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Sample records for hypothalamic magnocellular vasopressin

  1. Vasopressin regularizes the phasic firing pattern of rat hypothalamic magnocellular vasopressin neurons.

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    Gouzènes, L; Desarménien, M G; Hussy, N; Richard, P; Moos, F C

    1998-03-01

    Vasopressin (AVP) magnocellular neurons of hypothalamic nuclei express specific phasic firing (successive periods of activity and silence), which conditions the mode of neurohypophyseal vasopression release. In situations favoring plasmatic secretion of AVP, the hormone is also released at the somatodendritic level, at which it is believed to modulate the activity of AVP neurons. We investigated the nature of this autocontrol by testing the effects of juxtamembrane applications of AVP on the extracellular activity of presumed AVP neurons in paraventricular and supraoptic nuclei of anesthetized rats. AVP had three effects depending on the initial firing pattern: (1) excitation of faintly active neurons (periods of activity of <10 sec), which acquired or reinforced their phasic pattern; (2) inhibition of quasi-continuously active neurons (periods of silences of <10 sec), which became clearly phasic; and (3) no effect on neurons already showing an intermediate phasic pattern (active and silent periods of 10-30 sec). Consequently, AVP application resulted in a narrower range of activity patterns of the population of AVP neurons, with a Gaussian distribution centered around a mode of 57% of time in activity, indicating a homogenization of the firing pattern. The resulting phasic pattern had characteristics close to those established previously for optimal release of AVP from neurohypophyseal endings. These results suggest a new role for AVP as an optimizing factor that would foster the population of AVP neurons to discharge with a phasic pattern known to be most efficient for hormone release.

  2. 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....

  3. The hypothalamic magnocellular neurosecretory system in developing rats

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    E Farina Lipari

    2009-12-01

    Full Text Available Studies concerning the development of the magnocellular system are scarce and discordant in literature. We carried out an immunohistochemical study on supraotic and paraventricular hypothalamic nuclei using antivasopressin and antioxytocin antibodies in developing rats between the 15th day of intrauterine life and the 6th day of postnatal life. In addition, we performed RT-PCR experiments to establish the stage at which these hormones appear and neurosecretory activity commences. The results showed that supraoptic and paraventricular nuclei appear, respectively, on the 16th and the 18th day of intrauterine life and both immediately synthetize vasopressin neurohormone. By contrast, synthesis of oxytocin takes place from the 2nd day after birth. Probably, these nuclei synthetize oxytocin in conjunction with the decline of placental maternal oxytocin.

  4. Rhythmic activities of hypothalamic magnocellular neurons: autocontrol mechanisms.

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    Richard, P; Moos, F; Dayanithi, G; Gouzènes, L; Sabatier, N

    1997-12-01

    Electrophysiological recordings in lactating rats show that oxytocin (OT) and vasopressin (AVP) neurons exhibit specific patterns of activities in relation to peripheral stimuli: periodic bursting firing for OT neurons during suckling, phasic firing for AVP neurons during hyperosmolarity (systemic injection of hypertonic saline). These activities are autocontrolled by OT and AVP released somato-dentritically within the hypothalamic magnocellular nuclei. In vivo, OT enhances the amplitude and frequency of bursts, an effect accompanied with an increase in basal firing rate. However, the characteristics of firing change as facilitation proceeds: the spike patterns become very irregular with clusters of spikes spaced by long silences; the firing rate is highly variable and clearly oscillates before facilitated bursts. This unstable behaviour dramatically decreases during intense tonic activation which temporarily interrupts bursting, and could therefore be a prerequisite for bursting. In vivo, the effects of AVP depend on the initial firing pattern of AVP neurons: AVP excites weakly active neurons (increasing duration of active periods and decreasing silences), inhibits highly active neurons, and does not affect neurons with intermediate phasic activity. AVP brings the entire population of AVP neurons to discharge with a medium phasic activity characterised by periods of firing and silence lasting 20-40 s, a pattern shown to optimise the release of AVP from the neurohypophysis. Each of the peptides (OT or AVP) induces an increase in intracellular Ca2+ concentration, specifically in the neurons containing either OT or AVP respectively. OT evokes the release of Ca2+ from IP3-sensitive intracellular stores. AVP induces an influx of Ca2+ through voltage-dependent Ca2+ channels of T-, L- and N-types. We postulate that the facilitatory autocontrol of OT and AVP neurons could be mediated by Ca2+ known to play a key role in the control of the patterns of phasic neurons.

  5. Adenovirus-mediated gene delivery to hypothalamic magnocellular neurons in mice

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    Vasquez, E. C.; Beltz, T. G.; Meyrelles, S. S.; Johnson, A. K.

    1999-01-01

    Vasopressin is synthesized by magnocellular neurons in supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei and released by their axon terminals in the neurohypophysis (NH). With its actions as an antidiuretic hormone and vasoactive agent, vasopressin plays a pivotal role in the control of body fluids and cardiovascular homeostasis. Because of its well-defined neurobiology and functional importance, the SON/PVN-NH system is ideal to establish methods for gene transfer of genetic material into specific pathways in the mouse central nervous system. In these studies, we compared the efficiency of transferring the gene lacZ, encoding for beta-galactosidase (beta-gal), versus a gene encoding for green fluorescent protein by using replication-deficient adenovirus (Ad) vectors in adult mice. Transfection with viral concentrations up to 2 x 10(7) plaque-forming units per coverslip of NH, PVN, and SON in dissociated, cultured cells caused efficient transfection without cytotoxicity. However, over an extended period of time, higher levels (50% to 75% of the cells) of beta-gal expression were detected in comparison with green fluorescent protein (5% to 50% of the cells). With the use of a stereotaxic approach, the pituitary glands of mice were injected with Ad (4 x 10(6) plaque-forming units). In material from these animals, we were able to visualize the expression of the beta-gal gene in the NH and in magnocellular neurons of both the PVN and SON. The results of these experiments indicate that Ad-Rous sarcoma virus promoter-beta-gal is taken up by nerve terminals at the injection site (NH) and retrogradely transported to the soma of the neurons projecting to the NH. We conclude that the application of these experimental approaches will provide powerful tools for physiological studies and potential approaches to deliver therapeutic genes to treat diseases.

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

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    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......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...

  7. The V1a and V1b, but not V2, vasopressin receptor genes are expressed in the supraoptic nucleus of the rat hypothalamus, and the transcripts are essentially colocalized in the vasopressinergic magnocellular neurons.

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    Hurbin, A; Boissin-Agasse, L; Orcel, H; Rabié, A; Joux, N; Desarménien, M G; Richard, P; Moos, F C

    1998-11-01

    We have identified and visualized the vasopressin (VP) receptors expressed by hypothalamic magnocellular neurons in supraoptic and paraventricular nuclei. To do this, we used RT-PCR on total RNA extracts from supraoptic nuclei or on single freshly dissociated supraoptic neurons, and in situ hybridization on frontal sections of hypothalamus of Wistar rats. The RT-PCR on supraoptic RNA extracts revealed that mainly V1a, but also V1b, subtypes of VP receptors are expressed from birth to adulthood. No V2 receptor messenger RNA (mRNA) was detected. Furthermore, the single-cell RT-nested PCR indicated that the V1a receptor mRNA is present in vasopressinergic magnocellular neurons. In light of these results, in situ hybridization was performed to visualize the V1a and V1b receptor mRNAs in supraoptic and paraventricular nuclei. Simultaneously, we coupled this approach to: 1) in situ hybridization detection of oxytocin or VP mRNAs; or 2) immunocytochemistry to detect the neuropeptides. This provided a way of identifying the neurons expressing perceptible amounts of V1a or V1b receptor mRNAs as vasopressinergic neurons. Here, we suggest that the autocontrol exerted specifically by VP on vasopressinergic neurons is mediated through, at least, V1a and V1b subtype receptors.

  8. LPLRFamide exerts short-term anorexigenic effects that coincide with magnocellular division of the hypothalamic paraventricular nucleus activation.

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    Scheel, Amy; Deal, Nick; St John, Natalie; Wells, Amy; Caruso, Maggie; Gilbert, Elizabeth R; Cline, Mark

    2017-05-15

    LPLRFamide is a member of the RFamide peptide family that elicits an anorexigenic effect when centrally injected in chicks although the mechanism mediating this response is poorly understood. Therefore, the purpose of this experiment was to elucidate the hypothalamic mechanism of short-term anorexia after central administration of LPLRFamide in chicks. In Experiment 1 chicks centrally injected with LPLRFamide decreased food intake at 15min but not 30min following administration compared to vehicle-injected chicks. For Experiment 2, c-Fos immunoreactivity was quantified in several appetite-associated hypothalamic nuclei and in LPLRF-injected chicks, compared to vehicle-injected chicks, there was an increase in the number of reactive cells in the magnocellular division of the paraventricular nucleus. Lastly in Experiment 3, real time-PCR was performed and hypothalamic proopiomelanocortin (POMC) mRNA abundance was increased in LPRLFamide-injected chicks compared to vehicle-injected chicks. Thus, following central injection of LPLRFamide there is activation of the paraventricular nucleus of the hypothalamus and increased expression of hypothalamic POMC mRNA in chicks. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Vasopressin and the Output of the Hypothalamic Biological Clock

    NARCIS (Netherlands)

    Kalsbeek, A.; Fliers, E.; Hofman, M. A.; Swaab, D. F.; Buijs, R. M.

    2010-01-01

    The physiological effects of vasopressin as a peripheral hormone were first reported more than 100 years ago. However, it was not until the first immunocytochemical studies were carried out in the early 1970s, using vasopressin antibodies, and the discovery of an extensive distribution of

  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. Specific expression of optically active reporter gene in arginine vasopressin-secreting neurosecretory cells in the hypothalamic-neurohypophyseal system.

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    Ueta, Y; Fujihara, H; Dayanithi, G; Kawata, M; Murphy, D

    2008-06-01

    The anti-diuretic hormone arginine vasopressin (AVP) is synthesised in the magnocellular neurosecretory cells (MNCs) in the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) of the hypothalamus. AVP-containing MNCs that project their axon terminals to the posterior pituitary can be identified using immunohistochemical techniques with specific antibodies recognising AVP and neurophysin II, and by virtue of their electrophysiological properties. Recently, we generated transgenic rats expressing an AVP-enhanced green fluorescent protein (eGFP) fusion gene in AVP-containing MNCs. In this transgenic rat, eGFP mRNA was observed in the PVN and the SON, and eGFP fluorescence was seen in the PVN and the SON, and also in the posterior pituitary, indicating transport of transgene protein down MNC axons to storage in nerve terminals. The expression of the AVP-eGFP transgene and eGFP fluorescence in the PVN and the SON was markedly increased after dehydration and chronic salt-loading. On the other hand, AVP-containing parvocellular neurosecretory cells in the PVN that are involved in the activation of the hypothalamic-pituitary adrenal axis exhibit robust AVP-eGFP fluorescence after bilateral adrenalectomy and intraperitoneal administration of lipopolysaccharide. In the median eminence, the internal and external layer showed strong fluorescence for eGFP after osmotic stimuli and stressful conditions, respectively, again indicating appropriate transport of transgene traslation products. Brain slices and acutely-dissociated MNCs and axon terminals also exhibited strong fluorescence, as observed under fluorescence microscopy. The AVP-eGFP transgenic animals are thus unique and provide a useful tool to study AVP-secreting cells in vivo for electrophysiology, imaging analysis such as intracellular Ca(2+) imaging, organ culture and in vivo monitoring of dynamic change in AVP secretion.

  12. Immunoreactivity to vasopressin- but not oxytocin-associated neurophysin antiserum in phasic neurons of rat hypothalamic paraventricular nucleus.

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    Cobbett, P; Smithson, K G; Hatton, G I

    1986-01-01

    Bursts of action potentials were recorded intracellularly from 11 phasically firing magnocellular neurons in the paraventricular nucleus in slices of rat hypothalamus. The bursts of overshooting, often broadening action potentials (63-87 mV peak-to-peak) were superimposed on depolarizing plateau potentials. Phasic activity was recorded before and/or after the neurons were injected with the fluorescent dye Lucifer Yellow CH. Injected neurons were first examined in whole slices, and subsequently, in sectioned material, characterized immunocytochemically using antisera to vasopressin- and oxytocin-associated neurophysins (VP-NP and OT-NP respectively). The 11 injections produced 8 single dye filled neurons and 3 pairs of dye-coupled neurons, 14 dye-filled cells in all. Six of the single cells and all the dye coupled pairs were immunoreactive with VP-NP antiserum and not reactive with OT-NP antiserum. Most of these neurons were in areas of the nucleus in which VP-NP reactive cells predominated, but two were surrounded by OT-NP reactive cells. Two single, dye-filled, phasically active, magnocellular neurons failed to show immunoreactivity to either antiserum.

  13. Comparison of the expression of c-fos, nur77 and egr1 mRNAs in rat hypothalamic magnocellular neurons and their putative afferent projection neurons: cell- and stimulus-specific induction.

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    Luckman, S M

    1997-11-01

    Hypothalamic magnocellular neurons and their afferent inputs provide a model system in which to study the regulation of inducible transcription factors in the brain in vivo. Osmotic stimulation of rats produced by graded infusions of saline at different tonicities was found to lead to the induction of c-fos, nur77 and egr1 mRNAs in magnocellular neurons, as well as in putative afferent neurons, including those in structures of the forebrain (subfornical organ, median preoptic nucleus and organum vasculosum of the lamina terminalis). The results presented suggest that stronger levels of osmotic stimulation recruit additional afferents from the forebrain and brainstem that can act on magnocellular neurons via alternative receptors. A single systemic injection of the peptide cholecystokinin produced robust induction of c-fos and nur77 mRNAs in afferent neurons of the brainstem nucleus tractus solitarii and in magnocellular neurons. Despite the fact that these two neuronal populations are clearly electrically active, egr1 was not induced by this stimulus, providing examples of cell- and stimulus-specificity of its expression. This study re-emphasizes that the induction of transcription factors is largely dependent on the nature of the afferent input and does not correlate necessarily to the electrical activity of the neuron.

  14. Dye-coupled magnocellular peptidergic neurons of the rat paraventricular nucleus show homotypic immunoreactivity.

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    Cobbett, P; Smithson, K G; Hatton, G I

    1985-12-01

    Magnocellular neurons in rat hypothalamic slices are known to exhibit dye coupling: the transfer of the fluorescent dye, Lucifer Yellow, from an intracellularly-injected neuron to one or more nearby neurons. The question of the hormonal identity of coupled cells and the possibility of dye coupling as an artefact led us to determine the immunoreactivity of dye-coupled magnocellular neurons in the paraventricular nucleus of the rat hypothalamus using antisera to oxytocin- and vasopressin-associated neurophysins. In 23 pairs, one triplet, and one quadruplet, immunoreactivity to one or the other antiserum was always exclusive, and dye coupling was always homotypic, that is, coupled neurons in each instance were reactive to the same antiserum. The quadruplet, triplet and 17 pairs were immunoreactive to vasopressin-associated neurophysin, and oxytoxin-associated neurophysin immunoreactivity was observed in the remaining pairs. Immunoreactivity to each antiserum was found for somasomatic and non somasomatic modes of coupling and for coupled neurons in the three magnocellular areas of the nucleus. A relationship between mode of coupling and hormone content was not detected. The data support the hypothesis that coupling is a real, functionally significant mechanism for coordinating neuronal activity in this nucleus, particularly under conditions of high hormone demand. They do not support the idea that coupling is artefact. The possibility of a relationship between hormone content and mode of coupling, and the projection pathway(s) of the coupled neurons of each type require further study.

  15. Distinct vasopressin content in the hypothalamic supraoptic and paraventricular nucleus of rats exposed to low and high ambient temperature.

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    Jasnic, N; Dakic, T; Bataveljic, D; Vujovic, P; Lakic, I; Jevdjovic, T; Djurasevic, S; Djordjevic, J

    2015-08-01

    Both high and low ambient temperature represent thermal stressors that, among other physiological responses, induce activation of the hypothalamic-pituitary-adrenal (HPA) axis and secretion of arginine-vasopressin (AVP). The exposure to heat also leads to disturbance of osmotic homeostasis. Since AVP, in addition to its well-known peripheral effects, has long been recognized as a hormone involved in the modulation of HPA axis activity, the aim of the present study was to elucidate the hypothalamic AVP amount in the acutely heat/cold exposed rats. Rats were exposed to high (+38°C) or low (+4°C) ambient temperature for 60min. Western blot was employed for determining hypothalamic AVP levels, and the difference in its content between supraoptic (SON) and paraventricular nucleus (PVN) was detected using immunohistochemical analysis. The results showed that exposure to both high and low ambient temperature increased hypothalamic AVP levels, although the increment was higher under heat conditions. On the other hand, patterns of AVP level changes in PVN and SON were stressor-specific, given that exposure to cold increased the AVP level in both nuclei, while heat exposure affected the PVN AVP content alone. In conclusion, our results revealed that cold and heat stress influence hypothalamic AVP amount with different intensity. Moreover, different pattern of AVP amount changes in the PVN and SON indicates a role of this hormone not only in response to heat as an osmotic/physical threat, but to the non-osmotic stressors as well. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. A switch from GABA inhibition to excitation of vasopressin neurons exacerbates the development angiotensin II-dependent hypertension.

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    Korpal, Aaron K; Han, Su Young; Schwenke, Daryl O; Brown, Colin H

    2017-12-09

    Hypothalamic magnocellular neurons secrete vasopressin into the systemic circulation to maintain blood pressure by increasing renal water reabsorption and by vasoconstriction. When blood pressure rises, baroreflex activation normally inhibits vasopressin neurons via activation of GABAergic inputs. However, plasma vasopressin levels are paradoxically elevated in several models of hypertension and in some patients with essential hypertension, despite increased blood pressure. We have previously shown that vasopressin neuron activity is increased early in the development of moderate angiotensin II-dependent hypertension via blunted baroreflex inhibition of vasopressin neurons. Here, we show that antagonism of vasopressin-induced vasoconstriction slows the development of hypertension and that local administration of a GABAA receptor antagonist inhibits vasopressin neurons during, but not before, the onset of hypertension. Taken together, our data suggest that vasopressin exacerbates the increase in blood pressure evident early in the development hypertension and that blunted baroreflex inhibition of vasopressin neurons is underpinned by an excitatory shift in their response to endogenous GABA signalling. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. Space flight affects magnocellular supraoptic neurons of young prepuberal rats: transient and permanent effects

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    Garcia-Ovejero, D.; Trejo, J. L.; Ciriza, I.; Walton, K. D.; Garcia-Segura, L. M.

    2001-01-01

    Effects of microgravity on postural control and volume of extracellular fluids as well as stress associated with space flight may affect the function of hypothalamic neurosecretory neurons. Since environmental modifications in young animals may result in permanent alterations in neuroendocrine function, the present study was designed to determine the effect of a space flight on oxytocinergic and vasopressinergic magnocellular hypothalamic neurons of prepuberal rats. Fifteen-day-old Sprague-Dawley female rats were flown aboard the Space Shuttle Columbia (STS-90, Neurolab mission, experiment 150) for 16 days. Age-matched litters remained on the ground in cages similar to those of the flight animals. Six animals from each group were killed on the day of landing and eight animals from each group were maintained under standard vivarium conditions and killed 18 weeks after landing. Several signs of enhanced transcriptional and biosynthetic activity were observed in magnocellular supraoptic neurons of flight animals on the day of landing compared to control animals. These include increased c-Fos expression, larger nucleoli and cytoplasm, and higher volume occupied in the neuronal perikaryon by mitochondriae, endoplasmic reticulum, Golgi apparatus, lysosomes and cytoplasmic inclusions known as nematosomes. In contrast, the volume occupied by neurosecretory vesicles in the supraoptic neuronal perikarya was significantly decreased in flight rats. This decrease was associated with a significant decrease in oxytocin and vasopressin immunoreactive levels, suggestive of an increased hormonal release. Vasopressin levels, cytoplasmic volume and c-Fos expression returned to control levels by 18 weeks after landing. These reversible effects were probably associated to osmotic stimuli resulting from modifications in the volume and distribution of extracellular fluids and plasma during flight and landing. However, oxytocin levels were still reduced at 18 weeks after landing in flight

  18. Nav1.9 expression in magnocellular neurosecretory cells of supraoptic nucleus.

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    Black, J A; Vasylyev, D; Dib-Hajj, S D; Waxman, S G

    2014-03-01

    Osmoregulation in mammals is tightly controlled by the release of vasopressin and oxytocin from magnocellular neurosecretory cells (MSC) of the supraoptic nucleus (SON). The release of vasopressin and oxytocin in the neurohypophysis by axons of MSC is regulated by bursting activity of these neurons, which is influenced by multiple sources, including intrinsic membrane properties, paracrine contributions of glial cells, and extrinsic synaptic inputs. Previous work has shown that bursting activity of MSC is tetrodotoxin (TTX)-sensitive, and that TTX-S sodium channels Nav1.2, Nav1.6 and Nav1.7 are expressed by MSC and upregulated in response to osmotic challenge in rats. The TTX-resistant sodium channels, NaV1.8 and Nav1.9, are preferentially expressed, at relatively high levels, in peripheral neurons, where their properties are linked to repetitive firing and subthreshold electrogenesis, respectively, and are often referred to as "peripheral" sodium channels. Both sodium channels have been implicated in pain pathways, and are under study as potential therapeutic targets for pain medications which might be expected to have minimal CNS side effects. We show here, however, that Nav1.9 is expressed by vasopressin- and oxytocin-producing MSC of the rat supraoptic nucleus (SON). We also show that cultured MSC exhibit sodium currents that have characteristics of Nav1.9 channels. In contrast, Nav1.8 is not detectable in the SON. These results suggest that Nav1.9 may contribute to the firing pattern of MSC of the SON, and that careful assessment of hypothalamic function be performed as NaV1.9 blocking agents are studied as potential pain therapies. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Nicotine self-administration differentially regulates hypothalamic corticotropin-releasing factor and arginine vasopressin mRNAs and facilitates stress-induced neuronal activation.

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    Yu, Guoliang; Chen, Hao; Zhao, Wenyuan; Matta, Shannon G; Sharp, Burt M

    2008-03-12

    Acute nicotine is a potent stimulus for activation of the stress-responsive hypothalamic-pituitary-adrenal (HPA) axis, while chronic nicotine self-administration (SA) desensitizes the ACTH response to self-administered nicotine but cross-sensitizes to mild footshock stress (mFSS). To identify underlying mechanisms, we investigated (1) the effects of chronic nicotine SA on the coexpression of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) mRNAs, the primary hypothalamic neuropeptides regulating ACTH release, in the parvocellular division of paraventricular nucleus (pcPVN), and (2) mFSS-induced activation of these neurons during nicotine SA. Adult male Sprague Dawley rats were given 23 h/d unlimited access to self-administer nicotine (0.03 mg/kg per injection, i.v.) for 19 d. Brains were double labeled with fluorescence in situ hybridization of CRF and AVP mRNAs and triple labeled after mFSS exposure for CRF and AVP mRNAs and c-Fos protein. Chronic nicotine SA significantly increased AVP mRNA signal and the number of pcPVN AVP-positive (AVP(+)) neurons (twofold to threefold), reduced the number of CRF-positive (CRF(+)) neurons by approximately 60%, but increased pcPVN CRF(+)/AVP(+) neuronal number fivefold. Significantly, although chronic nicotine SA did not affect total c-Fos expression induced by mFSS in pcPVN CRF(+) neurons, the majority of the new CRF(+)/AVP(+) population was activated by this heterotypic stressor. These phenotypic neuronal alterations may provide the pivotal mechanism underlying the capacity of chronically self-administered nicotine to cross-sensitize the HPA response to specific stressors, suggesting that nicotine may augment HPA responsiveness to specific stressors in human smokers.

  20. [Vasopressin for treatment of hemodynamic disorders].

    Science.gov (United States)

    Adukauskiene, Dalia; Sirvinskas, Edmundas; Kevelaitis, Egidijus

    2008-01-01

    Vasopressin is a 9-amino acid peptide synthesized by magnocellular neurons of the hypothalamus and released from posterior pituitary gland. The primary physiological role of vasopressin is the maintenance of fluid homeostasis. In this review, the classification of vasopressin receptors, namely V1 vascular, V2 renal, V3 pituitary, oxytocin receptors, and purinergic receptors, and the effects of vasopressin on vascular smooth muscles, the heart, and the kidneys are discussed. Mortality rates of vasodilatory (or distributive), for example septic shock, are high. The use of vasopressin is an alternative therapy for vasodilatory shock with better outcome. Vasopressin is effective in resuscitation of adults after ventricular fibrillation or pulseless tachycardia, when epinephrine is not effective.

  1. Distribution of oxytocin and vasopressin neurons in the diencephalon of the Japanese horseshoe bat, Rhinolophus ferrumequinum. An immunohistochemical study.

    Science.gov (United States)

    Kumamoto, K; Ebara, S; Matsuura, T; Kawata, M

    1992-01-01

    The distribution of oxytocin (OXT) and vasopressin (VP) neurons in the diencephalon of the hibernating Japanese horseshoe bat, Rhinolophus ferrumequinum, was immunohistochemically investigated by the avidin-biotin complex method. Magnocellular OXT and VP neurons were localized mainly in the paraventricular nucleus and the supraoptic nucleus. In addition to these main nuclei, both kinds of magnocellular neurons were also found in the periventricular nucleus, perifornical area and lateral hypothalamic area. Extensively distributed parvocellular neurons containing only VP were observed in the rostral and middle portions of the suprachiasmatic nucleus. The size of OXT and VP magnocellular neurons was almost equal in the paraventricular and ventromedial supraoptic nuclei, whereas VP neurons were significantly larger than OXT neurons in the dorsolateral supraoptic nucleus. The OXT and VP cells in the ventral supraoptic nucleus showed a distinctive elliptical shape. Both OXT and VP fibers were distributed in the lateral habenular nucleus, stria medullaris thalami, lateral preoptic area, stria terminalis, and medial and supracapsular part of the bed nucleus of the stria terminalis. Moreover, OXT fibers were found in the substantia nigra, and VP fibers were noted in the nucleus reunions and the paraventricular nucleus of the thalamus.

  2. Cholinergic regulation of the vasopressin neuroendocrine system

    Energy Technology Data Exchange (ETDEWEB)

    Michels, K.M.

    1987-01-01

    To clarify the physical and functional relationship between the cholinergic system, and the neurodocrine cells of the supraoptic nucleus, a combination of experiments on receptor binding, localization and function were carried out. The putative nicotinic receptor probe (/sup 125/I)alpha bungarotoxin ((/sup 125/I)alpha BTX) bound with high affinity and specificity to the vasopressin and oxytocin magnocellular neurons of the supraoptic nucleus, nucleus circularis, and paraventricular nucleus. Binding of (/sup 125/I)alpha BTX within the neural lobe was very low. In contrast, the muscarinic cholinergic receptor probe (/sup 3/H)quinuclidinylbenzilate ((/sup 3/H)QNB) did not bind to magnocellular vasopressin and oxytocin cell groups. The median eminence, which contains the neurosecretory axons, and the neural lobe of the pituitary contain low levels of (/sup 3/H)QNB binding. The physiological significance of these cholinergic receptors in regulation of vasopressin release was tested using an in vitro preparation of the supraoptic - neural lobe system.

  3. Do “Magnocellular Tasks” Measure “Magnocellular Function”?

    Directory of Open Access Journals (Sweden)

    Patrick T Goodbourn

    2012-05-01

    Full Text Available Magnocellular deficit theories propose that certain cognitive disorders, such as developmental dyslexia, arise from a generalised deficit in the visual dorsal–magnocellular system and its auditory homologue. Psychophysical tasks requiring rapid temporal processing are often used to probe magnocellular function in this context. However, it is not clear whether performance on these various tasks is actually supported by a common substrate. This study investigated whether different putative measures of magnocellular function produce mutually consistent results, and thus evaluated the extent to which they target the same neural mechanisms. Within the PERGENIC project, 1060 participants completed four psychophysical tasks: detection of ‘frequency-doubled’ gratings (FD; detection of pulsed gratings of low spatial frequency on a steady luminance pedestal (SP; detection of coherent motion (CM; and auditory discrimination of temporal order (TO. Although all measures exhibited good test–retest reliability, only the correlation between the two grating detection tasks was of notable magnitude (FD–SP; ρ = .39; other correlations between measures were poor to modest, ranging from ρ = .06 to .20. For each measure, we also identified a group of participants with very low sensitivity, but found only limited consistency between these putative ‘magnocellular deficit’ groups. Our results suggest that performance on each of these measures is primarily determined by a different neural substrate. Accordingly, we recommend against interpreting such psychophysical tasks as general measures of ‘magnocellular function’. [Supported by the Gatsby Charitable Foundation.

  4. A Population Model of Vasopressin Secretion

    OpenAIRE

    Durie, Ruth Frances

    2008-01-01

    Computer modelling is a powerful tool for clarifying and testing theory. In neuroscience, this often means replicating firing patterns. Models need evaluation functions to quantify the significance of features in the firing patterns, but usually the effect of firing is insufficiently understood. The magnocellular vasopressin neurons of the hypothalamus do have an output that is both well understood and quantifiable: they secrete a hormone into the bloodstream in proportion to blood osmol...

  5. Osmotic Stress Induces Transcriptional Changes in Vasopressin and Vasopressin 1b Receptor Gene Expression

    Science.gov (United States)

    2000-08-29

    the extracellular space and into the plasma through fenestrated capillaries surrounding the nerve terminals. The release ofAVP is coupled to vasopressin... vesicles . ~1utations that disrupt membrane localization ofaquaporin were described by Deen and colleagues in 1994 (Deen et al., 1994), and more recently...COIlUS straitus venoms . J. Bioi. Chem. 262: 15821-15824. Dayanithi, G., N. Sabatier, and H. Widmer. 2000. Intracellular calcium signalling in magnocellular

  6. New aspects of firing pattern autocontrol in oxytocin and vasopressin neurones.

    Science.gov (United States)

    Moos, F; Gouzènes, L; Brown, D; Dayanithi, G; Sabatier, N; Boissin, L; Rabié, A; Richard, P

    1998-01-01

    In the rat, oxytocin (OT) and vasopressin (AVP) neurones exhibit specific electrical activities which are controlled by OT and AVP released from soma and dendrites within the magnocellular hypothalamic nuclei. OT enhances amplitude and frequency of suckling-induced bursts, and changes basal firing characteristics: spike patterning becomes very irregular (spike clusters separated by long silences), firing rate is highly variable, oscillating before facilitated bursts. This unstable behaviour which markedly decreases during hyperosmotic stimulation (interrupting bursting) could be a prerequisite for bursting. The effects of AVP depend on the initial phasic pattern of AVP neurones: AVP excites weakly active neurones (increasing burst duration, decreasing silences) and inhibits highly active neurones; neurones with intermediate phasic activity are unaffected. Thus, AVP ensures all AVP neurones discharge with moderate phasic activity (bursts and silences lasting 20-40 s), known to optimise systemic AVP release. V1a-type receptors are involved in AVP actions. In conclusion, OT and AVP control their respective neurones in a complex manner to favour the patterns of activity which are the best suited for an efficient systemic hormone release.

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

    Directory of Open Access Journals (Sweden)

    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

  8. Hypothalamic Vasopressinergic Projections Innervate Central Amygdala GABAergic Neurons: Implications for Anxiety and Stress Coping.

    Science.gov (United States)

    Hernández, Vito S; Hernández, Oscar R; Perez de la Mora, Miguel; Gómora, María J; Fuxe, Kjell; Eiden, Lee E; Zhang, Limei

    2016-01-01

    The arginine-vasopressin (AVP)-containing hypothalamic magnocellular neurosecretory neurons (VPMNNs) are known for their role in hydro-electrolytic balance control via their projections to the 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 receptor mRNAs were not detected, using the same method. Water-deprivation (WD) for 24 h, which increased the metabolic activity of VPMNNs, also increased anxiety-like behavior measured using the elevated plus maze (EPM) test, and this effect was mimicked by bilateral microinfusion of AVP into the CeA. Anxious behavior induced by either WD or AVP infusion was reversed by CeA infusion of V1a antagonist. VPMNNs are thus a newly discovered source of CeA inhibitory circuit modulation, through which both early-life and adult stress coping signals are conveyed from the hypothalamus to the amygdala.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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.

  11. 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.

  12. Hypothalamic tumor

    Science.gov (United States)

    Hypothalamic glioma; Hypothalamus - tumor ... The exact cause of hypothalamic tumors is not known. It is likely that they result from a combination of genetic and environmental factors. In children, ...

  13. 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.

  14. Incidence of dye coupling among magnocellular paraventricular nucleus neurons in male rats is testosterone dependent.

    Science.gov (United States)

    Cobbett, P; Yang, Q Z; Hatton, G I

    1987-03-01

    Recently published work in the rat has shown that: the incidence of electrical coupling, as measured by dye coupling, is decreased from control levels by 8 days of drinking hypertonic saline; an index of circulating testosterone, seminal vesicle weight, is also decreased by 8 days of saline drinking; and both plasma and urinary vasopressin levels are reduced in castrated males, but can be returned to normal with testosterone replacement. These findings have led to the hypothesis that dye coupling, particularly that involving vasopressinergic cells, may be affected by gonadal steroids. We have investigated the effects of castration and testosterone replacement on the incidence of dye coupling among the neurons of the predominantly vasopressinergic magnocellular lateral paraventricular nucleus in slices of male rat hypothalamus. Incidence of dye coupling in this nucleus of castrated rats was found to be decreased by 67% from sham castrated control levels. Testosterone-filled Silastic capsules (but not empty capsules) implanted subcutaneously at the time of castration abolished the effect of castration on dye coupling. We conclude that testosterone has a powerful influence upon coupling among PVN vasopressinergic neurons and may participate in the control of vasopressin release in intact animals.

  15. Distribution of hypophysiotropic thyrotropin-releasing hormone (TRH)-synthesizing neurons in the hypothalamic paraventricular nucleus of the mouse.

    Science.gov (United States)

    Kádár, Andrea; Sánchez, Edith; Wittmann, Gábor; Singru, Praful S; Füzesi, Tamás; Marsili, Alessandro; Larsen, P Reed; Liposits, Zsolt; Lechan, Ronald M; Fekete, Csaba

    2010-10-01

    Hypophysiotropic thyrotropin-releasing hormone (TRH) neurons, the central regulators of the hypothalamic-pituitary-thyroid axis, are located in the hypothalamic paraventricular nucleus (PVN) in a partly overlapping distribution with non-hypophysiotropic TRH neurons. The distribution of hypophysiotropic TRH neurons in the rat PVN is well understood, but the localization of these neurons is unknown in mice. To determine the distribution and phenotype of hypophysiotropic TRH neurons in mice, double- and triple-labeling experiments were performed on sections of intact mice, and mice treated intravenously and intraperitoneally with the retrograde tracer Fluoro-Gold. TRH neurons were located in all parts of the PVN except the periventricular zone. Hypophysiotropic TRH neurons were observed only at the mid-level of the PVN, primarily in the compact part. In this part of the PVN, TRH neurons were intermingled with oxytocin and vasopressin neurons, but based on their size, the TRH neurons were parvocellular and did not contain magnocellular neuropeptides. Co-localization of TRH and cocaine- and amphetamine-regulated transcript (CART) were observed only in areas where hypophysiotropic TRH neurons were located. In accordance with the morphological observations, hypothyroidism increased TRH mRNA content of neurons only at the mid-level of the PVN. These data demonstrate that the distribution of hypophysiotropic TRH neurons in mice is vastly different from the pattern in rats, with a dominant occurrence of these neurosecretory cells in the compact part and adjacent regions at the mid-level of the PVN. Furthermore, our data demonstrate that the organization of the PVN is markedly different in mice and rats.

  16. Inhibition of the Jak-STAT pathway prevents CNTF-mediated survival of axotomized oxytocinergic magnocellular neurons in organotypic cultures of the rat supraoptic nucleus

    Science.gov (United States)

    Askvig, Jason M.; Lo, David Y.; Sudbeck, Adam W.; Behm, Kathryn E.; Leiphon, Laura J.; Watt, John A.

    2012-01-01

    Previous studies have demonstrated that ciliary neurotrophic factor (CNTF) enhances survival and process outgrowth from magnocellular neurons in the paraventricular (PVN) and the supraoptic (SON) nuclei. However, the mechanisms by which CNTF facilitates these processes remain to be determined. Therefore, the aim of this study was to identify the immediate signal transduction events that occur within the rat SON following administration of exogenous rat recombinant CNTF (rrCNTF) and to determine the contribution of those intracellular signaling pathway(s) to neuronal survival and process outgrowth, respectively. Immunohistochemical and Western blot analysis demonstrated that axonal injury and acute unilateral pressure injection of 100 ng/μl of rrCNTF directly over the rat SON resulted in a rapid and transient increase in phosphorylated-STAT3 (pSTAT3) in astrocytes but not neurons in the SON in vivo. Utilizing rat hypothalamic organotypic explant cultures, we then demonstrated that administration of 25 ng/ml rrCNTF for 14 days significantly increased the survival and process outgrowth of OT magnocellular neurons. In addition, pharmacological inhibition of the Jak-STAT pathway via AG490 and cucurbitacin I significantly reduced the survival of OT magnocellular neurons in the SON and PVN; however, the contribution of the Jak-STAT pathway to CNTF-mediated process outgrowth remains to be determined. Together, these data indicate that CNTF-induced survival of OT magnocellular neurons is mediated indirectly through astrocytes via the Jak-STAT signaling pathway. PMID:23123407

  17. Projections from bed nuclei of the stria terminalis, magnocellular nucleus: implications for cerebral hemisphere regulation of micturition, defecation, and penile erection.

    Science.gov (United States)

    Dong, Hong-Wei; Swanson, Larry W

    2006-01-01

    The basic structural organization of axonal projections from the small but distinct magnocellular and ventral nuclei (of the bed nuclei of the stria terminalis) was analyzed with the Phaseolus vulgaris leucoagglutinin anterograde tract tracing method in adult male rats. The former's overall projection pattern is complex, with over 80 distinct terminal fields ipsilateral to injection sites. Innervated regions in the cerebral hemisphere and brainstem fall into nine general functional categories: cerebral nuclei, behavior control column, orofacial motor-related, humorosensory/thirst-related, brainstem autonomic control network, neuroendocrine, hypothalamic visceromotor pattern-generator network, thalamocortical feedback loops, and behavioral state control. The most novel findings indicate that the magnocellular nucleus projects to virtually all known major parts of the brain network that controls pelvic functions, including micturition, defecation, and penile erection, as well as to brain networks controlling nutrient and body water homeostasis. This and other evidence suggests that the magnocellular nucleus is part of a corticostriatopallidal differentiation modulating and coordinating pelvic functions with the maintenance of nutrient and body water homeostasis. Projections of the ventral nucleus are a subset of those generated by the magnocellular nucleus, with the obvious difference that the ventral nucleus does not project detectably to Barrington's nucleus, the subfornical organ, the median preoptic and parastrial nuclei, the neuroendocrine system, and midbrain orofacial motor-related regions.

  18. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Fernstrom, J.D.; Fernstrom, M.H.; Kwok, R.P. (Univ. of Pittsburgh School of Medicine, PA (USA))

    1990-04-01

    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.

  20. 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

  1. 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.

  2. 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...

  3. Distribution of MT1 melatonin receptor immunoreactivity in the human hypothalamus and pituitary gland: colocalization of MT1 with vasopressin, oxytocin, and corticotropin-releasing hormone.

    Science.gov (United States)

    Wu, Ying-Hui; Zhou, Jiang-Ning; Balesar, Rawien; Unmehopa, Unga; Bao, Aimin; Jockers, Ralf; Van Heerikhuize, Joop; Swaab, Dick F

    2006-12-20

    Melatonin is implicated in numerous physiological processes, including circadian rhythms, stress, and reproduction, many of which are mediated by the hypothalamus and pituitary. The physiological actions of melatonin are mainly mediated by melatonin receptors. We here describe the distribution of the melatonin receptor MT1 in the human hypothalamus and pituitary by immunocytochemistry. MT1 immunoreactivity showed a widespread pattern in the hypothalamus. In addition to the area of the suprachiasmatic nucleus (SCN), a number of novel sites, including the paraventricular nucleus (PVN), periventricular nucleus, supraoptic nucleus (SON), sexually dimorphic nucleus, the diagonal band of Broca, the nucleus basalis of Meynert, infundibular nucleus, ventromedial and dorsomedial nucleus, tuberomamillary nucleus, mamillary body, and paraventricular thalamic nucleus were observed to have neuronal MT1 receptor expression. No staining was observed in the nucleus tuberalis lateralis and bed nucleus of the stria terminalis. The MT1 receptor was colocalized with some vasopressin (AVP) neurons in the SCN, colocalized with some parvocellular and magnocellular AVP and oxytocine (OXT) neurons in the PVN and SON, and colocalized with some parvocellular corticotropin-releasing hormone (CRH) neurons in the PVN. In the pituitary, strong MT1 expression was observed in the pars tuberalis, while a weak staining was found in the posterior and anterior pituitary. These findings provide a neurobiological basis for the participation of melatonin in the regulation of various hypothalamic and pituitary functions. The colocalization of MT1 and CRH suggests that melatonin might directly modulate the hypothalamus-pituitary-adrenal axis in the PVN, which may have implications for stress conditions such as depression.

  4. On Using Vernier Acuity to Assess Magnocellular Sensitivity

    Science.gov (United States)

    Skottun, Bernt C.; Skoyles, John R.

    2010-01-01

    A recent study [Keri, S., & Benedek, G. (2009). Visual pathway deficit in female fragile x premutation carriers: A potential endophenotype. "Brain and Cognition", 69, 291-295] has found Vernier acuity deficiencies together with contrast sensitivity defects consistent with a magnocellular deficit in female fragile x premutation carriers. This may…

  5. Polycystic Kidney Disease and the Vasopressin Pathway

    NARCIS (Netherlands)

    van Gastel, Maatje D. A.; Torres, Vicente E.

    Vasopressin, also known as arginine vasopressin or antidiuretic hormone, plays a pivotal role in maintaining body homeostasis. Increased vasopressin concentrations, measured by its surrogate copeptin, have been associated with disease severity as well as disease progression in polycystic kidney

  6. 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.

  7. Gene regulation in the magnocellular hypothalamo-neurohypophysial system

    NARCIS (Netherlands)

    Burbach, JPH; Luckman, SM; Murphy, D; Gainer, H

    The hypothalamo-neurohypophysial system (HNS) is the major peptidergic neurosecretory system through which the brain controls peripheral physiology. The hormones vasopressin and oxytocin released from the HNS at the neurohypophysis serve homeostatic functions of water balance and reproduction. From

  8. Visual-evoked response, pattern electroretinogram, and psychophysical magnocellular thresholds in glaucoma, optic atrophy, and dyslexia

    National Research Council Canada - National Science Library

    Vaegan; Hollows, F C

    2006-01-01

    ...) and psychophysical thresholds to the same stimulus, designed to be optimal for the magnocellular system, in suspects and patients with early glaucoma, patients with optic nerve disease, dyslexic...

  9. 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.

    2015-01-01

    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-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. PMID:25670790

  10. Vernier Acuity and the Magnocellular System Revisited: Response to Skottun and Skoyles

    Science.gov (United States)

    Keri, Szabolcs; Benedek, Gyorgy

    2010-01-01

    Skottun and Skoyles (2009) recently presented a comment on Vernier acuity and magnocellular dysfunctions in fragile X premutation carriers (Keri & Benedek, 2009). The authors concluded that our finding that the magnocellular deficit, as revealed by luminance-contrast sensitivity measurements, is associated with impaired Vernier acuity for…

  11. Efects of plasma corticosteroid concentration on the osmotic threshold for vasopressin releasing in Chagas' disease

    Directory of Open Access Journals (Sweden)

    Tatsuto Kimachi

    1983-09-01

    Full Text Available The osmotic threshold for vasopressin release was studied in normal patients (n = 7 and in patients with the chronic form of Chagas'disease (n = 11. Positive correlation between osmotic threshold and plasma cortisol concentration was obtained for the Controls (y1 = 273,30 + 0,75x i; r = 0,78;P < 0,05, suggesting a modulating effect of cortisol on vasopressin release. The lack of correlation between the two parameters for the chronic chagasic patients was interpreted, on the basis of the general denervation associated with Chagas ' disease, to be the result of neuronal destruction in hypothalamic and/or extrahypothalamic centers related to the secretory control of vasopressin.

  12. [Mutations in the arginine vasopressin neurophysin-II gene in familial neurohypophyseal diabetes insipidus patients].

    Science.gov (United States)

    Peralta-Leal, Valeria; Durán-González, Jorge; Leal-Ugarte, Evelia

    2008-01-01

    Neurogenic diabetes insipidus (NDI) is a rare condition characterized by polyuria and polydipsia caused by deficient arginine vasopressin hormone production. More than a 50 mutations have been identified for familial autosomic dominant neurogenic diabetes insipidus (FadNDI). These mutations can cause citotoxicity and lead to the degeneration of magnocellular neurons of the hipofisis by aberrant protein accumulation. The NDI diagnosis is based on the water deprivation test, quantification of AVP hormone and Magnetic Resonance Image (MRI), and in families with history of FadNDI has been suggested the molecular analysis of mutation in the arginine vasopressin neurophisin II gene before the signs and symptoms development, with the purpose of offering a suitable diagnosis, clinical follow up and treatment. The treatment with a synthetic analogue of AVP hormone allows the remission of the signs and symptoms in NDI patients and the advances in gene therapy in animal models has been promising, as much for NDI as for other diseases in which the mutant protein production has been involved.

  13. Nitric Oxide Modulates HCN Channels in Magnocellular Neurons of the Supraoptic Nucleus of Rats by an S-Nitrosylation-Dependent Mechanism.

    Science.gov (United States)

    Pires da Silva, Melina; de Almeida Moraes, Davi José; Mecawi, André de Souza; Rodrigues, José Antunes; Varanda, Wamberto Antonio

    2016-11-02

    The control of the excitability in magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus has been attributed mainly to synaptic inputs from circunventricular organs. However, nitric oxide (NO), a gaseous messenger produced in this nucleus during isotonic and short-term hypertonic conditions, is an example of a modulator that can act directly on MNCs to modulate their firing rate. NO inhibits the electrical excitability of MNCs, leading to a decrease in the release of vasopressin and oxytocin. Although the effects of NO on MNCs are well established, the mechanism by which this gas produces its effect is, so far, unknown. Because NO acts independently of synaptic inputs, we hypothesized that ion channels present in MNCs are the targets of NO. To investigate this hypothesis, we used the patch-clamp technique in vitro and in situ to measure currents carried by hyperpolarization-activated and nucleotide-gated cation (HCN) channels and establish their role in determining the electrical excitability of MNCs in rats. Our results show that blockade of HCN channels by ZD7288 decreases MNC firing rate with significant consequences on the release of OT and VP, measured by radioimmunoassay. NO induced a significant reduction in HCN currents by binding to cysteine residues and forming S-nitrosothiol complexes. These findings shed new light on the mechanisms that control the electrical excitability of MNCs via the nitrergic system and strengthen the importance of HCN channels in the control of hydroelectrolyte homeostasis. Cells in our organism live in a liquid environment whose composition and osmolality are maintained within tight limits. Magnocellular neurons (MNCs) of the supra optic nucleus can sense osmolality and control the synthesis and secretion of vasopressin (VP) and oxytocin (OT) by the neurohypophysis. OT and VP act on the kidneys controlling the excretion of water and sodium to maintain homeostasis. Here we combined electrophysiology, molecular

  14. Hypothalamic neurosecretory and circadian vasopressinergic neuronal systems in the blind cone-rod homeobox knock out mouse (Crx(-/-) ) and the 129sv wild type mouse

    DEFF Research Database (Denmark)

    Rovsing, Louise; Rath, Martin Fredensborg; Møller, Morten

    2013-01-01

    Vasopressin (AVP) is both a neuroendocrine hormone located in magnocellular neurosecretory neurons of the hypothalamus of mammals but also a neurotransmitter/neuromodulator in the parvocellular suprachiasmatic nucleus (SCN). The SCN is the endogenous clock of the brain and exhibits a prominent...... circadian AVP-rhythm. We have in this study of the brown 129sv mouse and the visual blind cone-rod homeobox gene knock out mouse (Crx(-/-) ) with degeneration of the retinal rods and cones, but a preserved non-image forming optic system, studied the temporal Avp-expression in both the neurosecretory...

  15. Vasopressin – Emerging Importance in Sepsis

    African Journals Online (AJOL)

    QuickSilver

    currently being used in CPR, Septic shock, Post CPB shock and in other areas requiring a vasopressor. Vasopressin and Sepsis. Vasopressin's use in sepsis stemmed originally from Landry's observation in 1994 that patients in vasodilatory septic shock were very sensitive to the vasopressor action of infused Vaso- pressin.

  16. [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.

  17. 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.

  18. The Role of the Magnocellular and Parvocellular Pathways in the Attentional Blink

    Science.gov (United States)

    Nieuwenhuis, Sander; Jepma, Marieke; La Fors, Sabrina; Olivers, Christian N. L.

    2008-01-01

    The attentional blink refers to the transient impairment in perceiving the 2nd of two targets presented in close temporal proximity in a rapid serial visual presentation (RSVP) stream. The purpose of this study was to examine the effect on human attentional-blink performance of disrupting the function of the magnocellular pathway--a major…

  19. Mathematical impairment associated with high-contrast abnormalities in change detection and magnocellular visual evoked response.

    Science.gov (United States)

    Jastrzebski, Nicola R; Crewther, Sheila G; Crewther, David P

    2015-10-01

    The cause of developmental dyscalculia, a specific deficit in acquisition of arithmetic skills, particularly of enumeration, has never been investigated with respect to the patency of the visual magnocellular system. Here, the question of dysfunction of the afferent magnocellular cortical input and its dorsal stream projections was tested directly using nonlinear analysis of the visual evoked potential (VEP) and through the psychophysical ability to rapidly detect visual change. A group of young adults with self-reported deficiencies of arithmetical ability, showed marked impairment in magnitude estimation and enumeration performance-though not in lexical decision reaction times when compared with an arithmetically capable group controlled for age and handedness. Multifocal nonlinear VEPs were recorded at low (24 %) and high (96 %) contrast. First- and second-order VEP kernels were comparable between groups at low contrast, but not at high contrast. The mathematically impaired group showed an abnormal lack of contrast saturation in the shortest latency first-order peak (N60) and a delayed P100 positivity in the first slice of the second-order kernel. Both features have previously been argued to be physiological markers of magnocellular function. Mathematically impaired participants also performed worse on a gap paradigm change detection for digit task showing increased reaction times for high-contrast stimuli but not for low-contrast stimuli compared with controls. The VEP results give direct evidence of abnormality in the occipital processing of magnocellular information in those with mathematical impairment. The anomalous high visual contrast physiological and psychophysical performance suggests an abnormality in the inhibitory processes that normally result in saturation of contrast gain in the magnocellular system.

