in the programming of offspring for the development of obesity and diabetes. We hypothesized that maternal programming causes epigenetic changes in fetal hypothalamic pathways regulating metabolism. This study used sheep to examine the effect of moderate maternal undernutrition (60 d before to 30 d after mating) and twinning to investigate changes in the key metabolic regulators proopiomelanocortin (POMC) and the glucocorticoid receptor (GR) in fetal hypothalami. Methylation of the fetal hypothalamic POMC promoter was reduced in underfed singleton, fed twin, and underfed twin groups (60, 73, and 63% decrease, respectively). This was associated with reduced DNA methyltransferase activity and altered histone methylation and acetylation. Methylation of the hypothalamic GR promoter was decreased in both twin groups and in maternally underfed singleton fetuses (52, 65, and 55% decrease, respectively). This correlated with changes in histone methylation and acetylation and increased GR mRNA expression in the maternally underfed singleton group. Alterations in GR were hypothalamic specific, with no changes in hippocampi. Unaltered levels of OCT4 promoter methylation indicated gene-specific effects. In conclusion, twinning and periconceptional undernutrition are associated with epigenetic changes in fetal hypothalamic POMC and GR genes, potentially resulting in altered energy balance regulation in the offspring.

  10. Stereotaxic approach to hypothalamic nuclei of the shiba goat with radiographic monitoring

    International Nuclear Information System (INIS)

    Mori, Y.; Takeuchi, Y.; Shimada, M.; Hayashi, S.; Hoshino, K.

    1990-01-01

    Practical method was devised for precise approach to hypothalamic nuclei in the Shiba goat. A stereotaxic instrument and a brain atlas with stereotaxic coordinates were developed. For an accurate placement of probes into specific hypothalamic regions a radiographic method was employed in which radio-opaque material was injected into the lateral ventricle and the ventricular outline was depicted. A sagittal diagram showing the arrangement of hypothalamic nuclei in relation to the brain ventricular system was constructed from the transverse stereotaxic atlas. This diagram was revealed extremely useful in pinpointing the target on the radiographs of lateral view. Precision of this method was evaluated in female Shiba goats (n = 4) by comparing radiographically estimated positions of hypothalamic nuclei with those histologically determined. Despite of cranial variability among individual animals these two parameters matched well each other in all the nuclei examined. Furthermore, chronic cannulae were implanted into different hypothalamic structures of one goat and the accuracy of their placement was confirmed histologically. Thus, it was revealed that the stereotaxy by aid of radiography herein described was accurate enough to apply to various neuroendocrinological studies in the Shiba goat

  11. Chronic exercise reduces hypothalamic transforming growth factor-β1 in middle-aged obese mice.

    Science.gov (United States)

    Silva, Vagner R R; Katashima, Carlos K; Lenhare, Luciene; Silva, Carla G B; Morari, Joseane; Camargo, Rafael L; Velloso, Licio A; Saad, Mario A; da Silva, Adelino S R; Pauli, Jose Rodrigo; Ropelle, Eduardo Rochete

    2017-08-28

    Obesity and aging are associated with hypothalamic inflammation, hyperphagia and abnormalities in the thermogenesis control. It has been demonstrated that the association between aging and obesity induces hypothalamic inflammation and metabolic disorders, at least in part, through the atypical hypothalamic transforming growth factor-β (TGF-β1). Physical exercise has been used to modulate several metabolic parameters. Thus, the aim of this study was to evaluate the impact of chronic exercise on TGF-β1 expression in the hypothalamus of Middle-Aged mice submitted to a one year of high-fat diet (HFD) treatment. We observed that long-term of HFD-feeding induced hypothalamic TGF-β1 accumulation, potentiated the hypothalamic inflammation, body weight gain and defective thermogenesis of Middle-Aged mice when compared to Middle-Aged animals fed on chow diet. As expected, chronic exercise induced negative energy balance, reduced food consumption and increasing the energy expenditure, which promotes body weight loss. Interestingly, exercise training reduced the TGF-β1 expression and IkB-α ser32 phosphorylation in the hypothalamus of Middle-Aged obese mice. Taken together our study demonstrated that chronic exercise suppressed the TGF-β1/IkB-α axis in the hypothalamus and improved the energy homeostasis in an animal model of obesity-associated to aging.

  12. Hypothalamic response to the chemo-signal androstadienone in gender dysphoric children and adolescents

    Directory of Open Access Journals (Sweden)

    Sarah M Burke

    2014-05-01

    Full Text Available The odorous steroid androstadienone, a putative male chemo-signal, was previously reported to evoke sex differences in hypothalamic activation in adult heterosexual men and women. In order to investigate whether puberty modulated this sex difference in response to androstadienone we measured the hypothalamic responsiveness to this chemo-signal in 39 prepubertal and 41 adolescent boys and girls by means of functional magnetic resonance imaging. We then investigated whether 36 prepubertal children and 38 adolescents diagnosed with Gender Dysphoria (GD; DSM-5 exhibited sex-atypical (in accordance with their experienced gender, rather than sex-typical (in accordance with their natal sex hypothalamic activations during olfactory stimulation with androstadienone. We found that the sex difference in responsiveness to androstadienone was already present in prepubertal control children and thus likely developed during early perinatal development instead of during sexual maturation. Adolescent girls and boys with GD both responded remarkably like their experienced gender, thus sex-atypical. In contrast, prepubertal girls with GD showed neither a typically male nor female hypothalamic activation pattern and prepubertal boys with GD had hypothalamic activations in response to androstadienone that were similar to control boys, thus sex-typical. We present here a unique data set of boys and girls diagnosed with GD at two different developmental stages, showing that these children possess certain sex-atypical functional brain characteristics and may have undergone atypical sexual differentiation of the brain.