  20. Therapeutic applications of vasopressin in pediatric patients

    National Research Council Canada - National Science Library

    Agrawal, Amit; Singh, Vishal K; Varma, Amit; Sharma, Rajesh

    2012-01-01

    ...”, “shock”, “septic shock”, “vasodilatory shock”, “cardiac arrest”, and “resuscitation” for reports on vasopressin/terlipressin use in children and manual review of article bibliographies...

  1. Adipsic hypernatremia without hypothalamic lesions accompanied by autoantibodies to subfornical organ.

    Science.gov (United States)

    Hiyama, Takeshi Y; Utsunomiya, Akari N; Matsumoto, Masahito; Fujikawa, Akihiro; Lin, Chia-Hao; Hara, Keiichi; Kagawa, Reiko; Okada, Satoshi; Kobayashi, Masao; Ishikawa, Mayumi; Anzo, Makoto; Cho, Hideo; Takayasu, Shinobu; Nigawara, Takeshi; Daimon, Makoto; Sato, Tomohiko; Terui, Kiminori; Ito, Etsuro; Noda, Masaharu

    2017-05-01

    Adipsic (or essential) hypernatremia is a rare hypernatremia caused by a deficiency in thirst regulation and vasopressin release. In 2010, we reported a case in which autoantibodies targeting the sensory circumventricular organs (sCVOs) caused adipsic hypernatremia without hypothalamic structural lesions demonstrable by magnetic resonance imaging (MRI); sCVOs include the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), which are centers for the monitoring of body-fluid conditions and the control of water and salt intakes, and harbor neurons innervating hypothalamic nuclei for vasopressin release. We herein report three newly identified patients (3- to 8-year-old girls on the first visit) with similar symptoms. The common features of the patients were extensive hypernatremia without any sensation of thirst and defects in vasopressin response to serum hypertonicity. Despite these features, we could not detect any hypothalamic structural lesions by MRI. Immunohistochemical analyses using the sera of the three patients revealed that antibodies specifically reactive to the mouse SFO were present in the sera of all cases; in one case, the antibodies also reacted with the mouse OVLT. The immunoglobulin (Ig) fraction of serum obtained from one patient was intravenously injected into wild-type mice to determine whether the mice developed similar symptoms. Mice injected with a patient's Ig showed abnormalities in water/salt intake, vasopressin release, and diuresis, which resultantly developed hypernatremia. Prominent cell death and infiltration of reactive microglia was observed in the SFO of these mice. Thus, autoimmune destruction of the SFO may be the cause of the adipsic hypernatremia. This study provides a possible explanation for the pathogenesis of adipsic hypernatremia without demonstrable hypothalamus-pituitary lesions. © 2016 International Society of Neuropathology.

  2. [The role of oxytocin and vasopressin in central nervous system activity and mental disorders].

    Science.gov (United States)

    Wójciak, Paweł; Remlinger-Molenda, Agnieszka; Rybakowski, Janusz

    2012-01-01

    Oxytocin and vasopressin, "peptides of love and fear", except for their classic role in control of labor and breastfeeding and blood pressure regulation, are also implicated in various processes like sexual behaviours, social recognition and stress response. These hormones seems to be essential for appropriate and beneficial social interactions, play a very important role in maternal care and closeness, promote general trust and cooperation and prolong social memory. They also play a very important role in modulating fear and anxiety response, especially by regulating the hypothalamic-pituitary-adrenal axis and amygdala activity by its projections to the brain stem and hypothalamic structures. Both hormones, particularly oxytocin, appears to be activating sexual behaviour or is responsible for increased sexual arousal. Evidence from clinical trials suggests their potential role in pathogenesis of schizophrenia, depression, autism and addiction together with possible therapeutic use in the above conditions. In schizophrenia, patients with higher peripheral oxytocin levels showed less severe positive, general and social symptoms and better prosocial behaviours. Literature suggests that exogenous oxytocin may be effective as an adjunctive therapy for that illness. Some data suggest that naturally occurring autoantibodies reacting with oxytocin and vasopressin are involved in depression, eating disorders and conduct disorder genesis.

  3. The vasopressin V1b receptor modulates plasma corticosterone responses to dehydration-induced stress.

    Science.gov (United States)

    Roberts, E M; Pope, G R; Newson, M J F; Lolait, S J; O'Carroll, A-M

    2011-01-01

    Vasopressin V1b receptor knockout (V1b⁻/⁻) mice were used to investigate a putative role for the V1b receptor (V1bR) in fluid regulation and in the hypothalamic-neurohypophysial system (HNS) and hypothalamic-pituitary-adrenal (HPA) axis responses to osmotic stress induced by water deprivation (WD). Male wild-type and V1b⁻/⁻ mice were housed in metabolic cages to allow determination of water intake and urine volume and osmolality. When provided with food and water ad lib., spontaneous urine volume and urine osmolality did not differ between genotypes. Similarly, WD for 24 h caused comparable decreases in urine volume and increases in urine osmolality irrespective of genotype. WD resulted in an increase in plasma corticosterone concentration in wild-type animals; however, this WD-induced increase in plasma corticosterone was significantly attenuated in V1b⁻/⁻ mice. Comparable increases in neuronal activation, indicated by increased c-fos mRNA expression, and in vasopressin mRNA expression occurred in both the supraoptic nucleus and paraventricular nucleus (PVN) of wild-type and V1b⁻/⁻ mice following WD; however, the WD-induced decrease in corticotrophin-releasing hormone mRNA expression seen in the PVN of wild-type mice was not observed in the PVN of V1b⁻/⁻ mice. These data suggest that, although the vasopressin V1bR is not required for normal HNS function, it is necessary for a full HPA-axis response to the osmotic stress of WD. © 2010 The Authors. Journal of Neuroendocrinology © 2010 Blackwell Publishing Ltd.

  4. Angiotensin II in the paraventricular nucleus stimulates sympathetic outflow to the cardiovascular system and make vasopressin release in rat.

    Science.gov (United States)

    Khanmoradi, Mehrangiz; Nasimi, Ali

    2016-10-06

    The hypothalamic paraventricular nucleus (PVN) plays essential roles in neuroendocrine and autonomic functions, including cardiovascular regulation. It was shown that microinjection of angiotensin II (AngII) into the PVN produced a pressor response. In this study, we explored the probable mechanisms of this pressor response. AngII was microinjected into the PVN and cardiovascular responses were recorded. Then, the responses were re-tested after systemic injection of a ganglionic blocker, Hexamethonium, or a vasopressin V1 receptor blocker. Hexamethonium pretreatment (i.v.) greatly and significantly attenuated the pressor response to AngII, with no significant effect on heart rate, indicating that the sympathetic system is involved in the cardiovascular effect of AngII in the PVN. Systemic pretreatment (i.v.) with V1 antagonist greatly and significantly attenuated the pressor response to AngII, with no significant effect on heart rate, indicating that vasopressin release is involved in the cardiovascular effect of AngII in the PVN. Overall, we found that AngII microinjected into the PVN produced a pressor response mediated by the sympathetic system and vasopressin release, indicating that other than circulating AngII, endogenous AngII of the PVN increases the vasopressin release from the PVN. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Stereotaxic probabilistic maps of the magnocellular cell groups in human basal forebrain

    Science.gov (United States)

    Zaborszky, L.; Hoemke, L.; Mohlberg, H.; Schleicher, A.; Amunts, K.; Zilles, K.

    2008-01-01

    The basal forebrain contains several interdigitating anatomical structures, including the diagonal band of Broca, the basal nucleus of Meynert, the ventral striatum, and also cell groups underneath the globus pallidus that bridge the centromedial amygdala to the bed nucleus of the stria terminalis. Among the cell populations, the magnocellular, cholinergic corticopetal projection neurons have received particular attention due to their loss in Alzheimer’s disease. In MRI images, the precise delineation of these structures is difficult due to limited spatial resolution and contrast. Here, using microscopic delineations in ten human postmortem brains, we present stereotaxic probabilistic maps of the basal forebrain areas containing the magnocellular cell groups. Cytoarchitectonic mapping was performed in silver stained histological serial sections. The positions and the extent of the magnocellular cell groups within the septum (Ch1-2), the horizontal limb of the diagonal band (Ch3), and in the sublenticular part of the basal forebrain (Ch4) were traced in high-resolution digitized histological sections, 3D reconstructed, and warped to the reference space of the MNI single subject brain. The superposition of the cytoarchitectonic maps in the MNI brain shows the intersubject variability of the various Ch compartments and their stereotaxic position relative to other brain structures. Both the right and left Ch4 regions showed significantly smaller volumes when age was considered as a covariate. Probabilistic maps of compartments of the basal forebrain magnocellular system are now available as an open source reference for correlation with fMRI, PET, and structural MRI data of the living human brain. PMID:18585468

  6. C-terminals in the mouse branchiomotor nuclei originate from the magnocellular reticular formation.

    Science.gov (United States)

    Matsui, Toshiyasu; Hongo, Yu; Haizuka, Yoshinori; Kaida, Kenichi; Matsumura, George; Martin, Donna M; Kobayashi, Yasushi

    2013-08-26

    Large cholinergic synaptic boutons called "C-terminals" contact motoneurons and regulate their excitability. C-terminals in the spinal somatic motor nuclei originate from cholinergic interneurons in laminae VII and X that express a transcription factor Pitx2. Cranial motor nuclei contain another type of motoneuron: branchiomotor neurons. Although branchiomotor neurons receive abundant C-terminal projections, the neural source of these C-terminals remains unknown. In the present study, we first examined whether cholinergic neurons express Pitx2 in the reticular formation of the adult mouse brainstem, as in the spinal cord. Although Pitx2-positive cholinergic neurons were observed in the magnocellular reticular formation and region around the central canal in the caudal medulla, none was present more rostrally in the brainstem tegmentum. We next explored the origin of C-terminals in the branchiomotor nuclei by using biotinylated dextran amine (BDA). BDA injections into the magnocellular reticular formation of the medulla and pons resulted in the labeling of numerous C-terminals in the branchiomotor nuclei: the ambiguous, facial, and trigeminal motor nuclei. Our results revealed that the origins of C-terminals in the branchiomotor nuclei are cholinergic neurons in the magnocellular reticular formation not only in the caudal medulla, but also at more rostral levels of the brainstem, which lacks Pitx2-positive neurons. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Dye coupling in hypothalamic slices: dependence on in vivo hydration state and osmolality of incubation medium.

    Science.gov (United States)

    Cobbett, P; Hatton, G I

    1984-12-01

    Electrotonic coupling is one mechanism which may coordinate the electrophysiological activity of a population of neurons. By measuring the incidence of dye coupling, we have investigated whether conditions that stimulate hormone secretion by hypothalamic magnocellular neuroendocrine cells affect coupling between these neurons. Neurons in the magnocellular regions of the paraventricular nucleus (PVN), in slices prepared from normally hydrated or chronically dehydrated male rats, were intracellularly injected with the fluorescent dye Lucifer Yellow CH. The dye coupling index (DCI), the ratio of the number of dye-coupled neurons to the total number of filled cells, was determined for each treatment group. The DCI for slices from dehydrated animals incubated in 310 milliosmoles/kg of medium (0.121) was significantly lower than that for slices for hydrated animals incubated in medium of the same osmolality (0.333). This decrease was reversed when slices from dehydrates were incubated in medium having an osmolality of 340 milliosmoles/kg (DCI = 0.307). There was also evidence for an interaction between slices incubated in the same chamber: the DCI in slices from dehydrated animals was significantly higher (0.475) when slices from normally hydrated rats were also present in the incubation chamber. Based on these data and on cited evidence, we suggest that the osmolality of the extracellular fluid and the local concentration of sex steroid hormones may influence dye coupling in the PVN.

  8. 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.

  9. 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

  10. Insensitivity to Fearful Emotion for Early ERP Components in High Autistic Tendency Is Associated with Lower Magnocellular Efficiency

    Directory of Open Access Journals (Sweden)

    Adelaide Burt

    2017-10-01

    Full Text Available Low spatial frequency (LSF visual information is extracted rapidly from fearful faces, suggesting magnocellular involvement. Autistic phenotypes demonstrate altered magnocellular processing, which we propose contributes to a decreased P100 evoked response to LSF fearful faces. Here, we investigated whether rapid processing of fearful facial expressions differs for groups of neurotypical adults with low and high scores on the Autistic Spectrum Quotient (AQ. We created hybrid face stimuli with low and high spatial frequency filtered, fearful, and neutral expressions. Fearful faces produced higher amplitude P100 responses than neutral faces in the low AQ group, particularly when the hybrid face contained a LSF fearful expression. By contrast, there was no effect of fearful expression on P100 amplitude in the high AQ group. Consistent with evidence linking magnocellular differences with autistic personality traits, our non-linear VEP results showed that the high AQ group had higher amplitude K2.1 responses than the low AQ group, which is indicative of less efficient magnocellular recovery. Our results suggest that magnocellular LSF processing of a human face may be the initial visual cue used to rapidly and automatically detect fear, but that this cue functions atypically in those with high autistic tendency.

  11. Comparison of ex vivo stability of copeptin and vasopressin.

    Science.gov (United States)

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

    2017-06-27

    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. Blood of ten healthy volunteers was collected in EDTA tubes. Next, we studied the effect of various pre-analytical conditions on measured vasopressin and copeptin levels: centrifugation speed, short-term storage temperature and differences between whole blood and plasma, long-term storage temperature and repeated freezing and thawing. The acceptable change limit (ACL), indicating the maximal percentage change that can be explained by assay variability, was used as cut-off to determine changes in vasopressin and copeptin. The ACL was 25% for vasopressin and 19% for copeptin. Higher centrifugation speed resulted in lower vasopressin levels, whereas copeptin concentration was unaffected. In whole blood, vasopressin was stable up to 2 h at 25°C and 6 h at 4°C. In plasma, vasopressin was stable up to 6 h at 25°C and 24 h at 4°C. In contrast, copeptin was stable in whole blood and plasma for at least 24h at both temperatures. At -20°C, vasopressin was stable up to 1 month and copeptin for at least 4 months. Both vasopressin and copeptin were stable after 4 months when stored at -80°C and -150°C. Vasopressin concentration decreased after four freeze-thaw cycles, whereas copeptin concentration was unaffected. Vasopressin levels were considerably affected by pre-analytical conditions, while copeptin levels were stable. Therefore, a strict sample handling protocol for measurement of vasopressin is recommended.

  12. Estimation of Plasma Arginine Vasopressin Concentration Using ...

    African Journals Online (AJOL)

    olayemitoyin

    increase in plasma osmolality and increase in ADH and thirst. The purpose of this study was to estimate plasma arginine vasopressin (PAVP) using thirst perception (TP) and plasma osmolality (POSM) values before and at 60 minutes in control or euhydrate (group A, 0.0 ml/kg body weight of distilled water), hydrated (group ...

  13. 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.

  14. Inappropriate Vasopressin Secretion (SIADH) in Burned Patients

    Science.gov (United States)

    1983-03-01

    et al.: Role of vasopressin in his colleagues have once again set a very high standard for us the impaired water excretion of glucocorticoid ...were unable to define, that set in motion this persistent anti- diuresis . Subsequently, Leaf, Bartter, Santos, and Wrong DR. KHAN Z. SHIRANI

  15. Intravenous injection of Evans Blue labels magnocellular neuroendocrine cells of the rat supraoptic nucleus in situ and after dissociation.

    Science.gov (United States)

    Weiss, M L; Cobbett, P

    1992-01-01

    Previous work has demonstrated that intravenous injection of neuronal tracers, e.g. horseradish peroxidase or Fast Blue, can retrogradely label neurons in brain areas that project outside the blood-brain barrier, e.g. magnocellular neuroendocrine neurons of the hypothalamus. Here we have shown that 24 h after intravenous injection of the fluorescent retrograde tracer Evans Blue, the same population of magnocellular neuroendocrine neurons is labeled in the paraventricular, supraoptic and accessory magnocellular nuclei. Parvicellular neuroendocrine cells in the paraventricular nuclei are also labeled. Most Evans Blue-labeled magnocellular neuroendocrine cells in the supraoptic nucleus could be stained immunocytochemically for neurophysins, suggesting that these neurons continue to produce their peptide hormones after taking up the fluorescent dye. Ultrastructural observation of supraoptic cells retrogradely labeled with Evans Blue shows that 95% of the neurons appeared healthy. There was no ultrastructural evidence of degeneration, hyperstimulation, or interruption of the axoplasmic flow. Labeling the neuroendocrine cells with Evans Blue did not alter the size of magnocellular cells, the animal's fluid balance or ingestive behavior. Following enzymatic/mechanical dissociation of the supraoptic nucleus from animals that had been injected with Evans Blue 24 h previously, phase-bright neurons that often contained fluorescent material were observed, thus identifying these neurons as neuroendocrine. Recording from identified neuroendocrine cells showed that these neurons generated spontaneous or current-evoked overshooting action potentials with an afterhyperpolarization and had negative resting membrane potentials. Action potential broadening, a feature of magnocellular neurons, was observed during bursts of action potentials elicited by depolarizing current injection. Taken together, this work would suggest that Evans Blue is non-toxic at the doses used and that it

  16. 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......RNA and peptide level, AVP plasma concentration, and AVP-regulated renal transport protein abundances were measured. In male COX-2(-/-), basal urine output and water intake were elevated while urine osmolality was decreased compared with WT. Water deprivation resulted in lower urine osmolality, higher plasma...... 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...

  17. In situ hybridization of oxytocin messenger RNA: macroscopic distribution and quantitation in rat hypothalamic cell groups

    Energy Technology Data Exchange (ETDEWEB)

    Burbach, J.P.; Voorhuis, T.A.; van Tol, H.H.; Ivell, R.

    1987-05-29

    Oxytocin mRNA was detected in the rat hypothalamus by in situ hybridization to a single stranded /sup 35/S-labelled DNA probe and the distribution of oxytocin mRNA-containing cell groups was studied at the macroscopic level. Specificity of hybridization was confirmed by comparison to vasopressin mRNA hybridization in parallel tissue sections. Cell groups containing oxytocin mRNA were confined to a set of hypothalamic cell groups, i.c. the supraoptic, paraventricular, anterior commissural nuclei, nucleus circularis and scattered hypothalamic islets. These cell groups displayed similar densities of autoradiographic signals indicating that the oxytocin gene is expressed at approximately the same average level at these various sites.

  18. 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.

  19. Role of central and peripheral chemoreceptors in vasopressin secretion control.

    Science.gov (United States)

    Iovino, Michele; Guastamacchia, Edoardo; Giagulli, Vito Angelo; Fiore, Giorgio; Licchelli, Brunella; Iovino, Emanuela; Triggiani, Vincenzo

    2013-09-01

    In this review, we analyzed the role played by central and peripheral chemoreceptors (CHRs) in vasopressin (AVP) secretion control. Central neural pathways subserving osmotic and non-osmotic control of AVP secretion are strictly correlated to brain areas participating in chemoreception mechanisms. Among the different brain areas involved in central chemoreception, the most important site has been localized in the retrotrapezoid nucleus of the rostral ventrolateral medulla. These central CHRs are able to detect very small pH/CO2 fluctuations, participating in brain blood flow regulation, acid-base balance and blood pressure control. Decreases in arterial pH and increases in arterial pCO2 stimulate AVP release by the Supraoptic and Paraventricular Nuclei. Carotid CHRs transduce low arterial O2 tension into increased action potential activity, leading to bradycardia and coronary vasodilatation via vagal stimulation, and systemic vasoconstriction via catecholaminergic stimulation. Stimulation of carotid CHRs by hypoxia increases neurohypophyseal blood flow and AVP release, an effect inhibited by CHRs denervation. Two renal CHRs have been identified: Type R1 CHRs do not have a resting discharge but are activated by renal ischemia and hypotension; Type R2 CHRs have a resting discharge and respond to backflow of urine into the renal pelvis. Signals arising from renal CHRs modulate the activity of hypothalamic AVPergic neurons: activation of R1 and R2 CHRs, following increased intrapelvic pressure with solutions of mannitol, NaCl and KCl, produces a significant increase of AVP secretion and the same effect has been obtained by the intrarenal infusion of bradykinin, which excites afferent renal nerves, as well as by the electrical stimulation of these nerves.

  20. Interaction of a vasopressin antagonist with vasopressin receptors in the septum of the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Dorsa, D.M.; Brot, M.D.; Shewey, L.M.; Meyers, K.M.; Szot, P.; Miller, M.A.

    1988-01-01

    The ability of d(CH2)5-Tyr(Me)-arginine-8-vasopressin, an antagonist of peripheral pressoric (V1-type) vasopressin receptors, to label vasopressin binding sites in the septum of the rat brain was evaluated. Using crude membrane preparations from the septum, /sup 3/H-arginine-8-vasopressin (AVP) specifically labels a single class of binding sites with a Kd of 2.9 nM and maximum binding site concentration of 19.8 fmole/mg protein. /sup 3/H-Antag also labels a single class of membrane sites but with higher affinity (Kd = 0.47 nM) and lower capacity (10.1 fmole/mg protein) than /sup 3/H-AVP. The rank order of potency of various competitor peptides for /sup 3/H-AVP and /sup 3/H-Antag binding was similar. Oxytocin was 100-1,000 fold less potent than AVP in competing for binding with both ligands. /sup 3/H-AVP and /sup 3/H-Antag showed similar labeling patterns when incubated with septal tissue slices. Unlabeled Antag also effectively antagonized vasopressin-stimulated phosphatidylinositol hydrolysis in septal tissue slices.

  1. 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...

  2. Eliciting Dyslexic Symptoms in Proficient Readers by Simulating Deficits in Grapheme-to-Phoneme Conversion and Visuo-Magnocellular Processing

    Science.gov (United States)

    Tholen, Nicole; Weidner, Ralph; Grande, Marion; Amunts, Katrin; Heim, Stefan

    2011-01-01

    Among the cognitive causes of dyslexia, phonological and magnocellular deficits have attracted a substantial amount of research. Their role and their exact impact on reading ability are still a matter of debate, partly also because large samples of dyslexics are hard to recruit. Here, we report a new technique to simulate dyslexic symptoms in…

  3. Oxytocin and vasopressin: distinct receptors in myometrium

    Energy Technology Data Exchange (ETDEWEB)

    Guillon, G.; Balestre, M.N.; Roberts, J.M.; Bottari, S.P.

    1987-06-01

    The binding characteristics of (/sup 3/H)oxytocin (( /sup 3/H)OT) and (/sup 3/H)lysine vasopressin (( /sup 3/H)LVP) to nonpregnant human myometrium were investigated. Binding of both radioligands was saturable, time dependent, and reversible. Whereas (/sup 3/H)OT was found to bind to a single class of sites with high affinity (Kd, 1.5 +/- 0.4 (+/- SEM) nM) and low capacity (maximum binding (Bmax), 34 +/- 6 fmol/mg protein), (/sup 3/H)LVP bound to two classes of sites, one with high affinity (Kd, 2.2 +/- 0.1 nM) and low capacity (Bmax, 198 +/- 7 fmol/mg protein) and another with low affinity (Kd, 655 +/- 209 nM) and high capacity (Bmax, 5794 +/- 1616 fmol/mg protein). The binding of the labeled peptides also displayed a marked difference in sensitivity to Mg2+ and guanine nucleotides. These differences in binding characteristics as well as the differences in potency of analogs in competing for (/sup 3/H)OT and (/sup 3/H)LVP binding indicate the presence of distinct receptors for OT and vasopressin in human myometrium. Pharmacological characterization of the high affinity binding sites for (/sup 3/H)LVP indicated that these are of the V1 subtype. Although, as suggested by others, vasopressin and OT can bind to the same sites, the presence of distinct receptors for both peptides provides an explanation for the previously reported difference in myometrial responsiveness to OT and vasopressin.

  4. Arginine Vasopressin and Copeptin in Perinatology

    OpenAIRE

    Evers, Katrina Suzanne; Wellmann, Sven

    2016-01-01

    Arginine vasopressin (AVP) plays a major role in the homeostasis of fluid balance, vascular tonus, and the regulation of the endocrine stress response. The measurement of AVP levels is difficult due to its short half-life and laborious method of detection. Copeptin is a more stable peptide derived from the same precursor molecule, is released in an equimolar ratio to AVP, and has a very similar response to osmotic, hemodynamic, and stress-related stimuli. In fact, copeptin has been propagated...

  5. 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.

  6. 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

  7. Glucocorticoids suppress corticotropin-releasing hormone and vasopressin expression in human hypothalamic neurons

    NARCIS (Netherlands)

    Erkut, Z. A.; Pool, C.; Swaab, D. F.

    1998-01-01

    Glucocorticoids are widely used in clinical practice in a variety of immune-mediated and neoplastic diseases, mostly for their immunosuppressive, leukopenic, antiedematous, or malignancy-suppressive actions. However, their usage is limited because of serious and sometimes life-threatening

  8. Effects of early life stress on adult male aggression and hypothalamic vasopressin and serotonin

    NARCIS (Netherlands)

    Veenema, Alexa H.; Blume, Annegret; Niederle, Daniela; Buwalda, Bauke; Neumann, Inga D.

    Early life stress in humans enhances the risk for psychopathologies, including excessive aggression and violence. In rodents, maternal separation is a potent early life stressor inducing long-lasting changes in emotional and neuroendocrine responsiveness to stress, associated with depression- and

  9. Electrophysiological identification of the functional presynaptic nerve terminals on an isolated single vasopressin neurone of the rat supraoptic nucleus.

    Science.gov (United States)

    Ohbuchi, T; Yokoyama, T; Fujihara, H; Suzuki, H; Ueta, Y

    2010-05-01

    Release of arginine vasopressin (AVP) and oxytocin from magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) is under the control of glutamate-dependent excitation and GABA-dependent inhibition. The possible role of the synaptic terminals attached to SON neurones has been investigated using whole-cell patch-clamp recording in in vitro rat brain slice preparations. Recent evidence has provided new insights into the repercussions of glial environment modifications on the physiology of MNCs at the synaptic level in the SON. In the present study, excitatory glutamatergic and inhibitory GABAergic synaptic inputs were recorded from an isolated single SON neurone cultured for 12 h, using the whole-cell patch clamp technique. Neurones expressed an AVP-enhanced green fluorescent protein (eGFP) fusion gene in MNCs. In addition, native synaptic terminals attached to a dissociated AVP-eGFP neurone were visualised with synaptic vesicle markers. These results suggest that the function of presynaptic nerve terminals may be evaluated directly in a single AVP-eGFP neurone. These preparations would be helpful in future studies aiming to electrophysiologically distinguish between the functions of synaptic terminals and glial modifications in the SON neurones.

  10. [Hypothalamic dysfunction in obesity].

    Science.gov (United States)

    van de Sande-Lee, Simone; Velloso, Licio A

    2012-08-01

    Obesity, defined as abnormal or excessive fat accumulation that may impair life quality, is one of the major public health problems worldwide. It results from an imbalance between food intake and energy expenditure. The control of energy balance in animals and humans is performed by the central nervous system (CNS) by means of neuroendocrine connections, in which circulating peripheral hormones, such as leptin and insulin, provide signals to specialized neurons of the hypothalamus reflecting body fat stores, and induce appropriate responses to maintain the stability of these stores. The majority of obesity cases are associated with central resistance to both leptin and insulin actions. In experimental animals, high-fat diets can induce an inflammatory process in the hypothalamus, which impairs leptin and insulin intracellular signaling pathways, and results in hyperphagia, decreased energy expenditure and, ultimately, obesity. Recent evidence obtained from neuroimaging studies and assessment of inflammatory markers in the cerebrospinal fluid of obese subjects suggests that similar alterations may be also present in humans. In this review, we briefly present the mechanisms involved with the loss of homeostatic control of energy balance in animal models of obesity, and the current evidence of hypothalamic dysfunction in obese humans.

  11. Prolactin induces Egr-1 gene expression in cultured hypothalamic cells and in the rat hypothalamus.

    Science.gov (United States)

    Blume, Annegret; Torner, Luz; Liu, Ying; Subburaju, Sivan; Aguilera, Greti; Neumann, Inga D

    2009-12-11

    Prolactin (PRL), the major lactogenic hormone, acts also as neuromodulator and regulator of neuronal and glial plasticity in the brain. There is an increase in synthesis and release of PRL within the hypothalamus during peripartum and in response to stress. To identify mechanisms by which PRL induces neuroplasticity, we studied the ability of PRL to induce the transcription factor Egr-1 in the hypothalamic cell line, 4B, in vitro, and in specific neuronal cell types of the hypothalamus in vivo. PRL induced Egr-1 mRNA expression in 4B cells, an effect which was prevented by the MEK inhibitor, U0126. In vivo, intracerebroventricular PRL (1 microg) increased Egr-1 mRNA levels in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) of female rats. The increase in mRNA paralleled elevated Egr-1 protein expression in the PVN and SON. Double staining immunohistochemistry revealed Egr-1 localization in oxytocin neurons of the PVN and SON, but not in vasopressin neurons in these regions. In the dorsomedial PVN, a population of non-oxytocin or vasopressin cells localized in a region corresponding to corticotropin-releasing hormone neurons also showed marked Egr-1 immunoreactivity. The data suggest that PRL modulates plasticity in oxytocinergic neurons, through MAP kinase-dependent induction of Egr-1.

  12. 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.

  13. Human Neuroimaging of Oxytocin and Vasopressin in Social Cognition

    Science.gov (United States)

    Zink, Caroline F; Meyer-Lindenberg, Andreas

    2012-01-01

    The neuropeptides oxytocin and vasopressin have increasingly been identified as modulators of human social behaviors and associated with neuropsychiatric disorders characterized by social dysfunction, such as autism. Identifying the human brain regions that are impacted by oxytocin and vasopressin in a social context is essential to fully characterize the role of oxytocin and vasopressin in complex human social cognition. Advances in human non-invasive neuroimaging techniques and genetics have enabled scientists to begin to elucidate the neurobiological basis of the influence of oxytocin and vasopressin on human social behaviors. Here we review the findings to-date from investigations of the acute and chronic effects of oxytocin and vasopressin on neural activity underlying social cognitive processes using “pharmacological fMRI” and “imaging genetics”, respectively. PMID:22326707

  14. Differential colocalization of estrogen receptor β (ERβ) with oxytocin and vasopressin in the paraventricular and supraoptic nuclei of the female rat brain: An immunocytochemical study

    Science.gov (United States)

    Alves, Stephen E.; Lopez, Veronica; McEwen, Bruce S.; Weiland, Nancy G.

    1998-01-01

    Evidence exists for the localization of the newly identified estrogen receptor β (ERβ) within the rat paraventricular nucleus (PVN) and supraoptic nucleus (SON), regions which lack ERα. Presently, we investigate whether ERβ-like-immunoreactivity (-ir) is found within cells of several major neuropeptide systems of these regions. Young adult Sprague–Dawley rats were ovariectomized (OVX), and 1 week later half of the animals received estradiol-17β (E). Dual-label immunocytochemistry was performed on adjacent sections by using an ERβ antibody, followed by an antibody to either oxytocin (OT), arginine-vasopressin (AVP), or corticotropin releasing hormone. Nuclear ERβ-ir was identified within SON and retrochiasmatic SON, and in specific PVN subnuclei: medial parvicellular part, ventral and dorsal zones, dorsal and lateral parvicellular parts, and in the posterior magnocellular part, medial and lateral zones. However, the ERβ-ir within magnocellular areas was noticeably less intense. OT-/ERβ-ir colocalization was confirmed in neurons of the parvicellular subnuclei, in both OVX and OVX+E brains (≈50% of OT and 25% of ERβ-labeled cells between bregma −1.78 and −2.00). In contrast, few PVN parvicellular neurons contained both AVP- and ERβ-ir. As well, very little overlap was observed in the distribution of cells containing corticotropin releasing hormone- or ERβ-ir. In the SON, most nuclear ERβ-ir colocalized with AVP-ir, whereas few OT-/ERβ-ir dual-labeled cells were observed. These findings suggest that estrogen can directly modulate specific OT and AVP systems through an ERβ-mediated mechanism, in a tissue-specific manner. PMID:9501254

  15. Developmental Perspectives on Oxytocin and Vasopressin

    Science.gov (United States)

    Hammock, Elizabeth A D

    2015-01-01

    The related neuropeptides oxytocin and vasopressin are involved in species-typical behavior, including social recognition behavior, maternal behavior, social bonding, communication, and aggression. A wealth of evidence from animal models demonstrates significant modulation of adult social behavior by both of these neuropeptides and their receptors. Over the last decade, there has been a flood of studies in humans also implicating a role for these neuropeptides in human social behavior. Despite popular assumptions that oxytocin is a molecule of social bonding in the infant brain, less mechanistic research emphasis has been placed on the potential role of these neuropeptides in the developmental emergence of the neural substrates of behavior. This review summarizes what is known and assumed about the developmental influence of these neuropeptides and outlines the important unanswered questions and testable hypotheses. There is tremendous translational need to understand the functions of these neuropeptides in mammalian experience-dependent development of the social brain. The activity of oxytocin and vasopressin during development should inform our understanding of individual, sex, and species differences in social behavior later in life. PMID:24863032

  16. Evidence for a vasopressin receptor-GTP binding protein complex

    Energy Technology Data Exchange (ETDEWEB)

    Fitzgerald, T.J.; Uhing, R.J.; Exton, J.H.

    1986-05-01

    Plasma membranes from the livers of rats were able to hydrolyze the ..gamma..-phosphate from guanosine-5'-triphosphate (GTP). The rate of GTP hydrolysis could be decreased to 10% of its initial rate by the addition of adenosine-5'-triphosphate with a concomitant decrease in the K/sub m/ for GTP from approx. 10/sup -3/ M to 10/sup -6/ M. The low K/sub m/ GTPase activity was inhibited by the addition of nonhydrolyzable analogs of GTP. In addition, the GTPase activity was stimulated from 10 to 30% over basal by the addition of vasopressin. A dose dependency curve showed that the maximum stimulation was obtained with 10/sup -8/ M vasopressin. Identical results were obtained from plasma membranes that had been solubilized with 1% digitonin. When membranes that had been solubilized in the presence of (Phenylalanyl-3,4,5-/sup 3/H(N))vasopressin were subjected to sucrose gradient centrifugation, the majority of bound (/sup 3/H)vasopressin migrated with an approximate molecular weight of 300,000. Moreover, there was a GTPase activity that migrated with the bound (/sup 3/H)vasopressin. This peak of bound (/sup 3/H)vasopressin was decreased by 90% when the sucrose gradient centrifugation was run in the presence of 10/sup -5/ M guanosine-5'-O-(3-thiotriphosphate). These results support the conclusion that liver plasma membranes contain a GTP-binding protein that can complex with the vasopressin receptor.

  17. Magnocellular-Dorsal Pathway and Sub-Lexical Route in Developmental Dyslexia

    Directory of Open Access Journals (Sweden)

    Simone eGori

    2014-06-01

    Full Text Available Although developmental dyslexia (DD is frequently associate to a phonological deficit, the underlying neurobiological cause remain undetermined. One prominent hypothesis suggests a specific deficit in magnocellular-dorsal (M-D pathway. Here we investigated the visual M-D and parvocellular-ventral (P-V pathway in dyslexic and in chronological age and IQ-matched normally reading children by measuring dynamic (frequency doubling illusion and static stimuli sensibility, respectively. A specific deficit in M-D task was found. Importantly, the M-D deficit was selectively shown in poor phonological decoders. M-D deficit appears to be frequent because 75% of poor pseudo-word readers were at least 1 SD below the mean of the controls. Finally, a replication study by using a new group of poor phonological decoders and reading level controls suggests a possible role of M-D deficit in DD. These results showed that a M-D deficit might impair the sub-lexical mechanisms that are critical for reading development. The possible link between these findings and the oscillatory temporal sampling framework is discussed.

  18. 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.

  19. The visual magnocellular-dorsal dysfunction in Chinese children with developmental dyslexia impedes Chinese character recognition.

    Science.gov (United States)

    Zhao, Jing; Qian, Yi; Bi, Hong-Yan; Coltheart, Max

    2014-11-20

    The visual magnocellular-dorsal (M-D) deficit theory of developmental dyslexia (DD) is still highly debated. Many researchers have made great efforts to investigate the relationship between M-D dysfunction and reading disability. Given that visual analysis plays an important role in Chinese reading, the present study tried to examine how the M-D dysfunction affected Chinese character recognition in Chinese children with DD. Sixteen DD children with M-D deficit, fifteen DD children with normal M-D function and twenty-seven age-matched typically developing children participated in this study. A global/local decision task was adopted, in which we manipulated the spatial frequency of target characters to separate an M-D condition from an unfiltered condition. Results of reaction times and error rates showed that in the M-D condition both M-D normal dyslexics and controls exhibited a significant global precedence effect, with faster responses and lower error rates in global decision than in local decision. In contrast, this global advantage was absent for the M-D impaired dyslexics. Accordingly, we propose that the M-D impairment present in some but not all dyslexics might influence global recognition of Chinese characters in this subgroup of children with DD, which might be implicated in their difficulties in learning to read.

  20. Probing the magnocellular and parvocellular visual pathways in facial emotion perception in schizophrenia.

    Science.gov (United States)

    Jahshan, Carol; Wolf, Maor; Karbi, Yinnon; Shamir, Eyal; Rassovsky, Yuri

    2017-07-01

    Schizophrenia patients have well-established deficits in facial emotion perception, which contribute to their poor social functioning. A number of studies have related these deficits to a differential dysfunction in the magnocellular (M) versus parvocellular (P) visual pathway. We assessed 35 schizophrenia patients and 35 healthy individuals on an emotion identification task, in which facial stimuli were either unaltered (broad spatial frequency, BSF) or manipulated to contain only high (HSF) or low (LSF) spatial frequencies, thereby respectively biasing the visual system toward the P- or M- pathways. As expected, patients were less accurate and slower in recognizing emotions across all conditions, relative to controls. Performance was best in the BSF condition followed by the HSF and finally the LSF condition, in both groups. A significant group by spatial frequency interaction reflected a smaller magnitude of impairment in the HSF condition, compared to the other two conditions that preferentially engage the M-system. These findings are consistent with studies showing a differential M-pathway abnormality in schizophrenia with a less pronounced impairment in P-function. The current study suggests that patients have less difficulty extracting emotional content from faces when LSFs are attenuated and supports the need to remediate basic visual processing deficits in schizophrenia. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  1. HYPOTHALAMIC NEUROHORMONES AND IMMUNE RESPONSES

    Directory of Open Access Journals (Sweden)

    J. Luis eQuintanar

    2013-08-01

    Full Text Available The aim of this review is to provide a comprehensive examination of the current literature describing the neural-immune interactions, with emphasis on the most recent findings of the effects of neurohormones on immune system. Particularly, the role of hypothalamic hormones such as Thyrotropin-releasing hormone, Corticotropin-releasing hormone and Gonadotropin-releasing hormone. In the past few years, interest has been raised in extrapituitary actions of these neurohormones due to their receptors have been found in many non-pituitary tissues. Also, the receptors are present in immune cells, suggesting an autocrine or paracrine role within the immune system. In general, these neurohormones have been reported to exert immunomodulatory effects on cell proliferation, immune mediators release and cell function. The implications of these findings in understanding the network of hypothalamic neuropeptides and immune system are discussed.

  2. Hypothalamic obesity: causes, consequences, treatment.

    Science.gov (United States)

    Lustig, Robert H

    2008-12-01

    Hypothalamic obesity, or intractable weight gain after hypothalamic damage, is one of the most pernicious and agonizing late effects of CNS insult. Such patients gain weight even in response to 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 mimicing 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. Pharmacologic treatment is difficult, consisting of adrenergics to mimick sympathetic activity, or suppression of insulin secretion with octreotide, or both. Recently, bariatric surgery (Roux-en-Y gastric bypass, laparoscopic gastric banding, vagotomy) have also been attempted with variable results. Early and intensive management is required to stave off the obesity and its consequences.

  3. Hypothalamic signaling mechanisms in hypertension.

    Science.gov (United States)

    Carmichael, Casey Y; Wainford, Richard D

    2015-05-01

    The etiology of hypertension, a critical public health issue affecting one in three US adults, involves the integration of the actions of multiple organ systems, including the central nervous system. Increased activation of the central nervous system, driving enhanced sympathetic outflow and increased blood pressure, has emerged as a major contributor to the pathogenesis of hypertension. The hypothalamus is a key brain site acting to integrate central and peripheral inputs to ultimately impact blood pressure in multiple disease states that evoke hypertension. This review highlights recent advances that have identified novel signal transduction mechanisms within multiple hypothalamic nuclei (e.g., paraventricular nucleus, arcuate nucleus) acting to drive the pathophysiology of hypertension in neurogenic hypertension, angiotensin II hypertension, salt-sensitive hypertension, chronic intermittent hypoxia, and obesity-induced hypertension. Increased understanding of hypothalamic activity in hypertension has the potential to identify novel targets for future therapeutic interventions designed to treat hypertension.

  4. Magnocellular-dorsal pathway and sub-lexical route in developmental dyslexia.

    Science.gov (United States)

    Gori, Simone; Cecchini, Paolo; Bigoni, Anna; Molteni, Massimo; Facoetti, Andrea

    2014-01-01

    Although developmental dyslexia (DD) is frequently associate with a phonological deficit, the underlying neurobiological cause remains undetermined. Recently, a new model, called "temporal sampling framework" (TSF), provided an innovative prospect in the DD study. TSF suggests that deficits in syllabic perception at a specific temporal frequencies are the critical basis for the poor reading performance in DD. This approach was presented as a possible neurobiological substrate of the phonological deficit of DD but the TSF can also easily be applied to the visual modality deficits. The deficit in the magnocellular-dorsal (M-D) pathway - often found in individuals with DD - fits well with a temporal oscillatory deficit specifically related to this visual pathway. This study investigated the visual M-D and parvocellular-ventral (P-V) pathways in dyslexic and in chronological age and IQ-matched normally reading children by measuring temporal (frequency doubling illusion) and static stimuli sensitivity, respectively. A specific deficit in M-D temporal oscillation was found. Importantly, the M-D deficit was selectively shown in poor phonological decoders. M-D deficit appears to be frequent because 75% of poor pseudo-word readers were at least 1 SD below the mean of the controls. Finally, a replication study by using a new group of poor phonological decoders and reading level controls suggested a crucial role of M-D deficit in DD. These results showed that a M-D deficit might impair the sub-lexical mechanisms that are critical for reading development. The possible link between these findings and TSF 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. Outward potassium currents of supraoptic magnocellular neurosecretory cells isolated from the adult guinea-pig.

    Science.gov (United States)

    Hlubek, M D; Cobbett, P

    1997-07-01

    1. Several types of whole-cell outward K+ current recorded from magnocellular neurosecretory cells (MNCs) dissociated from the supraoptic nucleus of the adult guinea-pig were identified on the basis of their voltage dependence, kinetics, pharmacology and Ca2+ dependence. 2. The predominant K+ current evoked from a holding potential of -40 mV was slowly activating, long-lasting, tetraethylammonium (TEA) sensitive and showed little steady-state inactivation. Also, this current was reduced by extracellular Cd2+. These data suggest that in supraoptic MNCs classical Ca(2+)-insensitive, delayed rectifier channels (KV) and Ca(2+)-sensitive, non-inactivating channels (KCa) both contribute to the sustained current. 3. A transient, low-threshold K+ current, which was 4-aminopyridine (4-AP) sensitive and showed significant steady-state inactivation, was evoked along with the sustained current from a holding potential of -90 mV. Based on these characteristics, this current corresponds to the A-current (IK(A)) described in other neurons. 4. IK(A) was activated when Ca2+ influx was blocked or when Ca2+ was absent from the extracellular medium, suggesting that Ca2+ influx is not necessary for activation of the current. 5. In many recordings, a transient 4-AP-insensitive outward current was evoked from a holding potential of -40 mV. This high-threshold transient K+ current was abolished by extracellular Cd2+ or TEA and was absent when extracellular Ca2+ was replaced by Sr2+, suggesting that it is a transient Ca(2+)-dependent K+ current. 6. We conclude that the presence of multiple types of K+ current may, in part, underlie the complex firing patterns of oxytocinergic and vasopressinergic MNCs.

  7. P2-8: Applications of the Magnocellular Advantage Model: Developmental Aspects of Dorsal Stream Processing

    Directory of Open Access Journals (Sweden)

    Melanie Murphy

    2012-10-01

    Full Text Available Differential timing of the development of the dorsal and ventral visual streams is well accepted, with the latency of the M pathway to V1 not reaching adult levels until 10 years of age (Crewther et al., 1999 Electroencephalography and Clinical Neurophysiology 49 123–128. This could have major consequences for how children perceive and attend to the environment. Thus, how the later development of the dorsal visual stream impacts the transient visual processing abilities in children was investigated within a framework of the Magnocellular Advantage model of the mature visual system. Typically developing participants (N= 110 grouped as Younger Children (4–7 yrs, Older Children (10–13 yrs, and Adults (18–30 yrs completed a series of customised computer motion and form coherence tasks designed to provide a functional measure of dorsal/ventral pathway performance. Dorsal involvement in a traditionally ventrally dominated object-recognition task was achieved by biasing onset/offset conditions to preferentially stimulate the temporal characteristics of both pathways. Adults performed better than children on all tasks except motion coherence thresholds. A significant improvement in performance was seen between younger children and older groups on dorsal tasks (Motion Coherence and Navon Global Accuracy but not on all ventral tasks (Form Coherence and Navon Local Exposure Time. Results support earlier psychophysical and electrophysiological investigations indicating that the dorsal stream matures later than the ventral stream. Therefore, in young children the underdeveloped dorsal visual pathway may rely more on slower ventral stream visual processing, which has important implications for the perception and attentional processing of transient events.

  8. Oxytocin release in magnocellular nuclei: neurochemical mediators and functional significance during gestation

    Science.gov (United States)

    Armstrong, William E.; Crowley, William R.

    2010-01-01

    When released from dendrites within the supraoptic (SON) and paraventricular (PVN) nuclei (intranuclear release) during suckling, oxytocin exerts autocrine and paracrine effects on oxytocin neurons that are necessary for the unique timing and episodic pattern of oxytocin release into the systemic circulation that is characteristic of lactation. Recent reports have shown that stimulation of central noradrenergic and histaminergic receptors are both necessary for intranuclear release of oxytocin in response to suckling. In addition, in vitro studies indicate that excitatory amino acids may also be critical for central oxytocin secretion, although in vivo experiments have not provided direct support for this hypothesis. In addition to a critical role in intranuclear oxytocin release during lactation, norepinephrine has also been shown to stimulate central oxytocin during gestation. Stimulation of central oxytocin receptors during gestation appears critical for normal systemic oxytocin secretion in responses to suckling during the subsequent period of lactation. Oxytocin receptor blockade during pregnancy alters normal timing of systemic oxytocin release during suckling and reduces milk delivery. Several adaptations occur in the central oxytocin system that are necessary for determining the unique response characteristic observed during parturition and gestation. Central oxytocin receptor stimulation during gestation has been implicated in pregnancy-related morphological changes in magnocellular oxytocin neurons, disinhibition of oxytocin neurons to GABA, and adaptations in membrane response characteristics of oxytocin neurons. In conclusion, intranuclear oxytocin release during gestation and lactation are critical for establishing, and then evoking the unique pattern of systemic oxytocin secretion in response to the suckling offspring necessary for adequate milk delivery. Furthermore, activation of central noradrenergic receptors appears to be critical for release of

  9. A genomic atlas of mouse hypothalamic development

    Science.gov (United States)

    Shimogori, Tomomi; Lee, Daniel A; Miranda-Angulo, Ana; Yang, Yanqin; Wang, Hong; Jiang, Lizhi; Yoshida, Aya C; Kataoka, Ayane; Mashiko, Hiromi; Avetisyan, Marina; Qi, Lixin; Qian, Jiang; Blackshaw, Seth

    2014-01-01

    The hypothalamus is a central regulator of many behaviors that are essential for survival, such as temperature regulation, food intake and circadian rhythms. However, the molecular pathways that mediate hypothalamic development are largely unknown. To identify genes expressed in developing mouse hypothalamus, we performed microarray analysis at 12 different developmental time points. We then conducted developmental in situ hybridization for 1,045 genes that were dynamically expressed over the course of hypothalamic neurogenesis. We identified markers that stably labeled each major hypothalamic nucleus over the entire course of neurogenesis and constructed a detailed molecular atlas of the developing hypothalamus. As a proof of concept of the utility of these data, we used these markers to analyze the phenotype of mice in which Sonic Hedgehog (Shh) was selectively deleted from hypothalamic neuroepithelium and found that Shh is essential for anterior hypothalamic patterning. Our results serve as a resource for functional investigations of hypothalamic development, connectivity, physiology and dysfunction. PMID:20436479

  10. 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...

  11. 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.

  12. 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.

  13. Central Diabetes Insipidus in Infancy With or Without Hypothalamic Adipsic Hypernatremia Syndrome: Early Identification and Outcome.

    Science.gov (United States)

    Djermane, Adel; Elmaleh, Monique; Simon, Dominique; Poidvin, Amélie; Carel, Jean-Claude; Léger, Juliane

    2016-02-01

    Neonatal central diabetes insipidus (CDI) with or without adipsia is a very rare complication of various complex hypothalamic disorders. It is associated with greater morbidity and a high risk of developing both hypernatremia and hyponatremia, due to the condition itself or secondary to treatment with vasopressin analogs or fluid administration. Its outcomes have yet to be evaluated. To investigate the clinical outcomes of patients with neonatal-onset CDI or adipsic CDI with hypernatremia. All patients diagnosed with neonatal CDI in a university hospital-based observational study and followed between 2005 and 2015 were included and analyzed retrospectively. The various causes of CDI were grouped. Clinical outcome and comorbidities were analyzed. Ten of the 12 patients had an underlying condition with brain malformations: optic nerve hypoplasia (n = 3), septo-optic dysplasia (n = 2), semilobar holoprosencephaly (n = 1), ectopic neurohypophysis (n = 3), and unilateral absence of the internal carotid artery (n = 1). The other two were idiopathic cases. During the median follow-up period of 7.8 (4.9-16.8) years, all but one patient displayed anterior pituitary deficiency. Transient CDI was found in three (25%) patients for whom a posterior pituitary hyperintense signal was observed with (n = 2) and without (n = 1) structural hypothalamic pituitary abnormalities, and with no other underlying cerebral malformations. Patients with permanent CDI with persistent adipsia (n = 4) and without adipsia (n = 5) required adequate fluid intake and various doses of desamino-D-arginine-8-vasopressin. Those with adipsia were more likely to develop hypernatremia (45 vs 33%), hyponatremia (16 vs 4%) (P < .0001), and severe neurodevelopmental delay (P < .05) than those without adipsia. Comorbidities were common. The underlying cause remains unknown at the age of 23 years for one patient with CDI and normal thirst. Neonatal CDI may be transient or permanent. These vulnerable patients have

  14. 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.

  15. 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.

  16. 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.