  13. Lack of arginine vasopressin-induced phosphorylation of aquaporin-2 mutant AQP2-R254L explains dominant nephrogenic diabetes insipidus.

    NARCIS (Netherlands)

    Mattia, F.P. de; Savelkoul, P.J.M.; Kamsteeg, E.J.; Konings, I.B.M.; Sluijs, P. van der; Mallmann, R.; Oksche, A.; Deen, P.M.T.

    2005-01-01

    Water homeostasis in humans is regulated by vasopressin, which induces the translocation of homotetrameric aquaporin-2 (AQP2) water channels from intracellular vesicles to the apical membrane of renal principal cells. For this process, phosphorylation of AQP2 at S256 by cAMP-dependent protein kinase

  14. Copeptin, a surrogate marker for arginine vasopressin, is associated with cardiovascular and all-cause mortality in patients with type 2 diabetes (ZODIAC-31)

    NARCIS (Netherlands)

    Riphagen, Ineke J.; Boertien, Wendy E.; Alkhalaf, Alaa; Kleefstra, Nanno; Gansevoort, Ron T.; Groenier, Klaas H.; van Hateren, Kornelis J. J.; Struck, Joachim; Navis, Gerjan; Bilo, Henk J. G.; Bakker, Stephan J. L.

    2013-01-01

    OBJECTIVE: Copeptin, a surrogate marker for arginine vasopressin, has been associated with cardiovascular (CV) events and mortality in patients with type 2 diabetes complicated by end-stage renal disease or acute myocardial infarction. For stable outpatients, these associations are unknown. Our aim

  15. Clinical and molecular evidence of abnormal processing and trafficking of the vasopressin preprohormone in a large kindred with familial neurohypophyseal diabetes insipidus due to a signal peptide mutation

    DEFF Research Database (Denmark)

    Siggaard, C; Rittig, S; Corydon, T J

    1999-01-01

    The autosomal dominant form of familial neurohypophyseal diabetes insipidus (adFNDI) is a rare disease characterized by postnatal onset of polyuria and a deficient neurosecretion of the antidiuretic hormone, arginine vasopressin (AVP). Since 1991, adFNDI has been linked to 31 different mutations...

  16. Hypotonicity-induced reduction of aquaporin-2 transcription in mpkCCD cells is independent of the tonicity responsive element, vasopressin, and cAMP

    NARCIS (Netherlands)

    Kortenoeven, M.L.A.; van den Brand, M.; Wetzels, J.F.M.; Deen, P.M.T.

    2011-01-01

    The syndrome of inappropriate antidiuretic hormone secretion is characterized by excessive water uptake and hyponatremia. The extent of hyponatremia, however, is less than anticipated, which is ascribed to a defense mechanism, the vasopressin-escape, and is suggested to involve a tonicity-determined

  17. In mpkCCD cells, long-term regulation of aquaporin-2 by vasopressin occurs independent of protein kinase A and CREB but may involve Epac.

    NARCIS (Netherlands)

    Kortenoeven, M.L.A.; Trimpert, C.; Brand, M. van den; Li, Y.; Wetzels, J.F.M.; Deen, P.M.T.

    2012-01-01

    Urine concentration involves the hormone vasopressin (AVP), which stimulates cAMP production in renal principal cells, resulting in translocation and transcription of aquaporin-2 (AQP2) water channels, greatly increasing the water permeability, leading to a concentrated urine. As cAMP levels

  18. Influence of conformationally constrained amino acids replacing positions 2 and 3 of arginine vasopressin (AVP) and its analogues on their pharmacological properties

    Czech Academy of Sciences Publication Activity Database

    Sobolewski, D.; Prahl, A.; Derdowska, I.; Kwiatkowska, A.; Slaninová, Jiřina; Lammek, B.

    2007-01-01

    Roč. 14, č. 3 (2007), s. 213-217 ISSN 0929-8665 Grant - others:PSCSR(PL) 0066/H03/2006/30; PSCSR(PL) 1312/T09/2005/29 Institutional research plan: CEZ:AV0Z40550506 Keywords : vasopressin * analogues * Abz * Ach Subject RIV: CE - Biochemistry Impact factor: 1.097, year: 2007

  19. A Two-Year Randomized Trial of Interventions to Decrease Stress Hormone Vasopressin Production in Patients with Meniere's Disease-A Pilot Study.

    Science.gov (United States)

    Kitahara, Tadashi; Okamoto, Hidehiko; Fukushima, Munehisa; Sakagami, Masaharu; Ito, Taeko; Yamashita, Akinori; Ota, Ichiro; Yamanaka, Toshiaki

    2016-01-01

    Meniere's disease, a common inner ear condition, has an incidence of 15-50 per 100,000. Because mental/physical stress and subsequent increase in the stress hormone vasopressin supposedly trigger Meniere's disease, we set a pilot study to seek new therapeutic interventions, namely management of vasopressin secretion, to treat this disease. We enrolled 297 definite Meniere's patients from 2010 to 2012 in a randomized-controlled and open-label trial, assigning Group-I (control) traditional oral medication, Group-II abundant water intake, Group-III tympanic ventilation tubes and Group-IV sleeping in darkness. Two hundred sixty-three patients completed the planned 2-year-follow-up, which included assessment of vertigo, hearing, plasma vasopressin concentrations and changes in stress/psychological factors. At 2 years, vertigo was completely controlled in 54.3% of patients in Group-I, 81.4% in Group-II, 84.1% in Group-III, and 80.0% in Group-IV (statistically I management for Meniere's disease. However, avoidance of stress is unrealistic for patients who live in demanding social environments. Our findings in this pilot study suggest that interventions to decrease vasopressin secretion by abundant water intake, tympanic ventilation tubes and sleeping in darkness is feasible in treating Meniere's disease, even though these therapies did not alter reported mental/physical stress levels. ClinicalTrials.gov NCT01099046.

  20. Potent Antidiuretic Agonists, Deamino-Vasopressin and Desmopressin, and Their Inverso Analogs: NMR Structure and Interactions With Micellar and Liposomic Models of Cell Membrane

    Czech Academy of Sciences Publication Activity Database

    Lubecka, E. A.; Sikorska, E.; Sobolewski, D.; Prahl, A.; Slaninová, Jiřina; Ciarkowski, J.

    2016-01-01

    Roč. 106, č. 3 (2016), s. 245-259 ISSN 0006-3525 Institutional support: RVO:61388963 Keywords : desmopressin * deamino-vasopressin * anionic-zwitterionic micelles * liposomes * inverso analogs Subject RIV: CE - Biochemistry Impact factor: 1.908, year: 2016

  1. Individual variation in plasma oxytocin and vasopressin levels in relation to the development of combat-related PTSD in a large military cohort

    NARCIS (Netherlands)

    Reijnen, Alieke; Geuze, Elbert; Vermetten, Eric

    2017-01-01

    In an attempt to decrease the risk of developing mental health problems after military deployment, it is important to find biological markers to identify those at risk. Oxytocin (OT) and arginine vasopressin (AVP) are potential biomarkers for the development of posttraumatic stress disorder (PTSD)

  2. Arginine vasopressin and its analogues--the influence of position 2 modification with 3,3-diphenylalanine enantiomers. Highly potent V2 agonists

    Czech Academy of Sciences Publication Activity Database

    Kwiatkowska, A.; Sobolewski, D.; Prahl, A.; Borovičková, Lenka; Slaninová, Jiřina; Lammek, B.

    2009-01-01

    Roč. 44, č. 7 (2009), s. 2862-2867 ISSN 0223-5234 Institutional research plan: CEZ:AV0Z40550506 Keywords : arginine vasopressin analogues * AVP * 3,3-diphenylalanine enantiomers * V2 agonists * antidiuretic activity Subject RIV: CC - Organic Chemistry Impact factor: 3.269, year: 2009

  3. The Vasopressin Type-2 Receptor and Prostaglandin Receptors EP2 and EP4 can Increase Aquaporin-2 Plasma Membrane Targeting Through a cAMP Independent Pathway

    DEFF Research Database (Denmark)

    Olesen, Emma Tina Bisgaard; Moeller, Hanne Bjerregaard; Assentoft, Mette

    2016-01-01

    Apical membrane targeting of the collecting duct water channel aquaporin-2 (AQP2) is essential for body water balance. As this event is regulated by Gs coupled 7-transmembrane receptors such as the vasopressin type 2 receptor (V2R) and the prostanoid receptors EP2 and EP4, it is believed to be c...

  4. Effects of the vasopressin agonist terlipressin on plasma cAMP and ENaC excretion in the urine in patients with cirrhosis and water retention

    DEFF Research Database (Denmark)

    Krag, Aleksander; Pedersen, Erling B; Møller, Søren

    2011-01-01

    Terlipressin is a vasopressin analogue used for its potent V1a effects in cirrhotic patients. Recent data suggest that terlipressin has affinity to renal V2 receptors and modulates Aquaporin 2 (AQP2) expression and free water clearance. Stimulation of renal V2 receptors may also affect sodium...

  5. The vasopressin precursor is not processed in the hypothalamus of Wolfram syndrome patients with diabetes insipidus: evidence for the involvement of PC2 and 7B2

    NARCIS (Netherlands)

    Gabreëls, B. A.; Swaab, D. F.; de Kleijn, D. P.; Dean, A.; Seidah, N. G.; van de Loo, J. W.; van de Ven, W. J.; Martens, G. J.; van Leeuwen, F. W.