  17. Examining the role of vasopressin in the modulation of parental and sexual behaviors

    Directory of Open Access Journals (Sweden)

    Josi Maria eZimmermann-Peruzatto

    2015-09-01

    Full Text Available Vasopressin (VP and VP-like neuropeptides are evolutionarily stable peptides found in all vertebrate species. In non-mammalian vertebrates, vasotocin (VT plays a role similar to mammalian VP, whereas mesotocin and isotocin are functionally similar to mammalian oxytocin (OT. Here, we review the involvement of VP in brain circuits, synaptic plasticity, evolution, and function, highlighting the role of VP in social behavior. In all studied species, VP is encoded on chromosome 20p13, and in mammals, VP is produced in specific hypothalamic nuclei and released by the posterior pituitary. The role of VP is mediated by the stimulation of the V1a, V2, and V1b receptors, as well as the oxytocinergic and purinergic receptors. VT and VP functions are usually related to osmotic and cardiovascular homeostasis when acting peripherally. However, these neuropeptides are also critically involved in the central modulation of social behavior displays, such as pairing recognition, pair-bonding, social memory, sexual behavior, parental care, maternal and aggressive behavior. Evidence suggests that these effects are primarily mediated by V1a receptor in specific brain circuits that provide important information for the onset and control of social behaviors in normal and pathological conditions.

  18. 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.

  19. Arginine vasopressin and copeptin in perinatology

    Directory of Open Access Journals (Sweden)

    Katrina Suzanne Evers

    2016-08-01

    Full Text Available Arginine vasopressin (AVP plays a major role in the homeostasis of fluid balance, vascular tonus and the regulation of the endocrine stress response. The measurement of AVP levels is difficult due to its short half-life and laborious method of detection. Copeptin is a more stable peptide derived from the same precursor molecule, is released in an equimolar ratio to AVP and has a very similar response to osmotic, hemodynamic and stress-related stimuli. In fact, copeptin has been propagated as surrogate marker to indirectly determine circulating AVP concentrations in various conditions. Here, we present an overview of the current knowledge on AVP and copeptin in perinatology with a particular focus on the baby’s transition from placenta to lung breathing. We performed a systematic review of the literature on fetal stress hormone levels, including norepinephrine, cortisol, AVP and copeptin, in regard to birth stress. Finally, diagnostic and therapeutic options for copeptin measurement and AVP functions are discussed.

  20. 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

  1. Bench-to-bedside review: Vasopressin in the management of septic shock

    Science.gov (United States)

    2011-01-01

    This review of vasopressin in septic shock differs from previous reviews by providing more information on the physiology and pathophysiology of vasopressin and vasopressin receptors, particularly because of recent interest in more specific AVPR1a agonists and new information from the Vasopressin and Septic Shock Trial (VASST), a randomized trial of vasopressin versus norepinephrine in septic shock. Relevant literature regarding vasopressin and other AVPR1a agonists was reviewed and synthesized. Vasopressin, a key stress hormone in response to hypotension, stimulates a family of receptors: AVPR1a, AVPR1b, AVPR2, oxytocin receptors and purinergic receptors. Rationales for use of vasopressin in septic shock are as follows: first, a deficiency of vasopressin in septic shock; second, low-dose vasopressin infusion improves blood pressure, decreases requirements for norepinephrine and improves renal function; and third, a recent randomized, controlled, concealed trial of vasopressin versus norepinephrine (VASST) suggests low-dose vasopressin may decrease mortality of less severe septic shock. Previous clinical studies of vasopressin in septic shock were small or not controlled. There was no difference in 28-day mortality between vasopressin-treated versus norepinephrine-treated patients (35% versus 39%, respectively) in VASST. There was potential benefit in the prospectively defined stratum of patients with less severe septic shock (5 to 14 μg/minute norepinephrine at randomization): vasopressin may have lowered mortality compared with norepinephrine (26% versus 36%, respectively, P = 0.04 within stratum). The result was robust: vasopressin also decreased mortality (compared with norepinephrine) if less severe septic shock was defined by the lowest quartile of arterial lactate or by use of one (versus more than one) vasopressor at baseline. Other investigators found greater hemodynamic effects of higher dose of vasopressin (0.06 units/minute) but also unique adverse

  2. SPAK Differentially Mediates Vasopressin Effects on Sodium Cotransporters

    Science.gov (United States)

    Saritas, Turgay; Borschewski, Aljona; McCormick, James A.; Paliege, Alexander; Dathe, Christin; Uchida, Shinichi; Terker, Andrew; Himmerkus, Nina; Bleich, Markus; Demaretz, Sylvie; Laghmani, Kamel; Delpire, Eric; Ellison, David H.

    2013-01-01

    Activation of the Na+-K+-2Cl−-cotransporter (NKCC2) and the Na+-Cl−-cotransporter (NCC) by vasopressin includes their phosphorylation at defined, conserved N-terminal threonine and serine residues, but the kinase pathways that mediate this action of vasopressin are not well understood. Two homologous Ste20-like kinases, SPS-related proline/alanine-rich kinase (SPAK) and oxidative stress responsive kinase (OSR1), can phosphorylate the cotransporters directly. In this process, a full-length SPAK variant and OSR1 interact with a truncated SPAK variant, which has inhibitory effects. Here, we tested whether SPAK is an essential component of the vasopressin stimulatory pathway. We administered desmopressin, a V2 receptor–specific agonist, to wild-type mice, SPAK-deficient mice, and vasopressin-deficient rats. Desmopressin induced regulatory changes in SPAK variants, but not in OSR1 to the same degree, and activated NKCC2 and NCC. Furthermore, desmopressin modulated both the full-length and truncated SPAK variants to interact with and phosphorylate NKCC2, whereas only full-length SPAK promoted the activation of NCC. In summary, these results suggest that SPAK mediates the effect of vasopressin on sodium reabsorption along the distal nephron. PMID:23393317

  3. Altered hypothalamic function in diet-induced obesity

    National Research Council Canada - National Science Library

    Velloso, L A; Schwartz, M W

    2011-01-01

    Energy homeostasis involves a complex network of hypothalamic and extra-hypothalamic neurons that transduce hormonal, nutrient and neuronal signals into responses that ultimately match caloric intake...

  4. The Effect of Renal Function and Hemodialysis Treatment on Plasma Vasopressin and Copeptin Levels

    NARCIS (Netherlands)

    Ettema, Esmée M; Heida, Judith; Casteleijn, Niek F; Boesten, Lianne; Westerhuis, Ralf; Gaillard, Carlo A J M; Gansevoort, Ron T; Franssen, Casper F M; Zittema, Debbie

    2017-01-01

    Introduction: Copeptin is increasingly used in epidemiological studies as a substitute for vasopressin. The effect of renal function per se on copeptin and vasopressin concentrations as well as their ratio have, however, not been well described. Methods: Copeptin and vasopressin levels were measured

  5. Copeptin, a surrogate marker of vasopressin, is associated with microalbuminuria in a large population cohort

    NARCIS (Netherlands)

    Meijer, Esther; Bakker, Stephan J. L.; Halbesma, Nynke; de Jong, Paul E.; Struck, Joachim; Gansevoort, Ron T.

    Urinary albumin excretion is a powerful predictor of progressive cardiovascular and renal disease. In rats and humans, administration of a synthetic vasopressin analogue, 1-desamino-8-D-arginine-vasopressin, increases urinary albumin excretion; however, it is unknown if endogenous vasopressin levels

  6. 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

  7. Bidirectional Anticipation of Future Osmotic Challenges by Vasopressin Neurons.

    Science.gov (United States)

    Mandelblat-Cerf, Yael; Kim, Angela; Burgess, Christian R; Subramanian, Siva; Tannous, Bakhos A; Lowell, Bradford B; Andermann, Mark L

    2017-01-04

    Ingestion of water and food are major hypo- and hyperosmotic challenges. To protect the body from osmotic stress, posterior pituitary-projecting, vasopressin-secreting neurons (VPpp neurons) counter osmotic perturbations by altering their release of vasopressin, which controls renal water excretion. Vasopressin levels begin to fall within minutes of water consumption, even prior to changes in blood osmolality. To ascertain the precise temporal dynamics by which water or food ingestion affect VPpp neuron activity, we directly recorded the spiking and calcium activity of genetically defined VPpp neurons. In states of elevated osmolality, water availability rapidly decreased VPpp neuron activity within seconds, beginning prior to water ingestion, upon presentation of water-predicting cues. In contrast, food availability following food restriction rapidly increased VPpp neuron activity within seconds, but only following feeding onset. These rapid and distinct changes in activity during drinking and feeding suggest diverse neural mechanisms underlying anticipatory regulation of VPpp neurons. Published by Elsevier Inc.

  8. Relaxation of human isolated mesenteric arteries by vasopressin and desmopressin.

    Science.gov (United States)

    Martínez, M C; Vila, J M; Aldasoro, M; Medina, P; Flor, B; Lluch, S

    1994-01-01

    1. The effects of vasopressin and deamino-8-D-arginine vasopressin (DDAVP, desmopressin) were studied in artery rings (0.8-1 mm in external diameter) obtained from portions of human omentum during the course of abdominal operations (27 patients). 2. In arterial rings under resting tension, vasopressin produced concentration-dependent, endothelium-independent contractions with an EC50 of 0.59 +/- 0.12 nM. The V1 antagonist d(CH2)5Tyr(Me)AVP (1 microM) and the mixed V1-V2 antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (0.01 microM) displaced the control curve to vasopressin to the right in a parallel manner without differences in the maximal responses. In the presence of indomethacin (1 microM) the contractile response to vasopressin was significantly increased (P < 0.01). 3. In precontracted arterial rings, previously treated with the V1 antagonist, d(CH2)5Tyr(Me)AVP (1 microM), vasopressin produced endothelium-dependent relaxation. This relaxation was reduced significantly (P < 0.05) by indomethacin (1 microM) and unaffected by the V1-V2 receptor antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (1 microM) or by NG-nitro-L-arginine methyl ester (L-NAME, 0.1 mM). 4. The selective V2 receptor agonist, DDAVP, caused endothelium-independent, concentration-dependent relaxations in precontracted arterial rings that were inhibited by the mixed V1-V2 receptor antagonist, but not by the V1 receptor antagonist or by pretreatment with indomethacin or L-NAME. 5. Results from this study suggest that vasopressin is primarily a constrictor of human mesenteric arteries by V1 receptor stimulation; vasopressin causes dilatation only during V1 receptor blockade. The relaxation appears to be mediated by the release of vasodilator prostaglandins from the endothelial cell layer and is independent of V2 receptor stimulation or release of nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7834191

  9. 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.

  10. 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...

  11. 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 ...

  12. 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 ap...

  13. Hyponatraemia in imported malaria: The pathophysiological role of vasopressin

    NARCIS (Netherlands)

    E.J. Hoorn (Ewout); M.E. van Wolfswinkel (Marlies); D.A. Hesselink (Dennis); Y.B. de Rijke (Yolanda); R. Koelewijn (Rob); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2012-01-01

    textabstractBackground. In the pathophysiology of hyponatraemia in malaria, the relative contribution of appropriate and inappropriate arginine vasopressin (AVP) release is unknown; the trigger for inappropriate AVP release is also unknown. Methods. Serum copeptin, a stable and sensitive marker for

  14. 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 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.

  15. 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

  16. Vasopressinergic regulation of the hypothalamic pituitary adrenal axis and stress adaptation.

    Science.gov (United States)

    Volpi, Simona; Rabadan-Diehl, Cristina; Aguilera, Greti

    2004-06-01

    Vasopressin (VP) stimulates pituitary ACTH secretion through interaction with receptors of the V1b subtype (V1bR, V3R), located in the plasma membrane of the pituitary corticotroph, mainly by potentiating the stimulatory effects of corticotropin releasing hormone (CRH). Chronic stress paradigms associated with corticotroph hyperresponsiveness lead to preferential expression of hypothalamic VP over CRH and upregulation of pituitary V1bR, suggesting an important role for VP during adaptation of the hypothalamic-pituitary-adrenal (HPA) axis to stress. Vasopressinergic regulation of ACTH secretion depends on the number of V1bRs as well as coupling of the receptor to phospholipase C (PLC) in the pituitary. Regulation of V1bR gene transcription may involve a number of regulatory elements in the promoter region, of which a GAGA box was shown to be essential. Although V1bR gene transcription is necessary to maintain V1bR mRNA levels, the lack of correlation between VP binding and V1bR mRNA suggests that regulation of mRNA translation is a major regulatory step of the number of V1bRs. V1bR translation appears to be under tonic inhibition by upstream minicistrons and positive regulation through protein kinase C (PKC) activation of an internal ribosome entry site (IRES) in the 5' untranslated region (5'UTR) of the mRNA. The data provide mechanisms by which regulation of hypothalamic VP and pituitary V1bR content contribute to controlling HPA axis activity during chronic stress.

  17. Novel aspects of hypothalamic-pituitary-adrenal axis regulation and glucocorticoid actions

    Science.gov (United States)

    Uchoa, Ernane Torres; Aguilera, Greti; Herman, James P.; Fiedler, Jenny L.; Deak, Terrence; Cordeiro de Sousa, Maria Bernardete

    2014-01-01

    Normal hypothalamic-pituitary-adrenal (HPA) axis activity leading to rhythmic and episodic release of adrenal glucocorticoids is essential for body homeostasis and survival during stress. Acting through specific intracellular receptors in the brain and periphery, glucocorticoids regulate behavior, metabolic, cardiovascular, immune, and neuroendocrine activities. In contrast to chronic elevated levels, circadian and acute stress-induced increases in glucocorticoids are necessary for hippocampal neuronal survival and memory acquisition and consolidation, through inhibiting apoptosis, facilitating glutamate transmission and inducing immediate early genes and spine formation. In addition to its metabolic actions leading to increasing energy availability, glucocorticoids have profound effects on feeding behavior, mainly through modulation of orexigenic and anorixegenic neuropeptides. Evidence is also emerging that in addition to the recognized immune suppressive actions of glucocorticoids by counteracting adrenergic proinflammatory actions, circadian elevations have priming effects in the immune system, potentiating acute defensive responses. In addition, negative feedback by glucocorticoids involves multiple mechanisms leading to limiting HPA axis activation and preventing deleterious effects of excessive glucocorticoid production. Adequate glucocorticoid secretion to meet body demands is tightly regulated by a complex neural circuitry controlling hypothalamic corticotrophin releasing hormone (CRH) and vasopressin secretion, the main regulators of pituitary adrenocorticotrophic hormone (ACTH). Rapid feedback mechanisms, likely involving non-genomic actions of glucocorticoids, mediate immediate inhibition of hypothalamic CRH and ACTH secretion, while intermediate and delayed mechanisms mediated by genomic actions involve modulation of limbic circuitry and peripheral metabolic messengers. Consistent with their key adaptive roles, HPA axis components are evolutionarily

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

    National Research Council Canada - National Science Library

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

    2013-01-01

    Gelastic seizures associated with hypothalamic hamartomas ( HH s) are a clinicoradiologic syndrome presenting with a variety of symptoms, including pharmacoresistant epilepsy with multiple seizure types, electroencephalography ( EEG...

  19. 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 < 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). 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

  20. Metabolic Actions of Hypothalamic SIRT1

    Science.gov (United States)

    Coppari, Roberto

    2012-01-01

    The hypothalamus is a small structure located in the ventral diencephalon. Hypothalamic neurons sense changes in circulating metabolic cues (e.g.: leptin, insulin, glucose), and coordinate responses aimed at maintaining normal body weight and glucose homeostasis. Recent findings indicate that a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase (namely, SIRT1) expressed by hypothalamic neurons is crucial for mounting responses against diet-induced obesity and type 2 diabetes mellitus (T2DM). Here, the repercussions of these findings will be discussed and particular emphasis will be given to the potential exploitation of hypothalamic SIRT1 as a target for the treatment of the rapidly-spreading metabolic disorders of obesity and T2DM. The possible roles of hypothalamic SIRT1 on regulating metabolic ageing processes will also be addressed. PMID:22382036

  1. 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

  2. Changes in vasopressin-converting aminopeptidase activity in the rat pineal gland during summer : Relationship to vasopressin contents

    NARCIS (Netherlands)

    Liu, B.; Burbach, J.P.H.

    Vasopressin (VP)-converting aminopeptidase (VP-AP) activity and VP contents were measured in single rat pineal glands during the summer of two successive years. The peptidase activity decreased significantly in August. The lowest activity (±SEM) of 0.18±0.02 pmol·hour−1 was recorded on August 14,

  3. Changes in vasopressin-converting aminopeptidase activity in the rat pineal gland during summer : Relationship to vasopressin contents

    NARCIS (Netherlands)

    Liu, B.; Burbach, J.P.H.

    1988-01-01

    Vasopressin (VP)-converting aminopeptidase (VP-AP) activity and VP contents were measured in single rat pineal glands during the summer of two successive years. The peptidase activity decreased significantly in August. The lowest activity (±SEM) of 0.18±0.02 pmol·hour−1 was recorded on August 14,

  4. Hypothalamic adipsic syndrome: diagnosis and management.

    Science.gov (United States)

    Ball, S G; Vaidja, B; Baylis, P H

    1997-10-01

    Patients with hypothalamic adipsic syndrome, especially in conjunction with diabetes insipidus, pose management difficulties. They are at risk of both under- and over-hydration. We present 4 patients with hypothalamic adipsic syndromes, due to different causes, illustrating the practical difficulties encountered in this condition. The principles of management, with a sliding scale of water intake related to changes in daily body weight, are discussed.

  5. Neuropeptide Y stimulates autophagy in hypothalamic neurons.

    Science.gov (United States)

    Aveleira, Célia A; Botelho, Mariana; Carmo-Silva, Sara; Pascoal, Jorge F; Ferreira-Marques, Marisa; Nóbrega, Clévio; Cortes, Luísa; Valero, Jorge; Sousa-Ferreira, Lígia; Álvaro, Ana R; Santana, Magda; Kügler, Sebastian; Pereira de Almeida, Luís; Cavadas, Cláudia

    2015-03-31

    Aging is characterized by autophagy impairment that contributes to age-related disease aggravation. Moreover, it was described that the hypothalamus is a critical brain area for whole-body aging development and has impact on lifespan. Neuropeptide Y (NPY) is one of the major neuropeptides present in the hypothalamus, and it has been shown that, in aged animals, the hypothalamic NPY levels decrease. Because caloric restriction (CR) delays aging, at least in part, by stimulating autophagy, and also increases hypothalamic NPY levels, we hypothesized that NPY could have a relevant role on autophagy modulation in the hypothalamus. Therefore, the aim of this study was to investigate the role of NPY on autophagy in the hypothalamus. Using both hypothalamic neuronal in vitro models and mice overexpressing NPY in the hypothalamus, we observed that NPY stimulates autophagy in the hypothalamus. Mechanistically, in rodent hypothalamic neurons, NPY increases autophagy through the activation of NPY Y1 and Y5 receptors, and this effect is tightly associated with the concerted activation of PI3K, MEK/ERK, and PKA signaling pathways. Modulation of hypothalamic NPY levels may be considered a potential strategy to produce protective effects against hypothalamic impairments associated with age and to delay aging.

  6. Transcriptional profiling of fetal hypothalamic TRH neurons.

    Science.gov (United States)

    Guerra-Crespo, Magdalena; Pérez-Monter, Carlos; Janga, Sarath Chandra; Castillo-Ramírez, Santiago; Gutiérrez-Rios, Rosa María; Joseph-Bravo, Patricia; Pérez-Martínez, Leonor; Charli, Jean-Louis

    2011-05-10

    During murine hypothalamic development, different neuroendocrine cell phenotypes are generated in overlapping periods; this suggests that cell-type specific developmental programs operate to achieve complete maturation. A balance between programs that include cell proliferation, cell cycle withdrawal as well as epigenetic regulation of gene expression characterizes neurogenesis. Thyrotropin releasing hormone (TRH) is a peptide that regulates energy homeostasis and autonomic responses. To better understand the molecular mechanisms underlying TRH neuron development, we performed a genome wide study of its transcriptome during fetal hypothalamic development. In primary cultures, TRH cells constitute 2% of the total fetal hypothalamic cell population. To purify these cells, we took advantage of the fact that the segment spanning -774 to +84 bp of the Trh gene regulatory region confers specific expression of the green fluorescent protein (GFP) in the TRH cells. Transfected TRH cells were purified by fluorescence activated cell sorting, various cell preparations pooled, and their transcriptome compared to that of GFP- hypothalamic cells. TRH cells undergoing the terminal phase of differentiation, expressed genes implicated in protein biosynthesis, intracellular signaling and transcriptional control. Among the transcription-associated transcripts, we identified the transcription factors Klf4, Klf10 and Atf3, which were previously uncharacterized within the hypothalamus. To our knowledge, this is one of the first reports identifying transcripts with a potentially important role during the development of a specific hypothalamic neuronal phenotype. This genome-scale study forms a rational foundation for identifying genes that might participate in the development and function of hypothalamic TRH neurons.

  7. Sex differences in vasopressin V2 receptor expression and vasopressin-induced antidiuresis

    Science.gov (United States)

    Sharma, Nikhil; Zheng, Wei; Ji, Hong; Tam, Helen; Wu, Xie; Manigrasso, Michaele B.; Sandberg, Kathryn; Verbalis, Joseph G.

    2011-01-01

    The renal vasopressin V2 receptor (V2R) plays a critical role in physiological and pathophysiological processes associated with arginine vasopressin (AVP)-induced antidiuresis. Because clinical data suggests that females may be more prone to hyponatremia from AVP-mediated antidiuresis, we investigated whether there are sex differences in the expression and function of the renal V2R. In normal Sprague-Dawley rat kidneys, V2R mRNA and protein expression was 2.6- and 1.7-fold higher, respectively, in females compared with males. To investigate the potential physiological implications of this sex difference, we studied changes in urine osmolality induced by the AVP V2R agonist desmopressin. In response to different doses of desmopressin, there was a graded increase in urine osmolality and decrease in urine volume during a 24-h infusion. Females showed greater mean increases in urine osmolality and greater mean decreases in urine volume at 0.5 and 5.0 ng/h infusion rates. We also studied renal escape from antidiuresis produced by water loading in rats infused with desmopressin (5.0 ng/h). After 5 days of water loading, urine osmolality of both female and male rats escaped to the same degree physiologically, but V2R mRNA and protein in female kidneys was reduced to a greater degree (−63% and −73%, respectively) than in males (−32% and −48%, respectively). By the end of the 5-day escape period, renal V2R mRNA and protein expression were reduced to the same relative levels in males and females, thereby abolishing the sex differences in V2R expression seen in the basal state. Our results demonstrate that female rats express significantly more V2R mRNA and protein in kidneys than males, and that this results physiologically in a greater sensitivity to V2R agonist administration. The potential pathophysiological implications of these results are that females may be more susceptible to the development of dilutional hyponatremia because of a greater sensitivity to

  8. Hypothalamic hamartoma: Neuropathology and epileptogenesis.

    Science.gov (United States)

    Kerrigan, John F; Parsons, Angela; Tsang, Candy; Simeone, Kristina; Coons, Stephen; Wu, Jie

    2017-06-01

    Hypothalamic hamartomas (HHs) are congenital malformations of the ventral hypothalamus resulting in treatment-resistant epilepsy and are intrinsically epileptogenic for the gelastic seizures that are the hallmark symptom of this disorder. This paper reviews the neuropathologic features of HHs associated with epilepsy, with an emphasis on characterizing neuron phenotypes and an ultimate goal of understanding the cellular model of ictogenesis occurring locally within this tissue. We also present previously unpublished findings on Golgi staining of HH. The microarchitecture of HH is relatively simple, with nodular clusters of neurons that vary in size and abundance with poorly defined boundaries. Approximately 80-90% of HH neurons have an interneuron-like phenotype with small, round soma and short, unbranched processes that lack spines. These neurons express glutamic acid decarboxylase and likely utilize γ-aminobutyric acid (GABA) as their primary neurotransmitter. They have intrinsic membrane properties that lead to spontaneous pacemaker-like firing activity. The remaining HH neurons are large cells with pleomorphic, often pyramidal, soma and dendrites that are more likely to be branched and have spines. These neurons appear to be excitatory, projection-type neurons, and have the functionally immature behavior of depolarizing and firing in response to GABA ligands. We hypothesize that the irregular neuronal clusters are the functional unit for ictogenesis. Further research to define and characterize these local networks is required to fully understand the cellular mechanisms responsible for gelastic seizures. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  9. In vivo biosynthesis of L-(/sup 35/S)Cys-arginine vasopressin, -oxytocin, and -somatostatin: rapid estimation using reversed phase high pressure liquid chromatography. [Rats

    Energy Technology Data Exchange (ETDEWEB)

    Franco-Bourland, R.E.; Fernstrom, J.D.

    1981-01-01

    L(/sup 35/S)Cys-arginine vasopressin, -oxytocin, and -somatostatin were purified from hypothalami and neurohypophyses 4 h after rats received L(/sup 35/S)Cys via the third ventricle. After acetic acid extraction, Sephadex G-25 filtration, and chemoadsorption to C18-silica (Sep-Pak cartridges), the labeled peptides were rapidly separated by gradient elution, reversed phase, high pressure liquid chromatography (HPLC). The identity and isotopic purity of the labeled peptides were determined by several reversed phase HPLC procedures in conjunction with chemical modification. The labeled peptide fractions were at least 50% radiochemically pure. Using this HPLC isolation procedure, incorporation of L-(/sup 35/S)Cys into each peptide was determined in hydrated and dehydrated rats. Label incorporation into arginine vasopressin and oxytocin in the hypothalamus and the neurohypophysis of dehydrated rats was 2-3 times greater than that in hydrated rats. Incorporation of label into hypothalamic and neurohypophyseal somatostatin was unaffected by the hydration state of the animal. This procedure thus provides a very rapid, but sensitive, set of techniques for studying the control of small peptide biosynthesis in the brain.

  10. 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.

  11. Effect of arginine vasopressin on the behavioral activity in the behavior despair depression rat model.

    Science.gov (United States)

    Yang, Jun; Pan, Yan-Juan; Yin, Zhi-Kui; Hai, Guang-Fan; Lu, Lu; Zhao, Ying; Wang, Da-Xin; Wang, Huan; Wang, Gen

    2012-06-01

    Arginine vasopressin (AVP), a nonapeptide posterior hormone of the pituitary, is mainly synthesized and secreted in the hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON). Large numbers of studies have reported that AVP plays a role in depression. The present study was to investigate by which level, brain or periphery, AVP affects the behavioral activity in the behavior despair depression rat model. The results showed that (1) either forced swimming or tail suspension significantly increased AVP concentration not only in the brain (PVN, SON, frontal of cortex, hippocampus, amygdala, lumber spinal cord) but also in the periphery (posterior pituitary and serum); (2) intraventricular injection (icv) of AVP decreased the animal immobility time, whereas V₁ receptor antagonist d(CH₂)₅Tyr(Me)AVP (icv) increased the animal immobility time in a dose-dependent manner not only in FST but also in TST, but the V₂ receptor antagonist d(CH₂)₅[D-Ile, Ile, Ala-NH₉]AVP did not change the animal immobility time in FST or TST; (3) V₁, not V₂ receptor antagonist could inhibit the animal immobility time decrease induced by AVP (icv); (4) neither AVP nor its receptor antagonist (including V₁ and V₂ receptor antagonist) influenced the animal immobility time in both FST and TST. The data suggested that AVP in the brain rather than the periphery played a role in the behavior despair depression by V₁, not V₂ receptors, which behavior despair might have a positive feedback effect on central AVP and blood AVP might have a negative feedback on central AVP in the depressive process. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Vasopressin vs Dopamine for Treatment of Hypotension in ELBW Infants: A Randomized, Blinded Pilot Study

    Science.gov (United States)

    Rios, Danielle R.; Kaiser, Jeffrey R.

    2015-01-01

    Objective To evaluate vasopressin vs dopamine as initial therapy in ELBW infants with hypotension during the first 24 hours of life. Study design Hypotensive ELBW infants ≤ 30 weeks’ gestation and ≤ 24 hours old randomly received treatment with vasopressin or dopamine in a blinded fashion. Normotensive infants not receiving vasopressor support served as a comparison group. Results Twenty hypotensive ELBW infants received vasopressin (n=10) or dopamine (n=10), and 50 were enrolled for comparison. Mean gestational age was 25.6 ± 1.4 weeks and birth weight 705 ± 154 g. Response to vasopressin paralleled that of dopamine in time to adequate mean BP (Kaplan-Meier curve, p=0.986); 90% of infants in each treatment group responded with adequate BP. The vasopressin group received fewer doses of surfactant (phypotension appeared safe. This pilot study supports a larger randomized controlled trial of vasopressin vs dopamine therapy in ELBW infants with hypotension. PMID:25641242

  13. Nerve cells immunoreactive for p62 in select hypothalamic and brainstem nuclei of controls and Parkinson's disease cases.

    Science.gov (United States)

    Braak, Heiko; Thal, Dietmar R; Del Tredici, Kelly

    2011-05-01

    The protein p62 plays an important role in the proteasomal and/or autophagic clearance of misfolded and aggregation-prone proteins. Immunoreactivity for p62, however, not only characterizes pathological proteinaceous inclusions but also occurs in the form of homogeneous nerve cell labeling in brains of both healthy and diseased individuals, e.g., in the vagal dorsal motor nucleus and other subcortical nuclei. In sporadic Parkinson's disease (PD), the pathological process initially involves preganglionic neurons of the parasympathetic and sympathetic system and probably advances caudo-rostrally from there along the neuroaxis. Since all subsequently affected nuclei (lower raphe nuclei, magnocellular reticular formation, locus coeruleus, and central subnucleus of the amygdala) generate descending projections that terminate in the vagal dorsal motor nucleus and intermediolateral column, it has been conjectured that retrograde axonal transport and transsynaptic transmission of a pathogen contribute to the pathogenesis of PD. The hypothalamic paraventricular nucleus also sends projections to the preganglionic nuclei under consideration and, thus, should belong to the nuclei endangered by the pathological process. However, it remains uninvolved for the duration of the disorder. For this reason, we performed a retrospective study of the relevant nuclei in a cohort of 36 individuals, including 17 with clinically documented PD, one case with incidental Lewy body disease (ILBD), and 18 controls using p62-immunocytochemistry. Remarkably, the neurosecretory cells of the paraventricular nucleus were among the sites showing homogeneous p62-immunolabeling with the greatest consistency. Its p62-immunoreactive profile may indicate that the hypothalamic paraventricular nucleus is somehow capable of effectively metabolizing misfolded proteins and/or preventing their aggregation.

  14. Projections from Bed Nuclei of the Stria Terminalis, Magnocellular Nucleus: Implications for Cerebral Hemisphere Regulation of Micturition, Defecation, and Penile Erection

    OpenAIRE

    DONG, HONG-WEI; SWANSON, LARRY W.

    2006-01-01

    The basic structural organization of axonal projections from the small but distinct magnocellular and ventral nuclei (of the bed nuclei of the stria terminalis) were analyzed with the PHAL anterograde tract tracing method in adult male rats. The former's overall projection pattern is complex, with over 80 distinct terminal fields ipsilateral to injection sites. Innervated regions in the cerebral hemisphere and brainstem fall into 9 general functional categories: cerebral nuclei, behavior cont...

  15. A novel splicing mutation in the V2 vasopressin receptor

    DEFF Research Database (Denmark)

    Kamperis, Konstantinos; Siggaard, C; Herlin, Troels

    2000-01-01

    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......In order to elucidate the molecular basis and the clinical characteristics of X-linked recessive nephrogenic diabetes insipidus (CNDI) in a kindred of Danish descent, we performed direct sequencing of the arginine vasopressin receptor 2 (AVPR2) gene in five members of the family, as well...... 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...

  16. Correlation of plasma copeptin and vasopressin concentrations in hypo-, iso-, and hyperosmolar states

    OpenAIRE

    Balanescu, Sandrina; Kopp, Peter; Gaskill, Mary Beth; Morgenthaler, Nils G.; Schindler, Christian; Rutishauser, Jonas

    2011-01-01

    Background: Copeptin, the C-terminal moiety of provasopressin, is cosecreted with vasopressin. Copeptin may be a useful parameter to characterize disorders of water homeostasis and can be readily measured in plasma or serum. However, it is unknown to date how circulating copeptin and vasopressin levels correlate at different plasma osmolalites. Objective: To correlate plasma copeptin with plasma osmolality and vasopressin concentrations in healthy subjects during iso-, hypo-, and hyperosmolar...

  17. The Effect of Renal Function and Hemodialysis Treatment on Plasma Vasopressin and Copeptin Levels.

    Science.gov (United States)

    Ettema, Esmée M; Heida, Judith; Casteleijn, Niek F; Boesten, Lianne; Westerhuis, Ralf; Gaillard, Carlo A J M; Gansevoort, Ron T; Franssen, Casper F M; Zittema, Debbie

    2017-05-01

    Copeptin is increasingly used in epidemiological studies as a substitute for vasopressin. The effect of renal function per se on copeptin and vasopressin concentrations as well as their ratio have, however, not been well described. Copeptin and vasopressin levels were measured in 127 patients with various stages of chronic kidney disease, including 42 hemodialysis patients and 16 healthy participants in this observational study. Linear (segmental) regression analyses were performed to assess the association between renal function and copeptin, vasopressin and the C/V ratio. In addition, clearance of copeptin and vasopressin by hemodialysis was calculated. Both copeptin and vasopressin levels were higher when renal function was lower, and both showed associations with plasma osmolality. The C/V ratio was stable across renal function in subjects with an eGFR >28 ml/min per 1.73 m2. In contrast, the C/V ratio increased with worsening renal function in patients with eGFR ≤28 ml/min per 1.73 m2. During hemodialysis, the initial decrease in vasopressin levels was greater compared with copeptin and, consequently, the C/V ratio increased. This was, at least in part, explained by a greater dialytic clearance of vasopressin compared with copeptin. Our data indicate that copeptin is a reliable substitute for vasopressin in subjects with an eGFR >28 ml/min per 1.73 m2, whereas at an eGFR ≤28 ml/min per 1.73 m2, that is, CKD stages 4 and 5, a correction for renal function is required in epidemiological studies that use copeptin as a marker for vasopressin. Intradialytic copeptin levels do not adequately reflect vasopressin levels because vasopressin clearance by hemodialysis is higher than that of copeptin.

  18. Chronic social stress alters levels of corticotropin-releasing factor and arginine vasopressin mRNA in rat brain.

    Science.gov (United States)

    Albeck, D S; McKittrick, C R; Blanchard, D C; Blanchard, R J; Nikulina, J; McEwen, B S; Sakai, R R

    1997-06-15

    In the visible burrow system model of chronic social stress, male rats housed in mixed-sex groups quickly form a dominance hierarchy in which the subordinates appear to be severely stressed. A subgroup of subordinates have an impaired corticosterone response after presentation of a novel restraint stressor, leading to their designation as nonresponsive subordinates. To examine the mechanism underlying the blunted corticosterone response in these animals, in situ hybridization histochemistry was used to quantify corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) mRNA expression in the brain. In two separate visible burrow system experiments, the nonresponsive subordinates expressed a significantly lower average number of CRF mRNA grains per cell in the paraventricular hypothalamic nucleus compared with stress-responsive subordinates, dominants (DOM), or cage-housed control (CON) rats. The number of CRF mRNA labeled cells was also significantly lower in nonresponders than in responsive subordinates or DOM. In the central amygdala, CRF mRNA levels were increased in both groups of subordinates compared with CON rats, whereas responsive subordinates exhibited higher levels than the DOM rats as well. AVP mRNA levels did not vary with behavioral rank in any subdivision of the paraventricular hypothalamic nucleus. In the medial amygdala, the number of cells expressing AVP mRNA was significantly greater in CON rats compared with both groups of subordinates, although the average number of AVP mRNA grains per cell did not vary with rank. In addition, the number of AVP-positive cells significantly correlated with plasma testosterone level.

  19. Serotonin and arginine-vasopressin mediate sex differences in the regulation of dominance and aggression by the social brain.

    Science.gov (United States)

    Terranova, Joseph I; Song, Zhimin; Larkin, Tony E; Hardcastle, Nathan; Norvelle, Alisa; Riaz, Ansa; Albers, H Elliott

    2016-11-15

    There are profound sex differences in the incidence of many psychiatric disorders. Although these disorders are frequently linked to social stress and to deficits in social engagement, little is known about sex differences in the neural mechanisms that underlie these phenomena. Phenotypes characterized by dominance, competitive aggression, and active coping strategies appear to be more resilient to psychiatric disorders such as posttraumatic stress disorder (PTSD) compared with those characterized by subordinate status and the lack of aggressiveness. Here, we report that serotonin (5-HT) and arginine-vasopressin (AVP) act in opposite ways in the hypothalamus to regulate dominance and aggression in females and males. Hypothalamic injection of a 5-HT1a agonist stimulated aggression in female hamsters and inhibited aggression in males, whereas injection of AVP inhibited aggression in females and stimulated aggression in males. Striking sex differences were also identified in the neural mechanisms regulating dominance. Acquisition of dominance was associated with activation of 5-HT neurons within the dorsal raphe in females and activation of hypothalamic AVP neurons in males. These data strongly indicate that there are fundamental sex differences in the neural regulation of dominance and aggression. Further, because systemically administered fluoxetine increased aggression in females and substantially reduced aggression in males, there may be substantial gender differences in the clinical efficacy of commonly prescribed 5-HT-active drugs such as selective 5-HT reuptake inhibitors. These data suggest that the treatment of psychiatric disorders such as PTSD may be more effective with the use of 5-HT-targeted drugs in females and AVP-targeted drugs in males.

  20. Bardoxolone methyl prevents obesity and hypothalamic dysfunction.

    Science.gov (United States)

    Camer, Danielle; Yu, Yinghua; Szabo, Alexander; Wang, Hongqin; Dinh, Chi H L; Huang, Xu-Feng

    2016-08-25

    High-fat (HF) diet-induced obesity is associated with hypothalamic leptin resistance and low grade chronic inflammation, which largely impairs the neuroregulation of negative energy balance. Neuroregulation of negative energy balance is largely controlled by the mediobasal and paraventricular nuclei regions of the hypothalamus via leptin signal transduction. Recently, a derivative of oleanolic acid, bardoxolone methyl (BM), has been shown to have anti-inflammatory effects. We tested the hypothesis that BM would prevent HF diet-induced obesity, hypothalamic leptin resistance, and inflammation in mice fed a HF diet. Oral administration of BM via drinking water (10 mg/kg daily) for 21 weeks significantly prevented an increase in body weight, energy intake, hyperleptinemia, and peripheral fat accumulation in mice fed a HF diet. Furthermore, BM treatment prevented HF diet-induced decreases in the anorexigenic effects of peripheral leptin administration. In the mediobasal and paraventricular nuclei regions of the hypothalamus, BM administration prevented HF diet-induced impairments of the downstream protein kinase b (Akt) pathway of hypothalamic leptin signalling. BM treatment also prevented an increase in inflammatory cytokines, tumour necrosis factor alpha (TNFα) and interleukin 6 (IL-6) in these two hypothalamic regions. These results identify a potential novel neuropharmacological application for BM in preventing HF diet-induced obesity, hypothalamic leptin resistance, and inflammation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. The Effect of Renal Function and Hemodialysis Treatment on Plasma Vasopressin and Copeptin Levels

    Directory of Open Access Journals (Sweden)

    Esmée M. Ettema

    2017-05-01

    Discussion: Our data indicate that copeptin is a reliable substitute for vasopressin in subjects with an eGFR >28 ml/min per 1.73 m2, whereas at an eGFR ≤28 ml/min per 1.73 m2, that is, CKD stages 4 and 5, a correction for renal function is required in epidemiological studies that use copeptin as a marker for vasopressin. Intradialytic copeptin levels do not adequately reflect vasopressin levels because vasopressin clearance by hemodialysis is higher than that of copeptin.

  2. Selective V₂-Agonist of Vasopressin Desmopressin Stimulates Activity of Serum Hyaluronidase.

    Science.gov (United States)

    Dzgoev, S G

    2015-08-01

    Effects of desmopressin (arginine vasopressin V2 receptor agonist) were studied for elucidation of the possible role of the kidneys in the regulation of blood hyaluronidase activity. Similar to vasopressin, intraperitoneal administration of desmopressin to Wistar rats increased blood hyaluronidase activity by 30%. Against the background of water load, nether desmopressin nor vasopressin increased blood hyaluronidase activity. The possibility of renal secretion of hyaluronidase into the blood as a mechanism of antidiuretic activity of vasopressin and its role in the regulation of water metabolism are discussed.

  3. 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.

  4. 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

  5. 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...

  6. Different relationship of magnocellular-dorsal function and reading-related skills between Chinese developing and skilled readers.

    Science.gov (United States)

    Zhao, Jing; Bi, Hong-Yan; Coltheart, Max

    2017-01-01

    Previous studies have indicated that the relationship between magnocellular-dorsal (M-D) function and reading-related skills may vary with reading development in readers of alphabetic languages. Since this relationship could be affected by the orthographic depth of writing systems, the present study explored the relationship between M-D function and reading-related skills in Chinese, a writing system with a deeper orthography than alphabetic languages. Thirty-seven primary school students and fifty-one undergraduate students participated. Orthographic and phonological awareness tests were adopted as reading-related skill measurements. A steady-pedestal paradigm was used to assess the low-spatial-frequency contrast thresholds of M-D function. Results showed that M-D function was only correlated with orthographic awareness for adults, revealing an enhancement with reading development; while being related to phonological awareness only for children revealing a developmental decrement. It suggested that the mechanism responsible for the relationship between M-D activity and reading-related skills was affected by the characteristics of literacy development in Chinese.

  7. Hypothalamic inflammation and gliosis in obesity.

    Science.gov (United States)

    Dorfman, Mauricio D; Thaler, Joshua P

    2015-10-01

    Hypothalamic inflammation and gliosis are recently discovered mechanisms that may contribute to obesity pathogenesis. Current research in this area suggests that investigation of these central nervous system responses may provide opportunities to develop new weight loss treatments. In rodents, hypothalamic inflammation and gliosis occur rapidly with high-fat diet consumption prior to significant weight gain. In addition, sensitivity or resistance to diet-induced obesity in rodents generally correlates with the presence or absence of hypothalamic inflammation and reactive gliosis (brain response to injury). Moreover, functional interventions that increase or decrease inflammation in neurons and glia correspondingly alter diet-associated weight gain. However, some conflicting data have recently emerged that question the contribution of hypothalamic inflammation to obesity pathogenesis. Nevertheless, several studies have detected gliosis and disrupted connectivity in obese humans, highlighting the potential translational importance of this mechanism. There is growing evidence that obesity is associated with brain inflammation in humans, particularly in the hypothalamus where its presence may disrupt body weight control and glucose homeostasis. More work is needed to determine whether this response is common in human obesity and to what extent it can be manipulated for therapeutic benefit.

  8. 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.

  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. 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

  11. 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.

  12. Radioimmunoassay of vasopressin during pregnancy. Use and removal of cystylaminopeptidase inhibitors

    NARCIS (Netherlands)

    van der Post, J. A.; van Heerikhuize, J. J.; Boer, K.; van Boxtel, C. E.; Swaab, D. F.

    1994-01-01

    This paper describes a radioimmunoassay (RIA) for arginine-vasopressin in which o-phenanthroline effectively inhibits cystyl-amino-peptidase activity in whole blood and plasma from pregnant women but in which o-phenanthroline is removed during the extraction of vasopressin from plasma to prevent

  13. 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.

  14. Modified forms of vasopressin and oxytocin in a bovine pineal preparation

    NARCIS (Netherlands)

    Noteborn, H.P.J.M.; Burbach, J.P.H.; Ebels, I.

    1987-01-01

    A bovine pineal acid extract displays a vasotocin-like bioactivity in several bioassays, and is recognized by antibodies against the Pro-Arg-Gly-amide ending common to vasopressin and vasotocin. By using molecular sieve filtration and reversed-phase HPLC, a vasopressin- and oxytocin-like peptide was

  15. Expression patterns of corticotropin-releasing factor, arginine vasopressin, histidine decarboxylase, melanin-concentrating hormone, and orexin genes in the human hypothalamus.

    Science.gov (United States)

    Krolewski, David M; Medina, Adriana; Kerman, Ilan A; Bernard, Rene; Burke, Sharon; Thompson, Robert C; Bunney, William E; Schatzberg, Alan F; Myers, Richard M; Akil, Huda; Jones, Edward G; Watson, Stanley J

    2010-11-15

    The hypothalamus regulates numerous autonomic responses and behaviors. The neuroactive substances corticotropin-releasing factor (CRF), arginine-vasopressin (AVP), histidine decarboxylase (HDC), melanin-concentrating hormone (MCH), and orexin/hypocretins (ORX) produced in the hypothalamus mediate a subset of these processes. Although the expression patterns of these genes have been well studied in rodents, less is known about them in humans. We combined classical histological techniques with in situ hybridization histochemistry to produce both 2D and 3D images and to visually align and quantify expression of the genes for these substances in nuclei of the human hypothalamus. The hypothalamus was arbitrarily divided into rostral, intermediate, and caudal regions. The rostral region, containing the paraventricular nucleus (PVN), was defined by discrete localization of CRF- and AVP-expressing neurons, whereas distinct relationships between HDC, MCH, and ORX mRNA-expressing neurons delineated specific levels within the intermediate and caudal regions. Quantitative mRNA signal intensity measurements revealed no significant differences in overall CRF or AVP expression at any rostrocaudal level of the PVN. HDC mRNA expression was highest at the level of the premammillary area, which included the dorsomedial and tuberomammillary nuclei as well as the dorsolateral hypothalamic area. In addition, the overall intensity of hybridization signal exhibited by both MCH and ORX mRNA-expressing neurons peaked in distinct intermediate and caudal hypothalamic regions. These results suggest that human hypothalamic neurons involved in the regulation of the HPA axis display distinct neurochemical patterns that may encompass multiple local nuclei. Copyright © 2010 Wiley-Liss, Inc.

  16. Expanding the definition of hypothalamic obesity.

    Science.gov (United States)

    Hochberg, I; Hochberg, Z

    2010-10-01

    Hypothalamic obesity (HyOb) was first defined as the significant polyphagia and weight gain that occurs after extensive suprasellar operations for excision of hypothalamic tumours. However, polyphagia and weight gain complicate other disorders related to the hypothalamus, including those that cause structural damage to the hypothalamus like tumours, trauma, radiotherapy; genetic disorders such as Prader-Willi syndrome; side effects of psychotropic drugs; and mutations in several genes involved in hypothalamic satiety signalling. Moreover, 'simple' obesity is associated with polymorphisms in several genes involved in hypothalamic weight-regulating pathways. Thus, understanding HyOb may enhance our understanding of 'simple' obesity. This review will claim that HyOb is a far wider phenomenon than hitherto understood by the narrow definition of post-surgical weight gain. It will emphasize the similarity in clinical characteristics and therapeutic approaches for HyOb, as well as its mechanisms. HyOb, regardless of its aetiology, is a result of impairment in hypothalamic regulatory centres of body weight and energy expenditure. The pathophysiology includes loss of sensitivity to afferent peripheral humoral signals, such as, leptin on the one hand and dysfunctional afferent signals, on the other hand. The most important afferent signals deranged are energy regulation by the sympathetic nervous system and regulation of insulin secretion. Dys-regulation of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) activity and melatonin may also have a role in the development of HyOb. The complexity of the syndrome requires simultaneous targeting of several mechanisms that are deranged in the HyOb patient. We review the studies evaluating possible treatment strategies, including sympathomimetics, somatostatin analogues, triiodothyronine, sibutramine, and surgery. © 2010 The Authors. obesity reviews © 2010 International Association for the Study of Obesity.

  17. Dehydration-induced modulation of kappa-opioid inhibition of vasopressin neurone activity.

    Science.gov (United States)

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

    2009-12-01

    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 kappa-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 kappa-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 -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 kappa-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.

  18. 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...

  19. 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...... applied after pretreatment with intracerebroventricular infusion of saline or different 5-HT antagonists. RESULTS: Restraint stress (5 min), hypotensive hemorrhage or dehydration for 24 h increased AVP secretion fivefold and OT secretion threefold. Swim stress for 3 min had no effect on AVP secretion...

  20. Hypothalamic integration of immune function and metabolism.

    Science.gov (United States)

    Guijarro, Ana; Laviano, Alessandro; Meguid, Michael M

    2006-01-01

    The immune and neuroendocrine systems are closely involved in the regulation of metabolism at peripheral and central hypothalamic levels. In both physiological (meals) and pathological (infections, traumas and tumors) conditions immune cells are activated responding with the release of cytokines and other immune mediators (afferent signals). In the hypothalamus (central integration), cytokines influence metabolism by acting on nucleus involved in feeding and homeostasis regulation leading to the acute phase response (efferent signals) aimed to maintain the body integrity. Peripheral administration of cytokines, inoculation of tumor and induction of infection alter, by means of cytokine action, the normal pattern of food intake affecting meal size and meal number suggesting that cytokines acted differentially on specific hypothalamic neurons. The effect of cytokines-related cancer anorexia is also exerted peripherally. Increase plasma concentrations of insulin and free tryptophan and decrease gastric emptying and d-xylose absorption. In addition, in obesity an increase in interleukin (IL)-1 and IL-6 occurs in mesenteric fat tissue, which together with an increase in corticosterone, is associated with hyperglycemia, dyslipidemias and insulin resistance of obesity-related metabolic syndrome. These changes in circulating nutrients and hormones are sensed by hypothalamic neurons that influence food intake and metabolism. In anorectic tumor-bearing rats, we detected upregulation of IL-1beta and IL-1 receptor mRNA levels in the hypothalamus, a negative correlation between IL-1 concentration in cerebro-spinal fluid and food intake and high levels of hypothalamic serotonin, and these differences disappeared after tumor removal. Moreover, there is an interaction between serotonin and IL-1 in the development of cancer anorexia as well as an increase in hypothalamic dopamine and serotonin production. Immunohistochemical studies have shown a decrease in neuropeptide Y (NPY) and

  1. 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.

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

    Science.gov (United States)

    Goncharova, Nadezhda D

    2013-01-01

    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 adrenocorticotropic hormone (ACTH) release through specific G-protein-coupled membrane receptors on pituitary corticotrophs, CRHR1 for CRH and V1b for AVP; the adrenal gland cortex secretes glucocorticoids in response to 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.

  3. 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.

  4. Vasopressin receptor antagonists and their role in clinical medicine

    Directory of Open Access Journals (Sweden)

    Girish Narayen

    2012-01-01

    Full Text Available Hyponatremia is the most common electrolyte abnormality in hospitalized patients. Its treatment is based not only on extracellular fluid volume status of patients but also on its pathogenetic mechanisms. Conventional treatment of hyponatremia like fluid restriction, which is useful in euvolemic and hypervolemic hyponatremia, has very poor patient compliance over long term. Vasopressin receptor antagonists (Vaptans are a new group of nonpeptide drugs which have been used in various clinical conditions with limited success. Whereas conivaptan is to be administered intravenously, the other vaptans like tolvaptan, lixivaptan, and satavaptan are effective as oral medication. They produce aquaresis by their action on vasopressin type 2 (V2R receptors in the collecting duct and thus increase solute free water excretion. Vaptans are being used as an alternative to fluid restriction in euvolemic and hypervolemic hyponatremic patients. Efficacy of vaptans is now well accepted for management of correction of hyponatremia over a short period. However, its efficacy in improving the long-term morbidity and mortality in patients with chronic hyponatremia due to cirrhosis and heart failure is yet to be established. Vaptans have not become the mainstay treatment of hyponatremia yet.