    1998-01-01

    Wolfram syndrome (WS) is characterized by optic atrophy, insulin-dependent diabetes mellitus, vasopressin (VP)-sensitive diabetes insipidus, and neurosensory hearing loss. Here we report a disturbance in VP precursor processing in the supraoptic and paraventricular nuclei of WS patients. In these

  6. Efficacy of vasopressin-epinephrine compared to epinephrine alone for out of hospital cardiac arrest patients: A systematic review and meta-analysis.

    Science.gov (United States)

    Zhang, Qiang; Liu, Bo; Zhao, Lianxing; Qi, Zhijiang; Shao, Huan; An, Le; Li, Chunsheng

    2017-10-01

    The aim of this study was to conduct a meta-analysis to evaluate the efficacy of vasopressin-epinephrine compared to epinephrine alone in patients who suffered out-of-hospital cardiac arrest (OHCA). Relevant studies up to February 2017 were identified by searching in PubMed, EMBASE, the Cochrane Library, Wanfang for randomized controlled trials(RCTs) assigning adults with cardiac arrest to treatment with vasopressin-epinephrine (VEgroup) vs adrenaline (epinephrine) alone (E group). The outcome point was return of spontaneous circulation (ROSC) for patients suffering from OHCA. Heterogeneity, subgroup analysis, sensitivity analysis and publication bias were explored. Individual patient data were obtained from 5047 participants who experienced OHCA in nine studies. Odds ratios (ORs) were calculated using a random-effects model and results suggested that vasopressin-epinephrine was associated with higher rate of ROSC (OR=1.67, 95% CI=1.13-2.49, Padrenaline can improve ROSC of OHCA from Asia, but patients from other regions who suffered from OHCA cannot benefit from combination of vasopressin and epinephrine. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Effect of Rehydration Fluid Osmolality on Plasma Volume and Vasopressin in Resting Dehydrated Men

    Science.gov (United States)

    Geelen, Ghislaine; Greenleaf, J. E.; Keil, L. C.; Wade, Charles E. (Technical Monitor)

    1994-01-01

    Elevated plasma vasopressin concentration [PVP], which may act as a dipsogen, decreases promptly following the ingestion of fluids in many mammals including humans. The purpose for this study was to determine whether fluids of varied electrolyte and carbohydrate composition and osmolality (Osm] would modify post-drinking decreases in [PVP] which could be attributed to interaction with plasma volume (PV)- or fluid-electrolyte interactive hormones. Five men (23-41 yr, 78.0 +/- SD 8.2 kg), water deprived for 24 h, drank six fluids (12 ml/kg, at 16.5C in 4.0-6.2 min): water (30 m0sm/kg), NaCl (70 mOsm/kg), NaCl + NaCitrate (270 mOsm/kg), NaCl + 9.7% glucose (650 mOsm/kg), and two commercial drinks containing various ionic and carbohydrate contents (380 and 390 mOsm/kg). Blood (20 ml/sample) was drawn at -5 min before and at +3, +9, +15, +30, and +70 min after drinking. Heart rate, blood pressures, and plasma renin activity, {Na+], [K+], [Osm], aldosterone, atrial natriuretic peptide, and epinephrine concentrations were unchanged after drinking. Post-drinking [PVP] decreased from 1.7 - 3.7 pg/ml within 3 min with all fluids independently of their composition, [Osm], or delta PV; with maximal depression to 0.1-0.7 pg/ml (p<0.05) by 15 min. The continued [PVP] depression with all fluids from 15 to 70 min was accompanied by unchanged plasma (Osm] but 1.8-7.6% increases (p<0.05) in PV with 3) fluids (2 commercial and NaCitrate) and no change with the others. Percent changes in mean [PVP] and plasma norepinephrine concentrations [PNE] at 15 min correlated -0.70 (P<0.10) suggesting that about half the variability in [PVP I I depression was associated with [PNE]. Thus, part of the mechanism for post-drinking [PVP] depression may involve a drinking stimulated norepinephrine (neural) factor.

  8. Effects of Affiliative Human–Animal Interaction on Dog Salivary and Plasma Oxytocin and Vasopressin

    Directory of Open Access Journals (Sweden)

    Evan L. MacLean

    2017-09-01

    Full Text Available Oxytocin (OT and vasopressin (AVP are neuropeptides with diverse effects on social behavior, cognition and stress responses. Recent studies suggest that OT facilitates and responds to affiliative forms of human–animal interaction (HAI. However, previous studies measuring OT and AVP in dogs have been limited to measures from blood or urine, which present concerns related to the invasiveness of sample collection, the potential for matrix interference in immunoassays, and whether samples can be collected at precise time points to assess event-linked endocrine responses. Previous studies from our laboratory validated salivary measures of OT and AVP in dogs, however, it is currently unknown whether these measures respond dynamically to aspects of HAI. Here, we investigated the effects of affiliative forms of HAI on both plasma and salivary OT and AVP in dogs. We employed a within- and between-subjects design with a group of Labrador retrievers and Labrador retriever × golden retriever crosses (23 females, 15 males. Half of the dogs engaged in 10 min of free-form friendly interaction with a human experimenter (HAI condition, and the other half rested quietly in the same environment, without human interaction (control condition. We collected blood and saliva samples before, and immediately following both experimental conditions, and all samples were analyzed using enzyme-linked immunosorbent assays (ELISAs following previously validated protocols. Dogs participating in HAI exhibited a significant increase in both salivary OT (+39% and plasma OT (+5.7% whereas dogs in the control group did not. Salivary AVP showed no change in the HAI group but increased significantly (+33% in the control group. Plasma AVP decreased significantly following HAI (-13% but did not change across time in the control condition. Within the dogs exposed to HAI, increases in salivary OT, and decreases in plasma AVP, were predicted by the extent of affiliative behavior between

  9. Vasopressin and oxytocin levels during normal pregnancy: effects of chronic dietary sodium restriction.

    Science.gov (United States)

    van der Post, J A; van Buul, B J; Hart, A A; van Heerikhuize, J J; Pesman, G; Legros, J J; Steegers, E A; Swaab, D F; Boer, K

    1997-03-01

    Neurohypophysial hormones are thought to be involved in alterations in fluid balance during pregnancy and delivery. In the course of normal pregnancy intravascular volume is increased whereas sodium restriction is thought to reduce plasma volume and cardiac output. In the present study, we measured the effect of long-term severe sodium restriction on vasopressin (AVP) and oxytocin (OT) levels during normal pregnancy and after delivery. Fifty-nine healthy nulliparous women were randomized either for a low sodium diet (20 mmol sodium daily) or for a normal diet from week 12 of pregnancy onwards. Circulating plasma levels and urinary excretion of AVP and OT, their neurophysins (Np-AVP and Np-OT) and AVP bound to platelets were determined at regular intervals during pregnancy and after delivery. After completion of the study, women on a sodium-restricted diet were compared with control women on a normal diet using repeated measurement ANOVA with adjustment for potentially confounding variables. After randomization, a reduction in urinary sodium excretion of, on average, 40-82% was found. In general, no effect of sodium restriction could be demonstrated on the various parameters (0.53 sodium restriction compared with non-smokers having a normal diet (P = 0.018). For all parameters, clear changes were found in the course of pregnancy and puerperium (P pregnancy. After birth, free plasma AVP, platelet-bound AVP, OT, osmolality, sodium and potassium increased, while Np-AVP and Np-OT decreased. Although elevated Np-AVP and Np-OT levels during pregnancy seem to indicate increased release of neurohypophysial hormones, pregnancy up to 36 weeks of gestation is accompanied by low circulating AVP and OT levels. Long-term severe sodium restriction diminishes urinary AVP excretion in (non-smoking) pregnant women, without changing circulating levels of AVP and OT, despite the known reduction in circulating volume. The reduced circulating (platelet-bound) AVP levels during pregnancy

  10. Topography of subnuclei of the hypothalamic paraventricular nucleus in rats and sensitivity of their neurons to insulin defficiency

    International Nuclear Information System (INIS)

    Goufman, E.I.

    1985-01-01

    This investigation was undertaken to study the reaction of paraventricular nuclei (PVN) subnuclei to insulin deficiency and to elevation of the blood glucose level under conditions of experimental alloxan diabetes. Experiments were carried out on 15 control and 15 experimental mature male Wistar rats. The state of the carbohydrate metabolism of the diabetic and control animals was judged by the blood glucose and radioimmune insulin levels. The results of these investigations show that both magnocellular and parvocellular neurons of PVN react to alloxan diabetes, which supports the hypothesis that PVN of the hypothalamus participates in the control of carbohydrate metabolism

  11. Hypotonicity-induced reduction of aquaporin-2 transcription in mpkCCD cells is independent of the tonicity responsive element, vasopressin, and cAMP.

    Science.gov (United States)

    Kortenoeven, Marleen L A; van den Brand, Michiel; Wetzels, Jack F M; Deen, Peter M T

    2011-04-15

    The syndrome of inappropriate antidiuretic hormone secretion is characterized by excessive water uptake and hyponatremia. The extent of hyponatremia, however, is less than anticipated, which is ascribed to a defense mechanism, the vasopressin-escape, and is suggested to involve a tonicity-determined down-regulation of the water channel aquaporin-2 (AQP2). The underlying mechanism, however, is poorly understood. To study this, we used the mouse cortical collecting duct (mpkCCD) cell line. MpkCCD cells, transfected with an AQP2-promoter luciferase construct showed a reduced and increased AQP2 abundance and transcription following culture in hypotonic and hypertonic medium, respectively. This depended on tonicity rather than osmolality and occurred independently of the vasopressin analog dDAVP, cAMP levels, or protein kinase A activity. Although prostaglandins and nitric oxide reduced AQP2 abundance, inhibition of their synthesis did not influence tonicity-induced AQP2 transcription. Also, cells in which the cAMP or tonicity-responsive element (CRE/TonE) in the AQP2-promoter were mutated showed a similar response to hypotonicity. Instead, the tonicity-responsive elements were pin-pointed to nucleotides -283 to -252 and -157 to -126 bp. In conclusion, our data indicate that hypotonicity reduces AQP2 abundance and transcription, which occurs independently of vasopressin, cAMP, and the known TonE and CRE in the AQP2-promoter. Increased prostaglandin and nitric oxide, as found in vivo, may contribute to reduced AQP2 in vasopressin-escape, but do not mediate the effect of hypotonicity on AQP2 transcription. Our data suggest that two novel segments (-283 to -252 and -157 to -126 bp) in the AQP2-promoter mediate the hypotonicity-induced AQP2 down-regulation during vasopressin-escape.