  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. Hypothalamic survival circuits: blueprints for purposive behaviors.

    Science.gov (United States)

    Sternson, Scott M

    2013-03-06

    Neural processes that direct an animal's actions toward environmental goals are critical elements for understanding behavior. The hypothalamus is closely associated with motivated behaviors required for survival and reproduction. Intense feeding, drinking, aggressive, and sexual behaviors can be produced by a simple neuronal stimulus applied to discrete hypothalamic regions. What can these "evoked behaviors" teach us about the neural processes that determine behavioral intent and intensity? Small populations of neurons sufficient to evoke a complex motivated behavior may be used as entry points to identify circuits that energize and direct behavior to specific goals. Here, I review recent applications of molecular genetic, optogenetic, and pharmacogenetic approaches that overcome previous limitations for analyzing anatomically complex hypothalamic circuits and their interactions with the rest of the brain. These new tools have the potential to bridge the gaps between neurobiological and psychological thinking about the mechanisms of complex motivated behavior. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Hormonal regulation of the hypothalamic melanocortin system.

    Science.gov (United States)

    Kim, Jung D; Leyva, Stephanie; Diano, Sabrina

    2014-01-01

    Regulation of energy homeostasis is fundamental for life. In animal species and humans, the Central Nervous System (CNS) plays a critical role in such regulation by integrating peripheral signals and modulating behavior and the activity of peripheral organs. A precise interplay between CNS and peripheral signals is necessary for the regulation of food intake and energy expenditure in the maintenance of energy balance. Within the CNS, the hypothalamus is a critical center for monitoring, processing and responding to peripheral signals, including hormones such as ghrelin, leptin, and insulin. Once in the brain, peripheral signals regulate neuronal systems involved in the modulation of energy homeostasis. The main hypothalamic neuronal circuit in the regulation of energy metabolism is the melanocortin system. This review will give a summary of the most recent discoveries on the hormonal regulation of the hypothalamic melanocortin system in the control of energy homeostasis.

  8. Hormonal regulation of the hypothalamic melanocortin system

    Directory of Open Access Journals (Sweden)

    Jung Dae eKim

    2014-12-01

    Full Text Available Regulation of energy homeostasis is fundamental for life. In animal species and humans, the Central Nervous System (CNS plays a critical role in such regulation by integrating peripheral signals and modulating behavior and the activity of peripheral organs. A precise interplay between CNS and peripheral signals is necessary for the regulation of food intake and energy expenditure in the maintenance of energy balance. Within the CNS, the hypothalamus is a critical center for monitoring, processing and responding to peripheral signals, including hormones such as ghrelin, leptin and insulin. Once in the brain, peripheral signals regulate neuronal systems involved in the modulation of energy homeostasis. The main hypothalamic neuronal circuit in the regulation of energy metabolism is the melanocortin system. This review will give a summary of the most recent discoveries on the hormonal regulation of the hypothalamic melanocortin system in the control of energy homeostasis.

  9. Ghrelin-Induced Enhancement of Vasopressin and Oxytocin Secretion in Rat Neurohypophyseal Cell Cultures.

    Science.gov (United States)

    Gálfi, M; Radács, M; Molnár, Zs; Budai, I; Tóth, G; Pósa, A; Kupai, K; Szalai, Z; Szabó, R; Molnár, H A; Gardi, J; László, Ferenc A; Varga, Cs

    2016-12-01

    The effects of ghrelin on vasopressin and oxytocin secretion were studied in 13-14-day cell cultures of isolated rat neurohypophyseal tissue. The vasopressin and oxytocin contents of the supernatant were determined by radioimmunoassay after a 1- or 2-h incubation. Significantly increased levels of vasopressin and oxytocin production were detected in the cell culture media following ghrelin administration, depending on the ghrelin doses. The oxytocin level proved to be more elevated than that of vasopressin. The increase of vasopressin and oxytocin secretion could be totally blocked by previous administration of the ghrelin receptor antagonist ([D-Lys 3 ]-growth hormone-releasing peptide-6). Application of the ghrelin receptor antagonist after ghrelin administration proved ineffective. The results indicate that vasopressin and oxytocin release is influenced directly by the ghrelin system, and the effects of ghrelin on vasopressin and oxytocin secretion from the neurohypophyseal tissue in rats can occur at the level of the posterior pituitary. Our observations lend support to the view that neurohypophysis contains ghrelin receptors.

  10. Ontogeny of the hypothalamic neuropeptide Y system.

    Science.gov (United States)

    Grove, Kevin L; Smith, M Susan

    2003-06-01

    Early onset obesity and type II diabetes is rapidly becoming an epidemic, especially within the United States. This dramatic increase is likely due to many factors including both prenatal and postnatal environmental cues. The purpose of this review is to highlight some of the recent advances in our knowledge of the development of the hypothalamic circuits involved in the regulation of energy balance, with a focus on the neuropeptide Y (NPY) system. Unlike the adult rat, during the postnatal period NPY is transiently expressed in several hypothalamic regions, along with the expected expression within the arcuate nucleus (ARH). These transient populations of NPY neurons during the postnatal period may provide local NPY production to sustain the necessary energy intake during this critical growth phase. This may be physiologically important since ARH-NPY projections do not fully develop until the 3rd postnatal week. The significance of this ontogeny is that many peripheral metabolic signals have little effect of feeding prior to the development of the ARH projections. The essential questions now are whether prenatal and/or postnatal exposure to high levels of insulin or leptin during development can cause permanent changes in the function of hypothalamic circuits. It is vital to understand not only the natural development of the hypothalamic circuits that regulate energy homeostasis, but also their abnormal development caused by maternal and postnatal environmental cues. This will be pivotal for designing intervention and therapeutics to treat early onset obesity/type II diabetes, which may very well need to be different from those designed to prevent/treat adult onset obesity/type II diabetes.

  11. Risk of Hyponatremia in Patients with Aneurysmal Subarachnoid Hemorrhage Treated with Exogenous Vasopressin Infusion.

    Science.gov (United States)

    Marr, Nancy; Yu, Jessica; Kutsogiannis, Demetrios J; Mahmoud, Sherif Hanafy

    2017-04-01

    Vasopressin is one of the vasopressors used to augment blood pressure in subarachnoid hemorrhage (SAH) patients with clinically significant vasospasm. The purpose of the present study was to determine whether the administration of vasopressin to a population of SAH patients was an independent predictor of developing hyponatremia. A retrospective review on the health records of 106 patients admitted to the University of Alberta Hospital Neurosciences ICU, Edmonton AB, Canada, with SAH from June 2013 to December 2015 was conducted. Serum sodium changes in patients receiving vasoactive drugs were compared. In addition, independent predictors for hyponatremia (Na < 135 mmol/L) were determined using a multivariate logistic regression model. Patients treated with vasopressin in addition to other vasoactive drugs had significantly higher sodium changes compared to those treated with other vasoactive drugs (-4.7 ± 6 vs -0.1 ± 2.4 mmol/L, respectively, p value 0.001). Hyponatremia occurred in 14 patients (70 %) treated with vasopressin, 10 patients (44 %) treated with vasoactive drugs other than vasopressin (p value 0.081), and 24 patients (38 %) who did not receive any vasoactive drug (p value 0.013). In multivariate logistic regression analysis, when adjusting for disease severity, age, sex, aneurysm location, and treatment, vasopressin was associated with hyponatremia (OR 3.58, 95 % CI, 1.02-12.5, p value 0.046). The results of the present study suggest that hyponatremia may be more common in SAH patients treated with exogenous vasopressin compared to those who did not receive it. Serum sodium should be monitored closely when vasopressin is being used in the SAH population. Further studies are needed to confirm the effect of exogenous vasopressin on serum sodium levels in SAH populations.

  12. Hypothalamic innate immune reaction in obesity.

    Science.gov (United States)

    Kälin, Stefanie; Heppner, Frank L; Bechmann, Ingo; Prinz, Marco; Tschöp, Matthias H; Yi, Chun-Xia

    2015-06-01

    Findings from rodent and human studies show that the presence of inflammatory factors is positively correlated with obesity and the metabolic syndrome. Obesity-associated inflammatory responses take place not only in the periphery but also in the brain. The hypothalamus contains a range of resident glial cells including microglia, macrophages and astrocytes, which are embedded in highly heterogenic groups of neurons that control metabolic homeostasis. This complex neural-glia network can receive information directly from blood-borne factors, positioning it as a metabolic sensor. Following hypercaloric challenge, mediobasal hypothalamic microglia and astrocytes enter a reactive state, which persists during diet-induced obesity. In established mouse models of diet-induced obesity, the hypothalamic vasculature displays angiogenic alterations. Moreover, proopiomelanocortin neurons, which regulate food intake and energy expenditure, are impaired in the arcuate nucleus, where there is an increase in local inflammatory signals. The sum total of these events is a hypothalamic innate immune reactivity, which includes temporal and spatial changes to each cell population. Although the exact role of each participant of the neural-glial-vascular network is still under exploration, therapeutic targets for treating obesity should probably be linked to individual cell types and their specific signalling pathways to address each dysfunction with cell-selective compounds.

  13. 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...... inpatient study under standardized conditions for measurements of plasma vasopressin, oxytocin, sodium and osmolality. Urine was fractionally collected for measurements of electrolytes, aquaporin-2 and prostaglandin E2. ResultsPlasma vasopressin expressed a diurnal rhythm with a night-time increase in both...

  14. Differential effects of relaxin-3 and a selective relaxin-3 receptor agonist on food and water intake and hypothalamic neuronal activity in rats.

    Science.gov (United States)

    de Ávila, Camila; Chometton, Sandrine; Lenglos, Christophe; Calvez, Juliane; Gundlach, Andrew L; Timofeeva, Elena

    2018-01-15

    The neuropeptide relaxin-3 (RLN3) binds with high affinity to its cognate receptor, relaxin-family peptide receptor 3 (RXFP3), and with lower affinity to RXFP1, the cognate receptor for relaxin. Intracerebroventricular (icv) administration of RLN3 in rats strongly increases food and water intake and alters the activity of the hypothalamic-pituitary-adrenal (HPA) and gonadal (HPG) axes, but the relative involvement of RXFP3 and RXFP1 in these effects is not known. Therefore, the effects of icv administration of equimolar (1.1 nmol) amounts of RLN3 and the RXFP3-selective agonist RXFP3-A2 on food and water intake, plasma levels of corticosterone, testosterone, and oxytocin and c-fos mRNA expression in key hypothalamic regions in male rats were compared. Food intake was increased by both RLN3 and RXFP3-A2, but the orexigenic effects of RXFP3-A2 were significantly stronger than RLN3, 30 and 60min after injection. Water intake and plasma corticosterone and testosterone levels were significantly increased by RLN3, but not by RXFP3-A2. Conversely, RXFP3-A2 but not RLN3 decreased oxytocin plasma levels. RLN3, but not RXFP3-A2, increased c-fos mRNA levels in the parvocellular (PVNp) and magnocellular (PVNm) paraventricular and supraoptic (SON) hypothalamic nuclei, in the ventral medial preoptic area (MPAv), and in the organum vasculosum of the lamina terminalis (OVLT). A significant increase in c-fos mRNA expression was induced in the perifornical lateral hypothalamic area (LHApf) by RLN3 and RXFP3-A2. These results suggest that RXFP1 is involved in the RLN3 stimulation of water intake and activation of the HPA and HPG axes. The reduced food intake stimulation by RLN3 compared to RXFP3-A2 may relate to activation of both orexigenic and anorexigenic circuits by RLN3. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Pregnancy may favour the development of severe autoimmune central diabetes insipidus in women with vasopressin cell antibodies: description of two cases.

    Science.gov (United States)

    Bellastella, Giuseppe; Bizzarro, Antonio; Aitella, Ernesto; Barrasso, Mariluce; Cozzolino, Domenico; Di Martino, Sergio; Esposito, Katherine; De Bellis, Annamaria

    2015-03-01

    Recently, an increased incidence of central diabetes insipidus (CDI) in pregnancy, and less frequently in the post partum period, has been reported, most probably favoured by some conditions occurring in pregnancy. This study was aimed at investigating the influence of pregnancy on a pre-existing potential/subclinical hypothalamic autoimmunity. We studied the longitudinal behaviour of arginine-vasopressin cell antibodies (AVPcAbs) and post-pituitary function in two young women with a positive history of autoimmune disease and presence of AVPcAbs, but without clinical CDI, and who became pregnant 5 and 7 months after our first observation. The behaviour of post-pituitary function and AVPcAbs (by immunofluorescence) was evaluated at baseline, during pregnancy and for 2 years after delivery. AVPcAbs, present at low/middle titres at baseline in both patients, showed a titre increase during pregnancy in one patient and after delivery in the other patient, with development of clinically overt CDI. Therapy with 1-deamino-8-d-arginine vasopressin (DDAVP) caused a prompt clinical remission. After a first unsuccessful attempt of withdrawal, the therapy was definitively stopped at the 6th and the 7th month of post partum period respectively, when AVPcAbs disappeared, accompanied by post-pituitary function recovery, persisting until the end of the follow-up. The determination of AVPcAbs is advisable in patients with autoimmune diseases planning their pregnancy, because they could be considered good predictive markers of gestational or post partum autoimmune CDI. The monitoring of AVPcAb titres and post-pituitary function during pregnancy in these patients may allow for an early diagnosis and an early replacement therapy, which could induce the disappearance of these antibodies with consequent complete remission of CDI. © 2015 European Society of Endocrinology.

  16. Involvement of progranulin in hypothalamic glucose sensing and feeding regulation.

    Science.gov (United States)

    Kim, Hyun-Kyong; Shin, Mi-Seon; Youn, Byung-Soo; Namkoong, Churl; Gil, So Young; Kang, Gil Myoung; Yu, Ji Hee; Kim, Min-Seon

    2011-12-01

    Progranulin (PGRN) is a secreted glycoprotein with multiple biological functions, including modulation of wound healing and inflammation. Hypothalamic PGRN has been implicated in the development of sexual dimorphism. In the present study, a potential role for PGRN in the hypothalamic regulation of appetite and body weight was investigated. In adult rodents, PGRN was highly expressed in periventricular tanycytes and in hypothalamic neurons, which are known to contain glucose-sensing machinery. Hypothalamic PGRN expression levels were decreased under low-energy conditions (starvation and 2-deoxy-D-glucose administration) but increased under high-energy condition (postprandially). Intracerebrovetricular administration of PGRN significantly suppressed nocturnal feeding as well as hyperphagia induced by 2-deoxyglucose, neuropeptide Y, and Agouti-related peptide. Moreover, the inhibition of hypothalamic PGRN expression or action increased food intake and promoted weight gain, suggesting that endogenous PGRN functions as an appetite suppressor in the hypothalamus. Investigation of the mechanism of action revealed that PGRN diminished orexigenic neuropeptide Y and Agouti-related peptide production but stimulated anorexigenic proopiomelanocortin production, at least in part through the regulation of hypothalamic AMP-activated protein kinase. Notably, PGRN was also expressed in hypothalamic microglia. In diet-induced obese mice, microglial PGRN expression was increased, and the anorectic response to PGRN was blunted. These findings highlight a physiological role for PGRN in hypothalamic glucose-sensing and appetite regulation. Alterations in hypothalamic PGRN production or action may be linked to appetite dysregulation in obesity.

  17. Syndrome of alternating hypernatremia and hyponatremia after hypothalamic hamartoma surgery

    National Research Council Canada - National Science Library

    Abla, Adib A; Wait, Scott D; Forbes, Jonathan A; Pati, Sandipan; Johnsonbaugh, Roger E; Kerrigan, John F; Ng, Yu-Tze

    2011-01-01

    In this paper, the authors' goal was to describe the occurrence of alternating hypernatremia and hyponatremia in pediatric patients who underwent resection of hypothalamic hamartomas (HHs) for epilepsy...

  18. A newly identified mouse hypothalamic area having bidirectional neural connections with the lateral septum: the perifornical area of the anterior hypothalamus rich in chondroitin sulfate proteoglycans.

    Science.gov (United States)

    Horii-Hayashi, Noriko; Sasagawa, Takayo; Hashimoto, Takashi; Kaneko, Takeshi; Takeuchi, Kosei; Nishi, Mayumi

    2015-09-01

    While previous studies and brain atlases divide the hypothalamus into many nuclei and areas, uncharacterised regions remain. Here, we report a new region in the mouse anterior hypothalamus (AH), a triangular-shaped perifornical area of the anterior hypothalamus (PeFAH) between the paraventricular hypothalamic nucleus and fornix, that abundantly expresses chondroitin sulfate proteoglycans (CSPGs). The PeFAH strongly stained with markers for chondroitin sulfate/CSPGs such as Wisteria floribunda agglutinin and antibodies against aggrecan and chondroitin 6 sulfate. Nissl-stained sections of the PeFAH clearly distinguished it as a region of comparatively low density compared to neighboring regions, the paraventricular nucleus and central division of the anterior hypothalamic area. Immunohistochemical and DNA microarray analyses suggested that PeFAH contains sparsely distributed calretinin-positive neurons and a compact cluster of enkephalinergic neurons. Neuronal tract tracing revealed that both enkephalin- and calretinin-positive neurons project to the lateral septum (LS), while the PeFAH receives input from calbindin-positive LS neurons. These results suggest bidirectional connections between the PeFAH and LS. Considering neuronal subtype and projection, part of PeFAH that includes a cluster of enkephalinergic neurons is similar to the rat perifornical nucleus and guinea pig magnocellular dorsal nucleus. Finally, we examined c-Fos expression after several types of stimuli and found that PeFAH neuronal activity was increased by psychological but not homeostatic stressors. These findings suggest that the PeFAH is a source of enkephalin peptides in the LS and indicate that bidirectional neural connections between these regions may participate in controlling responses to psychological stressors. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  19. 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.

  20. 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.

  1. Structures of an unliganded neurophysin and its vasopressin complex: Implications for binding and allosteric mechanisms

    National Research Council Canada - National Science Library

    Wu, Chia Kuei; Hu, Bing; Rose, John P; Liu, Zhi‐Jie; Nguyen, Tam L; Zheng, Changsheng; Breslow, Esther; Wang, Bi‐Cheng

    2001-01-01

    The structures of des 1–6 bovine neurophysin‐II in the unliganded state and as its complex with lysine vasopressin were determined crystallographically at resolutions of 2.4 Å and 2.3 Å, respectively...

  2. Vasopressin/oxytocin-related signaling regulates gustatory associative learning in C. elegans

    NARCIS (Netherlands)

    I. Beets (Isabel); T.W.J. Janssen (Tom); E. Meelkop (Ellen); L. Temmerman (Liesbeth); N. Suetens (Nick); S. Rademakers (Suzanne); G. Jansen (Gert); L. Schoofs (Liliane)

    2012-01-01

    textabstractVasopressin- and oxytocin-related neuropeptides are key regulators of animal physiology, including water balance and reproduction. Although these neuropeptides also modulate social behavior and cognition in mammals, the mechanism for influencing behavioral plasticity and the evolutionary

  3. 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.

  4. Effect of vasopressin on sublingual microcirculation in a patient with distributive shock.

    Science.gov (United States)

    Dubois, Marc J; De Backer, Daniel; Creteur, Jacques; Anane, Sami; Vincent, Jean-Louis

    2003-06-01

    To assess the sublingual microcirculation in a patient during vasopressin administration for a distributive shock after cardiopulmonary bypass. Case-report in the Department of Intensive Care of a university hospital. A 53 year-old man developed severe distributive shock after cardiac transplant, requiring massive doses of vasopressor agents. Vasopressin administered twice at a dose of 0.02 U/min increased mean blood pressure and allowed partial weaning of other vasopressor drugs. Microcirculatory alterations were assessed by orthogonal polarization spectral technique: 50% and 60% of capillaries were perfused at baseline, and these proportions did not worsen when vasopressin was administered. Despite its strong vasopressor effects vasopressin infusion did not worsen microcirculatory alterations in this patient with distributive shock following cardiac surgery.

  5. Vasopressin in Vasodilatory Shock for Both Left and Right Heart Anomalous Pediatric Patients after Cardiac Surgery.

    Science.gov (United States)

    Lu, Zhongyuan; Wang, Xu; Yang, Juxian; Li, Shoujun; Yan, Jun

    2017-11-03

    Although the use of vasopressin has become common place in pediatric patients with vasodilatory shock after cardiac surgery, its efficacy and hemodynamic effects have not been systematically documented. Furthermore, previous studies were mainly limited patients with left heart anomalies. To date, the use of vasopressin in patients with right heart anomalies hasn't yet been reported. To clarify the hemodynamic effects of vasopressin on pediatric patients with vasodilatory shock after cardiopulmonary bypass, 70 consecutive patients, most of whom with right heart anomalies were retrospectively analyzed in Fuwai Hospital from October 2013 to September 2015. Vasopressin was administered continuously at a dose of 0.0002-0.002 u/kg/min. Hemodynamics, urine output and catecholamine vasopressor doses were compared before and after vasopressin initiation. showed that besides of the significant increase in blood pressure at 2 hours after vasopressin administration, the systemic vascular resistance index also prominently elevated from 894.3 ± 190.8 to 1138.2 ± 161.4 dyn/s per cm per m, while the heart rate, right atrial pressure, pulmonary artery pressure had a trend of decline. Subsequently the fluid requirement, the catecholamine vasopressor requirement both decreased and urine output increased. Lactate concentration showed a later remarkable decline at 12 hours since vasopressin administration. All the 70 patients survived to hospital discharge. low dose of vasopressin administration was associated with great and timely hemodynamic improvement for pediatric patients with vasodilatory shock after cardiac surgery without any significant adverse effects.

  6. Do vasopressin V2 receptor antagonists benefit cirrhotics with refractory ascites?

    OpenAIRE

    Fukui, Hiroshi

    2015-01-01

    Hyponatremia is a frequent complication of advanced cirrhosis with ascites associated with increased morbidity and mortality. It is caused by an impairment in the renal capacity to eliminate solute-free water and is considered to be related to persistent secretion of vasopressin despite low serum osmolality. This nonosmotic release of vasopressin is mediated by the autonomic nervous system, which senses the underfilling of arterial vascular component. This reduction of effective arterial bloo...

  7. Increase in Alzheimer's related markers preceeds memory disturbances: studies in vasopressin-deficient Brattleboro rat.

    Science.gov (United States)

    Varga, János; Klausz, Barbara; Domokos, Ágnes; Kálmán, Sára; Pákáski, Magdolna; Szűcs, Szabina; Garab, Dénes; Zvara, Ágnes; Puskás, László; Kálmán, János; Tímár, Júlia; Bagdy, György; Zelena, Dóra

    2014-01-01

    Alzheimer's disease (AD) is the most common form of dementia in the elderly. For more effective therapy early diagnostic markers could be beneficial. Therefore we compared one year old rats with adults and examined if changes in possible brain markers of AD preceeded memory decline. We also tested if vasopressin-deficient animals were useful model of AD as vasopressin has well known positive effect on memory and AD patient has decreased vasopressin production. We compared adult (3 month) and old (12 month), normal and vasopressin-deficient Brattleboro rats. To receive a comprehensive picture about their memory we examined their social discrimination, object discrimination and conditioned learning abilities (shuttle box). Amyloid precursor protein (APP), mitogen-activated protein kinase 1 (MAPK1), β-actin and tryptophan 2,3-dioxygenase 2 (TDO2) mRNA levels was measured by quantitative PCR. There was no difference between the memory of adult and aged groups. The vasopressin-deficient rats at both ages showed a weaker performance in the course of social and object discrimination tests and a higher escape failure during the shuttle box experiment. The brain marker mRNAs of the elder animals were higher than the levels of the adults, but the absence of vasopressin had no influence on them. Thus, the one year old rats showed elevated levels of AD-related markers, but memory deficits were observable only in vasopressin deficient animals. Vasopressin does not seem to have pathogenic role in AD. Changes in the studied markers might predict later symptoms, although further studies are required for confirmation. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Oxytocin alleviates orofacial mechanical hypersensitivity associated with infraorbital nerve injury through vasopressin-1A receptors of the rat trigeminal ganglia.

    Science.gov (United States)

    Kubo, Asako; Shinoda, Masamichi; Katagiri, Ayano; Takeda, Mamoru; Suzuki, Tatsuro; Asaka, Junichi; Yeomans, David C; Iwata, Koichi

    2017-04-01

    Oxytocin (OXT) is a neuropeptide hormone synthesized and secreted by hypothalamic neurons and has been reported to play a significant role in pain modulation. However, the mechanisms underlying OXT's antinociceptive effect on neuropathic pain are not fully understood. In this study, we examined the peripheral effect of OXT on mechanical hypersensitivity induced by partial ligation of the infraorbital nerve (PNL) in rats. Mechanical hypersensitivity in the whisker pad skin after PNL was attenuated by the direct administration of OXT into the trigeminal ganglion (TG). The proportion of vasopressin-1A receptor (V1A-R)-immunoreactive, but not OXT-receptor-immunoreactive, neurons significantly increased among TG neurons innervating the whisker pad skin after PNL. In a patch-clamp recording from TG neurons isolated from PNL rats, the resting membrane potential of OXT-treated neurons was significantly decreased, and the current thresholds of OXT-treated neurons for spike generation (rheobases) were significantly greater than those of vehicle-treated neurons. In addition, OXT increased voltage-gated K channel currents in PNL animals. Furthermore, intra-TG administration of a selective V1A-R antagonist reversed the OXT-induced alleviation of mechanical hypersensitivity, and coapplication of the antagonist opposed OXT's effects on the resting membrane potential, rheobase, and K current. These findings suggest that OXT is effective at suppressing TG neuronal hyperexcitability after nerve injury, likely by modulation of voltage-gated K channels through V1A-R. This signaling mechanism represents a potential therapeutic target for the treatment of orofacial neuropathic pain.

  9. Familial vasopressin-sensitive ACTH-independent macronodular adrenal hyperplasia (VPs-AIMAH): clinical studies of three kindreds.

    Science.gov (United States)

    Gagliardi, Lucia; Hotu, Cheri; Casey, Graeme; Braund, Wilton J; Ling, King-Hwa; Dodd, Thomas; Manavis, James; Devitt, Peter G; Cutfield, Richard; Rudzki, Zbigniew; Scott, Hamish S; Torpy, David J

    2009-06-01

    Cushing's syndrome due to familial ACTH-independent macronodular adrenal hyperplasia (AIMAH) has been reported in small kindreds. In vasopressin-sensitive AIMAH (VPs-AIMAH), VP stimulates an aberrant, ACTH-independent increase in cortisol. The aims of this study were to (i) delineate the preclinical phenotype of VPs-AIMAH in a three-generation kindred (AIMAH-01) and two smaller kindreds (AIMAH-02 and AIMAH-03) and (ii) investigate the aetiology of VP sensitivity in AIMAH-01. Clinical studies of three kindreds for adrenal tumours or early Cushing's and molecular studies of adrenal tumours (AIMAH-01). Thirty-three individuals, from three kindreds, were screened for perturbations of the hypothalamic-pituitary-adrenal axis or adrenal tumours. Patients underwent clinical, biochemical and adrenal imaging investigations. Evaluation included low-dose (1 IU/70 kg) VP stimulation. Adrenal VP receptor (AVPR1A, AVPR1B, AVPR2) expression (AIMAH-01) was assessed using RT-PCR and immunohistochemistry (IHC). IHC for VP was also performed. AIMAH-01 had three siblings with Cushing's, and four individuals with suppressed ACTH/aberrant VP responses and/or adrenal nodules. In AIMAH-02, a father and son were affected. AIMAH-03 had three siblings with Cushing's. RT-PCR showed adrenal overexpression of AVPR1A and AVPR1B. IHC detected AVPR1A. The adrenal tumour from one patient also stained weakly for VP and AVPR2. Adrenal nodules, suppressed ACTH and increased VP sensitivity may represent preclinical disease, allowing early detection, and treatment, of affected individuals. In AIMAH-01, increased VP sensitivity may be due to adrenal VP receptor overexpression. In these kindreds, VPs-AIMAH is familial, and autosomal dominant inheritance is most likely.

  10. 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

  11. Arginine Vasopressin Effects on Subjective Judgments and Neural Responses to Same and Other-Sex Faces in Men and Women.

    Science.gov (United States)

    Rilling, James K; Li, Ting; Chen, Xiangchuan; Gautam, Pritam; Haroon, Ebrahim; Thompson, Richmond R

    2017-01-01

    Arginine vasopressin (AVP) influences social and emotional behaviors across a wide range of species. In humans, intranasal AVP has been previously shown to alter physiological responses to and subjective judgments of same-sex faces in both men and women. The present study attempted to elucidate the neural mechanism for these effects by randomizing 40 healthy men and 40 healthy women to treatment with either 40 IU intranasal AVP or a saline placebo approximately 30 min before imaging their brain function with fMRI as they viewed same and other-sex faces. All subjects were also scanned a second time several days later with no treatment to evaluate the persistence of AVP effects over time. AVP acutely increased positive ratings of same-sex faces in women, with some evidence that these effects persisted until the second scan. While AVP had no acute effects on same-sex ratings in men, AVP increased positive ratings of same-sex faces several days later. On the other hand, AVP had no effect on other-sex face judgments in either sex. AVP modulation of brain function was focused on the nucleus accumbens (NAc) and the lateral septum, two reward processing areas involved in the formation of social bonds. AVP provoked acute increases in right NAc and bilateral lateral septum responses to female faces among men, with left lateral septum responses persisting over time while right NAc responses reversed over time. Finally, AVP modulated hypothalamic activation to faces in both men and women. The present study therefore indicates that intranasal AVP affects subjective ratings and neural responses to same and other-sex faces in men and women, with some effects persisting and others emerging over time. Future studies should investigate whether AVP effects are modulated by individual variables such as genotype, personality, or attachment style as previously reported for other nonapeptides.

  12. Central vasopressin infusion prevents hibernation in the European hamster (Cricetus cricetus).

    Science.gov (United States)

    Hermes, M L; Buijs, R M; Masson-Pévet, M; van der Woude, T P; Pévet, P; Brenklé, R; Kirsch, R

    1989-01-01

    The amount of immunocytochemically detectable vasopressin in the brain of the European hamster (Cricetus cricetus) shows a seasonal variation; i.e., dense vasopressin immunoreactivity is present in the lateral septum during summer but is absent in autumn and winter [Buijs, R. M., Pévet, P., Masson-Pévet, M., Pool, C. W., De Vries, G. J., Canguilhem, B. & Vivien-Roels, B. (1986) Brain Res. 371, 193-196]. In the winter period the European hamster hibernates. Since vasopressin in the lateral septum is known to be involved in the control of body temperature, we investigated whether infusion of vasopressin in the lateral septum during autumn-winter could influence hypothermic patterns normally seen in hibernating animals. Hamsters whose lateral septum was infused with vasopressin showed almost no periods of hypothermia, whereas hamsters treated with control infusions displayed a normal hibernation pattern. The results indicate that persistence of vasopressin release in the lateral septum of the European hamster during winter can prevent hibernation. Images PMID:2762331

  13. Hypothalamic abnormality in patients with inflammatory demyelinating disorders.

    Science.gov (United States)

    Gao, Cong; Wu, Linzhan; Chen, Xiaohui; Long, Youming; Zhong, Rong; Yang, Ning; Chen, Yaotang

    2016-11-01

    Hypothalamic lesions in neuromyelitis optica (NMO) patients might be more specific for NMO than multiple sclerosis (MS). However, this is controversial. To characterize clinical features of patients with inflammatory demyelinating disorders (IDDs) with visible hypothalamic lesions using magnetic resonance imaging (MRI). Patients with IDDs (n = 429) were recruited retrospectively. Of 52 patients with hypothalamic images enrolled, 42 were positive for aquaporin-4 (AQP4) antibodies, including 28 patients with NMO, 6 with recurrent transverse myelitis, 3 with recurrent optic neuritis, and 5 with brainstem and brain syndrome. The remaining 10 patients were anti-AQP4-negative, including 3 with MS, 3 with acute disseminated encephalomyelitis, and 4 with other disorders. In the AQP4-positive group, manifestations, including ataxia, intractable hiccup and nausea, syndrome of inappropriate antidiuretic hormone secretion and encephalopathy were more frequent in those with hypothalamic lesions than those without. Cell counts of cerebrospinal fluid in patients with hypothalamic lesions differed from patients without lesions. Brain MRI abnormalities were more frequent in brainstem and hemisphere of the hypothalamic lesion group. Hypothalamic lesions were observed frequently in patients with AQP4 antibodies. Clinical manifestations and paraclinical features in AQP4-positive patients with hypothalamic lesions differed from those without lesions.

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

    DEFF Research Database (Denmark)

    Di Giglio, Maria Giulia; Muttenthaler, Markus; Harpsøe, Kasper

    2017-01-01

    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...

  15. Coordinated Regulation of Vasopressin Inactivation and Glucose Uptake by Action of TUG Protein in Muscle.

    Science.gov (United States)

    Habtemichael, Estifanos N; Alcázar-Román, Abel; Rubin, Bradley R; Grossi, Laura R; Belman, Jonathan P; Julca, Omar; Löffler, Michael G; Li, Hongjie; Chi, Nai-Wen; Samuel, Varman T; Bogan, Jonathan S

    2015-06-05

    In adipose and muscle cells, insulin stimulates the exocytic translocation of vesicles containing GLUT4, a glucose transporter, and insulin-regulated aminopeptidase (IRAP), a transmembrane aminopeptidase. A substrate of IRAP is vasopressin, which controls water homeostasis. The physiological importance of IRAP translocation to inactivate vasopressin remains uncertain. We previously showed that in skeletal muscle, insulin stimulates proteolytic processing of the GLUT4 retention protein, TUG, to promote GLUT4 translocation and glucose uptake. Here we show that TUG proteolysis also controls IRAP targeting and regulates vasopressin action in vivo. Transgenic mice with constitutive TUG proteolysis in muscle consumed much more water than wild-type control mice. The transgenic mice lost more body weight during water restriction, and the abundance of renal AQP2 water channels was reduced, implying that vasopressin activity is decreased. To compensate for accelerated vasopressin degradation, vasopressin secretion was increased, as assessed by the cosecreted protein copeptin. IRAP abundance was increased in T-tubule fractions of fasting transgenic mice, when compared with controls. Recombinant IRAP bound to TUG, and this interaction was mapped to a short peptide in IRAP that was previously shown to be critical for GLUT4 intracellular retention. In cultured 3T3-L1 adipocytes, IRAP was present in TUG-bound membranes and was released by insulin stimulation. Together with previous results, these data support a model in which TUG controls vesicle translocation by interacting with IRAP as well as GLUT4. Furthermore, the effect of IRAP to reduce vasopressin activity is a physiologically important consequence of vesicle translocation, which is coordinated with the stimulation of glucose uptake. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Structural characterization of arginine-vasopressin and lysine-vasopressin by Fourier- transform ion cyclotron resonance mass spectrometry and infrared multiphoton dissociation.

    Science.gov (United States)

    Bianco, Giuliana; Battista, Fabio; Buchicchio, Alessandro; Amarena, Concetta G; Schmitt-Kopplin, Philippe; Guerrieri, Antonio

    2015-01-01

    Arginine-vasopressin (AVP) and lysine-vasopressin (LVP) were analyzed by reversed-phase liquid chromatography/mass spectrometry (LC-MS) using Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) electrospray ionization (ESI) in the positive ion mode. LVP and AVP exhibited the protonated adduct [M+H](+) as the predominant ion at m/z 1056.43965 and at m/z 1084.44561, respectively. Infrared multiphoton dissociation (IRMPD), using a CO(2) laser source at a wavelength of 10.6 μm, was applied to protonated vasopressin molecules. The IRMPD mass spectra presented abundant mass fragments essential for a complete structural information. Several fragment ions, shared between two target molecules, are discussed in detail. Some previously unpublished fragments were identified unambiguously utilizing the high resolution and accurate mass information provided by the FT-ICR mass spectrometer. The opening of the disulfide loop and the cleavage of the peptide bonds within the ring were observed even under low-energy fragmentation conditions. Coupling the high-performance FT-ICR mass spectrometer with IRMPD as a contemporary fragmentation technique proved to be very promising for the structural characterization of vasopressin.

  17. 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.

  18. Adolescent exposure to anabolic/androgenic steroids and the neurobiology of offensive aggression: a hypothalamic neural model based on findings in pubertal Syrian hamsters.

    Science.gov (United States)

    Melloni, Richard H; Ricci, Lesley A

    2010-06-01

    Considerable public attention has been focused on the issue of youth violence, particularly that associated with drug use. It is documented that anabolic steroid use by teenagers is associated with a higher incidence of aggressive behavior and serious violence, yet little is known about how these drugs produce the aggressive phenotype. Here we discuss work from our laboratory on the relationship between the development and activity of select neurotransmitter systems in the anterior hypothalamus and anabolic steroid-induced offensive aggression using pubertal male Syrian hamsters (Mesocricetus auratus) as an adolescent animal model, with the express goal of synthesizing these data into an cogent neural model of the developmental adaptations that may underlie anabolic steroid-induced aggressive behavior. Notably, alterations in each of the neural systems identified as important components of the anabolic steroid-induced aggressive response occurred in a sub-division of the anterior hypothalamic brain region we identified as the hamster equivalent of the latero-anterior hypothalamus, indicating that this sub-region of the hypothalamus is an important site of convergence for anabolic steroid-induced neural adaptations that precipitate offensive aggression. Based on these findings we present in this review a neural model to explain the neurochemical regulation of anabolic steroid-induced offensive aggression showing the hypothetical interaction between the arginine vasopressin, serotonin, dopamine, gamma-aminobutyric acid, and glutamate neural systems in the anterior hypothalamic brain region. Copyright 2009 Elsevier Inc. All rights reserved.

  19. Early changes of hypothalamic angiotensin II receptors expression in gestational protein-restricted offspring: effect on water intake, blood pressure and renal sodium handling.

    Science.gov (United States)

    de Lima, Marcelo Cardoso; Scabora, José Eduardo; Lopes, Agnes; Mesquita, Flávia Fernandes; Torres, Daniele; Boer, Patrícia Aline; Gontijo, José Antonio Rocha

    2013-09-01

    The current study examines changes in the postnatal hypothalamic angiotensin receptors by maternal protein restriction (LP), and its impact on in uteri programming of hypertension in adult life. The data show that LP male pup body weight was significantly reduced when compared to that of control (NP) pups. Also, immunoblotting analysis demonstrated a significantly decreased expression of type 1 AngII receptors (AT1R) in the entire hypothalamic tissue extract of LP rats at 12 days of age compared to age-matched NP offspring. Conversely, the expression of the type 2 AngII (AT2R) receptors in 12-day- and 16-week-old LP hypothalamus was significantly increased. The current data show the influence of central AngII administration on water consumption in a concentration-dependent fashion, but also demonstrate that the water intake response to AngII was strikingly attenuated in 16-week-old LP. These results may be related to decreased brain arginine vasopressin (AVP) expression appearing in maternal protein-restricted offspring. The present investigation shows an early decrease in fractional urinary sodium excretion in maternal protein-restricted offspring. The decreased fractional sodium excretion was accompanied by a fall in proximal sodium excretion and occurred despite unchanged creatinine clearance. These effects were associated with a significant enhancement in arterial blood pressure in the LP group, but the precise mechanism of these phenomena remains unknown.

  20. 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.

  1. The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on corticotrophin-releasing hormone, arginine vasopressin, and pro-opiomelanocortin mRNA levels in the hypothalamus of the cynomolgus monkey.

    Science.gov (United States)

    Shridhar, S; Farley, A; Reid, R L; Foster, W G; Van Vugt, D A

    2001-10-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental contaminant that has profound deleterious effects on development and reproduction. TCDD may act at one or more levels to alter the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. The objective of this study was to investigate whether TCDD modulates neuroendocrine systems by altering gene expression of arginine vasopressin (AVP), corticotrophin-releasing hormone (CRH), or pro-opiomelanocortin (POMC), which are important neuroregulators of the HPA and HPG axes. Four groups of female cynomolgus monkeys (Macaca fascicularis) were administered daily oral doses of gelatin capsule containing TCDD (0, 1, 5, or 25 ng/kg body weight) mixed with glucose 5 days a week for 1 year. At the end of the dosing period, animals were euthanized and brains were harvested. CRH, AVP, and POMC mRNA levels were semiquantified by in situ hybridization histochemistry on 30-microm coronal sections of the brain. Blood collected on the day of euthanasia was assayed for cortisol and progesterone. CRH mRNA levels in the paraventricular nucleus (PVN) were significantly increased by the 2 higher TCDD doses (5 and 25 ng/kg/day) compared to controls (p HPA axis by a central effect involving CRH, but had no effect on the HPG axis at the doses tested.

  2. Effects of cysteamine administration on the in vivo incorporation of (/sup 35/S)cysteine into somatostatin-14, somatostatin-28, arginine vasopressin, and oxytocin in rat hypothalamus

    Energy Technology Data Exchange (ETDEWEB)

    Cameron, J.L.; Fernstrom, J.D.

    1986-09-01

    The effect of cysteamine injection on the in vivo incorporation of (/sup 35/S)cysteine into somatostatin-14 (SRIF-14), SRIF-28, arginine vasopressin (AVP), and oxytocin (OXT) in rat hypothalamus was studied. (/sup 35/S)Cysteine was injected into the third ventricle 1 h, 4 h, or 1 week after cysteamine (300 mg/kg, sc) injection; animals were killed 4 h later. The drug was found to substantially reduce immunoreactive SRIF levels, but not OXT or AVP, 4 h after its injection. Cysteamine also caused large reductions in label incorporation into SRIF-14, SRIF-28, and OXT 1 and 4 h after drug injection. However, (/sup 35/S)cysteine incorporation into AVP was increased substantially at these time points, while that into acid-precipitable protein was normal. One week after cysteamine injection, label incorporation into all hypothalamic peptides was normal. Cysteine specific activity was also measured after (/sup 35/S)cysteine injection and was found to be similar in treatment and control groups. The results suggest that cysteamine inhibits the syntheses of SRIF-14, SRIF-28, and OXT and stimulates that of AVP.

  3. Endoplasmic reticulum stress in vasopressin neurons of familial diabetes insipidus model mice: aggregate formation and mRNA poly(A) tail shortening.

    Science.gov (United States)

    Arima, Hiroshi; Morishita, Yoshiaki; Hagiwara, Daisuke; Hayashi, Masayuki; Oiso, Yutaka

    2014-01-01

    The immunoglobulin heavy chain binding protein (BiP) is an endoplasmic reticulum (ER) chaperone, which binds to newly synthesized secretory and transmembrane proteins to facilitate protein folding. BiP mRNA is expressed in the arginine vasopressin (AVP) neurons in the supraoptic nucleus of wild-type mice even in basal conditions, and the expression levels increase in response to dehydration. These data suggest that AVP neurons are subjected to ER stress. Familial neurohypophysial diabetes insipidus (FNDI) is caused by mutations in the gene locus of AVP. The mutant proteins could accumulate in the ER and possibly increase ER stress in the AVP neurons. We bred mice possessing a mutation causing FNDI, which manifested progressive polyuria, as do the patients with FNDI. Electron microscopic analyses demonstrated that aggregates accumulated in the ER of AVP neurons in FNDI mice. Despite polyuria, which could potentially induce dehydration, AVP mRNA expression was decreased in the supraoptic nucleus, and the AVP mRNA poly(A) tail length was shortened in FNDI mice compared with wild-type mice. Incubation of hypothalamic explants of wild-type mice with ER stressors caused shortening of the poly(A) tail length of AVP mRNA, accompanied by decreases in the expression. These data revealed a mechanism by which ER stress decreases poly(A) tail length of AVP mRNA, and this reduces the load of unfolded proteins that form the aggregates in ER of the AVP neurons in FNDI mice.

  4. 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.

  5. 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

  6. 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.

  7. Oral hypertonic saline causes transient fall of vasopressin in humans

    Energy Technology Data Exchange (ETDEWEB)

    Seckl, J.R.; Williams, D.M.; Lightman, S.L.

    1986-08-01

    After dehydration, oral rehydration causes a fall in plasma arginine vasopressin (AVP) that precedes changes in plasma osmolality. To investigate further the stimulus for this effect, its specificity, and association with thirst, six volunteers were deprived of water for 24 h and given a salt load on two separate occasions. On each study day they then drank rapidly 10 ml/kg of either tap water or hypertonic saline (360 mosmol/kg). There was a significant fall in plasma AVP from 2.0 +/- 0.3 to 1.2 +/- 0.4 pmol/l 5 min after drinking water and from 1.8 +/- 0.3 to 0.9 +/- 0.2 pmol/l after hypertonic saline. Plasma osmolality fell 30-60 min after water and was unchanged after saline. Plasma renin activity, oxytocin, and total protein all remained unchanged. All subjects reported diminished thirst after hypertonic saline. Gargling with water reduced thirst but did not affect plasma AVP. There appears to be a drinking-mediated neuroendocrine reflex that decreases plasma AVP irrespective of the osmolality of the liquid consumed. The sensation of thirst did not correlate with plasma osmolality and was not always related to plasma AVP concentration. AVP was measured by radioimmunoassay.

  8. Hyponatraemia in imported malaria: the pathophysiological role of vasopressin

    Directory of Open Access Journals (Sweden)

    Hoorn Ewout J

    2012-01-01

    Full Text Available Abstract Background In the pathophysiology of hyponatraemia in malaria, the relative contribution of appropriate and inappropriate arginine vasopressin (AVP release is unknown; the trigger for inappropriate AVP release is also unknown. Methods Serum copeptin, a stable and sensitive marker for AVP release, was analysed in a large cohort of patients with imported malaria (204 patients and in a small prospective substudy (23 patients in which urine sodium and osmolality were also available. Hyponatraemia was classified as mild (serum sodium 131-134 mmol/l and moderate-to-severe ( Results Serum copeptin on admission was higher in patients with moderate-to-severe hyponatraemia (median 18.5 pmol/L compared with normonatraemic patients (12.7 pmol/L, p p s = -0.17, p = 0.017. Stronger correlations were identified between serum C-reactive protein and copeptin (rs = -0.36, p s = 0.33, p Conclusions In hyponatraemic patients with imported malaria, AVP release was uniformly increased and was either appropriate or inappropriate. Although the exact trigger for inappropriate AVP release remains unknown, the higher body temperatures, correlations with C-reactive protein and long normalization times of serum sodium, suggest an important role of the host inflammatory response to the invading malaria parasite.

  9. Vasopressin inhibits LTP in the CA2 mouse hippocampal area.

    Directory of Open Access Journals (Sweden)

    Magda Chafai

    Full Text Available Growing evidence points to vasopressin (AVP as a social behavior regulator modulating various memory processes and involved in pathologies such as mood disorders, anxiety and depression. Accordingly, AVP antagonists are actually envisaged as putative treatments. However, the underlying mechanisms are poorly characterized, in particular the influence of AVP on cellular or synaptic activities in limbic brain areas involved in social behavior. In the present study, we investigated AVP action on the synapse between the entorhinal cortex and CA2 hippocampal pyramidal neurons, by using both field potential and whole-cell recordings in mice brain acute slices. Short application (1 min of AVP transiently reduced the synaptic response, only following induction of long-term potentiation (LTP by high frequency stimulation (HFS of afferent fibers. The basal synaptic response, measured in the absence of HFS, was not affected. The Schaffer collateral-CA1 synapse was not affected by AVP, even after LTP, while the Schaffer collateral-CA2 synapse was inhibited. Although investigated only recently, this CA2 hippocampal area appears to have a distinctive circuitry and a peculiar role in controlling episodic memory. Accordingly, AVP action on LTP-increased synaptic responses in this limbic structure may contribute to the role of this neuropeptide in controlling memory and social behavior.

  10. Characterization of a novel nonpeptide vasopressin V2-agonist, OPC-51803, in cells transfected human vasopressin receptor subtypes

    Science.gov (United States)

    Nakamura, Shigeki; Yamamura, Yoshitaka; Itoh, Shuji; Hirano, Takahiro; Tsujimae, Kenji; Aoyama, Masashi; Kondo, Kazumi; Ogawa, Hidenori; Shinohara, Tomoichi; Kan, Keizo; Tanada, Yoshihisa; Teramoto, Shuji; Sumida, Takumi; Nakayama, Sunao; Sekiguchi, Kazuo; Kambe, Toshimi; Tsujimoto, Gozoh; Mori, Toyoki; Tominaga, Michiaki

    2000-01-01

    We discovered the first nonpeptide arginine-vasopressin (AVP) V2-receptor agonist, OPC-51803. Pharmacological properties of OPC-51803 were elucidated using HeLa cells expressing human AVP receptor subtypes (V2, V1a and V1b) and compared with those of 1-desamino-8-D-arginine vasopressin (dDAVP), a peptide V2-receptor agonist.OPC-51803 and dDAVP displaced [3H]-AVP binding to human V2- and V1a-receptors with Ki values of 91.9±10.8 nM (n=6) and 3.12±0.38 nM (n=6) for V2-receptors, and 819±39 nM (n=6) and 41.5±9.9 nM (n=6) for V1a-receptors, indicating that OPC-51803 was about nine times more selective for V2-receptors, similar to the selectivity of dDAVP. OPC-51803 scarcely displaced [3H]-AVP binding to human V1b-receptors even at 10−4 M, while dDAVP showed potent affinity to human V1b-receptors with the Ki value of 13.7±3.2 nM (n=4).OPC-51803 concentration-dependently increased cyclic adenosine 3′, 5′-monophosphate (cyclic AMP) production in HeLa cells expressing human V2-receptors with an EC50 value of 189±14 nM (n=6). The concentration-response curve for cyclic AMP production induced by OPC-51803 was shifted to the right in the presence of a V2-antagonist, OPC-31260.At 10−5 M, OPC-51803 did not increase the intracellular Ca2+ concentration ([Ca2+]i) in HeLa cells expressing human V1a-receptors. On the other hand, dDAVP increased [Ca2+]i in HeLa cells expressing human V1a- and V1b-receptors in a concentration-dependent fashion.From these results, OPC-51803 has been confirmed to be the first nonpeptide agonist for human AVP V2-receptors without agonistic activities for V1a- and V1b-receptors. OPC-51803 may be useful for the treatment of AVP-deficient pathophysiological states and as a tool for AVP researches. PMID:10780976

  11. Melatonin and hypothalamic-pituitary-gonadal axis.

    Science.gov (United States)

    Shi, L; Li, N; Bo, L; Xu, Z

    2013-01-01

    Melatonin (N-acetyl-5-methoxy-tryptamine), a principal product of the pineal gland, is produced mainly during the dark phase of the circadian cycle. This hormone plays a crucial role in the regulation of circadian and seasonal changes in various aspects of physiology and neuroendocrine functions. In mammals, melatonin can influence sexual maturation and reproductive functions via activation of its receptors and binding sites in the hypothalamic-pituitary-gonadal (HPG) axis. This review summarizes current knowledge of melatonin on the hypothalamus, pituitary gland, and gonads. We also review recent progress in clinical applications of melatonin or potentials of using melatonin, as a reducer of oxidative stress, to improve reproductive functions for the diseases such as women infertility.