  12. Hypothalamic pituitary abnormalities in tubercular meningitis at the time of diagnosis.

    Science.gov (United States)

    Dhanwal, Dinesh Kumar; Vyas, Anirudh; Sharma, Ashok; Saxena, Alpana

    2010-12-01

    Tubercular meningitis (TBM) is the most dreaded form of extra pulmonary tuberculosis associated with high morbidity and mortality. Various hypothalamic pituitary hormonal abnormalities have been reported to occur years after recovery from disease but there are no systematic studies in the literature to evaluate the pituitary hypothalamic dysfunction in patients with TBM at the time of presentation. Therefore, the present study was designed to evaluate hypothalamic pituitary abnormalities in newly diagnosed patients with TBM. Patient case series. This prospective study included 75 untreated adult patients with TBM diagnosed as "definite", "highly probable" and "probable" TBM by Ahuja's criteria and in clinical stage 1, 2 or 3 at the time of presentation to hospital. Basal hormonal profile was measured by electrochemilumniscence technique for serum cortisol, luetinizing hormone (LH), follicular stimulating hormone (FSH), prolactin (PRL), thyrotropin (TSH), free tri-iodothyronine (fT3), and free thyroxine (fT4). All patients were subjected to MRI to image brain and hypothalamic pituitary axis and CT for adrenal glands. Thirty-two (42.7%) cases showed relative or absolute cortisol insufficiency. Twenty-three (30.7%) cases showed central hypothyroidism and 37 (49.3%) cases had hyperprolactinemia. No patient had evidence of diabetes insipidus. Multiple hormone deficiency was seen in 22 (29.3%) cases. MRI of hypothalamic pituitary axis using dynamic scanning and thin cuts revealed abnormalities in 10 (13.3%) of the cases. CT adrenal gland was normal in all the patients. Tubercular meningitis is associated with both hormonal and structural abnormalities in the hypothalamic pituitary axis at the time of diagnosis.

  13. Anti-aging drugs reduce hypothalamic inflammation in a sex-specific manner.

    Science.gov (United States)

    Sadagurski, Marianna; Cady, Gillian; Miller, Richard A

    2017-08-01

    Aging leads to hypothalamic inflammation, but does so more slowly in mice whose lifespan has been extended by mutations that affect GH/IGF-1 signals. Early-life exposure to GH by injection, or to nutrient restriction in the first 3 weeks of life, also modulate both lifespan and the pace of hypothalamic inflammation. Three drugs extend lifespan of UM-HET3 mice in a sex-specific way: acarbose (ACA), 17-α-estradiol (17αE2), and nordihydroguaiaretic acid (NDGA), with more dramatic longevity increases in males in each case. In this study, we examined the effect of these anti-aging drugs on neuro-inflammation in hypothalamus and hippocampus. We found that age-associated hypothalamic inflammation is reduced in males but not in females at 12 months of age by ACA and 17αE2 and at 22 months of age in NDGA-treated mice. The three drugs blocked indices of hypothalamic reactive gliosis associated with aging, such as Iba-1-positive microglia and GFAP-positive astrocytes, as well as age-associated overproduction of TNF-α. This effect was not observed in drug-treated female mice or in the hippocampus of the drug-treated animals. On the other hand, caloric restriction (CR; an intervention that extends the lifespan in both sexes) significantly reduced hypothalamic microglia and TNF-α in both sexes at 12 months of age. Together, these results suggest that the extent of drug-induced changes in hypothalamic inflammatory processes is sexually dimorphic in a pattern that parallels the effects of these agents on mouse longevity and that mimics the changes seen, in both sexes, of long-lived nutrient restricted or mutant mice. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  14. Metabolic Impact on the Hypothalamic Kisspeptin-Kiss1r Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Fazal Wahab

    2018-03-01

    Full Text Available A large body of data has established the hypothalamic kisspeptin (KP and its receptor, KISS1R, as major players in the activation of the neuroendocrine reproductive axis at the time of puberty and maintenance of reproductive capacity in the adult. Due to its strategic location, this ligand-receptor pair acts as an integrator of cues from gonadal steroids as well as of circadian and seasonal variation-related information on the reproductive axis. Besides these cues, the activity of the hypothalamic KP signaling is very sensitive to the current metabolic status of the body. In conditions of energy imbalance, either positive or negative, a number of alterations in the hypothalamic KP signaling pathway have been documented in different mammalian models including nonhuman primates and human. Deficiency of metabolic fuels during fasting causes a marked reduction of Kiss1 gene transcript levels in the hypothalamus and, hence, decreases the output of KP-containing neurons. Food intake or exogenous supply of metabolic cues, such as leptin, reverses metabolic insufficiency-related changes in the hypothalamic KP signaling. Likewise, alterations in Kiss1 expression have also been reported in other situations of energy imbalance like diabetes and obesity. Information related to the body’s current metabolic status reaches to KP neurons both directly as well as indirectly via a complex network of other neurons. In this review article, we have provided an updated summary of the available literature on the regulation of the hypothalamic KP-Kiss1r signaling by metabolic cues. In particular, the potential mechanisms of metabolic impact on the hypothalamic KP-Kiss1r signaling, in light of available evidence, are discussed.