  12. The study of consistent properties of the vasopressin nasal dosage form

    Directory of Open Access Journals (Sweden)

    Al Nukarii Abdulkarim

    2016-12-01

    Full Text Available Evaluation of consistent properties is an important and integral part of investigations on the creation of semisolid nasal pharmacotherapeutic agents. The aim of this work is the study of consistent properties of developed nasal semisolid dosage form with synthetic analogue of vasopressin – arginine-vasopressin for the treatment of cognitive consequences of cerebral-vascular pathology. Materials and methods. The study of structural-mechanical characteristics of nasal ointment with 0.000005% arginine-vasopressin on the vaseline-lanolin-paraffin base was carried out by a rotary viscosimeter «Reotest-2» with cylindrical arrangement. It was established that consistent properties of arginine-vasopressin semisolid dosage form and «mechanical stability» (2.56 describe composition as a thixotropic system which provides with restorability after applying tension and allow to predict stability of consistent properties during a long-term storage. Calculated factors of dynamical flowing of arginine- vasopressin dosage form on the vaseline-lanolin-paraffin base (Кd1=28.7%; Kd2=53.84% quantitatively confirm satisfactory spreading degree of the system during application on the mucous membranes or in manufacturing process. Conclusions. The studies of consistent properties of nasal ointment with synthetic analogue of vasopressin – arginine-vasopressin 0.000005% on lipophilic basis for treatment of cognitive effects of cerebrovascular disease have been conducted by rotary viscometer «Reotest 2». It has been established that consistent properties of studied soft nasal dosage form of arginine-vasopressin and «mechanical stability» value of the system (2.56 characterize it as a thixotropic, that assure recovery from mechanical stress, that allows to predict the stability of consistent properties of the composition during prolonged storage. The calculated values of coefficients of dynamic flow of intranasal dosage form of arginine-vasopressin on vaseline

  13. Management of optic chiasmatic/hypothalamic astrocytomas in children

    Energy Technology Data Exchange (ETDEWEB)

    Steinbok, P.; Hentschel, S.; Almqvist, P.; Cochrane, D.D. [Univ. of British Columbia, British Columbia' s Children' s Hospital, Div. of Pediatric Neurosurgery, Dept. of Surgery, Vancouver, British Columbia (Canada); Poskitt, K. [Univ. of British Columbia, British Columbia' s Children' s Hospital, Dept. of Radiology, Vancouver, British Columbia (Canada)

    2002-05-01

    The management of optic chiasmatic gliomas is controversial, partly related to failure to separate out those tumors involving the optic chiasm only (chiasmatic tumors) from those also involving the hypothalamus (chiasmatic/hypothalamic tumors). The purpose of this study was: (i) to analyze the outcomes of chiasmatic and chiasmatic/hypothalamic tumors separately; and (ii) to determine the appropriateness of recommending radical surgical resection for the chiasmatic/hypothalamic tumors. A retrospective chart review of all newly diagnosed tumors involving the optic chiasm from 1982-1996 at British Columbia's Children's Hospital was performed. There were 32 patients less than 16 years of age, 14 with chiasmatic and 18 with chiasmatic/hypothalamic astrocytomas, with an average duration of follow-up of 5.8 years and 6.3 years, respectively. Ten of the patients with chiasmatic tumors and none with chiasmatic/hypothalamic tumors had neurofibromatosis I. Thirteen of the 14 chiasmatic tumors were managed with observation only, and none had progression requiring active intervention. For the chiasmatic/hypothalamic tumors. eight patients had subtotal resections (>95% resection), six had partial resections (50-95%), three had limited resections (<50%), and one had no surgery. There were fewer complications associated with the limited resections, especially with respect to hypothalamic dysfunction. There was no correlation between the extent of resection (subtotal, partial, or limited) and the time to tumor progression (average 18 months). In conclusion, chiasmatic and chiasmatic/hypothalamic tumors are different entities, which should be separated out for the Purposes of any study. For the chiasmatic/hypothalamic tumors, there was more morbidity and no prolongation of time to progression when radical resections were compared to more limited resections. Therefore, if surgery is performed, it may be appropriate to do a surgical procedure that strives only to provide a

  14. Successful treatment of severe anaphylactic shock with vasopressin. Two case reports.

    Science.gov (United States)

    Kill, Clemens; Wranze, Erich; Wulf, Hinnerk

    2004-07-01

    Severe anaphylactic shock is a life-threatening situation that needs immediate treatment of progressive hemodynamic failure. We report two cases of severe anaphylactic shock treated with arginine-vasopressin (AVP): In a 42-year-old male patient anaphylactic shock was caused by the sting of a hornet. At the scene, he was found unconscious, cyanotic, with a heart rate of 130/min without measurable blood pressure. The patient was intubated and ventilated with 100% oxygen, intravenous epinephrine (1 mg over 2 min) had no effect on blood pressure. After injection of 10 IU vasopressin, followed by infusion of 40 IU vasopressin, hemodynamics could be stabilized at once. In the second case, a 47-year-old male patient was stung by a wasp. At the scene he was unconscious, blood pressure was not measurable, heart rate was 140/min. The patient was treated with 40 IU vasopressin followed by rapid infusion of 500 ml NaCl 0.9%. After injection of vasopressin, blood pressure raised to 80/50 mm Hg and heart rate decreased to 90/min. Both patients needed ventilator therapy for several days and recovered fully. Copyright 2004 S. Karger AG, Basel

  15. Pituitary content of oxytocin, vasopressin and alpha-melanocyte-stimulating hormone in the fetus of the rat during labour

    NARCIS (Netherlands)

    Boer, K.; Dogterom, J.; Pronker, H. F.

    1980-01-01

    The pituitary contents of oxytocin, vasopressin and alpha-MSH were measured in fetal and newborn rats to assess possible changes in their release during the process of labour. In the 24 h period during which delivery is likely to occur in the Wistar rat, both the oxytocin and vasopressin content of

  16. 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...

  17. Associations between Vocal Symptoms and Genetic Variants in the Oxytocin Receptor and Arginine Vasopressin 1A Receptor Gene

    Science.gov (United States)

    Jämsen, Sofia Holmqvist; Johansson, Ada; Westberg, Lars; Santtila, Pekka; von der Pahlen, Bettina; Simberg, Susanna

    2017-01-01

    Purpose: Oxytocin and arginine vasopressin are associated with different aspects of the stress response. As stress is regarded as a risk factor for vocal symptoms, we wanted to explore the association between the oxytocin receptor gene ("OXTR") and arginine vasopressin 1A receptor gene ("AVPR1A") single-nucleotide polymorphisms…

  18. Hyper-responsiveness of adrenal gland to vasopressin resulting in enhanced plasma cortisol in patients with adrenal nodule(s).

    Science.gov (United States)

    Suzuki, Sawako; Uchida, Daigaku; Koide, Hisashi; Tanaka, Tomoaki; Noguchi, Yoshihiko; Saito, Yasushi; Tatsuno, Ichiro

    2008-10-01

    Hyper-responsiveness of plasma cortisol to vasopressin has been demonstrated in ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH) and some adrenal adenomas with Cushing's syndrome (CS). However, the clinical significance of hyper-responsiveness of plasma cortisol to vasopressin has not been investigated systematically in adrenal nodule(s). The aim of this study was to clarify the prevalence of hyper-responsiveness of plasma cortisol to vasopressin (vasopressin responder) and their clinical characteristics in terms of hormonal secretion using vasopressin-loading test in the patients with adrenal nodule(s) except pheochromocytomas. A vasopressin-loading test was performed on 61 consecutive patients with adrenal nodules (CS: 33, aldosterone-producing adenoma: 10, non-functional tumor: 18). Vasopressin responders were observed in 36.1% of adrenal nodule(s), 42.4% of CS and 28.5% of non-CS. In responders with CS, eight patients had bilateral nodules that were diagnosed as AIMAH, and the remaining six patients had a unilateral nodule. These patients had lower plasma cortisol than non-responders at both morning (Pcortisol was frequently observed among patients with adrenal nodule(s). The vasopressin responders among the patients with adrenal nodule(s) frequently had CS with low autonomous cortisol secretion.

  19. Effects of short- and long-duration hypothyroidism on hypothalamic-pituitary-adrenal axis function in rats: in vitro and in situ studies.

    Science.gov (United States)

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

    2012-12-01

    The purpose of this study is to assess the effects of hypothyroidism on the hypothalamic-pituitary-adrenal (HPA) axis; the functional integrity of each component of the HPA axis was examined in short-term and long-term hypothyroidism. Neuropeptide synthesis, release, and content were evaluated in vitro both in the hypothalamus and anterior pituitary, and corticosterone release was assessed in primary adrenal cell cultures at 7 (short-term) and 60 days (long-term hypothyroidism) after thyroidectomy in male rats. Hypothyroid rats showed adrenal insufficiency in several parameters, which were associated with the duration of hypothyroidism. Cerebrospinal (CSF) ACTH was decreased in all hypothyroid animals, while CSF corticosterone levels were significantly decreased only in long-term hypothyroidism. Long-term hypothyroid animals showed decreased corticotropin-releasing hormone (CRH) mRNA expression in the hypothalamic paraventricular nucleus under both basal and stress conditions, decreased CRH release from hypothalamic organ cultures after KCL and arginine vasopressin stimulation, as well as an increased number of anterior pituitary CRH receptors. In contrast, short-term hypothyroid rats showed changes in anterior pituitary function with an increased responsiveness to CRH that was associated with an increase in CRH receptors. Although both short- and long-term hypothyroidism was associated with significant decreases in adrenal weights, only long-term hypothyroid rats showed changes in adrenal function with a significant decrease of ACTH-induced corticosterone release from cultured adrenal cells. The data suggest that long-term hypothyroidism is associated with adrenal insufficiency with abnormalities in all three components of the HPA axis. Short-term hypothyroidism, on the other hand, is associated with increased pituitary corticotroph responsiveness to CRH.

  20. Prenatal ethanol exposure alters the effects of gonadectomy on hypothalamic-pituitary-adrenal activity in male rats.

    Science.gov (United States)

    Lan, N; Yamashita, F; Halpert, A G; Ellis, L; Yu, W K; Viau, V; Weinberg, J

    2006-09-01

    Prenatal ethanol exposure has marked effects on development of the hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes. In adulthood, ethanol-treated rats show altered gonadal hormone responses and reproductive function, and increased HPA responsiveness to stressors. Importantly, prenatal ethanol differentially alters stress responsiveness in adult males and females, raising the possibility that the gonadal hormones play a role in mediating prenatal ethanol effects on HPA function. To examine a possible testicular influence on HPA activity in males, we compared the effects of gonadectomy on HPA stress responses of adult male offspring from ethanol, pair-fed (PF) and ad libitum-fed control dams. Intact ethanol-treated rats showed increased adrenocorticotrophic hormone (ACTH) but blunted testosterone and luteinising hormone (LH) responses to restraint stress, and no stress-induced elevation in arginine vasopressin (AVP) mRNA levels compared to those observed in PF and/or control rats. Gonadectomy: (i) significantly increased ACTH responses to stress in control but not ethanol-treated and PF males; (ii) eliminated differences among groups in plasma ACTH and AVP mRNA levels; and (iii) altered LH and gonadotrophin-releasing hormone responses in ethanol-treated males. Taken together, these findings suggest that central regulation of both the HPA and HPG axes are altered by prenatal ethanol exposure, with normal testicular influences on HPA function markedly reduced in ethanol-treated animals. A decreased sensitivity to inhibitory effects of androgens could contribute to the HPA hyperresponsiveness typically observed in ethanol-treated males.

  1. Direct effect of hypothalamic neuropeptides on the release of catecholamines by adrenal medulla in sheep - study ex vivo.

    Science.gov (United States)

    Wrońska, D; Kania, B F; Błachuta, M

    2017-03-01

    Stress causes the activation of both the hypothalamic-pituitary-adrenocortical axis and sympatho-adrenal system, thus leading to the release from the adrenal medulla of catecholamines: adrenaline and, to a lesser degree, noradrenaline. It has been established that in addition to catecholamines, the adrenomedullary cells produce a variety of neuropeptides, including corticoliberine (CRH), vasopressin (AVP), oxytocin (OXY) and proopiomelanocortine (POMC) - a precursor of the adrenocorticotropic hormone (ACTH). The aim of this study was to investigate adrenal medulla activity in vitro depending, on a dose of CRH, AVP and OXY on adrenaline and noradrenaline release. Pieces of sheep adrenal medulla tissue (about 50 mg) were put on 24-well plates and were incubated in 1 mL of Eagle medium without hormone (control) or supplemented only once with CRH, AVP and OXY in three doses (10-7, 10-8 and 10-9 M) in a volume of 10 μL. The results showed that CRH stimulates adrenaline and noradrenaline release from the adrenal medulla tissue. The stimulating influence of AVP on adrenaline release was visible after the application of the two lower doses of this neuropeptide; however, AVP reduced noradrenaline release from the adrenal medulla tissue. A strong, inhibitory OXY effect on catecholamine release was observed, regardless of the dose of this hormone. Our results indicate the important role of OXY in the inhibition of adrenal gland activity and thus a better adaptation to stress on the adrenal gland level.

  2. 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.

  3. Hypothalamic lipid-laden astrocytes induce microglia migration and activation.

    Science.gov (United States)

    Kwon, Yoon-Hee; Kim, Jiye; Kim, Chu-Sook; Tu, Thai Hien; Kim, Min-Seon; Suk, Kyoungho; Kim, Dong Hee; Lee, Byung Ju; Choi, Hye-Seon; Park, Taesun; Choi, Myung-Sook; Goto, Tsuyoshi; Kawada, Teruo; Ha, Tae Youl; Yu, Rina

    2017-06-01

    Obesity-induced hypothalamic inflammation is closely associated with various metabolic complications and neurodegenerative disorders. Astrocytes, the most abundant glial cells in the central nervous system, play a crucial role in pathological hypothalamic inflammatory processes. Here, we demonstrate that hypothalamic astrocytes accumulate lipid droplets under saturated fatty acid-rich conditions, such as obese environment, and that the lipid-laden astrocytes increase astrogliosis markers and inflammatory cytokines (TNFα, IL-1β, IL-6, MCP-1) at the transcript and/or protein level. Medium conditioned by the lipid-laden astrocytes stimulate microglial chemotactic activity and upregulate transcripts of the microglia activation marker Iba-1 and inflammatory cytokines. These findings indicate that the lipid-laden astrocytes formed in free fatty acid-rich obese condition may participate in obesity-induced hypothalamic inflammation through promoting microglia migration and activation. © 2017 Federation of European Biochemical Societies.

  4. Hypothalamic obesity in children: pathophysiology to clinical management.

    Science.gov (United States)

    Haliloglu, Belma; Bereket, Abdullah

    2015-05-01

    Hypothalamic obesity (HyOb) is a complex neuroendocrine disorder caused by damage to the hypothalamus, which results in disruption of energy regulation. The key hypothalamic areas of energy regulation are the ARC (arcuate nucleus), the VMH (ventromedial hypothalamus), the PVN (paraventriculer nuclei) and the LHA (lateral hypothalamic area). These pathways can be disrupted mechanically by hypothalamic tumors, neurosurgery, inflammatory disorders, radiotherapy and trauma or functionally as such seen in genetic diseases. Rapid weight gain and severe obesity are the most striking features of HyOb and caused by hyperphagia, reduced basal metabolic rate (BMR) and decreased physical activity. HyOb is usually unresponsive to diet and exercise. Although, GLP-1 and its anologs seem to be a new agent, there is still no curative treatment. Thus, prevention is of prime importance and the clinicians should be alert and vigilant in patients at risk for development of HyOb.

  5. 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...

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

    Science.gov (United States)

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

    2015-01-01

    Background 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). Methods 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 arg8-vasopressin (V group), and 10 piglets received 0.4 U/kg of arg8-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. Results 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. Conclusion Combined use of vasopressin and adrenaline caused greater signs of cerebral and cardiac injury than use of vasopressin alone during experimental cardiopulmonary resuscitation. PMID:25645317

  7. 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.

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

    Science.gov (United States)

    MacLean, Evan L; Gesquiere, Laurence R; Gruen, Margaret E; Sherman, Barbara L; Martin, W Lance; Carter, C Sue

    2017-01-01

    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.

  9. Chimpanzee Personality and the Arginine Vasopressin Receptor 1A Genotype.

    Science.gov (United States)

    Wilson, V A D; Weiss, A; Humle, T; Morimura, N; Udono, T; Idani, G; Matsuzawa, T; Hirata, S; Inoue-Murayama, M

    2017-03-01

    Polymorphisms of the arginine vasopressin receptor 1a (AVPR1a) gene have been linked to various measures related to human social behavior, including sibling conflict and agreeableness. In chimpanzees, AVPR1a polymorphisms have been associated with traits important for social interactions, including sociability, joint attention, dominance, conscientiousness, and hierarchical personality dimensions named low alpha/stability, disinhibition, and negative emotionality/low dominance. We examined associations between AVPR1a and six personality domains and hierarchical personality dimensions in 129 chimpanzees (Pan troglodytes) living in Japan or in a sanctuary in Guinea. We fit three linear and three animal models. The first model included genotype, the second included sex and genotype, and the third included genotype, sex, and sex × genotype. All personality phenotypes were heritable. Chimpanzees possessing the long form of the allele were higher in conscientiousness, but only in models that did not include the other predictors; however, additional analyses suggested that this may have been a consequence of study design. In animal models that included sex and sex × genotype, chimpanzees homozygous for the short form of the allele were higher in extraversion. Taken with the findings of previous studies of chimpanzees and humans, the findings related to conscientiousness suggest that AVPR1a may be related to lower levels of impulsive aggression. The direction of the association between AVPR1a genotype and extraversion ran counter to what one would expect if AVPR1a was related to social behaviors. These results help us further understand the genetic basis of personality in chimpanzees.

  10. 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.

  11. 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.

  12. Hypothalamic germinoma masquerading as superior mesenteric artery (SMA) syndrome.

    Science.gov (United States)

    Vethakkan, Shireene R; Venugopal, Yogeswari; Tan, Alexander T B; Paramasivam, Sharmila S; Ratnasingam, Jeyakantha; Razak, Rohaya A; Alias, Azmi; Kassim, Fauziah; Choong, Karen

    2013-01-01

    To report a case of superior mesenteric artery (SMA) syndrome secondary to hypothalamic germinoma. We describe the clinical presentation, diagnostic work-up, management, and clinical course of a patient admitted with SMA syndrome who was subsequently found to have a hypothalamic germinoma. An adolescent boy was admitted to the surgical ward with progressive weight loss over a 2 year period and postprandial vomiting. He was diagnosed with SMA syndrome based on evidence of proximal duodenal dilatation, extrinsic compression of the distal duodenum, and a narrowed aortomesenteric angle (16°). Investigations performed to exclude thyrotoxicosis unexpectedly revealed secondary hypothyroidism and further evaluation demonstrated evidence of pan-hypopituitarism. Psychiatric evaluation excluded anorexia nervosa and bulimia. Magnetic resonance imaging (MRI) of the brain revealed a heterogeneously enhancing hypothalamic lesion, but a normal pituitary gland. Hormone replacement with hydrocortisone, desmopressin, testosterone, and thyroxine resulted in weight gain and resolution of gastrointestinal symptoms. A transventricular endoscopic biopsy subsequently confirmed a hypothalamic germinoma and he was referred to an oncologist. SMA syndrome secondary to severe weight loss is an uncommon cause of upper gastrointestinal obstruction. While there have been reports of poorly controlled diabetes mellitus and thyrotoxicosis manifesting as SMA syndrome, there are no published reports to date of SMA syndrome secondary to hypothalamic/pituitary disease. Management of SMA syndrome is conservative, as symptoms of intestinal obstruction resolve with weight gain following treatment of the underlying cause. Awareness of this uncommon presentation of endocrine cachexia/hypothalamic disease will prevent unnecessary laparotomies and a misdiagnosis of an eating disorder.

  13. Rax regulates hypothalamic tanycyte differentiation and barrier function in mice

    Science.gov (United States)

    Miranda-Angulo, Ana L.; Byerly, Mardi S.; Mesa, Janny; Wang, Hong; Blackshaw, Seth

    2013-01-01

    The wall of the ventral third ventricle is composed of two distinct cell populations: tanycytes and ependymal cells. Tanycytes regulate many aspects of hypothalamic physiology, but little is known about the transcriptional network that regulates their development and function. We observed that the retina and anterior neural fold homeobox transcription factor (Rax) is selectively expressed in hypothalamic tanycytes, and showed a complementary pattern of expression to markers of hypothalamic ependymal cells, such as Rarres2 (retinoic acid receptor responder). To determine whether Rax controls tanycyte differentiation and function, we generated Rax haploinsufficient mice and examined their cellular and molecular phenotype in adulthood. These mice appeared grossly normal, but careful examination revealed a thinning of the third ventricular wall and reduction of both tanycyte and ependymal markers. These experiments show that Rax is required for hypothalamic tanycyte and ependymal cell differentiation. Rax haploinsufficiency also resulted in the ectopic presence of ependymal cells in the α2 tanycytic zone, where few ependymal cells are normally found, suggesting that Rax is selectively required for α2 tanycyte differentiation. These changes in the ventricular wall were associated with reduced diffusion of Evans Blue tracer from the ventricle to the hypothalamic parenchyma, with no apparent repercussion on the gross anatomical or behavioral phenotype of these mice. In conclusion, we have provided evidence that Rax is required for the normal differentiation and patterning of hypothalamic tanycytes and ependymal cells, as well as for maintenance of the cerebrospinal fluid-hypothalamus barrier. PMID:23939786

  14. Proteomic analysis of hypothalamic injury in heatstroke rats.

    Science.gov (United States)

    Chao, Chien-Ming; Cheng, Bor-Chih; Chen, Chia-Ying; Lin, Mao-Tsun; Chang, Ching-Ping; Yang, Shun-Tai

    2015-06-01

    Ischemic and oxidative damage to the hypothalamus may be associated with decreased heat tolerance as well as heatstroke formation. The present study explores the hypothalamic proteome mechanisms associated with heatstroke-mediated hypothalamic ischemia, and oxidative damage. Heatstroke rats had hypotension, hypothalamic ischemia, and lethality. In addition, they had hyperthermia and hypothalamic blood-brain-barrier disruption, oxidative stress, activated inflammation, and neuronal apoptosis and degeneration. 2DE combined LC-MS/MS revealed that heatstroke-induced ischemic injury and apoptosis were associated with upregulation of L-lactate dehydrogenase but downregulation of both dihydropyriminase-related protein and 14-3-3 Zeta isoform protein. Heat-induced blood-brain-barrier disruption might be related to upregulation of glial fibrillary acidic protein. Oxidative stress caused by heatstroke might be related to upregulation of cytosolic dehydrogenase-1. Also, heat-induced overproduction of proinflammatory cytokines might be associated with downregulation of stathmin 1. Heat-induced hypothalamic ischemia, apoptosis, injury (or upregulation of L-lactate dehydrogenase), blood-brain-barrier disruption (or upregulation of glial fibrillary acidic protein), oxidative stress (or upregulation of cytosolic dehydrogenase-1), and activated inflammation (or downregulation of stathmin 1) were all significantly reversed by whole body cooling. Our data indicate that cooling therapy improves outcomes of heatstroke by modulating hypothalamic proteome mechanisms. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. 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 hypothalamic...

  16. 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.

  17. Hypothalamic effects of thyroid hormones on metabolism.

    Science.gov (United States)

    Martínez-Sánchez, Noelia; Alvarez, Clara V; Fernø, Johan; Nogueiras, Rubén; Diéguez, Carlos; López, Miguel

    2014-10-01

    Over the past few decades, obesity and its related metabolic disorders have increased at an epidemic rate in the developed and developing world. New signals and factors involved in the modulation of energy balance and metabolism are continuously being discovered, providing potential novel drug targets for the treatment of metabolic disease. A parallel strategy is to better understand how hormonal signals, with an already established role in energy metabolism, work, and how manipulation of the pathways involved may lead to amelioration of metabolic dysfunction. The thyroid hormones belong to the latter category, with dysregulation of the thyroid axis leading to marked alterations in energy balance. The potential of thyroid hormones in the treatment of obesity has been known for decades, but their therapeutic use has been hampered because of side-effects. Data gleaned over the past few years, however, have uncovered new features at the mechanisms of action involved in thyroid hormones. Sophisticated neurobiological approaches have allowed the identification of specific energy sensors, such as AMP-activated protein kinase and mechanistic target of rapamycin, acting in specific groups of hypothalamic neurons, mediating many of the effects of thyroid hormones on food intake, energy expenditure, glucose, lipid metabolism, and cardiovascular function. More extensive knowledge about these molecular mechanisms will be of great relevance for the treatment of obesity and metabolic syndrome. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Arginine Vasopressin and Arginine Vasopressin Receptor 1b Involved in Electroacupuncture‐Attenuated Hypothalamic‐Pituitary‐Adrenal Axis Hyperactivity in Hepatectomy Rats

    Science.gov (United States)

    Zhu, Jing; Chen, Zhejun; Zhu, LiTing; Meng, ZeHui; Wu, GenCheng

    2015-01-01

    Objective The study aims to know the effect of electroacupuncture (EA) in maintenance of the homeostasis of the neuroendocrine system in hepatectomy rats and the involvement of arginine vasopressin (AVP) signaling in hypothalamus after EA was observed. Materials and Methods Rats were randomly assigned to four groups, including the intact group, model group, sham‐EA group, and EA group. EA was given during the perioperative period at the Zusanli (ST36) and Sanyinjiao (SP6) points after hepatectomy. The serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were detected via radioimmunoassay. The expression of AVP, arginine vasopressin receptor 1a (AVPR1a), arginine vasopressin receptor 1b (AVPR1b), and glucocorticoid receptor (GR) was detected by Western blot after surgery. Results Compared with the intact group, the ACTH and CORT levels in the serum of model group were increased, whereas the ACTH and CORT levels were decreased in the EA group compared with the model group. Moreover, AVP and AVPR1b protein levels in the pituitary gland were increased in the model group and decreased in the EA group. Further, a distinct increase in the AVP and AVPR1a protein levels was observed in the model group, whereas they were significantly decreased in the EA group. Blockade of AVPR1b by nelivaptan reduced the increase of ACTH and CORT. D [Leu4, Lys8] vasopressin can inhibit the effect of EA in rectification of the hyperactivity of the hypothalamic‐pituitary‐adrenal (HPA) axis. Conclusions EA application at ST36 and SP6 can ameliorate the hyperactivity of the HPA axis via AVP signaling during the perioperative period. PMID:26573696

  19. The hypothalamic-pituitary-adrenal and the hypothalamic- pituitary-gonadal axes interplay.

    Science.gov (United States)

    Mastorakos, George; Pavlatou, Maria G; Mizamtsidi, Maria

    2006-01-01

    Vertebrates respond to stress with activation of the hypothalamic-pituitary-adrenal (HPA) axis, the adrenergic and the autonomic nervous systems. The principal central nervous system regulators of the HPA axis are corticotropin releasing hormone (CRH) and antidiuretic hormone (AVP). Apart from in the central nervous system, CRH has been found in the adrenal medulla, ovaries, myometrium, endometrium, placenta, testis and elsewhere. The activation of the HPA axis during stress affects all body systems. The reproductive axis is inhibited by the HPA axis for the sake of saving energy. The changes to the hypothalamic-pituitary-gonadal (HPG) axis during stress are species-specific, and depend on the type and duration of the stimulus. Several conditions may be associated with altered regulation of the HPA axis. Polycystic ovary syndrome, anorexia nervosa and pregnancy in the third trimester are all characterized by HPA axis activation. In contrast, during the postpartum period, HPA axis suppression is implicated in the "postpartum blues". The actions of CRH are also essential in fetal development and neonatal survival.

  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. Cloning and identification of an oxytocin/vasopressin-like receptor and its ligand from insects

    DEFF Research Database (Denmark)

    Stafflinger, Elisabeth; Hansen, Karina K; Hauser, Frank

    2008-01-01

    to the locust peptide, which we named inotocin (for insect oxytocin/vasopressin-like peptide) and a gene coding for an inotocin G protein-coupled receptor (GPCR). We cloned the Tribolium inotocin preprohormone and the inotocin GPCR and expressed the GPCR in CHO cells. This GPCR is strongly activated by low...

  2. 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 ...

  3. Atrial distension, arterial pulsation, and vasopressin release during negative pressure breathing in humans

    DEFF Research Database (Denmark)

    Pump, B; Damgaard, M; Gabrielsen, A

    2001-01-01

    During an antiorthostatic posture change, left atrial (LA) diameter and arterial pulse pressure (PP) increase, and plasma arginine vasopressin (AVP) is suppressed. By comparing the effects of a 15-min posture change from seated to supine with those of 15-min seated negative pressure breathing in ...

  4. Physiology and pathophysiology of the vasopressin-regulated renal water reabsorption.

    NARCIS (Netherlands)

    Boone, M.; Deen, P.M.T.

    2008-01-01

    To prevent dehydration, terrestrial animals and humans have developed a sensitive and versatile system to maintain their water homeostasis. In states of hypernatremia or hypovolemia, the antidiuretic hormone vasopressin (AVP) is released from the pituitary and binds its type-2 receptor in renal

  5. 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...

  6. Oxytocin/vasopressin and gonadotropin-releasing hormone from cephalopods to vertebrates.

    Science.gov (United States)

    Minakata, Hiroyuki

    2010-07-01

    Recent advances in peptide search methods have revealed two peptide systems that have been conserved through metazoan evolution. Members of the oxytocin/vasopressin-superfamily have been identified from protostomian and deuterostomian animals, indicating that the oxytocin/vasopressin hormonal system represents one of the most ancient systems. In most protostomian animals, a single member of the superfamily shares oxytocin-like and vasopressin-like actions. Co-occurrence of two members has been discovered in modern cephalopods, octopus, and cuttlefish. We propose that cephalopods have developed two peptides in the molluscan evolutionary lineage like vertebrates have established two lineages in the oxytocin/vasopressin superfamily. The existence of gonadotropin-releasing hormone (GnRH) in protostomian animals was initially suggested by immunohistochemical analysis using chordate GnRH antibodies. A peptide with structural features similar to those of chordate GnRHs was originally isolated from octopus, and an identical peptide has been characterized from squid and cuttlefish. Novel forms of GnRH-like molecules from other molluscs, an annelid, arthropods, and nematodes demonstrate somewhat conserved structures at the N-terminal regions; but structures of the C-terminal regions critical to gonadotropin-releasing activity are diverse. These findings may be important for the study of the molecular evolution of GnRH in protostomian animals.

  7. Activation of vasopressin neurons in the human supraoptic and paraventricular nucleus in senescence and senile dementia

    NARCIS (Netherlands)

    Hoogendijk, J. E.; Fliers, E.; Swaab, D. F.; Verwer, R. W.

    1985-01-01

    A recent study has shown that vasopressin (AVP) cells in the human supraoptic (SON) and paraventricular (PVN) nuclei increase in size after 60 years of age, suggesting that AVP production is increased in senescence. In the present study, the same brain material was used for the determination of

  8. Post-training vasopressin injections may facilitate or delay shuttle-box avoidance extinction

    NARCIS (Netherlands)

    Hagan, J.J.; Bohus, B.; Wied, D. de

    1982-01-01

    After training to avoid footshock in a two-way shuttle box rats were injected with lysine vasopressin (LVP) and returned to the shuttle box 24 hr later for 10 extinction trials. Experiment 1 shows that when injected 30 min after training subsequent extinction responding varied as an inverted

  9. Characterization of vasopressin V2 receptor mutants in nephrogenic diabetes insipidus in a polarized cell model

    NARCIS (Netherlands)

    Robben, J.H.; Knoers, N.V.A.M.; Deen, P.M.T.

    2005-01-01

    X-linked nephrogenic diabetes insipidus (NDI) is caused by mutations in the gene encoding the vasopressin V2 receptor (V2R). For the development of a tailored therapy for NDI, knowledge of the cellular fate of V2R mutants is needed. It would be useful when this fate could be predicted from the

  10. Use of Arginine Vasopressin in the Management of Vasodilatory Shock After CABG - A Clinical Tria.

    Directory of Open Access Journals (Sweden)

    Sanjay O

    2003-01-01

    Full Text Available Vasodilatory shock requiring treatment with catecholamines occurs in some patients following cardiopulmonary bypass. We investigated the use of vasopressin in the treatment of this syndrome. Forty patients with a left main coronary artery disease and a poor left ventricular function (ejection fraction <30% were studied. Only those patients (n=12, 30% in whom difficulty was experienced in maintaining a mean arterial pressure of > 60 mm Hg and a systemic vascular resistance of greater than 900 dynes.sec.cm5 on maximal doses of pharmacological and mechanical support were selected. Patients underwent a standard cardiac anaesthesia protocol. All patients had a Swan-ganz catheter inserted pre-operatively. Arginine vasopressin was administered as a bolus of 0.015 units/kg intravenously followed by an infusion of 0.03 units/kg/hour. This dose increased the mean arterial pressure from 67+/-7 to 95+/-5 mm Hg and the systemic vascular resistance from 860+/-55 to 1502+/-71 dynes.sec.cm-5. It was also associated with a decrease in pharmacological support. All subjects responded to vasopressin administration. Vasopressin is an effective pressor in vasodilatory shock after cardiopulmonary bypass.

  11. 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...

  12. Relief of nocturnal enuresis by desmopressin is kidney and vasopressin type 2 receptor independent.

    NARCIS (Netherlands)

    Robben, J.H.; Sze, M.; Knoers, N.V.A.M.; Eggert, P.; Deen, P.M.T.; Muller, D.

    2007-01-01

    Primary nocturnal enuresis (PNE) is a common problem in childhood and adolescence. Although various treatments are highly effective, a common underlying hypothesis on the pathogenesis is lacking. The success of desmopressin, a synthetic analogue of the antidiuretic hormone vasopressin, has been

  13. 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,

  14. Vasopressin receptors V1a and V2 are not osmosensors

    DEFF Research Database (Denmark)

    Pedersen, Kasper Lykke; Assentoft, Mette; Fenton, Robert A

    2015-01-01

    that was, however, independent of hyperosmotic challenges. Similarly, the cAMP production by the V2R was unaffected by hyperosmotic challenges although, in contrast to the V1aR, the V2R displayed an ability to support alternative signaling (IP production) at higher concentration of vasopressin. V1aR and V2...

  15. Neuroendocrine adaptation to stress in pigs, CRH and vasopressin in the paraventricular nucleus

    NARCIS (Netherlands)

    Karman, A.G.

    2003-01-01

    Differences in coping strategy present at birth as well as housing conditions may influence autonomic and endocrine stress responses.In rodents,corticotropin-releasing hormone (CRH) and vasopressin (VP) signaling in the

  16. Dorsomedial hypothalamic NPY and energy balance control.

    Science.gov (United States)

    Bi, Sheng; Kim, Yonwook J; Zheng, Fenping

    2012-12-01

    Neuropeptide Y (NPY) is a potent hypothalamic orexigenic peptide. Within the hypothalamus, Npy is primarily expressed in the arcuate nucleus (ARC) and the dorsomedial hypothalamus (DMH). While the actions of ARC NPY in energy balance control have been well studied, a role for DMH NPY is still being unraveled. In contrast to ARC NPY that serves as one of downstream mediators of actions of leptin in maintaining energy homeostasis, DMH NPY is not under the control of leptin. Npy gene expression in the DMH is regulated by brain cholecystokinin (CCK) and other yet to be identified molecules. The findings of DMH NPY overexpression or induction in animals with increased energy demands and in certain rodent models of obesity implicate a role for DMH NPY in maintaining energy homeostasis. In support of this view, adeno-associated virus (AAV)-mediated overexpression of NPY in the DMH causes increases in food intake and body weight and exacerbates high-fat diet-induced hyperphagia and obesity. Knockdown of NPY in the DMH via AAV-mediated RNAi ameliorates hyperphagia, obesity and glucose intolerance of Otsuka Long-Evans Tokushima Fatty rats in which DMH NPY overexpression has been proposed to play a causal role. NPY knockdown in the DMH also prevents high-fat diet-induced hyperphagia, obesity and impaired glucose homeostasis. A detailed examination of actions of DMH NPY reveals that DMH NPY specifically affects nocturnal meal size and produces an inhibitory action on within meal satiety signals. In addition, DMH NPY modulates energy expenditure likely through affecting brown adipocyte formation and thermogenic activity. Overall, the recent findings provide clear evidence demonstrating critical roles for DMH NPY in energy balance control, and also imply a potential role for DMH NPY in maintaining glucose homeostasis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. The DCDC2 intron 2 deletion impairs illusory motion perception unveiling the selective role of magnocellular-dorsal stream in reading (dis)ability.

    Science.gov (United States)

    Gori, Simone; Mascheretti, Sara; Giora, Enrico; Ronconi, Luca; Ruffino, Milena; Quadrelli, Ermanno; Facoetti, Andrea; Marino, Cecilia

    2015-06-01

    Developmental dyslexia (DD) is a heritable neurodevelopmental reading disorder that could arise from auditory, visual, and cross-modal integration deficits. A deletion in intron 2 of the DCDC2 gene (hereafter DCDC2d) increases the risk for DD and related phenotypes. In this study, first we report that illusory visual motion perception-specifically processed by the magnocellular-dorsal (M-D) stream-is impaired in children with DD compared with age-matched and reading-level controls. Second, we test for the specificity of the DCDC2d effects on the M-D stream. Children with DD and DCDC2d need significantly more contrast to process illusory motion relative to their counterpart without DCDC2d and to age-matched and reading-level controls. Irrespective of the genetic variant, children with DD perform normally in the parvocellular-ventral task. Finally, we find that DCDC2d is associated with the illusory motion perception also in adult normal readers, showing that the M-D deficit is a potential neurobiological risk factor of DD rather than a simple effect of reading disorder. Our findings demonstrate, for the first time, that a specific neurocognitive dysfunction tapping the M-D stream is linked with a well-defined genetic susceptibility. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Hyponatremia and V2 vasopressin receptor upregulation: a result of HSP90 inhibition.

    Science.gov (United States)

    Yang, Qiong; Puhm, Florian; Freissmuth, Michael; Nanoff, Christian

    2017-10-01

    Small-molecule inhibitors of heat-shock protein 90 (HSP90) have been under development as chemotherapeutic agents. The adverse events reported from early clinical trials included hyponatremia. Given the limited number of patients enrolled, the number of hyponatremia incidents was remarkable and repeatedly, the event was judged as severe. Inappropriate V2 vasopressin receptor stimulation is an established cause of hyponatremia. We explored the hypothesis that HSP90 inhibition produces hypersensitivity to vasopressin by upregulating V2-receptors. Experiments were carried out in cell culture using HEK293 cells with heterologous expression of the human V2-receptor and HELA cells with an endogenous V2-receptor complement. We tested the effect of HSP90 inhibition by three structurally unrelated compounds (alvespimycin, luminespib, radicicol) and asserted its specificity in cells depleted of cytosolic HSP90 (by RNA interference). Assays encompassed surface V2-receptor density and vasopressin-stimulated formation of cyclic AMP (cAMP). The results demonstrate a twofold increase in cell-surface receptor density following pre-incubation with each of the HSP90 inhibitors. The effect had a concentration-dependence consistent with the individual potencies to inhibit HSP90. Similarly, depletion of cytosolic HSP90 increased surface-receptor density and at the same time, reduced the inhibitor effect. Upregulated V2-receptors were fully functional; hence, in culture treated with an HSP90 inhibitor, addition of vasopressin resulted in higher levels of cAMP than in controls. Since formation of cAMP is the first signalling step in raising water permeability of the collecting duct epithelia, we suggest that V2-receptor upregulation generates hypersensitivity to vasopressin linking HSP90 inhibition to the development of hyponatremia.

  19. Changes in Copeptin and Bioactive Vasopressin in Runners With and Without Hyponatremia

    Science.gov (United States)

    Hew-Butler, Tamara; Hoffman, Martin D.; Stuempfle, Kristin J.; Rogers, Ian R.; Morgenthaler, Nils G.; Verbalis, Joseph G.

    2013-01-01

    Objective To evaluate changes in both the N-terminal (arginine vasopressin; AVP) and C-terminal (copeptin) fragments of the vasopressin prohormone before, during, and after an ultramarathon race and to assess vasopressin and copeptin concentrations in runners with and without hyponatremia. Design Observational study. Setting Three trials (2 sodium balance and 1 hyponatremia treatment) in 2 separate approximately 160-km footraces [Western States Endurance Run (WSER) and Javelina Jundred Mile Race (JJ100)]. Participants Six hyponatremic and 20 normonatremic runners; 19 finishers with 7 completing 100 km. Main Outcome Measures Plasma AVP ([AVP]p), copeptin ([copeptin]p), sodium ([Na+]p), and protein (%plasma volume change; %PV) concentrations. Results In the WSER Sodium Trial, a 3-fold prerace to postrace increase in both [AVP]p (0.7 ± 0.4 to 2.7 ± 1.9 pg/mL; P copeptin]p (10.3 ± 12.5 to 28.2 ± 16.3 pmol/L; nonsignificant) occurred, despite a 2 mEq/L decrease in [Na+]p (138.7 ± 2.3 to 136.7 ± 1.6 mEq/L; NS). A significant correlation was noted between [AVP]p and [copeptin]p postrace (r = 0.82; P copeptin]p (22.5 vs 24.9 pmol/L) were well above the detectable levels. A significant correlation was noted between [AVP]p and [copeptin]p 60 minutes after treatment (r = 0.94; P copeptin]p change and %PV change (r = −0.34; P Copeptin]p seems to be a reliable surrogate of stimulated [AVP]p during exercise. Nonosmotic vasopressin stimulation occurs during ultradistance running. [Copeptin]p may better reflect chronic (%PV) vasopressin secretion under conditions of endurance exercise. PMID:21519298

  20. Evaluation of Vasopressin for Septic Shock in Patients on Chronic Renin-Angiotensin-Aldosterone System Inhibitors.

    Science.gov (United States)

    Erwin, Beth L; Denaburg, Michael A; Barker, Andrew B; McArdle, Philip J; Windham, Samuel T; Morgan, Charity J

    2017-12-01

    To compare the hemodynamic response in septic shock patients receiving vasopressin who were on chronic renin-angiotensin-aldosterone system inhibitor therapy with those who were not. Single-center, retrospective cohort study. Medical and surgical ICUs at a 1,100-bed academic medical center. Medical and surgical ICU patients with septic shock who received vasopressin infusion added to at least one concomitant vasopressor agent between January 2014 and December 2015, then divided into two cohorts: 1) patients who were on chronic renin-angiotensin-aldosterone system inhibitor therapy as outpatients and 2) patients who were not on chronic renin-angiotensin-aldosterone system inhibitor therapy as outpatients. None. Mean arterial pressure at 6 hours was 72.2 mm Hg in the renin-angiotensin-aldosterone system inhibitor group versus 69.7 mm Hg in the non-renin-angiotensin-aldosterone system inhibitor group (p = 0.298). There was no difference in mean arterial pressure at 1, 24, or 48 hours between groups. Total concomitant vasopressor requirements, based on norepinephrine equivalents excluding vasopressin, were significantly lower at 24 hours in the renin-angiotensin-aldosterone system inhibitor group versus the non-renin-angiotensin-aldosterone system inhibitor group (10.7 vs 18.1 µg/min, respectively; p = 0.007), but no significant differences were seen at the other time points assessed. There were no significant differences in ICU or hospital length of stay or mortality. There was no significant difference in the primary outcome of 6-hour mean arterial pressure in septic shock patients receiving vasopressin who were on chronic renin-angiotensin-aldosterone system inhibitor therapy versus those receiving vasopressin who were not on chronic renin-angiotensin-aldosterone system inhibitor therapy. Renin-angiotensin-aldosterone system inhibitor patients had lower total concomitant vasopressor requirements at 24 hours compared with non-renin-angiotensin-aldosterone system

  1. Fatty-acid-mediated hypothalamic inflammation and epigenetic programming.

    Science.gov (United States)

    Cesar, Helena C; Pisani, Luciana Pellegrini

    2017-04-01

    A high-fat diet is the main environmental cue that has been studied in the hypothalamus since the discovery of its connection with hypothalamic inflammation. Current evidence shows hypothalamic inflammation as a likely mechanism for the dysregulation on the homeostatic control of energy balance, which leads to metabolic alterations and obesity. Although this mechanism seems to be reversible when set during adulthood, we argue whether dietary fatty acids, during critical periods of development, could affect hypothalamic function permanently and set an increased susceptibility to obesity. We found few experimental studies that looked at programming induced by different fatty acids on the hypothalamus. They clearly showed a connection between maternal fat diet, hypothalamic inflammation and metabolic alterations in the offspring. We found that not only a high-fat diet but also a normolipidic diet with unbalanced quantities of different fatty acids produced diverse inflammatory responses on the hypothalamus. Therefore, strategies of manipulating dietary fatty acids in pregnant and lactating women may have great impact on the population's future health. However, more research is still needed on the effects of fatty acids and the hypothalamic inflammation on programming. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Metabolic Context Regulates Distinct Hypothalamic Transcriptional Responses to Antiaging Interventions

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    Alexis M. Stranahan

    2012-01-01

    Full Text Available The hypothalamus is an essential relay in the neural circuitry underlying energy metabolism that needs to continually adapt to changes in the energetic environment. The neuroendocrine control of food intake and energy expenditure is associated with, and likely dependent upon, hypothalamic plasticity. Severe disturbances in energy metabolism, such as those that occur in obesity, are therefore likely to be associated with disruption of hypothalamic transcriptomic plasticity. In this paper, we investigated the effects of two well-characterized antiaging interventions, caloric restriction and voluntary wheel running, in two distinct physiological paradigms, that is, diabetic (db/db and nondiabetic wild-type (C57/Bl/6 animals to investigate the contextual sensitivity of hypothalamic transcriptomic responses. We found that, both quantitatively and qualitatively, caloric restriction and physical exercise were associated with distinct transcriptional signatures that differed significantly between diabetic and non-diabetic mice. This suggests that challenges to metabolic homeostasis regulate distinct hypothalamic gene sets in diabetic and non-diabetic animals. A greater understanding of how genetic background contributes to hypothalamic response mechanisms could pave the way for the development of more nuanced therapeutics for the treatment of metabolic disorders that occur in diverse physiological backgrounds.

  3. Arginine vasopressin, fluid balance and exercise: is exercise-associated hyponatraemia a disorder of arginine vasopressin secretion?

    Science.gov (United States)

    Hew-Butler, Tamara

    2010-06-01

    The ability of the human body to regulate plasma osmolality (POsm) within a very narrow and well defined physiological range underscores the vital importance of preserving water and sodium balance at rest and during exercise. The principle endocrine regulator of whole body fluid homeostasis is the posterior pituitary hormone, arginine vasopressin (AVP). Inappropriate AVP secretion may perpetuate either slow or rapid violation of these biological boundaries, thereby promoting pathophysiology, morbidity and occasional mortality. In the resting state, AVP secretion is primarily regulated by changes in POsm (osmotic regulation). The osmotic regulation of AVP secretion during exercise, however, may possibly be enhanced or overridden by many potential non-osmotic factors concurrently stimulated during physical activity, particularly during competition. The prevalence of these highly volatile non-osmotic AVP stimuli during strenuous or prolonged physical activity may reflect a teleological mechanism to promote water conservation during exercise. However, non-osmotic AVP secretion, combined with high fluid availability plus sustained fluid intake (exceeding fluid output), has been hypothesized to lead to an increase in both the incidence and related deaths from exercise-associated hyponatraemia (EAH) in lay and military populations. Inappropriately, high plasma AVP concentrations ([AVP](p)) associated with low blood sodium concentrations facilitate fluid retention and sodium loss, thereby possibly reconciling both the water intoxication and sodium loss theories of hyponatraemia that are currently under debate. Therefore, given the potential for a variety of exercise-induced non-osmotic stimuli for AVP secretion, hydration strategies must be flexible, individualized and open to change during competitive events to prevent the occurrence of rare, but life-threatening, EAH. This review focuses on the potential osmotic and non-osmotic stimuli to AVP secretion that may affect

  4. Involvement of non-NMDA glutamate receptors of the hypothalamic paraventricular nucleus in the cardiovascular response to the microinjection of noradrenaline into the dorsal periaqueductal gray area of rats.

    Science.gov (United States)

    Pelosi, Gislaine Garcia; Busnardo, Cristiane; Tavares, Rodrigo Fiacadori; Corrêa, Fernando Morgan Aguiar

    2015-03-30

    The dorsal periaqueductal gray area (dPAG) is involved in cardiovascular modulation. In a previous study, we showed that noradrenaline (NA) microinjected into the dPAG caused a vasopressin-mediated pressor response, involving a relay in the hypothalamic paraventricular nucleus (PVN). In the present study, we evaluated the involvement of ionotropic glutamate receptors within the PVN in the cardiovascular response to NA microinjection into the dPAG of unanesthetized rats. Microinjection of the selective NMDA glutamate receptor antagonist LY235959 (2nmol/100nL) unilaterally into the PVN did not affect the cardiovascular response evoked by microinjection of NA (15nmol/50nL) into the dPAG. On the other hand, unilateral PVN pretreatment with the non-NMDA glutamate receptor antagonist NBQX (2nmol/100nL) significantly reduced the pressor and cardiac response caused by microinjection of NA into the dPAG. In addition, bilateral PVN pretreatment with NBQX (2nmol/100nL) blocked the cardiovascular response to NA injected into the dPAG. In conclusion, the present results suggest that bilateral PVN activation of non-NMDA glutamate receptors mediates the vasopressin-related cardiovascular response to the microinjection of NA into the dPAG. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Identification of an oxytocinase/vasopressinase-like leucyl-cystinyl aminopeptidase (LNPEP) in teleost fish and evidence for hypothalamic mRNA expression linked to behavioral social status.

    Science.gov (United States)

    Elkins, Emma A; Walti, Kayla A; Newberry, Kathryn E; Lema, Sean C

    2017-09-01

    The vasotocin/vasopressin and isotocin/mesotocin/oxytocin family of nonapeptides regulate social behaviors and physiological functions associated with reproductive physiology and osmotic balance. While experimental and correlative studies provide evidence for these nonapeptides as modulators of behavior across all classes of vertebrates, mechanisms for nonapeptide inactivation in regulating these functions have been largely overlooked. Leucyl-cystinyl aminopeptidase (LNPEP) - also known as vasopressinase, oxytocinase, placental leucine aminopeptidase (P-LAP), and insulin-regulated aminopeptidase (IRAP) - is a membrane-bound zinc-dependent metalloexopeptidase enzyme that inactivates vasopressin, oxytocin, and select other cyclic polypeptides. In humans, LNPEP plays a key role in the clearance of oxytocin during pregnancy. However, the evolutionary diversity, expression distribution, and functional roles of LNPEP remain unresolved for other vertebrates. Here, we isolated and sequenced a full-length cDNA encoding a LNPEP-like polypeptide of 1033 amino acids from the ovarian tissue of Amargosa pupfish, Cyprinodon nevadensis. This deduced polypeptide exhibited high amino acid identity to human LNPEP both in the protein's active domain that includes the peptide binding site and zinc cofactor binding motif (53.1% identity), and in an intracellular region that distinguishes LNPEP from other aminopeptidases (70.3% identity). Transcripts encoding this LNPEP enzyme (lnpep) were detected at highest relative abundance in the gonads, hypothalamus, forebrain, optic tectum, gill and skeletal muscle of adult pupfish. Further evaluation of lnpep transcript abundance in the brain of sexually-mature pupfish revealed that lnpep mRNAs were elevated in the hypothalamus of socially subordinate females and males, and at lower abundance in the telencephalon of socially dominant males compared to dominant females. These findings provide evidence of an association between behavioral social

  6. 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.

  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. The role of NPY in hypothalamic mediated food intake.

    Science.gov (United States)

    Mercer, Rebecca E; Chee, Melissa J S; Colmers, William F

    2011-10-01

    Neuropeptide Y (NPY) is a highly conserved neuropeptide with orexigenic actions in discrete hypothalamic nuclei that plays a role in regulating energy homeostasis. NPY signals via a family of high affinity receptors that mediate the widespread actions of NPY in all hypothalamic nuclei. These actions are also subject to tight, intricate regulation by numerous peripheral and central energy balance signals. The NPY system is embedded within a densely-redundant network designed to ensure stable energy homeostasis. This redundancy may underlie compensation for the loss of NPY or its receptors in germline knockouts, explaining why conventional knockouts of NPY or its receptors rarely yield a marked phenotypic change. We discuss insights into the hypothalamic role of NPY from studies of its physiological actions, responses to genetic manipulations and interactions with other energy balance signals. We conclude that numerous approaches must be employed to effectively study different aspects of NPY action. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Efficient Generation of Hypothalamic Neurons from Human Pluripotent Stem Cells.

    Science.gov (United States)

    Wang, Liheng; Egli, Dieter; Leibel, Rudolph L

    2016-07-01

    The hypothalamus comprises neuronal clusters that are essential for body weight regulation and other physiological functions. Insights into the complex cellular physiology of this region of the brain are critical to understanding the pathogenesis of obesity, but human hypothalamic cells are largely inaccessible for direct study. Here we describe a technique for generation of arcuate-like hypothalamic neurons from human pluripotent stem (hPS) cells. Early activation of SHH signaling and inhibition of BMP and TGFβ signaling, followed by timed inhibition of NOTCH, can efficiently differentiate hPS cells into NKX2.1+ hypothalamic progenitors. Subsequent incubation with BDNF induces the differentiation and maturation of pro-opiomelanocortin and neuropeptide Y neurons, which are major cell types in the arcuate hypothalamus. These neurons have molecular and cellular characteristics consistent with arcuate neurons. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

  10. The Role of Hypothalamic Neuropeptides in Neurogenesis and Neuritogenesis

    Science.gov (United States)

    Bakos, Jan; Zatkova, Martina; Bacova, Zuzana; Ostatnikova, Daniela

    2016-01-01

    The hypothalamus is a source of neural progenitor cells which give rise to different populations of specialized and differentiated cells during brain development. Newly formed neurons in the hypothalamus can synthesize and release various neuropeptides. Although term neuropeptide recently undergoes redefinition, small-size hypothalamic neuropeptides remain major signaling molecules mediating short- and long-term effects on brain development. They represent important factors in neurite growth and formation of neural circuits. There is evidence suggesting that the newly generated hypothalamic neurons may be involved in regulation of metabolism, energy balance, body weight, and social behavior as well. Here we review recent data on the role of hypothalamic neuropeptides in adult neurogenesis and neuritogenesis with special emphasis on the development of food intake and social behavior related brain circuits. PMID:26881105

  11. Urinary concentration does not exclusively rely on plasma vasopressin. A study between genders. Gender and diurnal urine regulation.

    Science.gov (United States)

    Graugaard-Jensen, C; Hvistendahl, G M; Frøkiaer, J; Bie, P; Djurhuus, J C

    2014-09-01

    We investigated the influence of gender on the diurnal regulation of urine production with special focus on vasopressin, oxytocin and prostaglandin E2. Fifteen young women in mid-follicular phase and 22 young men (20-33 years) were included. All participants underwent a 24-h circadian inpatient study under standardized conditions for measurements of plasma vasopressin, oxytocin, sodium and osmolality. Urine was fractionally collected for measurements of electrolytes, aquaporin-2 and prostaglandin E2. Plasma vasopressin expressed a diurnal rhythm with a night-time increase in both genders (P genders. We found a trend towards a higher reabsorption of free water in males (P = 0.07). The excretion of prostaglandin E2 was higher in males (P gender difference, not only as a mediator of the vasopressin response, but also as an independent factor. These findings need further elucidation. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  12. [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 (Pdiabetes insipidus in patients with pituitary stalk excision and tumor close adhesion to the third ventricle floor at the early postoperation (Pdiabetes insipidus in the vasopressin tannate group was decreased compared with the control group (Pdiabetes insipidus and hypernatremia incidence at the early postoperative stage after microsurgery for craniopharyngioma.

  13. Candidate genes of anxiety-related behavior in HAB/LAB rats and mice: focus on vasopressin and glyoxalase-I.

    Science.gov (United States)

    Landgraf, Rainer; Kessler, Melanie S; Bunck, Mirjam; Murgatroyd, Chris; Spengler, Dietmar; Zimbelmann, Marina; Nussbaumer, Markus; Czibere, Ludwig; Turck, Christoph W; Singewald, Nicolas; Rujescu, Dan; Frank, Elisabeth

    2007-01-01

    Two animal models of trait anxiety, HAB/LAB rats and mice, are described, representing inborn extremes in anxiety-related behavior. The comprehensive phenotypical characterization included basal behavioral features, stress-coping strategies and neuroendocrine responses upon stressor exposure with HAB animals being hyper-anxious, preferring passive coping, emitting more stressor-induced ultrasonic vocalization calls and showing typical peculiarities of the hypothalamic-pituitary-adrenocortical axis and line-specific patterns of Fos expression in the brain indicative of differential neuronal activation. In most cases, unselected Wistar rats and CD1 mice, respectively, displayed intermediate behaviors. In both HAB/LAB rats and mice, the behavioral phenotype has been found to be significantly correlated with the expression of the neuropeptide arginine vasopressin (AVP) at the level of the hypothalamic paraventricular nucleus (PVN). Additional receptor antagonist approaches in HABs confirmed that intra-PVN release of AVP is likely to contribute to hyper-anxiety and depression-like behavior. As shown exemplarily in HAB rats and LAB mice, single nucleotide polymorphisms (SNPs) in regulatory structures of the AVP gene underlie AVP-mediated phenotypic phenomena; in HAB rats, a SNP in the promoter of the AVP gene leads to reduced binding of the transcriptional repressor CBF-A, thus causing AVP overexpression and overrelease. Conversely, in LAB mice, a SNP in the AVP gene seems to cause an amino acid exchange in the signal peptide, presumably leading to a deficit in bioavailable AVP likely to underlie the total hypo-anxiety of LAB mice in combination with signs of central diabetes insipidus. Another feature of LAB mice is overexpression of glyoxalase-I. The functional characterization of this enzyme will determine its involvement in anxiety-related behavior beyond that of a reliable biomarker. The further identification of quantitative trait loci, candidate genes (and their

  14. Electrophysiological and autoradiographical evidence of V1 vasopressin receptors in the lateral septum of the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Raggenbass, M.; Tribollet, E.; Dreifuss, J.J.

    1987-11-01

    Extracellular recordings were obtained from single neurons located in the lateral septum, an area known to receive a vasopressinergic innervation in the rat brain. Approximately half of the neurons tested responded to 8-L-arginine vasopressin (AVP) by a marked increase in firing rate at concentrations greater than 1 nM. The effect of vasopressin was blocked by synthetic structural analogues possessing antagonistic properties on peripheral vasopressin and oxytocin receptors. Oxytocin was much less potent than vasopressin in firing septal neurons, and a selective oxytocic agonist was totally ineffective. The action of vasopressin on neuronal firing was mimicked by the vasopressor agonist (2-phenylalanine,8-ornithine)vasotocin but not by the selective antidiuretic agonist 1-deamino(8-D-arginine)vasopressin. In a parallel study, sites that bind (/sup 3/H)AVP at low concentration (1.5 nM) were found by in vitro autoradiography in the lateral septum. Adjacent sections were also incubated with 1.5 mM (/sup 3/H)AVP and, in addition, with 100 nM (2-phenylalanine,8-ornithine)vasotocin or 1-deamino(8-D-arginine)vasopressin--i.e., the same compounds as those used for the electrophysiological study. Results showed that the vasopressor agonist, but not the antidiuretic agonist, displaced (/sup 3/H)AVP, thus indicating that the vasopressin binding sites detected by autoradiography in the septum were V1 (vasopressor type) rather than V2 (antidiuretic type) receptors. Based on the electrophysiological evidence, we conclude that these receptors, when occupied, lead to increased firing of lateral septal neurons.

  15. 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

  16. Evaluation of small hypothalamic hamartomas with 3D constructive interference in steady state (CISS) sequence

    Energy Technology Data Exchange (ETDEWEB)

    Yamura, Masayuki; Hirai, Toshinori; Kitajima, Mika; Hayashida, Yoshiko; Ikushima, Ichiro; Yamashita, Yasuyuki [Graduate School of Medical Sciences, Kumamoto University, Department of Diagnostic Radiology, Kumamoto (Japan); Korogi, Yukunori [University of Occupational and Environmental Health, School of Medicine, Department of Radiology, Kitakyushu (Japan); Endo, Fumio [Kumamoto University, Department of Pediatrics,Graduate School of Medical Sciences, Kumamoto (Japan)

    2005-03-01

    Hypothalamic hamartomas are relatively rare, non-neoplastic congenital malformations. With conventional MR images alone, small hypothalamic hamartomas may be difficult to diagnose because of artifacts from cerebrospinal fluid. We present the usefulness of three-dimensional constructive interference in steady state sequence for evaluating small hypothalamic hamartomas in three pediatric patients. (orig.)

  17. 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

  18. In vivo processing and release into the circulation of GFP fusion protein in arginine vasopressin enhanced GFP transgenic rats: response to osmotic stimulation.

    Science.gov (United States)

    Satoh, Keita; Oti, Takumi; Katoh, Akiko; Ueta, Yoichi; Morris, John F; Sakamoto, Tatsuya; Sakamoto, Hirotaka

    2015-07-01

    Arginine vasopressin (AVP) is a neurohypophysial hormone synthesized as a part of a prepropeptide precursor containing the signal peptide, AVP hormone, AVP-associated neurophysin II and copeptin in the hypothalamic neurosecretory neurons. A transgenic (Tg) rat line expressing the AVP-eGFP fusion gene has been generated. To establish the AVP-eGFP Tg rat as a unique model for an analysis of AVP dynamics in vivo, we first examined the in vivo molecular dynamics of the AVP-eGFP fusion gene, and then the release of GFP in response to physiological stimuli. Double immunoelectron microscopy demonstrated that GFP was specifically localized in neurosecretory vesicles of AVP neurons in this Tg rat. After stimulation of the posterior pituitary with high potassium we demonstrated the exocytosis of AVP neurosecretory vesicles containing GFP at the ultrastructural level. Biochemical analyses indicated that the AVP-eGFP fusion gene is subjected to in vivo post-translational modifications like the native AVP gene, and is packaged into neurosecretory vesicles as a fusion protein: copeptin1-14 -GFP. Moreover, GFP release into the circulating blood appeared to be augmented after osmotic stimulation, like native AVP. Thus, here we show for the first time the in vivo molecular processing of the AVP-eGFP fusion gene and stimulated secretion after osmotic stimulation in rats. Because GFP behaved like native AVP in the hypothalamo-pituitary axis, and in particular was released into the circulation in response to a physiological stimulus, the AVP-eGFP Tg rat model appears to be a powerful tool for analyzing neuroendocrine systems at the organismal level. © 2015 FEBS.

  19. Arginine Vasopressin Potentiates the Stimulatory Action of CRH on Pituitary Corticotropes via a Protein Kinase C-Dependent Reduction of the Background TREK-1 Current.

    Science.gov (United States)

    Lee, Andy K; Tse, Frederick W; Tse, Amy

    2015-10-01

    The hypothalamic hormone arginine vasopressin (AVP) potentiates the stimulatory action of CRH on ACTH secretion from pituitary corticotropes, but the underlying mechanism is elusive. Using the perforated patch-clamp technique to monitor membrane potentials in mouse corticotropes, we found that AVP triggered a transient hyperpolarization that was followed by a sustained depolarization. The hyperpolarization was caused by intracellular Ca(2+) release that in turn activated the small conductance Ca(2+)-activated K(+) (SK) channels. The depolarization was due to the suppression of background TWIK-related K(+) (TREK)-1 channels. Direct activation of protein kinase C (PKC) reduced the TREK-1 current, whereas PKC inhibition attenuated the AVP-mediated reduction of the TREK-1 current, implicating the involvement of PKC. The addition of CRH (which stimulates the protein kinase A pathway) in the presence of AVP, or vice versa, resulted in further suppression of the TREK-1 current. In corticotropes with buffered cytosolic Ca(2+) concentration ([Ca(2+)]i), AVP evoked a sustained depolarization, and the coapplication of AVP and CRH caused a larger depolarization than that evoked by AVP or CRH alone. In cells with minimal perturbation of [Ca(2+)]i and background TREK-1 channels, CRH evoked a sustained depolarization that was superimposed with action potentials, and the subsequent coapplication of AVP and CRH triggered a transient hyperpolarization that was followed by a larger depolarization. In summary, AVP and CRH have additive effects on the suppression of the TREK-1 current, resulting in a more robust depolarization in corticotropes. We suggest that this mechanism contributes to the potentiating action of AVP on CRH-evoked ACTH secretion.

  20. Individual differences in gene expression of vasopressin, D2 receptor, POMC and orexin: vulnerability to relapse to heroin-seeking in rats.

    Science.gov (United States)

    Zhou, Yan; Leri, Francesco; Cummins, Erin; Kreek, Mary Jeanne

    2015-02-01

    Individual vulnerability to stress-induced relapse during abstinence from chronic heroin exposure is a key feature of opiate addiction, with limited studies on this topic. Arginine vasopressin (AVP) and its V1b receptor, components of the brain stress responsive systems, play a role in heroin-seeking behavior triggered by foot shock (FS) stress in rats. In this study, we tested whether individual differences in the FS-induced heroin-seeking were associated with alterations of AVP and V1b, as well as other stress responsive systems, including pro-opiomelanocortin (POMC), orexin, plasma ACTH and corticosterone, as well as dopamine D2 receptor (D2) and plasma prolactin. Sprague-Dawley rats were subjected to 3-hour intravenous heroin self-administration (SA) and then tested in extinction, and FS-induced and heroin priming-induced reinstatements. The rats that self-administered heroin were divided into high and low reinstatement responders induced by FS (H-RI; L-RI). Over SA sessions, both the H-RI and L-RI displayed similar active lever responding, heroin infusion and total heroin intake. Compared to the L-RI, however, the H-RI showed greater active lever responses during stress-induced reinstatement, with higher AVP mRNA levels in medial/basolateral amygdala and lower D2 mRNA levels in caudate putamen. However, heroin priming resulted in similar reinstatement in both groups and produced similarly low POMC and high orexin mRNA levels in hypothalamus. Our results indicate that: 1) enhanced amygdalar AVP and reduced striatal D2 expression may be related to individual vulnerability to stress-induced reinstatement of heroin- seeking; and 2) heroin abstinence-associated alterations of hypothalamic orexin and POMC expression may be involved in drug priming-induced heroin-seeking. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Nitric oxide modulation of the hypothalamo-neurohypophyseal system

    Directory of Open Access Journals (Sweden)

    Kadekaro M.

    2004-01-01

    Full Text Available Nitric oxide (NO, a free radical gas produced endogenously from the amino acid L-arginine by NO synthase (NOS, has important functions in modulating vasopressin and oxytocin secretion from the hypothalamo-neurohypophyseal system. NO production is stimulated during increased functional activity of magnocellular neurons, in parallel with plastic changes of the supraoptic nucleus (SON and paraventricular nucleus. Electrophysiological data recorded from the SON of hypothalamic slices indicate that NO inhibits firing of phasic and non-phasic neurons, while L-NAME, an NOS inhibitor, increases their activity. Results from measurement of neurohypophyseal hormones are more variable. Overall, however, it appears that NO, tonically produced in the forebrain, inhibits vasopressin and oxytocin secretion during normovolemic, isosmotic conditions. During osmotic stimulation, dehydration, hypovolemia and hemorrhage, as well as high plasma levels of angiotensin II, NO inhibition of vasopressin neurons is removed, while that of oxytocin neurons is enhanced. This produces a preferential release of vasopressin over oxytocin important for correction of fluid imbalance. During late pregnancy and throughout lactation, fluid homeostasis is altered and expression of NOS in the SON is down- and up-regulated, respectively, in parallel with plastic changes of the magnocellular system. NO inhibition of magnocellular neurons involves GABA and prostaglandin synthesis and the signal-transduction mechanism is independent of the cGMP-pathway. Plasma hormone levels are unaffected by icv 1H-[1, 2, 4]oxadiazolo-[4,3-a]quinoxalin-1-one (a soluble guanylyl cyclase inhibitor or 8-Br-cGMP administered to conscious rats. Moreover, cGMP does not increase in homogenates of the neural lobe and in microdialysates of the SON when NO synthesis is enhanced during osmotic stimulation. Among alternative signal-transduction pathways, nitrosylation of target proteins affecting activity of ion

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

    Energy Technology Data Exchange (ETDEWEB)

    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 (/sup 3/H)LVP and (/sup 3/H)dDAVP in the Brattleboro rats did not differ significantly from that found in the control R-Amsterdam rats. The half-life of (/sup 3/H)dDAVP proved longer than that of (/sup 3/H)LVP in all three groups of animals. In the case of (/sup 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, (/sup 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.

  3. Vasopressin versus dopamine for treatment of hypotension in extremely low birth weight infants: a randomized, blinded pilot study.

    Science.gov (United States)

    Rios, Danielle R; Kaiser, Jeffrey R

    2015-04-01

    To evaluate vasopressin vs dopamine as initial therapy in extremely low birth weight (ELBW) infants with hypotension during the first 24 hours of life. ELBW infants with hypertension ≤ 30 weeks' gestation and ≤ 24 hours old randomly received treatment with vasopressin or dopamine in a blinded fashion. Normotensive infants not receiving vasopressor support served as a comparison group. Twenty ELBW infants with hypertension received vasopressin (n = 10) or dopamine (n = 10), and 50 were enrolled for comparison. Mean gestational age was 25.6 ± 1.4 weeks and birth weight 705 ± 154 g. Response to vasopressin paralleled that of dopamine in time to adequate mean blood pressure (Kaplan-Meier curve, P = .986); 90% of infants in each treatment group responded with adequate blood pressure. The vasopressin group received fewer doses of surfactant (P hypotension appeared safe. This pilot study supports a larger randomized controlled trial of vasopressin vs dopamine therapy in ELBW infants with hypotension. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Sodium-calcium exchanger and R-type Ca(2+) channels mediate spontaneous [Ca(2+)]i oscillations in magnocellular neurones of the rat supraoptic nucleus.

    Science.gov (United States)

    Kortus, Stepan; Srinivasan, Chinnapaiyan; Forostyak, Oksana; Zapotocky, Martin; Ueta, Yoichi; Sykova, Eva; Chvatal, Alexandr; Verkhratsky, Alexei; Dayanithi, Govindan

    2016-06-01

    Isolated supraoptic neurones generate spontaneous [Ca(2+)]i oscillations in isolated conditions. Here we report in depth analysis of the contribution of plasmalemmal ion channels (Ca(2+), Na(+)), Na(+)/Ca(2+) exchanger (NCX), intracellular Ca(2+) release channels (InsP3Rs and RyRs), Ca(2+) storage organelles, plasma membrane Ca(2+) pump and intracellular signal transduction cascades into spontaneous Ca(2+) activity. While removal of extracellular Ca(2+) or incubation with non-specific voltage-gated Ca(2+) channel (VGCC) blocker Cd(2+) suppressed the oscillations, neither Ni(2+) nor TTA-P2, the T-type VGCC blockers, had an effect. Inhibitors of VGCC nicardipine, ω-conotoxin GVIA, ω-conotoxin MVIIC, ω-agatoxin IVA (for L-, N-, P and P/Q-type channels, respectively) did not affect [Ca(2+)]i oscillations. In contrast, a specific R-type VGCC blocker SNX-482 attenuated [Ca(2+)]i oscillations. Incubation with TTX had no effect, whereas removal of the extracellular Na(+) or application of an inhibitor of the reverse operation mode of Na(+)/Ca(2+) exchanger KB-R7943 blocked the oscillations. The mitochondrial uncoupler CCCP irreversibly blocked spontaneous [Ca(2+)]i activity. Exposure of neurones to Ca(2+) mobilisers (thapsigargin, cyclopiazonic acid, caffeine and ryanodine); 4-aminopyridine (A-type K(+) current blocker); phospholipase C and adenylyl cyclase pathways blockers U-73122, Rp-cAMP, SQ-22536 and H-89 had no effect. Oscillations were blocked by GABA, but not by glutamate, apamin or dynorphin. In conclusion, spontaneous oscillations in magnocellular neurones are mediated by a concerted action of R-type Ca(2+) channels and the NCX fluctuating between forward and reverse modes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. 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

    /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...

  6. Early life stress experience may blunt hypothalamic leptin signalling

    Indian Academy of Sciences (India)

    2016-12-21

    Dec 21, 2016 ... are normally elevated in human obesity (Considine et al. 1996). Leptin is synthesized in adipocytes and released into the blood stream, and acts on its receptors in the hypothalamic arcuate nucleus (ARC) to regulate energy expenditure and weight gain. Anorexic efficacy of leptin; i.e. reducing food.

  7. 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)

  8. 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......-dependent feedback inhibition of the stimulation. Other agonists that might have a regulatory function in the testis were tested for possible effects on phosphoinositide metabolism. Of prostaglandin E (10 µm), angiotensin II (0.1 µM), and bradykinin (0.9 µM), only the latter induced a significant increase...

  9. The challenge of translation in social neuroscience: a review of oxytocin, vasopressin, and affiliative behavior.

    Science.gov (United States)

    Insel, Thomas R

    2010-03-25

    Social neuroscience is rapidly exploring the complex territory between perception and action where recognition, value, and meaning are instantiated. This review follows the trail of research on oxytocin and vasopressin as an exemplar of one path for exploring the "dark matter" of social neuroscience. Studies across vertebrate species suggest that these neuropeptides are important for social cognition, with gender- and steroid-dependent effects. Comparative research in voles yields a model based on interspecies and intraspecies variation of the geography of oxytocin receptors and vasopressin V1a receptors in the forebrain. Highly affiliative species have receptors in brain circuits related to reward or reinforcement. The neuroanatomical distribution of these receptors may be guided by variations in the regulatory regions of their respective genes. This review describes the promises and problems of extrapolating these findings to human social cognition, with specific reference to the social deficits of autism. (c) 2010 Elsevier Inc. All rights reserved.

  10. [Vasoplegic syndrome and its treatment with vasopressin during cardiac surgery with cardiopulmonary bypass].

    Science.gov (United States)

    Gilbert, Macarena; Lema, Guillermo

    2011-03-01

    Cardiac surgery with cardiopulmonary bypass is associated with systemic inflammatory response. In some cases this clinical condition is characterized by severe hypotension due to low systemic vascular resistance during and after cardiopulmonary bypass. A few of these cases do not respond to volume or catecholamines. This condition is known as vasoplegic syndrome. Its etiology is not fully understood today and carries associated morbidity and mortality In this syndrome, vasopressin levels are reduced, as in septic and hypovolemic shock. Supplementary vasopressin improves blood pressure and might be considered as an alternative treatment. Several reports have shown benefits when used alone or in combination with catecholamines. However, further studies are necessary to find the most appropriate use of the drug for vasoplegic syndrome.

  11. Local injection of diluted vasopressin followed by suction curettage for cervical ectopic pregnancy.

    Science.gov (United States)

    Ishikawa, Hiroshi; Unno, Youichi; Omoto, Akiko; Shozu, Makio

    2016-12-01

    To report the results of local injection of diluted vasopressin followed by suction curettage as a conservative treatment for women with cervical ectopic pregnancy, who wish to preserve their future fertility. This was a retrospective chart review in a university hospital and a municipal hospital. We injected diluted vasopressin (Pitressin R, total amount of 4-10 units) transvaginally into the cervix surrounding the gestational sac, but not directly into the gestational sac, and/or the lower segment of the uterine body under transvaginal ultrasonographic guidance. After cessation of fetal heartbeats, we aspirated the conceptus by performing suction curettage. We injected additional vasopressin into the gestational sac in cases with a viable fetus after the initial injection. Forced contraction of the cervical smooth muscle facilitated removal of the conceptus with minimal blood loss during curettage. We measured operative time, total blood loss, complications, and the need for additional treatment. We included 11 women. Mean patient age, gestational age, and serum human chorionic gonadotrophin (hCG) at the intervention were 31.2±6.4years, 6.0±0.6 weeks, and 18,370±21,570 IU/L, respectively. Mean size of the gestational sac was 19.6±9.5mm. The uterus was successfully preserved without any complications in all patients. All procedures were completed within 15min except for the first case (range: 5-33min). In 4 cases, the conceptus containing a gestational sac was spontaneously extruded en bloc from the external os after the injection. Additional systematic methotrexate administration was required in one case because of remaining villi at the implantation site with persistence of serum hCG levels after the procedure. Local injection of diluted vasopressin and subsequent suction curettage is a feasible conservative treatment for cervical ectopic pregnancy. Copyright © 2016 Elsevier Ireland Ltd. 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. Vasopressin and epinephrine in the treatment of cardiac arrest: an experimental study

    OpenAIRE

    Stroumpoulis, Konstantinos; Xanthos, Theodoros; Rokas, Georgios; Kitsou, Vassiliki; Papadimitriou, Dimitrios; Serpetinis, Ioannis; Perrea, Despina; Papadimitriou, Lila; Kouskouni, Evangelia

    2008-01-01

    Background Epinephrine remains the drug of choice for cardiopulmonary resuscitation. The aim of the present study is to assess whether the combination of vasopressin and epinephrine, given their different mechanisms of action, provides better results than epinephrine alone in cardiopulmonary resuscitation. Methods Ventricular fibrillation was induced in 22 Landrace/Large-White piglets, which were left untreated for 8 minutes before attempted resuscitation with precordial compression, mechanic...

  14. [Effect of vasopressin on changes in the behavioral reactions of rats induced by psychotropic substances].

    Science.gov (United States)

    Titov, S A; Usenko, A B; Ashmarin, I P

    1989-01-01

    The effect was studied of arginyl-8-vasopressin (AVP) on changes in rats behavioural reactions, elicited by reserpine, haloperidol, aminazine, amitriptyline or nialamide. It has been shown that AVP administered intraperitoneally in a dose of 0.001 mg/kg, eliminates the deficit of elaboration of conditioned reaction of active avoidance produced by psychotropic drugs, without influencing the motor activity reduction developed after administration of these substances.

  15. Arteriolar vasoconstrictive response: comparing the effects of arginine vasopressin and norepinephrine

    OpenAIRE

    Friesenecker, Barbara E; Tsai, Amy G; Martini, Judith; Ulmer, Hanno; Wenzel, Volker; Hasibeder, Walter R; Intaglietta, Marcos; D?nser, Martin W

    2006-01-01

    INTRODUCTION: This study was designed to examine differences in the arteriolar vasoconstrictive response between arginine vasopressin (AVP) and norepinephrine (NE) on the microcirculatory level in the hamster window chamber model in unanesthetized, normotonic hamsters using intravital microscopy. It is known from patients with advanced vasodilatory shock that AVP exerts strong additional vasoconstriction when incremental dosage increases of NE have no further effect on mean arterial blood pre...

  16. Electrophysiological effects of kainic acid on vasopressin-enhanced green fluorescent protein and oxytocin-monomeric red fluorescent protein 1 neurones isolated from the supraoptic nucleus in transgenic rats.

    Science.gov (United States)

    Ohkubo, J; Ohbuchi, T; Yoshimura, M; Maruyama, T; Ishikura, T; Matsuura, T; Suzuki, H; Ueta, Y

    2014-01-01

    The supraoptic nucleus (SON) contains two types of magnocellular neurosecretory cells: arginine vasopressin (AVP)-producing and oxytocin (OXT)-producing cells. We recently generated and characterised two transgenic rat lines: one expressing an AVP-enhanced green fluorescent protein (eGFP) and the other expressing an OXT-monomeric red fluorescent protein 1 (mRFP1). These transgenic rats enable the visualisation of AVP or OXT neurones in the SON. In the present study, we compared the electrophysiological responses of AVP-eGFP and OXT-mRFP1 neurones to glutamic acid in SON primary cultures. Glutamate mediates fast synaptic transmission through three classes of ionotrophic receptors: the NMDA, AMPA and kainate receptors. We investigated the contributions of the three classes of ionotrophic receptors in glutamate-induced currents. Three different antagonists were used, each predominantly selective for one of the classes of ionotrophic receptor. Next, we focused on the kainate receptors (KARs). We examined the electrophysiological effects of kainic acid (KA) on AVP-eGFP and OXT-mRFP1 neurones. In current clamp mode, KA induced depolarisation and increased firing rates. These KA-induced responses were inhibited by the non-NMDA ionotrophic receptor antagonist 6-cyano-7-nitroquinoxaline-2,3(1H4H)-dione in both AVP-eGFP and OXT-mRFP1 neurones. In voltage clamp mode, the application of KA evoked inward currents in a dose-dependent manner. The KA-induced currents were significantly larger in OXT-mRFP1 neurones than in AVP-eGFP neurones. This significant difference in KA-induced currents was abolished by the GluK1-containing KAR antagonist UBP302. At high concentrations (250-500 μm), the specific GluK1-containing KAR agonist (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA) induced significantly larger currents in OXT-mRFP1 neurones than in AVP-eGFP neurones. Furthermore, the difference between the AVP-eGFP and OXT-mRFP1 neurones in the ATPA currents

  17. Single-dose ethanol administration activates the hypothalamic-pituitary-adrenal axis: exploration of the mechanism of action.

    Science.gov (United States)

    Thiagarajan, A B; Mefford, I N; Eskay, R L

    1989-10-01

    Activation of the hypothalamic-pituitary-adrenal axis (HPAA) by single-dose ethanol administration, which achieved moderately high blood ethanol levels, was explored in naive rats in order to determine the mechanism of ethanol's activation of the stress axis. Adult male rats received a single dose (3.2 g/kg body weight-1 of a 12% solution of ethanol in physiological saline. The plasma concentration of immunoreactive (ir) adrenocorticotropic hormone (ACTH), beta-endorphin (BE) and corticosterone (CS) was determined by radioimmunoassay, whereas, plasma concentrations of epinephrine (E) and norepinephrine (NE) were quantified following reverse-phase liquid chromatographic separation and amperometric detection. Ethanol induced maximal plasma ACTH levels within minutes, which declined toward basal levels by 60 min, whereas, plasma concentration of CS rose rapidly and remained elevated at 60 min. Plasma ACTH and CS levels in saline-treated control animals did not vary significantly at any time point. Consistent with co-release of ACTH from corticotrophs, the plasma concentration of ir-BE increased 5-fold at 15 min and declined towards basal levels at 60 min after-ethanol challenge. Plasma E increased 10- to 20-fold as compared to saline controls or preinjection levels and returned to preinjection levels by 90 min, in a manner similar to ethanol-induced changes in proopiomelanocortin-derived peptides and CS. Removal of the adrenal medulla and thus the source of E prior to ethanol administration, did not attenuate activation of the HPAA. Passive immunoneutralization of arginine vasopressin (AVP), using a high-titer AVP antiserum and a protocol which was found to block ether-induced ACTH secretion by 40% in adult male rats, failed to even partially block ethanol-induced ACTH or CS secretion. The results of this study indicate that neither adrenal medulla-derived E nor AVP are significant regulators or coregulators of corticotroph secretions following a moderately high

  18. Eating behavior in frontotemporal dementia: Peripheral hormones vs hypothalamic pathology.

    Science.gov (United States)

    Ahmed, Rebekah M; Latheef, Sahar; Bartley, Lauren; Irish, Muireann; Halliday, Glenda M; Kiernan, Matthew C; Hodges, John R; Piguet, Olivier

    2015-10-13

    To contrast the relationships of hormonal eating peptides and hypothalamic volumes to eating behavior and metabolic changes (body mass index [BMI]) in behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA). Seventy-five patients with dementia (19 bvFTD, 26 svPPA, and 30 Alzheimer disease dementia) and 23 controls underwent fasting blood analyses of leptin, ghrelin, cholecystokinin, peptide tyrosine tyrosine (PYY), and agouti-related peptide (AgRP) levels. On brain MRI anterior, posterior, and total hypothalamic volumes were measured. Relationships between endocrine measures, hypothalamic volumes, eating behaviors, and BMI were investigated. Levels of AgRP were higher in patients with bvFTD (69 ± 89 pg/mL) and svPPA (62 ± 81 pg/mL) compared with controls (23 ± 19 pg/mL, p < 0.01). No differences were found for leptin, oxytocin, cholecystokinin, ghrelin, and PYY levels. Patients with bvFTD and svPPA had higher scores on questionnaires measuring eating behaviors. Atrophy of the posterior and total hypothalamus was observed in the bvFTD group only. Linear regression modeling revealed that leptin and AgRP levels predicted BMI. Eating abnormalities are multifactorial in FTD. In bvFTD, they are in part related to hypothalamic degeneration, with potential disintegration of the network connections between the hypothalamus and orbitofrontal cortex/reward pathways. In svPPA, although hypothalamic volumes are preserved, this group experiences elevated AgRP levels similar to bvFTD, which predicts BMI in both groups. This finding highlights the potential key role of AgRP in eating and metabolic changes and provides a potential target for treatment to modify disease progression. © 2015 American Academy of Neurology.

  19. 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

    Energy Technology Data Exchange (ETDEWEB)

    Kruisbrink, J.; Boer, G.J.

    1984-12-01

    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.

  20. A Two-Year Randomized Trial of Interventions to Decrease Stress Hormone Vasopressin Production in Patients with Meniere's Disease-A Pilot Study

    National Research Council Canada - National Science Library

    Kitahara, Tadashi; Okamoto, Hidehiko; Fukushima, Munehisa; Sakagami, Masaharu; Ito, Taeko; Yamashita, Akinori; Ota, Ichiro; Yamanaka, Toshiaki

    2016-01-01

    .... 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...

  1. The Effect of Drinking on Plasma Vasopressin and Renin in Dehydrated Human Subjects

    Science.gov (United States)

    Geelen, G.; Keil, L. C.; Kravik, S. E.; Wade, C. E.; Thrasher, T. N.; Barnes, P. R.; Pyka, G.; Nesvig, C.; Greenleaf, J. E.

    1996-01-01

    Oropharyngeal mechanisms activated by drinking have been shown to induce a rapid decline in plasma vasopressin which preceeds postabsorptive changes in plasma composition in the dehydrated dog. The present study was undertaken to determine what factor(s) inhibit(s) vasopressin secretion after rehydration in water deprived human subjects. Hematocrit (Hct) and hemoglobin (Hb) were determined on the day of the experiment, together with electrolytes and osmolalities which were measured on freshly separated serum. Plasma was immediately frozen and further analyzed by radioimmunoassay for renin activity (PRA), vasopressin (AVP), and aldosterone. The data were analyzed using an analysis of variance for repeated measurements and significant differences between the dehydrated control period and various time points after the start of rehydration were determined using a multiple-range test. began and reached water replete levels 15 minutes after drinking in the absence of any detectable decline in serum sodium or osmolality, we conclude that 427 oropharyngeal factors, alone or combined with gastric distension account for the extremely rapid inhibition of AVP secretion after drinking in the water-deprived human, as has been shown to be the case in dogs. Our findings are also in agreement wiht the recent demonstration that at the onset of drinking in the dehydrated monkey, there is an abrupt fall in plasma AVP concentration associated with a considerable decrease in the firing rate of the supraoptic neurosecretory neurons.

  2. Negative feedback from CaSR signaling to aquaporin-2 sensitizes vasopressin to extracellular Ca2.

    Science.gov (United States)

    Ranieri, Marianna; Tamma, Grazia; Di Mise, Annarita; Russo, Annamaria; Centrone, Mariangela; Svelto, Maria; Calamita, Giuseppe; Valenti, Giovanna

    2015-07-01

    We previously described that high luminal Ca(2+) in the renal collecting duct attenuates short-term vasopressin-induced aquaporin-2 (AQP2) trafficking through activation of the Ca(2+)-sensing receptor (CaSR). Here, we evaluated AQP2 phosphorylation and permeability, in both renal HEK-293 cells and in the dissected inner medullary collecting duct, in response to specific activation of CaSR with NPS-R568. In CaSR-transfected cells, CaSR activation drastically reduced the basal levels of AQP2 phosphorylation at S256 (AQP2-pS256), thus having an opposite effect to vasopressin action. When forskolin stimulation was performed in the presence of NPS-R568, the increase in AQP2-pS256 and in the osmotic water permeability were prevented. In the freshly isolated inner mouse medullar collecting duct, stimulation with forskolin in the presence of NPS-R568 prevented the increase in AQP2-pS256 and osmotic water permeability. Our data demonstrate that the activation of CaSR in the collecting duct prevents the cAMP-dependent increase in AQP2-pS256 and water permeability, counteracting the short-term vasopressin response. By extension, our results suggest the attractive concept that CaSR expressed in distinct nephron segments exerts a negative feedback on hormones acting through cAMP, conferring high sensitivity of hormone to extracellular Ca(2+). © 2015. Published by The Company of Biologists Ltd.

  3. Effect of stimulation of afferent renal nerves on plasma levels of vasopressin

    Energy Technology Data Exchange (ETDEWEB)

    Caverson, M.M.; Ciriello, J.

    1987-04-01

    Experiments were done in ..cap alpha..-chloralose-anesthetized, paralyzed and artificially ventilated cats with vagus, cervical sympathetic, aortic depressor, and carotid sinus nerves cut bilaterally to investigate the effect of afferent renal nerve (ARN) stimulation on circulating levels of vasopressin (AVP). Electrical stimulation of ARN elicited a pressor response that had two components, a primary (1/sup 0/) component locked in time with the stimulus and a secondary (2/sup 0/) component that had a long onset latency and that outlasted the stimulation period. The 1/sup 0/ and 2/sup 0/ components of the pressor response were largest at stimulation frequencies of 30 and 40 Hz, respectively. Autonomic blockage with hexamethonium bromide and atropine methylbromide abolished the 1/sup 0/ component. Administration of the vasopressin V/sub 1/-vascular receptor antagonist d(CH/sub 2/)/sub 5/ VAVP during autonomic blockade abolished the 2/sup 0/C component. Plasma concentrations of AVP measured by radioimmunoassay increased from control levels of 5.2 +/- 0.9 to 53.6 +/- 18.6 pg/ml during a 5-min period of stimulation of ARN. Plasma AVP levels measured 20-40 min after simulation were not significantly different from control values. These data demonstrate that sensory information originating in the kidney alters the release of vasopressin from the neurohypophysis and suggest that ARN are an important component of the neural circuitry involved in homeostatic mechanisms controlling arterial pressure.

  4. Noncanonical Control of Vasopressin Receptor Type 2 Signaling by Retromer and Arrestin*

    Science.gov (United States)

    Feinstein, Timothy N.; Yui, Naofumi; Webber, Matthew J.; Wehbi, Vanessa L.; Stevenson, Hilary P.; King, J. Darwin; Hallows, Kenneth R.; Brown, Dennis; Bouley, Richard; Vilardaga, Jean-Pierre

    2013-01-01

    The vasopressin type 2 receptor (V2R) is a critical G protein-coupled receptor (GPCR) for vertebrate physiology, including the balance of water and sodium ions. It is unclear how its two native hormones, vasopressin (VP) and oxytocin (OT), both stimulate the same cAMP/PKA pathway yet produce divergent antinatriuretic and antidiuretic effects that are either strong (VP) or weak (OT). Here, we present a new mechanism that differentiates the action of VP and OT on V2R signaling. We found that vasopressin, as opposed to OT, continued to generate cAMP and promote PKA activation for prolonged periods after ligand washout and receptor internalization in endosomes. Contrary to the classical model of arrestin-mediated GPCR desensitization, arrestins bind the VP-V2R complex yet extend rather than shorten the generation of cAMP. Signaling is instead turned off by the endosomal retromer complex. We propose that this mechanism explains how VP sustains water and Na+ transport in renal collecting duct cells. Together with recent work on the parathyroid hormone receptor, these data support the existence of a novel “noncanonical” regulatory pathway for GPCR activation and response termination, via the sequential action of β-arrestin and the retromer complex. PMID:23935101

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

    Science.gov (United States)

    Müller, Hermann L

    2016-02-01

    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 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. 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.

  6. Imidafenacin exerts the antidiuretic effect by enhancing vasopressin-related responses in orally water-loaded rats.

    Science.gov (United States)

    Yamazaki, Takanobu; Fukata, Ayako; Muraki, Yukiko

    2016-11-15

    Imidafenacin, an antimuscarinic agent for treating overactive bladder, has an antidiuretic effect, but the detailed mechanisms of action remain unclear. The cholinergic and vasopressin systems are known to interact, for example, in the suppression of vasopressin-induced water reabsorption through muscarinic stimulation in the renal collecting duct. We, therefore, investigated whether vasopressin signaling pathway would participate in the antidiuretic effect of imidafenacin. In female Sprague-Dawley rats, urine production was measured by collecting urine from cystostomy chatheter using a Bollman restraining cage for 2h after drug i.v. injection and water load (25ml/kg p.o.). Both imidafenacin and a vasopressin V2 receptor agonist desmopressin acetate (desmopressin) dose-dependently suppressed urine production. The combination of imidafenacin and desmopressin at the minimum effective doses suppressed the urine production more strongly than each alone. Mozavaptan hydrochloride (mozavaptan, 3mg/kg), a vasopressin V2 receptor antagonist, completely inhibited the antidiuretic effects of imidafenacin and desmopressin at their respective minimum effective doses. The antidiuretic effect of desmopressin emerged at the maximum antidiuretic dose level (0.1µg/kg) even under mozavaptan-treatment, whereas that of imidafenacin (300µg/kg) was still kept suppressed by mozavaptan. When 300µg/kg imidafenacin was added to the combination of mozavaptan 3mg/kg and desmopressin 0.1µg/kg, the antidiuretic effect was further enhanced. The present study suggests that vasopressin signaling pathway participates in the antidiuretic effect of imidafenacin, and that imidafenacin exerts its antidiuretic effects by enhancing some part of the vasopressin signaling pathway in orally water-loaded rats. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Vasopressin and its analogues for the treatment of refractory hypotension in neonates.

    Science.gov (United States)

    Shivanna, Binoy; Rios, Danielle; Rossano, Joseph; Fernandes, Caraciolo J; Pammi, Mohan

    2013-03-28

    Neonatal hypotension that is refractory to volume expansion, catecholamines, or corticosteroids has a mortality of about 50%. Optimization of blood pressure and tissue perfusion in refractory hypotension may be crucial to improve clinical outcomes. Vasopressin, a neuropeptide hormone, or its analogue terlipressin has been used to treat refractory hypotension in neonates and may be effective. Our primary objective was to evaluate the efficacy and safety of vasopressin and its synthetic analogues (e.g. terlipressin) in decreasing mortality and adverse neurodevelopmental outcomes, and improving survival in neonates with refractory hypotension. Our secondary objectives were to determine the effects of vasopressin and its analogues (terlipressin) on improvement in blood pressure, increase in urine output, decrease in inotrope score, necrotizing enterocolitis (NEC), periventricular leukomalacia, intraventricular hemorrhage, chronic lung disease, and retinopathy of prematurity (ROP) in neonates with refractory hypotension. We searched the literature in January 2012, using the search strategy recommended by the Cochrane Neonatal Group. We searched electronic databases (CENTRAL (The Cochrane Library), MEDLINE, CINAHL, EMBASE), abstracts of the Pediatric Academic Societies, web sites for registered trials at www.clinicaltrials.gov and www.controlled-trials.com and in the reference list of identified articles. Randomized or quasi-randomized trials evaluating vasopressin or its analogues, at any dosage or duration used as an adjunct to standard therapy (any combination of volume expansion, inotropic agents and corticosteroids) to treat refractory hypotension in neonates. We followed the standard methods of The Cochrane Collaboration for conducting a systematic review. Two review authors (BS and MP) independently assessed the titles and abstracts of studies identified by the search strategy for eligibility for inclusion. We obtained the full text version if eligibility could

  8. Cerebellar input to magnocellular neurons in the red nucleus of the mouse: synaptic analysis in horizontal brain slices incorporating cerebello-rubral pathways.

    Science.gov (United States)

    Jiang, M C; Alheid, G F; Nunzi, M G; Houk, J C

    2002-01-01

    We studied the synaptic input from the nucleus interpositus of the cerebellum to the magnocellular division of the red nucleus (RNm) in the mouse using combined electrophysiological and neuroanatomical methods. Whole-cell patch-clamp recordings were made from brain slices (125-150 microm) cut in a horizontal plane oriented to pass through both red nucleus and nucleus interpositus. Large cells that were visually selected and patched were injected with Lucifer Yellow and identified as RNm neurons. Using anterograde tracing from nucleus interpositus in vitro, we examined the course of interposito-rubral axons which are dispersed in the superior cerebellar peduncle. In vitro monosynaptic responses in RNm were elicited by an electrode array placed contralaterally in this pathway but near the midline. Mixed excitatory post-synaptic potentials (EPSPs)/inhibitory post-synaptic potentials (IPSPs) were observed in 48 RNm neurons. Excitatory components of the evoked potentials were studied after blocking inhibitory components with picrotoxin (100 microM) and strychnine (5 microM). All RNm neurons examined continued to show monosynaptic EPSPs after non-N-methyl-D-aspartate (NMDA) glutamate receptor components were blocked with 10 microM 6,7-dinitroquinoxaline-2,3-dione or 5 microM 2,3-dihydro-6-nitro-7-sulfamoyl-benzo(f)-quinoxaline (NBQX; n=12). The residual potentials were identified as NMDA receptor components since they (i) were blocked by the addition of the NMDA receptor antagonist, D,L-2-amino-5-phosphonovaleric acid (APV), (ii) were voltage-dependent, and (iii) were enhanced by Mg(2+) removal. Inhibitory components of the evoked potentials were studied after blocking excitatory components with NBQX and APV. Under these conditions, all RNm neurons studied continued to show IPSPs. Blockade of GABA(A) receptors reduced but did not eliminate the IPSPs. These were eliminated when GABA(A) receptor blockade was combined with strychnine to eliminate glycine components of the

  9. 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

  10. 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 greater diet-induced obesity when fed high-fat diet. Pharmacological and genetic inhibition of HDAC5 activity in the mediobasal hypothalamus increases food intake and modulates pathways implicated in leptin signalling. We show HDAC5 directly regulates STAT3 localization and transcriptional activity via...... reciprocal STAT3 deacetylation at Lys685 and phosphorylation at Tyr705. In vivo, leptin sensitivity is substantially impaired in HDAC5 loss-of-function mice. Hypothalamic HDAC5 overexpression improves leptin action and partially protects against HFD-induced leptin resistance and obesity. Overall, our data...

  11. 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

  12. 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.

  13. Hypothalamic-Pituitary-Gonadal Endocrine System in the Hagfish

    Directory of Open Access Journals (Sweden)

    Masumi eNozaki

    2013-12-01

    Full Text Available The hypothalamic-pituitary system is considered to be a seminal event that emerged prior to or during the differentiation of the ancestral agnathans (jawless vertebrates. Hagfishes as one of the only two extant members of the class of agnathans are considered the most primitive vertebrate known, living or extinct. Accordingly, studies on their reproduction are important for understanding the evolution and phylogenetic aspects of the vertebrate reproductive endocrine system. In gnathostomes (jawed vertebrates, the hormones of the hypothalamus and pituitary have been extensively studied and shown to have well-defined roles in the control of reproduction. In hagfish, it was thought that they did not have the same neuroendocrine control of reproduction as gnathostomes, since it was not clear whether the hagfish pituitary gland contained tropic hormones of any kind. This review highlights the recent findings of the hypothalamic-pituitary-gonadal endocrine system in the hagfish. In contrast to gnathostomes that have two gonadotropins (GTH: luteinizing hormone and follicle-stimulating hormone, only one pituitary GTH has been identified in the hagfish. Immunohistochemical and functional studies confirmed that this hagfish GTH was significantly correlated with the developmental stages of the gonads and showed the presence of a steroid (estradiol feedback system at the hypothalamic-pituitary levels. Moreover, while the identity of hypothalamic gonadotropin releasing hormone (GnRH has not been determined, immunoreactive (ir GnRH has been shown in the hagfish brain including seasonal changes of ir-GnRH corresponding to gonadal reproductive stages. In addition, a hagfish PQRFamide peptide was identified and shown to stimulate the expression of hagfish GTH mRNA in the hagfish pituitary. These findings provide evidence that there are neuroendocrine-pituitary hormones that share common structure and functional features compared to later evolved vertebrates.

  14. Hypothalamic regulation of metabolism: Role of thyroid hormone and estrogen

    OpenAIRE

    Zhang, Z.

    2017-01-01

    Thyroid hormone and estrogen both play an essential role in energy metabolism. The current thesis investigated the possible central effects of these hormones in the control of energy metabolism by administrating triiodothyronine (T3), estradiol (E2) and thyrotropin-releasing hormone (TRH) in distinct hypothalamic nuclei. We evaluated various aspects of metabolic alterations including glucose and lipid metabolism, food intake, body weight, body temperature, locomotor activity, energy expenditu...