  15. Rapid sensing of l-leucine by human and murine hypothalamic neurons: Neurochemical and mechanistic insights.

    Science.gov (United States)

    Heeley, Nicholas; Kirwan, Peter; Darwish, Tamana; Arnaud, Marion; Evans, Mark L; Merkle, Florian T; Reimann, Frank; Gribble, Fiona M; Blouet, Clemence

    2018-04-01

    Dietary proteins are sensed by hypothalamic neurons and strongly influence multiple aspects of metabolic health, including appetite, weight gain, and adiposity. However, little is known about the mechanisms by which hypothalamic neural circuits controlling behavior and metabolism sense protein availability. The aim of this study is to characterize how neurons from the mediobasal hypothalamus respond to a signal of protein availability: the amino acid l-leucine. We used primary cultures of post-weaning murine mediobasal hypothalamic neurons, hypothalamic neurons derived from human induced pluripotent stem cells, and calcium imaging to characterize rapid neuronal responses to physiological changes in extracellular l-Leucine concentration. A neurochemically diverse subset of both mouse and human hypothalamic neurons responded rapidly to l-leucine. Consistent with l-leucine's anorexigenic role, we found that 25% of mouse MBH POMC neurons were activated by l-leucine. 10% of MBH NPY neurons were inhibited by l-leucine, and leucine rapidly reduced AGRP secretion, providing a mechanism for the rapid leucine-induced inhibition of foraging behavior in rodents. Surprisingly, none of the candidate mechanisms previously implicated in hypothalamic leucine sensing (K ATP channels, mTORC1 signaling, amino-acid decarboxylation) were involved in the acute activity changes produced by l-leucine. Instead, our data indicate that leucine-induced neuronal activation involves a plasma membrane Ca 2+ channel, whereas leucine-induced neuronal inhibition is mediated by inhibition of a store-operated Ca 2+ current. A subset of neurons in the mediobasal hypothalamus rapidly respond to physiological changes in extracellular leucine concentration. Leucine can produce both increases and decreases in neuronal Ca 2+ concentrations in a neurochemically-diverse group of neurons, including some POMC and NPY/AGRP neurons. Our data reveal that leucine can signal through novel mechanisms to rapidly

  16. Increased concentration of. cap alpha. - and. gamma. -endorphin in post mortem hypothalamic tissue of schizophrenic patients

    Energy Technology Data Exchange (ETDEWEB)

    Wiegant, V.M.; Verhoef, C.J.; Burbach, J.P.H.; de Wied, D.

    1988-01-01

    The concentrations of ..cap alpha..-, ..beta..- and ..gamma..-endorphin were determined by radioimmunoassay in HPLC fractionated extracts of post mortem hypothalamic tissue obtained from schizophrenic patients and controls. The hypothalamic concentration of ..cap alpha..- and ..gamma..-endorphin was significantly higher in patients than in controls. No difference was found in the concentration of ..beta..-endorphin, the putative precursor of ..cap alpha..- and ..gamma..-endorphins. These results suggest a deviant metabolism of ..beta..-endorphin in the brain of schizophrenic patients. Whether this phenomenon is related to the psychopathology, or is a consequence of ante mortem farmacotherapy, remains to be established.

  17. Antidepressant-Like Effects of Fractions Prepared from Danzhi-Xiaoyao-San Decoction in Rats with Chronic Unpredictable Mild Stress: Effects on Hypothalamic-Pituitary-Adrenal Axis, Arginine Vasopressin, and Neurotransmitters

    Directory of Open Access Journals (Sweden)

    Li-Li Wu

    2016-01-01

    Full Text Available The aim of the present study was to investigate the antidepressant-like effects of two fractions, including petroleum ether soluble fraction (Fraction A, FA and water-EtOH soluble fraction (Fraction B, FB prepared from the Danzhi-xiaoyao-san (DZXYS by using chronic unpredictable mild stress-induced depressive rat model. The results indicated that DZXYS could ameliorate the depression-like behavior in chronic stress model of rats. The inhibition of hyperactivity of HPA axis and the modulation of monoamine and amino acid neurotransmitters in the hippocampus may be the important mechanisms underlying the action of DZXYS antidepressant-like effect in chronically stressed rats.