  15. Hypothalamic Inflammation and Energy Balance Disruptions: Spotlight on Chemokines

    OpenAIRE

    Le Thuc, Ophélia; Stobbe, Katharina; Cansell, Céline; Nahon, Jean-Louis; Blondeau, Nicolas; Rovère, Carole

    2017-01-01

    The hypothalamus is a key brain region in the regulation of energy balance as it controls food intake and both energy storage and expenditure through integration of humoral, neural, and nutrient-related signals and cues. Many years of research have focused on the regulation of energy balance by hypothalamic neurons, but the most recent findings suggest that neurons and glial cells, such as microglia and astrocytes, in the hypothalamus actually orchestrate together several metabolic functions....

  16. Hypothalamic Inflammation and Energy Balance Disruptions: Spotlight on Chemokines

    Directory of Open Access Journals (Sweden)

    Ophélia Le Thuc

    2017-08-01

    Full Text Available The hypothalamus is a key brain region in the regulation of energy balance as it controls food intake and both energy storage and expenditure through integration of humoral, neural, and nutrient-related signals and cues. Many years of research have focused on the regulation of energy balance by hypothalamic neurons, but the most recent findings suggest that neurons and glial cells, such as microglia and astrocytes, in the hypothalamus actually orchestrate together several metabolic functions. Because glial cells have been described as mediators of inflammatory processes in the brain, the existence of a causal link between hypothalamic inflammation and the deregulations of feeding behavior, leading to involuntary weight loss or obesity for example, has been suggested. Several inflammatory pathways that could impair the hypothalamic control of energy balance have been studied over the years such as, among others, toll-like receptors and canonical cytokines. Yet, less studied so far, chemokines also represent interesting candidates that could link the aforementioned pathways and the activity of hypothalamic neurons. Indeed, chemokines, in addition to their role in attracting immune cells to the inflamed site, have been suggested to be capable of neuromodulation. Thus, they could disrupt cellular activity together with synthesis and/or secretion of multiple neurotransmitters/mediators involved in the maintenance of energy balance. This review discusses the different inflammatory pathways that have been identified so far in the hypothalamus in the context of feeding behavior and body weight control impairments, with a particular focus on chemokines signaling that opens a new avenue in the understanding of the major role played by inflammation in obesity.

  17. Hypothalamic Inflammation and Energy Balance Disruptions: Spotlight on Chemokines.

    Science.gov (United States)

    Le Thuc, Ophélia; Stobbe, Katharina; Cansell, Céline; Nahon, Jean-Louis; Blondeau, Nicolas; Rovère, Carole

    2017-01-01

    The hypothalamus is a key brain region in the regulation of energy balance as it controls food intake and both energy storage and expenditure through integration of humoral, neural, and nutrient-related signals and cues. Many years of research have focused on the regulation of energy balance by hypothalamic neurons, but the most recent findings suggest that neurons and glial cells, such as microglia and astrocytes, in the hypothalamus actually orchestrate together several metabolic functions. Because glial cells have been described as mediators of inflammatory processes in the brain, the existence of a causal link between hypothalamic inflammation and the deregulations of feeding behavior, leading to involuntary weight loss or obesity for example, has been suggested. Several inflammatory pathways that could impair the hypothalamic control of energy balance have been studied over the years such as, among others, toll-like receptors and canonical cytokines. Yet, less studied so far, chemokines also represent interesting candidates that could link the aforementioned pathways and the activity of hypothalamic neurons. Indeed, chemokines, in addition to their role in attracting immune cells to the inflamed site, have been suggested to be capable of neuromodulation. Thus, they could disrupt cellular activity together with synthesis and/or secretion of multiple neurotransmitters/mediators involved in the maintenance of energy balance. This review discusses the different inflammatory pathways that have been identified so far in the hypothalamus in the context of feeding behavior and body weight control impairments, with a particular focus on chemokines signaling that opens a new avenue in the understanding of the major role played by inflammation in obesity.

  18. Methamphetamine and the hypothalamic-pituitary-adrenal axis

    OpenAIRE

    Damian Gabriel Zuloaga; Jason eJacobskind; Jacob eRaber

    2015-01-01

    Psychostimulants such as methamphetamine (MA) induce significant alterations in the function of the hypothalamic-pituitary-adrenal (HPA) axis. These changes in HPA axis function are associated with altered stress-related behaviors and might contribute to addictive processes such as relapse. In this mini-review we discuss acute and chronic effects of MA (adult and developmental exposure) on the HPA axis, including effects on HPA axis associated genes/proteins, brain regions, and behaviors suc...

  19. EJE PRIZE 2017: Hypothalamic AMPK: a golden target against obesity?

    Science.gov (United States)

    López, Miguel

    2017-05-01

    AMP-activated protein kinase (AMPK) is a cellular gauge that is activated under conditions, such as low energy, increasing energy production and reducing energy waste. Centrally, the AMPK pathway is a canonical route regulating energy homeostasis, by integrating peripheral signals, such as hormones and metabolites, with neuronal networks. Current evidence links hypothalamic AMPK with feeding, brown adipose tissue (BAT) thermogenesis and browning of white adipose tissue (WAT), as well as muscle metabolism, hepatic function and glucose homeostasis. The relevance of these data is interesting from a therapeutic point of view as several agents with potential anti-obesity and/or antidiabetic effects, some currently in clinical use, such as nicotine, metformin and liraglutide are known to act through AMPK, either peripherally or centrally. Furthermore, the orexigenic and weight-gaining effects of the worldwide use of antipsychotic drugs (APDs), such as olanzapine, are also mediated by hypothalamic AMPK. Overall, this evidence makes hypothalamic AMPK signaling an interesting target for the drug development, with its potential for controlling both sides of the energy balance equation, namely feeding and energy expenditure through defined metabolic pathways. © 2017 The authors.

  20. Role of leptin in energy expenditure: the hypothalamic perspective.

    Science.gov (United States)

    Pandit, R; Beerens, S; Adan, R A H

    2017-06-01

    The adipocyte-derived hormone leptin is a peripheral signal that informs the brain about the metabolic status of an organism. Although traditionally viewed as an appetite-suppressing hormone, studies in the past decade have highlighted the role of leptin in energy expenditure. Leptin has been shown to increase energy expenditure in particular through its effects on the cardiovascular system and brown adipose tissue (BAT) thermogenesis via the hypothalamus. The current review summarizes the role of leptin signaling in various hypothalamic nuclei and its effects on the sympathetic nervous system to influence blood pressure, heart rate, and BAT thermogenesis. Specifically, the role of leptin signaling on three different hypothalamic nuclei, the dorsomedial hypothalamus, the ventromedial hypothalamus, and the arcuate nucleus, is reviewed. It is known that all of these brain regions influence the sympathetic nervous system activity and thereby regulate BAT thermogenesis and the cardiovascular system. Thus the current work focuses on how leptin signaling in specific neuronal populations within these hypothalamic nuclei influences certain aspects of energy expenditure. Copyright © 2017 the American Physiological Society.

  1. Hypothalamic stimulation and baroceptor reflex interaction on renal nerve activity.

    Science.gov (United States)

    Wilson, M. F.; Ninomiya, I.; Franz, G. N.; Judy, W. V.

    1971-01-01

    The basal level of mean renal nerve activity (MRNA-0) measured in anesthetized cats was found to be modified by the additive interaction of hypothalamic and baroceptor reflex influences. Data were collected with the four major baroceptor nerves either intact or cut, and with mean aortic pressure (MAP) either clamped with a reservoir or raised with l-epinephrine. With intact baroceptor nerves, MRNA stayed essentially constant at level MRNA-0 for MAP below an initial pressure P1, and fell approximately linearly to zero as MAP was raised to P2. Cutting the baroceptor nerves kept MRNA at MRNA-0 (assumed to represent basal central neural output) independent of MAP. The addition of hypothalamic stimulation produced nearly constant increments in MRNA for all pressure levels up to P2, with complete inhibition at some level above P2. The increments in MRNA depended on frequency and location of the stimulus. A piecewise linear model describes MRNA as a linear combination of hypothalamic, basal central neural, and baroceptor reflex activity.

  2. The Level of Vasopressin is not solely resulted from the Concentration of Endotoxin but Proportional to Creatinine in Dogs with Pyometra

    Directory of Open Access Journals (Sweden)

    W. Y. Shia1, K. C. Tung1, 2, S. C. Chang1, 2, C. H. Yang1, 2, C. H. Lee2, C. C. Chou1 and W. M. Lee1, 2*

    2011-04-01

    Full Text Available Pyometra is one of the most common reproductive disorder characterized as fluid accumulation mainly pus and Gram-negative bacteria isolated from uterus in bitches. Impaired function of vasopressin is found in the disease. The impact of the circulating endotoxin concentration on vasopressin involved water regulation is still unclear. To document the effect of endotoxin on vasopressin-involved water regulation in dogs with pyometra, blood samples were collected for examination of circulating endotoxin concentration, osmolarity values, vasopressin concentrations, blood urea nitrogen (BUN, and creatinine. The results indicated that the concentration change of endotoxin was contrary to BUN and creatinine in dogs with pyometra. The trends of concentrations change of BUN and creatinine were similar with osmolarity and vasopressin. Pyometric dogs with high level of circulating endotoxin had significantly lower (P 20 mg/dL and creatinine (> 1.5 mg/dL also had plasma vasopressin significantly higher (P<0.05 than those with low levels of BUN and creatinine and control dogs. The overall results suggested that elevated vasopressin was not mainly associated with the circulating endotoxin concentration and some other factors may collaborate with endotoxin causing impaired function of vasopressin.

  3. Early, but not late therapy with a vasopressin V1a-antagonist ameliorates the development of renal damage after 5/6 nephrectomy

    NARCIS (Netherlands)

    Windt, Willemijn A K M; Tahara, Atsua; Kluppel, Alex C A; de Zeeuw, Dick; Henning, Robert H; van Dokkum, Richard P E

    2006-01-01

    INTRODUCTION: Vasopressin, mainly through the V1a-receptor, is thought to be a major player in the maintenance of hyperfiltration. Its inhibition could therefore lead to a decrease in progression of chronic renal failure. To this end, the effect of the vasopressin V1a-receptor-selective antagonist,

  4. Early, but not late therapy with a vasopressin V-1a-antagonist ameliorates the development of renal damage after 5/6 nephrectomy

    NARCIS (Netherlands)

    Windt, Willemijn A. K. M.; Tahara, Atsua; Kluppel, Alex C. A.; de Zeeuw, Dick; Henning, Robert H.; van Dokkum, Richard P. E.

    2006-01-01

    Introduction. Vasopressin, mainly through the VIA-receptor, is thought to be a major player in the maintenance of hyperfiltration. Its inhibition could therefore lead to a decrease in progression of chronic renal failure. To this end, the effect of the vasopressin V-1a-receptor-selective antagonist,

  5. 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.

  6. Norepinephrine content in discrete brain areas and neurohypophysial vasopressin in rats after a 9-d spaceflight (SLS-1)

    Science.gov (United States)

    Fareh, Jeannette; Cottet-Emard, Jean-Marie; Pequignot, Jean-Marc; Jahns, Gary; Meylor, John; Viso, Michel; Vassaux, Didier; Gauquelin, Guillemette; Gharib, Claude

    1993-01-01

    The norepinephrine (NE) content in discrete brain areas and the vasopressin content in the neurohypophysial system were assessed in rats after a 9-d spaceflight and after a recovery period. The NE content in the locus coeruleus decreased significantly in spaceflight rats, but showed no difference between control and flight animals after a 9-d recovery. These findings were probably due to an acute stress undergone during landing. The NE content was unchanged in the A2 and A5 cell groups. In rats flown aboard SLS-1, the vasopressin content was increased in the posterior pituitary, and was significantly decreased in the hypothalamus. We conclude that the NE depletion in the locus coeruleus and the alteration in vasopressin release were consistent with an acute stress, likely occurring during and/or after landing. These changes tend to mask the actual neuroendocrine modifications caused by microgravity.

  7. Employment of vasopressin receptor antagonists in management of hyponatraemia and volume overload in some clinical conditions.

    Science.gov (United States)

    Urso, C; Brucculeri, S; Caimi, G

    2015-08-01

    Hyponatraemia, the most common electrolyte imbalance occurring in hospitalized subjects, is usually classified as hypovolaemic, euvolaemic or hypervolaemic. Hyponatraemia is a predictor of death among subjects with chronic heart failure and cirrhosis. The inappropriate secretion of the antidiuretic hormone (AVP) seems to be of pivotal importance in the decline of serum sodium concentration in these clinical conditions. The objective of this review was to summarize recent progress in management of hyponatraemia in SIADH, cirrhosis and heart failure. Literature searches were conducted on the topics of hyponatraemia and vasopressin receptor antagonists, using PubMed, pharmaceutical company websites and news reports. The information was evaluated for relevance and quality, critically assessed and summarized. The initial treatment of severe hyponatraemia is directed towards the prevention or management of neurological manifestations and consists of an intravenous infusion of hypertonic saline. Fluid restriction is indicated in oedematous states. Diuretics alone or in combination with other specific drugs remain the main strategy in the management of volume overload in heart failure. In resistant cases, ultrafiltration can lead to effective removal of isotonic fluid preventing new episodes of decompensation; however, aquapheresis is associated with increased costs and other limits. In several trials, the efficacy of vasopressin receptor antagonists in euvolaemic patients (inappropriate antidiuretic hormone secretion) or in hypervolaemic hyponatraemia (chronic heart failure, cirrhosis) has been evaluated. It was found that vaptans, which promote aquaresis, were superior to a placebo in raising and maintaining serum sodium concentrations in these subjects. Combined with conventional therapy, vasopressin receptor antagonists (AVP-R antagonists) are able to increase the excretion of electrolyte-free water and the sodium concentration. Further studies are needed to assess

  8. Expression of aquaporins and vasopressin type 2 receptor in the stria vascularis of the cochlea.

    Science.gov (United States)

    Nishioka, R; Takeda, T; Kakigi, A; Okada, T; Takebayashi, S; Taguchi, D; Nishimura, M; Hyodo, M

    2010-02-01

    Recently, considerable evidence has been accumulated to support the novel view that water homeostasis in the inner ear is regulated via the vasopressin-aquaporin 2 (VP-AQP2) system in the same fashion as in the kidney. Indeed, multiple subtypes of AQPs including AQP-2 are reported to be expressed in the cochlea. However, the mechanism that underlies VP-AQP-2 mediated water homeostasis remains to be elucidated. In the present study, the localizations of AQP-1, -2, -3, -4, -5, -7, -8, -9, and vasopressin type 2 receptor (V2-R) in the stria vascularis (SV) were molecular biologically and immunohistochemically examined to evaluate the role of the AQP water channel system in water homeostasis of the SV. A RT-PCR study revealed that AQPs and V2-R mRNA are expressed in the cochlea. As for their immunohistochemical localization, the AQP-2 protein is expressed on the basal side of the basal cells of the SV, and proteins of AQP-3 and V2-R are expressed on the apical side of the basal cells. AQP-7 and -9 proteins are expressed on the apical side of marginal cells. AQP-4, -5, and -8 protein expressions could not be detected in the lateral wall of the cochlea. From the present results, water flux in the SV is thought to be regulated at the level of the basal cells by vasopressin. Furthermore, such a distribution of AQP-2, -3, and V2-R suggests that VP-AQP-2 mediated water transport might work actively in the basal cells from perilymph towards endolymph containing AQP-1, -7 and -9. Copyright 2009 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    MacGregor, Duncan J; Leng, Gareth

    2012-01-01

    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. These findings show

  10. 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

  11. Subcellular localization and internalization of the vasopressin V1B receptor.

    Science.gov (United States)

    Kashiwazaki, Aki; Fujiwara, Yoko; Tsuchiya, Hiroyoshi; Sakai, Nobuya; Shibata, Katsushi; Koshimizu, Taka-aki

    2015-10-15

    Only limited information is available on agonist-dependent changes in the subcellular localization of vasopressin V1B receptors. Our radioligand binding study of membrane preparations and intact cells revealed that a large fraction of the V1B receptor is located in the cytoplasm in unstimulated CHO cells, which is in contrast to the plasma membrane localization of the V1A and V2 receptors. Moreover, when the affinity of radiolabeled arginine-vasopressin ([3H]AVP) was compared between membrane preparations and intact cells, the affinity of [3H]AVP to the cell surface V1B receptors, but not the V1A receptors, was significantly reduced. Although the number and affinity of cell surface V1B receptors decreased, they became extensively internalized upon binding with [3H]AVP. Approximately 87% of cell surface-bound [3H]AVP was internalized and became resistant to acid wash during incubation with 1 nM [3H]AVP. By contrast, less ligand (35%) was internalized in the cells expressing the V1A receptor. Extensive internalization of the V1B receptors was partially attenuated by inhibitors of cytoskeletal proteins, siRNA against β-arrestin 2, or the removal of sodium chloride from the extracellular buffer, indicating that this internalization involves clathrin-coated pits. Together, these results indicate that the mechanism that regulates the number and affinity of V1B receptors in the plasma membrane is markedly distinct from the corresponding mechanisms for the V1A and V2 receptors and plays a critical role under stress conditions, when vasopressin release is augmented. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. 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.

  13. [Hypothalamic inflammation and energy balance deregulations: focus on chemokines.

    Science.gov (United States)

    Le Thuc, Ophélia; Rovère, Carole

    2016-01-01

    The hypothalamus is a key brain region in the regulation of energy balance. It especially controls food intake and both energy storage and expenditure through integration of humoral, neural and nutrient-related signals and cues. Hypothalamic neurons and glial cells act jointly to orchestrate, both spatially and temporally, regulated metabolic functions of the hypothalamus. Thus, the existence of a causal link between hypothalamic inflammation and deregulations of feeding behavior, such as involuntary weight-loss or obesity, has been suggested. Among the inflammatory mediators that could induce deregulations of hypothalamic control of the energy balance, chemokines represent interesting candidates. Indeed, chemokines, primarily known for their chemoattractant role of immune cells to the inflamed site, have also been suggested capable of neuromodulation. Thus, chemokines could disrupt cellular activity together with synthesis and/or secretion of multiple neurotransmitters/mediators that are involved in the maintenance of energy balance. Here, we relate, on one hand, recent results showing the primary role of the central chemokinergic signaling CCL2/CCR2 for metabolic and behavioral adaptation to high-grade inflammation, especially loss of appetite and weight, through its activity on hypothalamic neurons producing the orexigenic peptide Melanin-Concentrating Hormone (MCH) and, on the other hand, results that suggest that chemokines could also deregulate hypothalamic neuropeptidergic circuits to induce an opposite phenotype and eventually participate in the onset/development of obesity. In more details, we will emphasize a study recently showing, in a model of high-grade acute inflammation of LPS injection in mice, that central CCL2/CCR2 signaling is of primary importance for several aspects explaining weight loss associated with inflammation: after LPS injection, animals lose weight, reduce their food intake, increase their fat oxidation (thus energy consumption from

  14. 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.

  15. Endothelin and vasopressin influence splanchnic blood flow distribution during and after cardiopulmonary bypass.

    Science.gov (United States)

    Bomberg, Hagen; Bierbach, Benjamin; Flache, Stephan; Wagner, Isabell; Gläser, Lena; Groesdonk, Heinrich V; Menger, Michael D; Schäfers, Hans-Joachim

    2013-02-01

    Gastrointestinal blood flow can be compromised during and after cardiopulmonary bypass. Endothelin has been shown to be involved in the intestinal microcirculatory disturbance of sepsis. The aim of the present study was to analyze the involvement of the endothelin system on intestinal blood flow regulation during cardiopulmonary bypass and the effect of vasopressin given during cardiopulmonary bypass. A total of 24 pigs were studied in 4 groups (n = 6): group I, sham; group II, ischemia/reperfusion with 1 hour of superior mesenteric artery occlusion; group III, cardiopulmonary bypass for 1 hour; and group IV, 1 hour of cardiopulmonary bypass plus vasopressin administration, maintaining the baseline arterial pressure. All the pigs were reperfused for 90 minutes. During the experiment, the hemodynamics and jejunal microcirculation were measured continuously. The jejunal mucosal expression of endothelin-1 and its receptor subtypes A and B were determined using polymerase chain reaction. During cardiopulmonary bypass, superior mesenteric artery flow was preserved but marked jejunal microvascular impairment occurred compared with baseline (mucosal capillary density, 192.2 ± 5.4 vs 150.8 ± 5.1 cm/cm(2); P = .005; tissue blood flow, 501.7 ± 39.3 vs 332.3 ± 27.9 AU; P = .025). The expression of endothelin-1 after cardiopulmonary bypass (3.2 ± 0.4 vs 12.2 ± 0.8 RQ, P = .006) and endothelin subtype A (0.7 ± 0.2 vs 2.4 ± 0.6 RQ; P = .01) was significantly increased compared to the sham group. Vasopressin administration during cardiopulmonary bypass led to normal capillary density (189.9 ± 3.9 vs 178.0 ± 6.3; P = .1) and tissue blood flow (501.7 ± 39.3 vs 494.7 ± 44.4 AU; P = .4) compared with baseline. The expression of endothelin-1 (3.2 ± 0.4 vs 1.8 ± 0.3 RQ; P = .3) and endothelin subtype A (0.7 ± 0.2 vs 0.9 ± 0.2 RQ; P = .5) was not different from the sham group. Cardiopulmonary bypass leads to microvascular impairment of jejunal microcirculation, which is

  16. Defective regulation of POMC precedes hypothalamic inflammation in diet-induced obesity

    OpenAIRE

    Gabriela F. P. Souza; Carina Solon; Lucas F. Nascimento; Jose C. De-Lima-Junior; Guilherme Nogueira; Rodrigo Moura; Guilherme Z. Rocha; Milena Fioravante; Vanessa Bobbo; Joseane Morari; Daniela Razolli; Eliana P. Araujo; Licio A. Velloso

    2016-01-01

    Obesity is the result of a long-term positive energy balance in which caloric intake overrides energy expenditure. This anabolic state results from the defective activity of hypothalamic neurons involved in the sensing and response to adiposity. However, it is currently unknown what the earliest obesity-linked hypothalamic defect is and how it orchestrates the energy imbalance present in obesity. Using an outbred model of diet-induced obesity we show that defective regulation of hypothalamic ...

  17. 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

  18. Differentiation of hypothalamic-like neurons from human pluripotent stem cells.

    Science.gov (United States)

    Wang, Liheng; Meece, Kana; Williams, Damian J; Lo, Kinyui Alice; Zimmer, Matthew; Heinrich, Garrett; Martin Carli, Jayne; Leduc, Charles A; Sun, Lei; Zeltser, Lori M; Freeby, Matthew; Goland, Robin; Tsang, Stephen H; Wardlaw, Sharon L; Egli, Dieter; Leibel, Rudolph L

    2015-02-01

    The hypothalamus is the central regulator of systemic energy homeostasis, and its dysfunction can result in extreme body weight alterations. Insights into the complex cellular physiology of this region are critical to the understanding of obesity pathogenesis; however, human hypothalamic cells are largely inaccessible for direct study. Here, we developed a protocol for efficient generation of hypothalamic neurons from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) obtained from patients with monogenetic forms of obesity. Combined early activation of sonic hedgehog signaling followed by timed NOTCH inhibition in human ESCs/iPSCs resulted in efficient conversion into hypothalamic NKX2.1+ precursors. Application of a NOTCH inhibitor and brain-derived neurotrophic factor (BDNF) further directed the cells into arcuate nucleus hypothalamic-like neurons that express hypothalamic neuron markers proopiomelanocortin (POMC), neuropeptide Y (NPY), agouti-related peptide (AGRP), somatostatin, and dopamine. These hypothalamic-like neurons accounted for over 90% of differentiated cells and exhibited transcriptional profiles defined by a hypothalamic-specific gene expression signature that lacked pituitary markers. Importantly, these cells displayed hypothalamic neuron characteristics, including production and secretion of neuropeptides and increased p-AKT and p-STAT3 in response to insulin and leptin. Our results suggest that these hypothalamic-like neurons have potential for further investigation of the neurophysiology of body weight regulation and evaluation of therapeutic targets for obesity.

  19. Differentiation of hypothalamic-like neurons from human pluripotent stem cells

    Science.gov (United States)

    Wang, Liheng; Meece, Kana; Williams, Damian J.; Lo, Kinyui Alice; Zimmer, Matthew; Heinrich, Garrett; Martin Carli, Jayne; Leduc, Charles A.; Sun, Lei; Zeltser, Lori M.; Freeby, Matthew; Goland, Robin; Tsang, Stephen H.; Wardlaw, Sharon L.; Egli, Dieter; Leibel, Rudolph L.

    2015-01-01

    The hypothalamus is the central regulator of systemic energy homeostasis, and its dysfunction can result in extreme body weight alterations. Insights into the complex cellular physiology of this region are critical to the understanding of obesity pathogenesis; however, human hypothalamic cells are largely inaccessible for direct study. Here, we developed a protocol for efficient generation of hypothalamic neurons from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) obtained from patients with monogenetic forms of obesity. Combined early activation of sonic hedgehog signaling followed by timed NOTCH inhibition in human ESCs/iPSCs resulted in efficient conversion into hypothalamic NKX2.1+ precursors. Application of a NOTCH inhibitor and brain-derived neurotrophic factor (BDNF) further directed the cells into arcuate nucleus hypothalamic-like neurons that express hypothalamic neuron markers proopiomelanocortin (POMC), neuropeptide Y (NPY), agouti-related peptide (AGRP), somatostatin, and dopamine. These hypothalamic-like neurons accounted for over 90% of differentiated cells and exhibited transcriptional profiles defined by a hypothalamic-specific gene expression signature that lacked pituitary markers. Importantly, these cells displayed hypothalamic neuron characteristics, including production and secretion of neuropeptides and increased p-AKT and p-STAT3 in response to insulin and leptin. Our results suggest that these hypothalamic-like neurons have potential for further investigation of the neurophysiology of body weight regulation and evaluation of therapeutic targets for obesity. PMID:25555215

  20. Prediction of perinatal brain damage by cord plasma vasopressin, erythropoietin, and hypoxanthine values.

    Science.gov (United States)

    Ruth, V; Autti-Rämö, I; Granström, M L; Korkman, M; Raivio, K O

    1988-11-01

    For an assessment of whether cord plasma arginine vasopressin, erythropoietin, and hypoxanthine concentrations are predictors of perinatal brain damage, these concentrations were measured in 62 infants born after preeclampsia of pregnancy, 31 acutely asphyxiated infants, and 38 control infants. Follow-up at 2 years included neurologic examination and the determination of a Bayley mental score. Clear abnormality (death, cerebral palsy, or developmental delay) was found in four infants in the preeclampsia group and five in the asphyxia group; slight abnormality was found in 12 and 6 infants, respectively; and no abnormality was found in the remainder. Neither arginine vasopressin values nor hypoxanthine values predicted adverse outcome in either study group. A high erythropoietin level was found in infants born after preeclampsia regardless of outcome: normal outcome (geometric mean (GM), 102; 95% confidence interval [CI], 69 to 153 mU/ml), slightly abnormal outcome (GM, 100; 95% CI, 37 to 270 mU/ml) or clearly abnormal outcome (GM, 84; 95% CI, 19 to 378 mU/ml). However, asphyxiated infants with clearly abnormal outcome had higher erythropoietin values (GM, 67; 95% CI, 33 to 137 mU/ml; p less than 0.05) than the normal infants (GM, 37; 95% CI, 23 to 59 mU/ml). We conclude that a high erythropoietin level after normal pregnancy, but not after preeclampsia, indicates an increased risk for cerebral palsy or death.

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

    Energy Technology Data Exchange (ETDEWEB)

    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. (/sup 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/sub 1/ subtype receptors on Leydig cells. The ability of AVP to displace (/sup 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 (/sup 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.

  2. Number of X-chromosome genes influences social behavior and vasopressin gene expression in mice.

    Science.gov (United States)

    Cox, Kimberly H; Quinnies, Kayla M; Eschendroeder, Alex; Didrick, Paula M; Eugster, Erica A; Rissman, Emilie F

    2015-01-01

    Sex differences in behavior are widespread and often caused by hormonal differences between the sexes. In addition to hormones, the composition and numbers of the sex chromosomes also affect a variety of sex differences. In humans, X-chromosome genes are implicated in neurobehavioral disorders (i.e. fragile-X, autism). To investigate the role of X-chromosome genes in social behavior, we used a mouse model that has atypical sex chromosome configurations resembling Turner (45, XO) and Klinefelter syndromes (47, XXY). We examined a number of behaviors in juvenile mice. Mice with only one copy of most X-chromosome genes, regardless of gonadal sex, were less social in dyadic interaction and social preference tasks. In the elevated plus maze, mice with one X-chromosome spent less time in the distal ends of the open arms as compared to mice with two copies of X-chromosome genes. Using qRTPCR, we noted that amygdala from female mice with one X-chromosome had higher expression levels of vasopressin (Avp) as compared to mice in the other groups. Finally, in plasma from girls with Turner syndrome we detected reduced vasopressin (AVP) concentrations as compared to control patients. These novel findings link sex chromosome genes with social behavior via concentrations of AVP in brain, adding to our understanding of sex differences in neurobehavioral disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. 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

  4. Endogenous vasopressin and the central control of heart rate during dynamic exercise

    Directory of Open Access Journals (Sweden)

    L.C. Michelini

    1998-09-01

    Full Text Available The present article contains a brief review on the role of vasopressinergic projections to the nucleus tractus solitarii in the genesis of reflex bradycardia and in the modulation of heart rate control during exercise. The effects of vasopressin on exercise tachycardia are discussed on the basis of both the endogenous peptide content changes and the heart rate response changes observed during running in sedentary and trained rats. Dynamic exercise caused a specific vasopressin content increase in dorsal and ventral brainstem areas. In accordance, rats pretreated with the peptide or the V1 blocker into the nucleus tractus solitarii showed a significant potentiation or a marked blunting of the exercise tachycardia, respectively, without any change in the pressure response to exercise. It is proposed that the long-descending vasopressinergic pathway to the nucleus tractus solitarii serves as one link between the two main neural controllers of circulation, i.e., the central command and feedback control mechanisms driven by the peripheral receptors. Therefore, vasopressinergic input could contribute to the adjustment of heart rate response (and cardiac output to the circulatory demand during exercise.

  5. 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.

  6. The regulation of social recognition, social communication and aggression: vasopressin in the social behavior neural network.

    Science.gov (United States)

    Albers, H Elliott

    2012-03-01

    Neuropeptides in the arginine vasotocin/arginine vasopressin (AVT/AVP) family play a major role in the regulation of social behavior by their actions in the brain. In mammals, AVP is found within a circuit of recriprocally connected limbic structures that form the social behavior neural network. This review examines the role played by AVP within this network in controlling social processes that are critical for the formation and maintenance of social relationships: social recognition, social communication and aggression. Studies in a number of mammalian species indicate that AVP and AVP V1a receptors are ideally suited to regulate the expression of social processes because of their plasticity in response to factors that influence social behavior. The pattern of AVP innervation and V1a receptors across the social behavior neural network may determine the potential range and intensity of social responses that individuals display in different social situations. Although fundamental information on how social behavior is wired in the brain is still lacking, it is clear that different social behaviors can be influenced by the actions of AVP in the same region of the network and that AVP can act within multiple regions of this network to regulate the expression of individual social behaviors. The existing data suggest that AVP can influence social behavior by modulating the interpretation of sensory information, by influencing decision making and by triggering complex motor outputs. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. The vasopressin system: new insights for patients with kidney diseases: Epidemiological evidence and therapeutic perspectives.

    Science.gov (United States)

    Clark, W F; Devuyst, O; Roussel, R

    2017-10-01

    People with chronic kidney disease (CKD) are at risk of severe outcomes, such as end-stage renal disease or cardiovascular disease, and CKD is a globally increasing health burden with a high personal and economic cost. Despite major progresses in prevention and therapeutics in last decades, research is still needed to reverse this epidemic trend. The regulation of water balance and the state of activation of the vasopressin system have emerged as factors tightly associated with kidney health, in the general population but also in specific conditions; among them, various stages of CKD, diabetes and autosomal dominant polycystic kidney disease (ADPKD). Basic science findings and also epidemiological evidence have justified important efforts towards interventional studies supporting causality, and opening therapeutic avenues. On the basis of recent clinical data, the blockade of V2 vasopressin receptors using tolvaptan in patients with rapidly progressing ADPKD has been granted in several countries, and a long-term randomized trial evaluating the effect of an increase in water intake in patients with CKD is on-going. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  8. Spinal vasopressin alleviates formalin-induced nociception by enhancing GABAA receptor function in mice.

    Science.gov (United States)

    Peng, Fang; Qu, Zu-Wei; Qiu, Chun-Yu; Liao, Min; Hu, Wang-Ping

    2015-04-23

    Arginine vasopressin (AVP) plays a regulatory role in nociception. Intrathecal administration of AVP displays an antinociceptive effect. However, little is understood about the mechanism underlying spinal AVP analgesia. Here, we have found that spinal AVP dose dependently reduced the second, but not first, phase of formalin-induced spontaneous nociception in mice. The AVP analgesia was completely blocked by intrathecal injected SR 49059, a vasopressin-1A (V1A) receptor antagonist. However, spinal AVP failed to exert its antinociceptive effect on the second phase formalin-induced spontaneous nociception in V1A receptor knock-out (V1A-/-) mice. The AVP analgesia was also reversed by bicuculline, a GABAA receptor antagonist. Moreover, AVP potentiated GABA-activated currents in dorsal root ganglion neurons from wild-type littermates, but not from V1A-/- mice. Our results may reveal a novel spinal mechanism of AVP analgesia by enhancing the GABAA receptor function in the spinal cord through V1A receptors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

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    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.

  10. Antiproliferative effect of 1-deamino-8-D-arginine vasopressin analogs on human breast cancer cells.

    Science.gov (United States)

    Iannucci, Nancy B; Ripoll, Giselle V; Garona, Juan; Cascone, Osvaldo; Ciccia, Graciela N; Gomez, Daniel E; Alonso, Daniel F

    2011-12-01

    Desmopressin (dDAVP), a synthetic nonapeptide derivative of arginine vasopressin, is a safe antidiuretic and hemostatic compound that acts as a selective agonist for the vasopressin V2 membrane receptor (V2R). It is known that dDAVP can inhibit progression of residual metastatic cells in preclinical models. Among other mechanisms, the compound induces an agonist effect on V2R present in tumor cells. Looking for novel analogs with improved anti-tumor activity, positions 4 and 5, at the conformational peptide loop, were substituted. The analog [V(4)Q(5)]dDAVP ([4-valine 5-glutamine] desmopressin) exhibited a significantly higher antiproliferative effect than dDAVP in cultures of MCF-7, a V2R-expressing human breast carcinoma cell line. The chiral isomer of this analog and tetrapeptide fragments corresponding to the loop region were also assessed. Preclinical evaluation of the anti-tumor activity of [V(4)Q(5)]dDAVP in animal models is warranted.

  11. The Effect of Maternal Stress Activation on the Offspring during Lactation in Light of Vasopressin

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    Anna Fodor

    2014-01-01

    Full Text Available Although it is obvious that preconceptional effects as well as stressors during pregnancy profoundly influence the progeny, the lactation period seems to be at least as important. Here we summarize how maternal stressors during the lactation period affect the offspring. As vasopressin is one of the crucial components both for stress adaptation and social behavior, special emphasis was given to this neuropeptide. We can conclude that stressing the mother does not have the same acute effect on the hypothalamo-pituitary-adrenocortical axis (as the main target of stress adaptation of the pups as stressing the pups, but later endocrine and behavioral consequences can be similar. Vasopressin plays a role in acute and later consequences of perinatal stressor applied either to the mother or to the offspring, thereby contributing to transmitting the mothers’ stress to the progeny. This mother-infant interaction does not necessarily mean a direct transmission of molecules, but rather is the result of programming the brain development through changes in maternal behavior. Thus, there is a time lag between maternal stress and stress-related changes in the offspring. The interactions are bidirectional as not only stress in the dam but also stress in the progeny has an effect on nursing.

  12. Reduction in plasma vasopressin levels of dehydrated rats following acute stress

    Science.gov (United States)

    Keil, L. C.; Severs, W. B.

    1977-01-01

    Results are presented for an investigation directed to substantiate and extend preliminary findings of stress-induced reduction in plasma arginine vasopressin (pAVP). Since normally hydrated rats have very low levels of pAVP, it is difficult to measure reliably any decrease in pAVP that may result from stress. To overcome this problem, the pAVP levels of the tested rats were raised by dehydration prior to application of stress. A radioimmunoassay for pAVP is described and used to determine the levels of vasopressin in the plasma of nondehydrated and dehydrated rats after exposure to ether or acceleration stress. Plasma pAVP is also determined in rats following nicotine administration. It is shown that exposure of nondehydrated rats to ether or acceleration stress does not elicit any significant alterations in circulating pAVP levels while nicotine injections stimulate a marked increase. In particular, ether and acceleration stress produce a rapid reduction in the pAVP level of dehydrated rats, the decrease being observed in both large and small animals. The mechanism for this reduction in pAVP level following stress is yet unknown.

  13. Cardiorenal Syndrome: Role of Arginine Vasopressin and Vaptans in Heart Failure.

    Science.gov (United States)

    Vinod, Poornima; Krishnappa, Vinod; Chauvin, Abigail M; Khare, Anshika; Raina, Rupesh

    2017-06-01

    Heart and kidney failure continued to be of increasing prevalence in today's society, and their comorbidity has synergistic effect on the morbidity and mortality of patients. Cardiorenal syndrome (CRS) is a complex disease with multifactorial pathophysiology. Better understanding of this pathophysiological network is crucial for the successful intervention to prevent advancement of the disease process. One of the major factors in this process is neurohormonal activation, predominantly involving renin-angiotensin-aldosterone system (RAAS) and arginine vasopressin (AVP). Heart failure causes reduced cardiac output/cardiac index (CO/CI) and fall in renal perfusion pressures resulting in activation of baroreceptors and RAAS, respectively. Activated baroreceptors and RAAS stimulate the release of AVP (non-osmotic pathway), which acts on V2 receptors located in the renal collecting ducts, causing fluid retention and deterioration of heart failure. Effective blockade of AVP action on V2 receptors has emerged as a potential treatment option in volume overload conditions especially in the setting of hyponatremia. Vasopressin receptor antagonists (VRAs), such as vaptans, are potent aquaretics causing electrolyte-free water diuresis without significant electrolyte abnormalities. Vaptans are useful in hypervolemic hyponatremic conditions like heart failure and liver cirrhosis, and euvolemic hyponatremic conditions like syndrome of inappropriate anti-diuretic hormone secretion. Tolvaptan and conivaptan are pharmaceutical agents that are available for the treatment of these conditions.

  14. Selective localization of oxytocin receptors and vasopressin 1a receptors in the human brainstem.

    Science.gov (United States)

    Freeman, Sara M; Smith, Aaron L; Goodman, Mark M; Bales, Karen L

    2017-04-01

    Intranasal oxytocin (OT) affects a suite of human social behaviors, including trust, eye contact, and emotion recognition. However, it is unclear where oxytocin receptors (OXTR) and the structurally related vasopressin 1a receptors (AVPR1a) are expressed in the human brain. We have previously described a reliable, pharmacologically informed receptor autoradiography protocol for visualizing these receptors in postmortem primate brain tissue. We used this technique in human brainstem tissue to identify the neural targets of OT and vasopressin. To determine binding selectivity of the OXTR radioligand and AVPR1a radioligand, sections were incubated in four conditions: radioligand alone, radioligand with the selective AVPR1a competitor SR49059, and radioligand with a low or high concentration of the selective OXTR competitor ALS-II-69. We found selective OXTR binding in the spinal trigeminal nucleus, a conserved region of OXTR expression in all primate species investigated to date. We found selective AVPR1a binding in the nucleus prepositus, an area implicated in eye gaze stabilization. The tissue's postmortem interval (PMI) was not correlated with either the specific or nonspecific binding of either radioligand, indicating that it will not likely be a factor in similar postmortem studies. This study provides critical data for future studies of OXTR and AVPR1a in human brain tissue.

  15. Vasopressin in Hemorrhagic Shock: A Systematic Review and Meta-Analysis of Randomized Animal Trials

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    Andrea Pasquale Cossu

    2014-01-01

    Full Text Available Objective. The latest European guidelines for the management of hemorrhagic shock suggest the use of vasopressors (norepinephrine in order to restore an adequate mean arterial pressure when fluid resuscitation therapy fails to restore blood pressure. The administration of arginine vasopressin (AVP, or its analogue terlipressin, has been proposed as an alternative treatment in the early stages of hypovolemic shock. Design. A meta-analysis of randomized controlled animal trials. Participants. A total of 433 animals from 15 studies were included. Interventions. The ability of AVP and terlipressin to reduce mortality when compared with fluid resuscitation therapy, other vasopressors (norepinephrine or epinephrine, or placebo was investigated. Measurements and Main Results. Pooled estimates showed that AVP and terlipressin consistently and significantly improve survival in hemorrhagic shock (mortality: 26/174 (15% in the AVP group versus 164/259 (63% in the control arms; OR=0.09; 95% CI 0.05 to 0.15; P for effect < 0.001; P for heterogeneity = 0.30; I2=14%. Conclusions. Results suggest that AVP and terlipressin improve survival in the early phases of animal models of hemorrhagic shock. Vasopressin seems to be more effective than all other treatments, including other vasopressor drugs. These results need to be confirmed by human clinical trials.

  16. Thyroid hormone activation of retinoic acid synthesis in hypothalamic tanycytes

    Science.gov (United States)

    Stoney, Patrick N.; Helfer, Gisela; Rodrigues, Diana; Morgan, Peter J.

    2015-01-01

    Thyroid hormone (TH) is essential for adult brain function and its actions include several key roles in the hypothalamus. Although TH controls gene expression via specific TH receptors of the nuclear receptor class, surprisingly few genes have been demonstrated to be directly regulated by TH in the hypothalamus, or the adult brain as a whole. This study explored the rapid induction by TH of retinaldehyde dehydrogenase 1 (Raldh1), encoding a retinoic acid (RA)‐synthesizing enzyme, as a gene specifically expressed in hypothalamic tanycytes, cells that mediate a number of actions of TH in the hypothalamus. The resulting increase in RA may then regulate gene expression via the RA receptors, also of the nuclear receptor class. In vivo exposure of the rat to TH led to a significant and rapid increase in hypothalamic Raldh1 within 4 hours. That this may lead to an in vivo increase in RA is suggested by the later induction by TH of the RA‐responsive gene Cyp26b1. To explore the actions of RA in the hypothalamus as a potential mediator of TH control of gene regulation, an ex vivo hypothalamic rat slice culture method was developed in which the Raldh1‐expressing tanycytes were maintained. These slice cultures confirmed that TH did not act on genes regulating energy balance but could induce Raldh1. RA has the potential to upregulate expression of genes involved in growth and appetite, Ghrh and Agrp. This regulation is acutely sensitive to epigenetic changes, as has been shown for TH action in vivo. These results indicate that sequential triggering of two nuclear receptor signalling systems has the capability to mediate some of the functions of TH in the hypothalamus. GLIA 2016;64:425–439 PMID:26527258

  17. Neuropeptides, food intake and body weight regulation: a hypothalamic focus.

    Science.gov (United States)

    Hillebrand, J J G; de Wied, D; Adan, R A H

    2002-12-01

    Energy homeostasis is controlled by a complex neuroendocrine system consisting of peripheral signals like leptin and central signals, in particular, neuropeptides. Several neuropeptides with anorexigenic (POMC, CART, and CRH) as well as orexigenic (NPY, AgRP, and MCH) actions are involved in this complex (partly redundant) controlling system. Starvation as well as overfeeding lead to changes in expression levels of these neuropeptides, which act downstream of leptin, resulting in a physiological response. In this review the role of several anorexigenic and orexigenic (hypothalamic) neuropeptides on food intake and body weight regulation is summarized.

  18. Hypothalamic Inflammation in Obesity, Insulin Resistance and Ageing

    OpenAIRE

    Tsaousidou, Eva

    2014-01-01

    In this study, the role of hypothalamic inflammation in obesity, insulin resistance and the regulation of the ageing process is investigated. Activation of c-Jun N-terminal kinase (JNK)1- and inhibitor of nuclear factor kappa-B kinase (IKK)2-dependent signalling plays a crucial role in the development of obesity-associated insulin and leptin resistance not only in peripheral tissues but also in the CNS. This study demonstrates that constitutive JNK1 activation in agouti-related peptide (AgRP)...

  19. Hypothalamic miRNAs: emerging roles in energy balance control.

    Science.gov (United States)

    Schneeberger, Marc; Gomez-Valadés, Alicia G; Ramirez, Sara; Gomis, Ramon; Claret, Marc

    2015-01-01

    The hypothalamus is a crucial central nervous system area controlling appetite, body weight and metabolism. It consists in multiple neuronal types that sense, integrate and generate appropriate responses to hormonal and nutritional signals partly by fine-tuning the expression of specific batteries of genes. However, the mechanisms regulating these neuronal gene programmes in physiology and pathophysiology are not completely understood. MicroRNAs (miRNAs) are key regulators of gene expression that recently emerged as pivotal modulators of systemic metabolism. In this article we will review current evidence indicating that miRNAs in hypothalamic neurons are also implicated in appetite and whole-body energy balance control.

  20. Hypothalamic miRNAs: emerging roles in energy balance control

    Directory of Open Access Journals (Sweden)

    Marc eSchneeberger

    2015-02-01

    Full Text Available The hypothalamus is a crucial central nervous system area controlling appetite, body weight and metabolism. It consists in multiple neuronal types that sense, integrate and generate appropriate responses to hormonal and nutritional signals partly by fine-tuning the expression of specific batteries of genes. However, the mechanisms regulating these neuronal gene programmes in physiology and pathophysiology are not completely understood. MicroRNAs (miRNAs are key regulators of gene expression that recently emerged as pivotal modulators of systemic metabolism. In this article we will review current evidence indicating that miRNAs in hypothalamic neurons are also implicated in appetite and whole-body energy balance control.

  1. 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

  2. Methamphetamine and the hypothalamic-pituitary-adrenal axis

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    Damian Gabriel Zuloaga

    2015-05-01

    Full Text Available Psychostimulants such as methamphetamine (MA induce significant alterations in the function of the hypothalamic-pituitary-adrenal (HPA axis. These changes in HPA axis function are associated with altered stress-related behaviors and might contribute to addictive processes such as relapse. In this mini-review we discuss acute and chronic effects of MA (adult and developmental exposure on the HPA axis, including effects on HPA axis associated genes/proteins, brain regions, and behaviors such as anxiety and depression. A better understanding of the mechanisms through which MA affects the HPA axis may lead to more effective treatment strategies for MA addiction.

  3. Methamphetamine and the hypothalamic-pituitary-adrenal axis.

    Science.gov (United States)

    Zuloaga, Damian G; Jacobskind, Jason S; Jacosbskind, Jason S; Raber, Jacob

    2015-01-01

    Psychostimulants such as methamphetamine (MA) induce significant alterations in the function of the hypothalamic-pituitary-adrenal (HPA) axis. These changes in HPA axis function are associated with altered stress-related behaviors and might contribute to addictive processes such as relapse. In this mini-review we discuss acute and chronic effects of MA (adult and developmental exposure) on the HPA axis, including effects on HPA axis associated genes/proteins, brain regions, and behaviors such as anxiety and depression. A better understanding of the mechanisms through which MA affects the HPA axis may lead to more effective treatment strategies for MA addiction.

  4. Transcription factor CREB3L1 mediates cAMP and glucocorticoid regulation of arginine vasopressin gene transcription in the rat hypothalamus.

    Science.gov (United States)

    Greenwood, Mingkwan; Greenwood, Michael P; Mecawi, Andre S; Loh, Su Yi; Rodrigues, José Antunes; Paton, Julian F R; Murphy, David

    2015-10-26

    Arginine vasopressin (AVP), a neuropeptide hormone that functions in the regulation of water homeostasis by controlling water re-absorption at kidneys, is synthesised in supraoptic nucleus and paraventricular nucleus of the hypothalamus. An increase in plasma osmolality stimulates secretion of AVP to blood circulation and induces AVP synthesis in these nuclei. Although studies on mechanism of AVP transcriptional regulation in hypothalamus proposed that cAMP and glucocorticoids positively and negatively regulate Avp expression, respectively, the molecular mechanisms have remained elusive. Recently, we identified CREB3L1 (cAMP-responsive element binding protein 3 like 1) as a putative transcription factor of Avp transcription in the rat hypothalamus. However the mechanism of how CREB3L1 is regulated in response of hyperosmotic stress in the neurons of hypothalamus has never been reported. This study aims to investigate effect of previously reported regulators (cAMP and glucocorticoid) of Avp transcription on transcription factor CREB3L1 in order to establish a molecular explanation for cAMP and glucocorticoids effect on AVP expression. The effect of cAMP and glucocorticoid treatment on Creb3l1 was investigated in both AtT20 cells and hypothalamic organotypic cultures. The expression of Creb3l1 was increased in both mRNA and protein level by treatment with forskolin, which raises intracellular cAMP levels. Activation of cAMP by forskolin also increased Avp promoter activity in AtT20 cells and this effect was blunted by shRNA mediated silencing of Creb3l1. The forskolin induced increase in Creb3l1 expression was diminished by combined treatment with dexamethasone, and, in vivo, intraperitoneal dexamethasone injection blunted the increase in Creb3l1 and Avp expression induced by hyperosmotic stress. Here we shows that cAMP and glucocorticoid positively and negatively regulate Creb3l1 expression in the rat hypothalamus, respectively, and regulation of cAMP on AVP

  5. Low-Dose Vasopressin and Analogues to Treat Intraoperative Refractory Hypotension in Patients Prescribed Angiotensin-Converting Enzyme Inhibitors Undergoing General Anesthesia: A Systematic Review.

    Science.gov (United States)

    Hedman, Kara F; Mann, Carrie L; Spulecki, Cheryl; Castner, Jessica

    2016-12-01

    This review assessed the utility of vasopressin and vasopressin analogues for the treatment of refractory hypotension associated with angiotensin-converting enzyme (ACE) inhibitors in the perioperative setting. A systematic review of the literature was conducted using MEDLINE, Embase, and ProQuest. Six randomized controlled trials met eligibility criteria. In the perioperative setting, continued use of ACE inhibitors within 24 hours before surgery remains controversial. Authors of the reviewed studies suggested that the morning dose of the ACE inhibitor be held, and those patients experienced decreased catecholamine use postoperatively and shorter duration of decreased mean arterial pressure. No incidence of refractory hypertension from withholding the morning dose of the ACE inhibitor was mentioned. All of the patients receiving vasopressin demonstrated improved hemodynamic stability with small, intermittent doses, without profound ischemic changes. For management (prevention and treatment) of ACE inhibitor-associated hypotension in the perioperative setting, all studies showed statistically significant success with vasopressin or vasopressin analogues for improvement of systemic blood pressures. Before vasopressin is widely accepted as a standard of care, further studies are needed to confirm these findings and assess the general utility of vasopressin in surgical populations for management of ACE inhibitor-associated refractory hypotension. Copyright© by the American Association of Nurse Anesthetists.

  6. 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.