  18. Cocaine- and amphetamine-regulated transcript is present in hypothalamic neuroendocrine neurones and is released to the hypothalamic-pituitary portal circuit

    DEFF Research Database (Denmark)

    Larsen, P J; Seier, V; Fink-Jensen, A

    2003-01-01

    Cocaine- and amphetamine-regulated transcript (CART) is present in a number of hypothalamic nuclei. Besides actions in circuits regulating feeding behaviour and stress responses, the hypothalamic functions of CART are largely unknown. We report that CART immunoreactivity is present in hypothalami......, supraoptic, paraventricular (PVN) and periventricular nuclei of the hypothalamus. In the PVN, CART-positive neuroendocrine neurones were found in all of cytoarchitectonically identified nuclei. In the periventricular nucleus, approximately one-third of somatostatin cells were also CART......-immunoreactive. In the medial parvicellular subnucleus of the PVN, CART and FG coexisted with thyrotrophin-releasing hormone, whereas very few of the corticotrophin-releasing hormone containing cells were CART-immunoreactive. In the arcuate nucleus, CART was extensively colocalized with pro...

  19. ASD and genetic associations with receptors for oxytocin and vasopressin – AVPR1A, AVPR1B, and OXTR

    Directory of Open Access Journals (Sweden)

    Sunday M Francis

    2016-11-01

    Full Text Available Background: There are limited treatments available for autism spectrum disorder (ASD. Studies have reported significant associations between the receptor genes of oxytocin (OT and vasopressin (AVP and ASD diagnosis, as well as, ASD-related phenotypes. Researchers have also found the manipulation of these systems affect social and repetitive behaviors, core characteristics of ASD. Consequently, research involving the oxytocin/vasopressin pathways as intervention targets has increased. Therefore, further examination into the relationship between these neuropeptides and ASD was undertaken. In this study, we examined associations between variants in the receptor genes of vasopressin (AVPR1A, AVPR1B, oxytocin (OXTR and ASD diagnosis along with related subphenotypes.Methods: Probands were assessed using Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, and clinical DSM-IV-TR criteria. Single nucleotide polymorphisms (SNPs in AVPR1B and OXTR, and microsatellites in AVPR1A were genotyped in ~200 families with a proband with ASD. Family-based association testing (FBAT was utilized to determine associations between variants and ASD. Haplotypes composed of OXTR SNPs (i.e. rs53576-rs2254298-rs2268493 were also analyzed due to previously published associations.Results: Using the additive inheritance model in FBAT we found associations between AVPR1B SNPs (rs28632197, p=0.005, rs35369693, p=0.025 and diagnosis. As in other studies, OXTR rs2268493 (p=0.050 was associated with diagnosis. rs2268493 was also associated with ASD subphenotypes of social withdrawal (p=0.013 and insistence on sameness (p=0.039. Further analyses demonstrated that the haplotype, rs2254298-rs2268493 was found to be significantly associated with diagnosis (A-T; p=0.026. FBAT was also used to analyze AVPR1A microsatellites (RS1 and RS3. Both length variants were found to be associated with restrictive, repetitive behaviors, but not overall diagnosis. Correction

  20. ASD and Genetic Associations with Receptors for Oxytocin and Vasopressin-AVPR1A, AVPR1B, and OXTR.

    Science.gov (United States)

    Francis, Sunday M; Kim, Soo-Jeong; Kistner-Griffin, Emily; Guter, Stephen; Cook, Edwin H; Jacob, Suma

    2016-01-01

    Background: There are limited treatments available for autism spectrum disorder (ASD). Studies have reported significant associations between the receptor genes of oxytocin (OT) and vasopressin (AVP) and ASD diagnosis, as well as ASD-related phenotypes. Researchers have also found the manipulation of these systems affects social and repetitive behaviors, core characteristics of ASD. Consequently, research involving the oxytocin/vasopressin pathways as intervention targets has increased. Therefore, further examination into the relationship between these neuropeptides and ASD was undertaken. In this study, we examined associations between variants in the receptor genes of vasopressin ( AVPR1A, AVPR1B ), oxytocin ( OXTR ), and ASD diagnosis along with related subphenotypes. Methods: Probands were assessed using Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, and clinical DSM-IV-TR criteria. Single nucleotide polymorphisms (SNPs) in AVPR1B and OXTR , and microsatellites in AVPR1A were genotyped in ~200 families with a proband with ASD. Family-based association testing (FBAT) was utilized to determine associations between variants and ASD. Haplotypes composed of OXTR SNPs (i.e., rs53576-rs2254298-rs2268493) were also analyzed due to previously published associations. Results: Using the additive inheritance model in FBAT we found associations between AVPR1B SNPs (rs28632197, p = 0.005, rs35369693, p = 0.025) and diagnosis. As in other studies, OXTR rs2268493 ( p = 0.050) was associated with diagnosis. rs2268493 was also associated with ASD subphenotypes of social withdrawal ( p = 0.013) and Insistence on Sameness ( p = 0.039). Further analyses demonstrated that the haplotype, rs2254298-rs2268493 was found to be significantly associated with diagnosis (A-T; p = 0.026). FBAT was also used to analyze AVPR1A microsatellites (RS1 and RS3). Both length variants were found to be associated with restrictive, repetitive behaviors, but not overall