  7. Functional rescue of vasopressin V2 receptor mutants in MDCK cells by pharmacochaperones : relevance to therapy of nephrogenic diabetes insipidus

    NARCIS (Netherlands)

    Robben, J.H.; Sze, M.; Knoers, N.V.A.M.; Deen, P.M.T.

    2007-01-01

    Intracellular retention of a functional vasopressin V2 receptor (V2R) is a major cause of congenital nephrogenic diabetes insipidus (NDI) and rescue of V2R mutants by nonpeptide antagonists may restore their basolateral membrane (BM) localization and function. However, the criteria for efficient

  8. Copeptin, a surrogate marker of vasopressin, is associated with accelerated renal function decline in renal transplant recipients

    NARCIS (Netherlands)

    Meijer, Esther; Bakker, Stephan J. L.; de Jong, Paul E.; Homan van der Heide, Jaap J.; van Son, Willem J.; Struck, Joachim; Lems, Simon P. M.; Gansevoort, Ron T.

    2009-01-01

    Chronically elevated vasopressin (VP) plasma levels have been shown to induce accelerated renal function decline in rats with chronic renal failure. Whether endogenous VP is a renal risk factor in humans has not been investigated yet. We aimed to investigate whether, in renal transplant recipients,

  9. Copeptin, a surrogate marker for arginine vasopressin, is associated with disease severity and progression in IgA nephropathy patients

    NARCIS (Netherlands)

    Zittema, Debbie; van den Brand, Jan A J G; Bakker, Stephan J. L.; Wetzels, Jack F.; Gansevoort, Ron T.

    2017-01-01

    Background. Besides its essential role for water homeostasis, arginine vasopressin (AVP) may have deleterious effects on the kidney. Copeptin, a surrogate marker for AVP, has been shown to be related to renal outcome in patients with diabetic nephropathy and polycystic kidney disease. We

  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. Copeptin, a surrogate marker for arginine vasopressin, is associated with disease severity and progression in IgA nephropathy patients

    NARCIS (Netherlands)

    Zittema, D.; Brand, J. van den; Bakker, S.J.L.; Wetzels, J.F.M.; Gansevoort, R.T.

    2017-01-01

    Background.: Besides its essential role for water homeostasis, arginine vasopressin (AVP) may have deleterious effects on the kidney. Copeptin, a surrogate marker for AVP, has been shown to be related to renal outcome in patients with diabetic nephropathy and polycystic kidney disease. We

  12. Changes in cerebrospinal fluid levels of vasopressin and oxytocin of the rat during various light-dark regimes

    NARCIS (Netherlands)

    Mens, W.B.J.; Andringa-Bakker, E.A.D.; Wimersma Greidanus, T.B. van

    1982-01-01

    Levels of arginine-vasopressin (AVP) and oxytocin (OXT) in cerebrospinal fluid (CSF) of rats were determined at various times of the day and the night under normal and changed light-dark conditions. During a regular daily 14 h and 10 h dark cycle (lights on 06.00 h, off 20.00 h), AVP in CSF

  13. 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

  14. Vasopressin and oxytocin excretion in the Brown-Norway rat in relation to aging, water metabolism and testosterone

    NARCIS (Netherlands)

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

    1988-01-01

    There is considerable disagreement in the literature on changes in the hypothalamo-neurohypophyseal system (HNS) with aging: some reports support HNS degeneration, whereas others claim an activation of this system in senescence. In order to study age-related changes in vasopressin (VP) and oxytocin

  15. Morphometric analysis of vasopressin and vasoactive intestinal polypeptide neurons in the human suprachiasmatic nucleus: influence of microwave treatment

    NARCIS (Netherlands)

    Zhou, J. N.; Hofman, M. A.; Swaab, D. F.

    1996-01-01

    The vasopressin (VP) and vasoactive intestinal polypeptide (VIP)-expressing neurons in the human suprachiasmatic nucleus (SCN) were morphometrically determined with or without microwave (MW) treatment. Both an enlarged volume and an increased number of neurons were found in the VP and VIP subnucleus

  16. Dose-Titrated Vasopressin V2 Receptor Antagonist Improves Renoprotection in a Mouse Model for Autosomal Dominant Polycystic Kidney Disease

    NARCIS (Netherlands)

    Zittema, Debbie; Versteeg, Irina B.; Gansevoort, Ron T.; van Goor, Harry; de Heer, Emile; Veraar, Kimberley A. M.; Peters, Dorien J. M.; Meijer, Esther

    2016-01-01

    Background: In autosomal dominant polycystic kidney disease, renoprotective treatment with a vasopressin V2 receptor antagonist (V2RA) is given in a fixed dose (FD). Disease progression and drug habituation could diminish treatment efficacy. We investigated whether the renoprotective effect of the

  17. The vasopressin and oxytocin neurons in the human supraoptic and paraventricular nucleus; changes with aging and in senile dementia

    NARCIS (Netherlands)

    Fliers, E.; Swaab, D. F.; Pool, C. W.; Verwer, R. W.

    1985-01-01

    The neuropeptides vasopressin (AVP) and oxytocin (OXT) are supposed to be involved not only in peripheral functions (e.g. diuresis, labour and lactation) but also in central processes that are frequently disturbed during aging and senile dementia (e.g. fluid and electrolyte homeostasis and cognitive

  18. 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

  19. Potentiation effect of vasopressin on melatonin secretion as determined by trans-pineal microdialysis in the Rat

    NARCIS (Netherlands)

    Barassin, S.; Kalsbeek, A.; Saboureau, M.; Bothorel, B.; Vivien-Roels, B.; Malan, A.; Buijs, R. M.; Pevet, P.

    2000-01-01

    The mammalian pineal gland is known to receive a noradrenergic innervation originating from the superior cervical ganglion which corresponds to the primary regulatory input for melatonin synthesis. However, many peptidergic fibers containing peptides such as vasopressin and oxytocin have also been

  20. Gender differences in nighttime plasma arginine vasopressin and delayed compensatory urine output in the elderly population after desmopressin.

    Science.gov (United States)

    Hvistendahl, Gitte M; Frøkiaer, Jørgen; Nielsen, Søren; Djurhuus, Jens Christian

    2007-12-01

    Monosymptomatic polyuric nocturia is a consequence of aging. We investigated physiological differences between nonpolyuric and polyuric nocturia in the elderly population in relation to urine production regulation in young volunteers with special reference to gender. We performed a study in 37 elderly healthy volunteers 65 years or older and 30 young healthy volunteers 20 to 40 years old who were hospitalized for 48 hours. Before admittance and during hospitalization fluid intake was standardized. The first 24 hours were at baseline conditions. On night 2 participants were given a single oral dose of desmopressin (0.4 mg). During 48 hours urine and blood samples were taken at predetermined time points to measure urine output and plasma arginine vasopressin levels. Elderly individuals with nocturnal polyuria had an inverted rhythm in urine output, which was restored after a single dose of desmopressin. There was an age related change in the circadian rhythm of arginine vasopressin secretion, which was associated with the presence or absence of nocturnal polyuria. A novel and unexpected finding was a decreased circadian rhythm of arginine vasopressin secretion in young women, similar to the pattern observed in elderly women but with a preserved decrease in nighttime urine production. Compensatory diuresis following the induction of temporary antidiuresis was markedly postponed in elderly participants. Age and gender related decreased arginine vasopressin secretion at night underscores the fact that other factors modulate urine production. The pharmacodynamics of desmopressin as an antidiuretic in the elderly population are different from those in young individuals.

  1. The stimulatory effect of vasopressin on the luteinizing hormone surge in ovariectomized, estradiol-treated rats is time-dependent

    NARCIS (Netherlands)

    Palm, I. F.; van der Beek, E. M.; Wiegant, V. M.; Buijs, R. M.; Kalsbeek, A.

    2001-01-01

    The luteinizing hormone surge in the female rat is not only induced by the positive feedback of estradiol, but also by circadian signals originating in the suprachiasmatic nucleus (SCN). In a previous study we showed that administration of vasopressin, an SCN transmitter present in preoptic

  2. Arginine-Vasopressin Receptor Antagonists: A New Hope for Treatment of Hyponatremia in Patients with Heart Failure

    Directory of Open Access Journals (Sweden)

    Saepudin

    2015-06-01

    Full Text Available Hyponatremia is an important problem in patients with heart failure. It has also been known as a predictor both of short and long-term clinical outcome of heart failure patients. While evidences of clinical efficacy and safety of conventional options for treatment of hyponatremia resulted from clinical trials are very limited, several clinical trials have been conducted to evaluate the efficacy and safety of arginine vasopressin antagonists or also known as vaptan group. This paper reviews hyponatremia in patients with heart failure and the important roles of arginine vasopressin in its development, pharmacological aspects and clinical trials outcomes of some vaptans and several questions emerged from those clinical trials. Relevant research papers, reviews, and website information have been searched and included in this review using keyword of heart failure, hyponatremia, arginine-vasopressin, arginine-vasopressin receptor antagonist and vaptan. Generally, clinical trials have highlighted the efficacy and safety of vaptan groups in the management of hypervolemic hyponatremia in patients with heart failure. Those drugs can effectively increase serum sodium level with tolerable adverse reactions. Based on those clinical data two drugs of vaptan group, conivaptan and tolvaptan, have been approved by Food and Drug Administration in The United States to be used for the treatment of euvolemic and hypervolemic hyponatremia. However, many experts are still hesitant to recommend vaptans as treatment of choice for hyponatremia due to the lack of patients-focused outcomes measurements.

  3. Rescue of a nephrogenic diabetes insipidus-causing vasopressin V-2 receptor mutant by cell-penetrating peptides

    NARCIS (Netherlands)

    Oueslati, Morad; Hermosilla, Ricardo; Schoenenberger, Eva; Oorschot, Viola; Beyermann, Michael; Wiesner, Burkhard; Schmidt, Antje; Klumperman, Judith; Rosenthal, Walter; Schuelein, Ralf

    2007-01-01

    Mutant membrane proteins are frequently retained in the early secretory pathway by a quality control system, thereby causing disease. An example are mutants of the vasopressin V-2 receptor (V2R) leading to nephrogenic diabetes insipidus. Transport-defective V(2)Rs fall into two classes: those

  4. Consumption of a high‐fat diet, but not regular endurance exercise training, regulates hypothalamic lipid accumulation in mice

    National Research Council Canada - National Science Library

    Borg, Melissa L; Omran, Simin Fallah; Weir, Jacquelyn; Meikle, Peter J; Watt, Matthew J

    2012-01-01

    ...‐deficient ob / ob mouse fed a chow diet had normal hypothalamic lipid content. •  These data show that dietary lipids regulate hypothalamic lipid accumulation, which is not readily reversed by exercise training. Abstract...

  5. EFFECT OF ANESTHETIZING THE REGION OF THE PARAVENTRICULAR HYPOTHALAMIC NUCLEI ON ENERGY-METABOLISM DURING EXERCISE IN THE RAT

    NARCIS (Netherlands)

    VANDIJK, G; VISSING, J; STEFFENS, AB; GALBO, H

    The ventromedial and posterior hypothalamic nuclei are known to influence glucoregulation during exercise. The extensive projections of the paraventricular hypothalamic nucleus (PVN) to the sympathetic nervous system suggest that the PVN also may be involved in glucoregulation during exercise. The

  6. 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

  7. Semaphorin7A regulates neuroglial plasticity in the adult hypothalamic median eminence

    NARCIS (Netherlands)

    Parkash, Jyoti; Messina, Andrea; Langlet, Fanny; Cimino, Irene; Loyens, Anne; Mazur, Danièle; Gallet, Sarah; Balland, Eglantine; Malone, Samuel A.; Pralong, François; Cagnoni, Gabriella; Schellino, Roberta; De Marchis, Silvia; Mazzone, Massimiliano; Pasterkamp, R. Jeroen|info:eu-repo/dai/nl/197768814; Tamagnone, Luca; Prevot, Vincent; Giacobini, Paolo

    2015-01-01

    Reproductive competence in mammals depends on the projection of gonadotropin-releasing hormone (GnRH) neurons to the hypothalamic median eminence (ME) and the timely release of GnRH into the hypothalamic-pituitary-gonadal axis. In adult rodents, GnRH neurons and the specialized glial cells named

  8. HYPOTHALAMIC BLOOD-FLOW REMAINS UNALTERED FOLLOWING CHRONIC NITRIC-OXIDE SYNTHASE BLOCKADE IN RATS

    NARCIS (Netherlands)

    BENYO, Z; SZABO, C; STUIVER, BT; BOHUS, B; SANDOR, P

    1995-01-01

    The effect of the chronic oral application of N-G-nitro-L-arginine methyl eater (L-NAME), a potent inhibitor of nitric oxide (NO) production, was studied on hypothalamic blood flow (HBF) and hypothalamic nitric oxide synthase (NOS) activity in rats. L-NAME was dissolved in the drinking water, in a

  9. Surgical excision of hypothalamic hamartoma in a twenty months old boy with precocious puberty

    Directory of Open Access Journals (Sweden)

    Rajesh K Ghanta

    2011-01-01

    Full Text Available A twenty months old boy presented to our department with true precocious puberty due to hypothalamic hamartoma. Total surgical excision of pedunculated hypothalamic hamartoma was done successfully by the pterional trans-sylvian approach as he could not afford medical management. Patient had uneventful post-operative course with normalization of serum testosterone levels and regression of secondary sexual characters.

  10. Hypothalamic alterations in Huntington's disease patients: comparison with genetic rodent models.

    Science.gov (United States)

    van Wamelen, D J; Aziz, N A; Roos, R A C; Swaab, D F

    2014-11-01

    Unintended weight loss, sleep and circadian disturbances and autonomic dysfunction are prevalent features of Huntington's disease (HD), an autosomal dominantly inherited neurodegenerative disorder caused by an expanded CAG repeat sequence in the HTT gene. These features form a substantial contribution to disease burden in HD patients and appear to be accompanied by a number of neuroendocrine and metabolic changes, pointing towards hypothalamic pathology as a likely underlying mechanism. Neuronal inclusion bodies of mutant huntingtin, which are hallmarks of the disease, occur throughout the hypothalamus, and indicate local mutant huntingtin expression that could interfere with hypothalamic neuropeptide production. Also, several genetic rodent models of HD show features that could be related to hypothalamic pathology, such as weight loss and circadian rhythm disturbances. In these rodents, several hypothalamic neuropeptide populations are affected. In the present review, we summarise the changes in genetic rodent models of HD for individual hypothalamic nuclei, compare these observations to the hypothalamic changes that occur in HD patients, and make an inventory of the work that still needs to be done. Surprisingly, there is only limited overlap in the hypothalamic changes reported in HD patients and genetic rodent models. At present, the only similarity between the hypothalamic alterations in HD patients and genetic rodent models is a decrease in the number of orexin-expressing neurones in the lateral hypothalamus. Possible reasons for these discrepancies, as well as potential consequences for the development of novel therapeutic strategies, are discussed. © 2014 British Society for Neuroendocrinology.

  11. Horner Syndrome as the Only Focal Neurologic Manifestation of Hypothalamic Hemorrhage.

    Science.gov (United States)

    Sahin, Cansu B; Chaudhary, Neeraj; Trobe, Jonathan D

    2017-12-12

    A 70-year-old woman suffered an anterior dorsal hypothalamic hemorrhage that caused an ipsilateral Horner syndrome (HS) as the only focal neurologic manifestation. This is only the second reported case of hypothalamic hemorrhage producing HS. Because HS was the sole focal neurologic manifestation, its confirmation with topical apraclonidine drops was a valuable clue toward prompt localization of the patient's confusional state.

  12. Role of Hypothalamic Creb-Binding Protein in Obesity and Molecular Reprogramming of Metabolic Substrates

    NARCIS (Netherlands)

    Moreno, C.L.; Yang, L.; Dacks, P.A.; Isoda, F.; Deursen, J.M.A. van; Mobbs, C.V.

    2016-01-01

    We have reported a correlation between hypothalamic expression of Creb-binding protein (Cbp) and lifespan, and that inhibition of Cbp prevents protective effects of dietary restriction during aging, suggesting that hypothalamic Cbp plays a role in responses to nutritional status and energy balance.

  13. Vasopressin Bolus Protocol Compared to Desmopressin (DDAVP for Managing Acute, Postoperative Central Diabetes Insipidus and Hypovolemic Shock

    Directory of Open Access Journals (Sweden)

    Anukrati Shukla

    2017-01-01

    Full Text Available Introduction. Management of postoperative central diabetes insipidus (DI can be challenging from changes in volume status and serum sodium levels. We report a case successfully using a dilute vasopressin bolus protocol in managing hypovolemic shock in acute, postoperative, central DI. Case Report. Patient presented after bifrontal decompressive craniotomy for severe traumatic brain injury. He developed increased urine output resulting in hypovolemia and hypernatremia. He was resuscitated with intravenous fluids including a dilute vasopressin bolus protocol. This protocol consisted of 1 unit of vasopressin in 1 liter of 0.45% normal saline. This protocol was given in boluses based on the formula: urine output minus one hundred. Initial serum sodium was 148 mmol/L, and one-hour urine output was 1 liter. After 48 hours, he transitioned to 1-desamino-8-D-arginine vasopressin (DDAVP. Pre-DDAVP serum sodium was 149 mmol/L and one-hour urine output 320 cc. Comparing the bolus protocol to the DDAVP protocol, the average sodium was 143.8 ± 3.2 and 149.6 ± 3.2 mmol/L (p=0.0001, average urine output was 433.2 ± 354.4 and 422.3 ± 276.0 cc/hr (p=0.90, and average specific gravity was 1.019 ± 0.009 and 1.016 ± 0.01 (p=0.42, respectively. Conclusion. A protocol using dilute vasopressin bolus can be an alternative for managing acute, central DI postoperatively, particularly in setting of hypovolemic shock resulting in a consistent control of serum sodium.

  14. 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.

  15. 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.

  16. 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.)

  17. Vasopressina e morte encefálica Vasopressin and brain death

    Directory of Open Access Journals (Sweden)

    ELIANE DE ARAUJO CINTRA

    2000-03-01

    Full Text Available A morte encefálica (ME resulta numa perda completa dos mecanismos centrais de regulação da estabilidade hemodinâmica mesmo em pacientes com suporte adequado da ventilação, correção hidroeletrolítica e ácido-básica e suporte farmacológico convencional máximo da circulação. Acredita-se que a diminuição da vasopressina circulante influencia de maneira preponderante a estabilidade cardiocirculatória de pacientes com ME, sendo a sua administração exógena defendida por alguns autores no manuseio do potencial doador de órgãos. O artigo analisa e discute alguns estudos experimentais e clínicos relevantes em relação ao comportamento da vasopressina na ME e seu papel na manutenção da estabilidade cardiocirculatória, bem como sua potencial utilidade no manuseio destes pacientes. Desta análise concluímos que o comportamento da vasopressina na ME e o seu real valor na manutenção do potencial doador ainda não estão totalmente esclarecidos, necessitando de investigações futuras.Brain death results in the breakdown of effective central regulatory mechanisms of cardiocirculatory stability, even in patients with artificial mechanical ventilation, correction of electrolytic and acid-basic disorders and maximal conventional pharmacological support of the circulation. Recent evidences have shown that the fall of vasopressin levels in the blood circulation significantly influences the cardiocirculatory stability of patients with brain death, and its exogenous administration is defended by many authors for the management of multiorgan donor patients. In this brief review we analyse and discuss some experimental and clinical relevant studies about the role of vasopressin in the control of cardiocirculatory stability in brain death, and its potential usefulness in the management of multiorgan donor. We conclude that the role of vasopressin in the pathophysiology of brain death and its usefulness as a pharmacological agent in the

  18. 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

  19. Role of testosterone in mediating prenatal ethanol effects on hypothalamic-pituitary-adrenal activity in male rats.

    Science.gov (United States)

    Lan, Ni; Hellemans, Kim G C; Ellis, Linda; Viau, Victor; Weinberg, Joanne

    2009-10-01

    Prenatal ethanol (E) exposure programs the fetal hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes such that E rats show HPA hyperresponsiveness to stressors and altered HPG and reproductive function in adulthood. Importantly, prenatal ethanol may differentially alter stress responsiveness in adult male and female offspring compared to their control counterparts. To test the hypothesis that alterations in HPA activity in E males are mediated, at least in part, by ethanol-induced changes in the capacity of testosterone to regulate HPA activity, we explored dose-related effects of testosterone on HPA and HPG function in adult male offspring from prenatal E, pair-fed (PF) and ad libitum-fed control (C) dams. Our data suggest that E males show changes in both HPA and HPG regulation, as well as altered sensitivity to the inhibitory effects of testosterone. While gonadectomy (GDX) reduced weight gain in all animals, low testosterone replacement restored body weights in PF and C but not E males. Further, sensitivity of the thymus and adrenal to circulating testosterone was reduced in E rats. In addition, stress-induced corticosterone (CORT) levels were increased in PF and C but not E males following GDX, and while low dose testosterone replacement restored CORT levels for PF and C, high testosterone levels were needed to normalize CORT levels for E males. A negative correlation between pre-stress testosterone and post-stress CORT levels in C but not in E and PF males further supports the finding of reduced sensitivity to testosterone. Importantly, testosterone appeared to have reduced effects on central corticotrophin releasing hormone (CRH) pathways in E, but greater effects on central arginine vasopressin (AVP) pathways in E and/or PF compared to C males. Testosterone also had less of an inhibitory effect on stress-induced luteinizing hormone increases in E than in PF and C males following GDX. In addition, androgen receptor mRNA levels in the medial preoptic

  20. 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...

  1. Management of severe hyponatremia: infusion of hypertonic saline and desmopressin or infusion of vasopressin inhibitors?

    Science.gov (United States)

    Tzamaloukas, Antonios H; Shapiro, Joseph I; Raj, Dominic S; Murata, Glen H; Glew, Robert H; Malhotra, Deepak

    2014-11-01

    Rapid correction of severe hyponatremia carries the risk of osmotic demyelination. Two recently introduced methods of correction of hyponatremia have diametrically opposite effects on aquaresis. Inhibitors of vasopressin V2 receptor (vaptans) lead to the production of dilute urine, whereas infusion of desmopressin causes urinary concentration. Identification of the category of hyponatremia that will benefit from one or the other treatment is critical. In general, vaptans are effective in hyponatremias presenting with concentrated urine and, with the exception of hypovolemic hyponatremia, can be used as their primary treatment. Desmopressin is effective in hyponatremias presenting with dilute urine or developing urinary dilution after saline infusion. In this setting, desmopressin infusion helps prevent overcorrection of the hyponatremia. Monitoring of the changes in serum sodium concentration as a guide to treatment changes is imperative regardless of the initial treatment of severe hyponatremia.

  2. Effect of L-ornithine 8-vasopressin on blood loss during liposuction.

    Science.gov (United States)

    Lalinde, E; Sanz, J; Ballesteros, A; Elejabeitia, J; Mesa, F; Bazán, A; Paloma, V

    1995-06-01

    In this comparative study, we carried out liposuction on 20 patients randomly divided in two groups to find an alternative medication to epinephrine that would not result in secondary effects at the cardiovascular level but would offer a similar vasoconstricting capacity. Also, a variation of the wet technique is described that decreases blood loss secondary to liposuction. The area to undergo liposuction is infiltrated with a cannula of our own design. Epinephrine is not used as a vasoconstrictor but rather L-ornithine 8-vasopressin at a concentration of 0.01 IU/ml chilled saline. With this new technique, the amount of blood removed is minimal, even in the case of extraction of large volumes of fat.

  3. Copeptin, a Marker of Vasopressin, Predicts Vascular Dementia but not Alzheimer's Disease.

    Science.gov (United States)

    Nilsson, Erik D; Melander, Olle; Elmståhl, Sölve; Lethagen, Eva; Minthon, Lennart; Pihlsgård, Mats; Nägga, Katarina

    2016-04-12

    Copeptin is a reliable surrogate marker for the neurohypophyseal hormone vasopressin. Elevated plasma level of copeptin has been associated with cardiovascular and metabolic disease risk. To investigate the association between copeptin and risk of dementia. In all, 18,240 individuals from Malmö, Sweden, were examined between 2002 and 2006 (mean age 69.3 years, 69.8% men). Incident cases of dementia until 31 December 2009 were identified by linkage with the Swedish National Patient Register. To validate the dementia diagnoses, medical records as well as laboratory and neuroimaging data were carefully reviewed. Baseline level of copeptin was measured in frozen plasma in: (1) all participants who were diagnosed with dementia during follow-up, (2) a random sample of 5100 individuals of the cohort. During a median follow-up of 4.2 years, there were 374 incident dementia cases (age range 60-83 years at baseline): 120 were classified as Alzheimer's disease (AD), 84 as vascular dementia (VaD), and 102 as mixed dementia. In logistic regressions adjusted for cardiovascular risk factors, baseline level of copeptin predicted incident VaD (Odds ratio (OR) 1.30 per 1 SD increase in log copeptin, 95% CI 1.03-1.64). Copeptin did not predict incidence of all-cause dementia (OR 1.05, 95% CI 0.94-1.18), AD (OR 0.97, 95% CI 0.79-1.18), or mixed dementia (OR 0.85, 95% CI 0.68-1.05). Elevated plasma level of copeptin is a risk marker for incident VaD, but not for incident AD. This suggests that the vasopressin hormonal system might be involved in the development of VaD.

  4. 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.

  5. Thirst perception and osmoregulation of vasopressin secretion are altered during recovery from septic shock.

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    Shidasp Siami

    Full Text Available OBJECTIVE: Vasopressin (AVP secretion during an osmotic challenge is frequently altered in the immediate post-acute phase of septic shock. We sought to determine if this response is still altered in patients recovering from septic shock. DESIGN: Prospective interventional study. SETTING: Intensive care unit (ICU at Raymond Poincaré and Etampes Hospitals. PATIENTS: Normonatremic patients at least 5 days post discontinuation of catecholamines given for a septic shock. INTERVENTION: Osmotic challenge involved infusing 500 mL of hypertonic saline solution (with cumulative amount of sodium not exceeding 24 g over 120 minutes. MEASUREMENTS AND MAIN RESULTS: Plasma AVP levels were measured 15 minutes before the infusion and then every 30 minutes for two hours. Non-responders were defined as those with a slope of the relation between AVP and plasma sodium levels less than < 0.5 ng/mEq. Among the 30 included patients, 18 (60% were non-responders. Blood pressure and plasma sodium and brain natriuretic peptide levels were similar in both responders and non-responders during the course of the test. Critical illness severity, hemodynamic alteration, electrolyte disturbances, treatment and outcome did not differ between the two groups. Responders had more severe gas exchange abnormality. Thirst perception was significantly diminished in non-responders. The osmotic challenge was repeated in 4 non-responders several months after discharge and the abnormal response persisted. CONCLUSION: More than half of patients recovering from septic shock have an alteration of osmoregulation characterised by a dramatic decrease in vasopressin secretion and thirst perception during osmotic challenge. The mechanisms of this alteration but also of the relationship between haematosis and normal response remain to be elucidated.

  6. Dehydration, electrolyte imbalances and renin-angiotensin-aldosterone-vasopressin axis in successful and unsuccessful endurance horses.

    Science.gov (United States)

    Muñoz, A; Riber, C; Trigo, P; Castejón-Riber, C; Castejón, F M

    2010-11-01

    Limited information exists concerning the defence of homeostasis during endurance competitions and the relationship with performance. This research analysed renin (REN), angiotensin II (ANG), aldosterone (ALD) and vasopressin (AVP) in horses covering different distances, assesses differences between successful and eliminated horses and evaluates correlations between hydration status, renal function, electrolytes, REN, ANG, ALD and AVP. Packed cell volume (PCV), velocity and serum concentrations of REN, ANG, ALD, AVP, Na, K, Cl, Ca, Mg, P, creatine kinase, aspartate aminotransferase, lactate dehydrogenase, total proteins (TSP), albumin (ALB), serum uric nitrogen (SUN), creatinine (CREAT) and lactate were analysed in both successful horses (SH) and in horses eliminated due to metabolic problems (MH). Two types of competition were studied: 91 km in one day (Competition A: 20 SH, 9 MH) and 166 km in 2 days, 83 km/day (Competition B: 10 SH and 5 MH). Research analysed renin was not affected by exercise, whereas ANG, ALD and AVP increased. In the SH group, resting ALD and AVP concentrations at the beginning of the second day of Competition B were higher than preride values. Vasopressin did not change during the second day of Competition B, whereas ALD progressively increased. Metabolic problems of both groups showed more evident dehydration (higher PCV, TSP, ALB, SUN and CREAT) and electrolyte alterations (more intense decreases of Na and Cl) than SH at the different sampling times. Metabolic problems presented higher ALD and AVP concentrations. Angiotensin II was higher at certain sampling times in the horses. Endurance horses with dehydration and electrolyte disturbances showed a more intense activation of the REN-ANG-ALD-AVP axis. The study of the response of the REN-ANG-ALD-AVP axis during prolonged exercise in horses with different performance will aid to minimise the risk of metabolic diseases during competitions. © 2010 EVJ Ltd.

  7. Sweet taste signaling functions as a hypothalamic glucose sensor

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    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

  8. 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.

  9. Hypothalamic-pituitary-adrenal axis hypersensitivity in female rats on a post-weaning high-fat diet after chronic mild stress.

    Science.gov (United States)

    Liu, Lian; Yang, Junqiang; Qian, Feng; Lu, Chengbiao

    2017-07-01

    A high-fat diet (HFD) is highly correlated to obesity, metabolic diseases and certain behavioral changes. However, the effects of post-weaning HFD in rats during puberty and the role of the hypothalamic-pituitary-adrenal (HPA) axis in this process have remained elusive. The present study hypothesized that the HPA axis mediates the behavioral alterations induced by a post-weaning HFD. To investigate this, female rats were divided into two groups, one of which was fed a HFD from postnatal weeks (PWs) 4-12, while the other group received standard chow. Rats in each group were then subdivided into two subgroups each, and from PW 9-12, animals from one of the two subgroups were subjected to chronic mild stress (CMS), while the other subgroup received no stress. At PW 12, the body weight of rats receiving a HFD but no DMS was significantly higher than that in the control group. The frequency of crossing and rearing in the open field test and the time in the center of the Y-maze were decreased following CMS. Total time to escape was decreased in rats receiving HFD and after CMS. The serum levels of adrenocorticotropic hormone and corticosterone were increased in rats receiving an HFD and after CMS, and the mRNA levels of corticotropin-releasing hormone and arginine vasopressin in the hypothalamus were increased in the HFD + CMS group compared to that in the control group. The mRNA expression of glucocorticoid receptor (GR) in the hippocampi of rats in the HFD + CMS group was significantly decreased and the mineralocorticoid receptor/GR ratio was increased compared to that in the groups receiving either CMS or a HFD. In conclusion, these results indicated that female rats fed a post-weaning HFD showed HPA axis hypersensitivity under CMS, which may mediate behavioral alterations.

  10. Low-dose vasopressin infusion results in increased mortality and cardiac dysfunction following ischemia-reperfusion injury in mice.

    Science.gov (United States)

    Indrambarya, Toonchai; Boyd, John H; Wang, Yingjin; McConechy, Melissa; Walley, Keith R

    2009-01-01

    Arginine vasopressin is a vasoactive drug commonly used in distributive shock states including mixed shock with a cardiac component. However, the direct effect of arginine vasopressin on the function of the ischemia/reperfusion injured heart has not been clearly elucidated. We measured left ventricular ejection fraction using trans-thoracic echocardiography in C57B6 mice, both in normal controls and following ischemia/reperfusion injury induced by a one hour ligation of the left anterior descending coronary artery. Mice were treated with one of normal saline, dobutamine (8.33 microg/kg/min), or arginine vasopressin (0.00057 Units/kg/min, equivalent to 0.04 Units/min in a 70 kg human) delivered by an intraperitoneal micro-osmotic pump. Arterial blood pressure was measured using a micromanometer catheter. In addition, mortality was recorded and cardiac tissues processed for RNA and protein. Baseline left ventricular ejection fraction was 65.6% (60 to 72). In normal control mice, there was no difference in left ventricular ejection fraction according to infusion group. Following ischemia/reperfusion injury, AVP treatment significantly reduced day 1 left ventricular ejection fraction 46.2% (34.4 to 52.0), both in comparison with baseline and day 1 saline treated controls 56.9% (42.4 to 60.2). There were no significant differences in preload (left ventricular end diastolic volume), afterload (blood pressure) or heart rate to account for the effect of AVP on left ventricular ejection fraction. The seven-day mortality rate was highest in the arginine vasopressin group. Following ischemia/reperfusion injury, we found no change in cardiac V1 Receptor expression but a 40% decrease in Oxytocin Receptor expression. Arginine vasopressin infusion significantly depressed the myocardial function in an ischemia/reperfusion model and increased mortality in comparison with both saline and dobutamine treated animals. The use of vasopressin may be contraindicated in non

  11. Pathophysiology and clinical characteristics of hypothalamic obesity in children and adolescents

    Directory of Open Access Journals (Sweden)

    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.

  12. Leptin Elongates Hypothalamic Neuronal Cilia via Transcriptional Regulation and Actin Destabilization.

    Science.gov (United States)

    Kang, Gil Myoung; Han, Yu Mi; Ko, Hyuk Whan; Kim, Joon; Oh, Byung Chul; Kwon, Ijoo; Kim, Min-Seon

    2015-07-17

    Terminally differentiated neurons have a single, primary cilium. The primary cilia of hypothalamic neurons play a critical role in sensing metabolic signals. We recently showed that mice with leptin deficiency or resistance have shorter cilia in the hypothalamic neurons, and leptin treatment elongates cilia in hypothalamic neurons. Here, we investigated the molecular mechanisms by which leptin controls ciliary length in hypothalamic neurons. In N1 hypothalamic neuronal cells, leptin treatment increased the expression of intraflagellar transport proteins. These effects occurred via phosphatase and tensin homolog/glycogen synthase kinase-3β-mediated inhibition of the transcriptional factor RFX1. Actin filament dynamics were also involved in leptin-promoted ciliary elongation. Both leptin and cytochalasin-D treatment induced F-actin disruption and cilium elongation in hypothalamic neurons that was completely abrogated by co-treatment with the F-actin polymerizer phalloidin. Our findings suggest that leptin elongates hypothalamic neuronal cilia by stimulating the production of intraflagellar transport proteins and destabilizing actin filaments. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Regulation of energy balance by the hypothalamic lipoprotein lipase regulator Angptl3.

    Science.gov (United States)

    Kim, Hyun-Kyong; Shin, Mi-Seon; Youn, Byung-Soo; Kang, Gil Myoung; Gil, So Young; Lee, Chan Hee; Choi, Jong Han; Lim, Hyo Sun; Yoo, Hyun Ju; Kim, Min-Seon

    2015-04-01

    Hypothalamic lipid sensing is important for the maintenance of energy balance. Angiopoietin-like protein 3 (Angptl3) critically regulates the clearance of circulating lipids by inhibiting lipoprotein lipase (LPL). The current study demonstrated that Angptl3 is highly expressed in the neurons of the mediobasal hypothalamus, an important area in brain lipid sensing. Suppression of hypothalamic Angptl3 increased food intake but reduced energy expenditure and fat oxidation, thereby promoting weight gain. Consistently, intracerebroventricular (ICV) administration of Angptl3 caused the opposite metabolic changes, supporting an important role for hypothalamic Angptl3 in the control of energy balance. Notably, ICV Angptl3 significantly stimulated hypothalamic LPL activity. Moreover, coadministration of the LPL inhibitor apolipoprotein C3 antagonized the effects of Angptl3 on energy metabolism, indicating that LPL activation is critical for the central metabolic actions of Angptl3. Increased LPL activity is expected to promote lipid uptake by hypothalamic neurons, leading to enhanced brain lipid sensing. Indeed, ICV injection of Angptl3 increased long-chain fatty acid (LCFA) and LCFA-CoA levels in the hypothalamus. Furthermore, inhibitors of hypothalamic lipid-sensing pathways prevented Angptl3-induced anorexia and weight loss. These findings identify Angptl3 as a novel regulator of the hypothalamic lipid-sensing pathway. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  14. 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.

  15. Hypothalamic Dysfunction and Multiple Sclerosis: Implications for Fatigue and Weight Dysregulation.

    Science.gov (United States)

    Burfeind, Kevin G; Yadav, Vijayshree; Marks, Daniel L

    2016-11-01

    Signs and symptoms of multiple sclerosis are usually attributed to demyelinating lesions in the spinal cord or cerebral cortex. The hypothalamus is a region that is often overlooked yet controls many important homeostatic functions, including those that are perturbed in multiple sclerosis. In this review we discuss how hypothalamic dysfunction may contribute to signs and symptoms in people with multiple sclerosis. While dysfunction of the hypothalamic-pituitary-adrenal axis is common in multiple sclerosis, the effects and mechanisms of this dysfunction are not well understood. We discuss three hypothalamic mechanisms of fatigue in multiple sclerosis: (1) general hypothalamic-pituitary-adrenal axis hyperactivity, (2) disordered orexin neurotransmission, (3) abnormal cortisol secretion. We then review potential mechanisms of weight dysregulation caused by hypothalamic dysfunction. Lastly, we propose future studies and therapeutics to better understand and treat hypothalamic dysfunction in multiple sclerosis. Hypothalamic dysfunction appears to be common in multiple sclerosis, yet current studies are underpowered and contradictory. Future studies should contain larger sample sizes and standardize hormone and neuropeptide measurements.

  16. Pathophysiology and clinical characteristics of hypothalamic obesity in children and adolescents.

    Science.gov (United States)

    Kim, Ja Hye; Choi, Jin-Ho

    2013-12-01

    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.

  17. The TRH neuron: a hypothalamic integrator of energy metabolism.

    Science.gov (United States)

    Lechan, Ronald M; Fekete, Csaba

    2006-01-01

    Thyrotropin-releasing hormone (TRH) has an important role in the regulation of energy homeostasis not only through effects on thyroid function orchestrated through hypophysiotropic neurons in the hypothalamic paraventricular nucleus (PVN), but also through central effects on feeding behavior, thermogenesis, locomotor activation and autonomic regulation. Hypophysiotropic TRH neurons are located in the medial and periventricular parvocellular subdivisions of the PVN and receive direct monosynaptic projections from two, separate, populations of leptin-responsive neurons in the hypothalamic arcuate nucleus containing either alpha-melanocyte-stimulating hormone (alpha-MSH) and cocaine- and amphetamine-regulated transcript (CART), peptides that promote weight loss and increase energy expenditure, or neuropeptide Y (NPY) and agouti-related protein (AGRP), peptides that promote weight gain and reduce energy expenditure. During fasting, the reduction in TRH mRNA in hypophysiotropic neurons mediated by suppression of alpha-MSH/CART simultaneously with an increase in NPY/AGRP gene expression in arcuate nucleus neurons contributes to the fall in circulating thyroid hormone levels, presumably by increasing the sensitivity of the TRH gene to negative feedback inhibition by thyroid hormone. Endotoxin administration, however, has the paradoxical effect of increasing circulating levels of leptin and melanocortin signaling and CART gene expression in arcuate nucleus neurons, but inhibiting TRH gene expression in hypophysiotropic neurons. This may be explained by an overriding inhibitory effect of endotoxin to increase type 2 iodothyroine deiodinase (D2) in a population of specialized glial cells, tanycytes, located in the base and infralateral walls of the third ventricle. By increasing the conversion of T4 into T3, tanycytes may increase local tissue concenetrations of thyroid hormone, and thereby induce a state of local tissue hyperthyroidism in the region of hypophysisotrophic

  18. Effects of neonatal programming on hypothalamic mechanisms controlling energy balance.

    Science.gov (United States)

    Contreras, C; Novelle, M G; Leis, R; Diéguez, C; Skrede, S; López, M

    2013-12-01

    The prevalence of overweight and obesity in most developed countries has markedly increased during the last decades. In addition to genetic, hormonal, and metabolic influences, environmental factors like fetal and neonatal nutrition play key roles in the development of obesity. Interestingly, overweight during critical developmental periods of fetal and/or neonatal life has been demonstrated to increase the risk of obesity throughout juvenile life into adulthood. In spite of this evidence, the specific mechanisms underlying this fetal/neonatal programming are not perfectly understood. However, it is clear that circulating hormones such as insulin and leptin play a critical role in the development and programming of hypothalamic circuits regulating energy balance. Here, we review what is currently known about the impact of perinatal malnutrition on the mechanisms regulating body weight homeostasis. Understanding these molecular mechanisms may provide new targets for the treatment of obesity. © Georg Thieme Verlag KG Stuttgart · New York.

  19. The Minimal Model of the Hypothalamic-Pituitary-Adrenal Axis

    DEFF Research Database (Denmark)

    Vinther, Frank; Andersen, Morten; Ottesen, Johnny T.

    2011-01-01

    This paper concerns ODE modeling of the hypothalamic-pituitary-adrenalaxis (HPA axis) using an analytical and numerical approach, combined with biological knowledge regarding physiological mechanisms and parameters. The three hormones, CRH, ACTH, and cortisol, which interact in the HPA axis are m...... thereof. The second part of the paper concerns a specific realization of the minimal model in which feedback functions are built explicitly using receptor dynamics. Using physiologically reasonable parameter values, along with the results of the general case, it is demonstrated that un......-physiological values of the parameters are needed in order to achieve local instability of the fixed point. Small changes inphysiologically relevant parameters cause the system to be globally stable using the analytical criteria. All simulations show a globally stable fixed point, ruling out periodic solutions even...

  20. Hypothalamic and brainstem neuronal circuits controlling homeostatic energy balance.

    Science.gov (United States)

    Schneeberger, Marc; Gomis, Ramon; Claret, Marc

    2014-02-01

    Alterations in adequate energy balance maintenance result in serious metabolic disturbances such as obesity. In mammals, this complex process is orchestrated by multiple and distributed neuronal circuits. Hypothalamic and brainstem neuronal circuits are critically involved in the sensing of circulating and local factors conveying information about the energy status of the organism. The integration of these signals culminates in the generation of specific and coordinated physiological responses aimed at regulating energy balance through the modulation of appetite and energy expenditure. In this article, we review current knowledge on the homeostatic regulation of energy balance, emphasizing recent advances in mouse genetics, electrophysiology, and optogenetic techniques that have greatly contributed to improving our understanding of this central process.

  1. HYPOTHALAMIC HAMARTOMA REPORT OF ONE CASE TO PRECOCIOUS PUBERTY.

    Directory of Open Access Journals (Sweden)

    Silvia Massetta

    2008-07-01

    Full Text Available The Hypothalamic Hamartomas (HH are masses with low frequency of appearance that usually appear in nodes united to Tuber Cinereum or to the Mamillary Bodies. Since the development of the computerized tomography, hipotalamic hamartoma is considered as one of the the most common cause of precocious puberty, representing the 16% of the subjects in girls and up to 50% in boys. Despite the studies, little it is known about hipotalamic hamartoma natural history. It is considered of interest to present the case of a6 year old child, Patricia, who was diagnosed with (HH that induced precocious puberty ; reviewing part of the clinical manifestations followed by the realised evaluation as well as the therapeutic strategy and its results after a year from the initial diagnosis.

  2. Hypothalamic obesity after craniopharyngioma: mechanisms, diagnosis, and treatment

    Directory of Open Access Journals (Sweden)

    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.

  3. Genetic Approaches to Hypothalamic-Pituitary-Adrenal Axis Regulation

    Science.gov (United States)

    Arnett, Melinda G; Muglia, Lisa M; Laryea, Gloria; Muglia, Louis J

    2016-01-01

    The normal function of the hypothalamic-pituitary-adrenal (HPA) axis, and resultant glucocorticoid (GC) secretion, is essential for human health. Disruption of GC regulation is associated with pathologic, psychological, and physiological disease states such as depression, post-traumatic stress disorder, hypertension, diabetes, and osteopenia, among others. As such, understanding the mechanisms by which HPA output is tightly regulated in its responses to environmental stressors and circadian cues has been an active area of investigation for decades. Over the last 20 years, however, advances in gene targeting and genome modification in rodent models have allowed the detailed dissection of roles for key molecular mediators and brain regions responsible for this control in vivo to emerge. Here, we summarize work done to elucidate the function of critical neuropeptide systems, GC-signaling targets, and inflammation-associated pathways in HPA axis regulation and behavior, and highlight areas for future investigation. PMID:26189452

  4. Bilateral descending hypothalamic projections to the spinal trigeminal nucleus caudalis in rats.

    Science.gov (United States)

    Abdallah, Khaled; Artola, Alain; Monconduit, Lénaic; Dallel, Radhouane; Luccarini, Philippe

    2013-01-01

    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.

  5. Endoscopic resection of hypothalamic hamartomas for refractory symptomatic epilepsy.

    Science.gov (United States)

    Ng, Y-T; Rekate, H L; Prenger, E C; Wang, N C; Chung, S S; Feiz-Erfan, I; Johnsonbaugh, R E; Varland, M R; Kerrigan, J F

    2008-04-22

    Hypothalamic hamartomas (HHs), rare developmental abnormalities of the inferior hypothalamus, often cause refractory, symptomatic, mixed epilepsy, including gelastic seizures. We present 37 patients with HH who underwent transcortical transventricular endoscopic resection. Between October 2003 and April 2005, 42 consecutive patients with refractory epilepsy who underwent endoscopic resection of HH were studied prospectively. The endoscope was held by an articulated pneumatic arm and tracked with a frameless stereotactic neuronavigation system. Data collection and follow-up were performed by personal interview. Five patients were excluded. The remaining 37 patients (22 males, 15 females; median age 11.8 years; range 8 months to 55 years) had frequent and usually multiple types of seizures. Postoperative MRI confirmed 100% resection of the HH from the hypothalamus in 12 patients. At last follow-up (median 21 months; range 13-28 months), 18 (48.6%) patients were seizure free. Seizures were reduced more than 90% in 26 patients (70.3%) and by 50% to 90% in 8 patients (21.6%). Overall, the mean postoperative stay was shorter in the endoscopic patients compared with our previously reported patients who underwent transcallosal resection (mean 4.1 days vs 7.7 days, respectively; p = 0.0006). The main complications were permanent short-term memory loss in 3 patients and small thalamic infarcts in 11 patients (asymptomatic in 9). Endoscopic resection of hypothalamic hamartoma (HH) is a safe and effective treatment for seizures. Its efficacy seems to be comparable to that of transcallosal resection of HH, but postoperative recovery time is significantly shorter.

  6. 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.

  7. 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

  8. Neuromodulation by oxytocin and vasopressin in the central nervous system as a basis for their rapid behavioral effects.

    Science.gov (United States)

    Stoop, Ron

    2014-12-01

    The last several years have seen an increasing number of studies that describe effects of oxytocin and vasopressin on the behavior of animals or humans. Studies in humans have reported behavioral changes and, through fMRI, effects on brain function. These studies are paralleled by a large number of reports, mostly in rodents, that have also demonstrated neuromodulatory effects by oxytocin and vasopressin at the circuit level in specific brain regions. It is the scope of this review to give a summary of the most recent neuromodulatory findings in rodents with the aim of providing a potential neurophysiological basis for their behavioral effects. At the same time, these findings may point to promising areas for further translational research towards human applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. 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.

  10. Evidence for involvement of a limbic paraventricular hypothalamic inhibitory network in hypothalamic-pituitary-adrenal axis adaptations to repeated stress.

    Science.gov (United States)

    Radley, Jason J; Sawchenko, Paul E

    2015-12-15

    Emotional stressors activate a stereotyped set of limbic forebrain cell groups implicated in constraining stress-induced hypothalamic-pituitary-adrenal (HPA) axis activation by inhibiting hypophysiotropic neurons in the paraventricular hypothalamic nucleus (PVH). We previously identified a circumscribed, anterior part of the bed nuclei of the stria terminalis (aBST) that houses stress-sensitive, PVH-projecting, γ-aminobutyric acid (GABA)-ergic neurons as representing a site of convergence of stress-inhibitory influences originating from medial prefrontal and hippocampal cortices. Here we investigate whether exaggerated HPA axis responses associated with chronic variable stress (CVS; daily exposure to different stressors at unpredictable times over 14 days, followed by restraint stress on day 15) and diminished HPA output seen following repeated (14 days) restraint-stress exposure are associated with differential engagement of the limbic modulatory network. Relative to acutely restrained rats, animals subjected to CVS showed the expected increase (sensitization) in HPA responses and diminished levels of activation (Fos) of GABAergic neurons and glutamic acid decarboxylase (GAD) mRNA expression in the aBST. By contrast, repeated restraint stress produced habituation in HPA responses, maintained levels of activation of GABAergic neurons, and increased GAD expression in the aBST. aBST-projecting neurons in limbic sites implicated in HPA axis inhibition tended to show diminished activational responses in both repeated-stress paradigms, with the exception of the paraventricular thalamic nucleus, in which responsiveness was maintained in repeatedly restrained animals. The results are consistent with the view that differential engagement of HPA inhibitory mechanisms in the aBST may contribute to alterations in HPA axis responses to emotional stress in sensitization and habituation paradigms. © 2015 Wiley Periodicals, Inc.

  11. Effects of Chronic Social Stress and Maternal Intranasal Oxytocin and Vasopressin on Offspring Interferon-γ and Behavior

    OpenAIRE

    Chris Anthony Murgatroyd; Alexandria Hicks-Nelson; Alexandra Fink; Gillian Beamer; Kursat Gurel; Fawzy Elnady; Florent Pittet; Nephew, Benjamin C.

    2016-01-01

    Recent studies support the hypothesis that the adverse effects of early life adversity and transgenerational stress on neural plasticity and behavior are mediated by inflammation. The objective of the present study was to investigate the immune and behavioural programming effects of intranasal (IN) vasopressin (AVP) and oxytocin (OXT) treatment of chronic social stress (CSS) exposed F1 dams on F2 juvenile female offspring. It was hypothesized that maternal AVP and OXT treatment would have p...

  12. Long-term opiate receptor antagonism in a patient with panhypopituitarism: effects on appetite, prolactin and demand for vasopressin.

    Science.gov (United States)

    Kraft, K; Vetter, H

    1991-02-01

    As endogenous opiates are known to be involved in regulation of appetite, an obese patient with panhypopituitarism and frequent episodes of ravenous hunger was treated with the oral opiate antagonist naltrexone for 13 months. This resulted in loss of body weight and attacks of severe hunger. The increased serum prolactin concentration and the dose of vasopressin required for substitution could be reduced. Long-term application of opiate antagonists may be useful in related cases.

  13. [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.

  14. Chromosomal localization of the human V3 pituitary vasopressin receptor gene (AVPR3) to 1q32

    Energy Technology Data Exchange (ETDEWEB)

    Rousseau-Merck, M.F.; Derre, J.; Berger, R. [INSERM, Paris (France)] [and others

    1995-11-20

    Vasopressin exerts its physiological effects on liver metabolism, fluid osmolarity, and corticotrophic response to stress through a set of at least three receptors, V1a, V2, and V3 (also called V1b), respectively. These receptors constitute a distinct group of the superfamily of G-protein-coupled cell surface receptors. When bound to vasopressin, they couple to G proteins activating phospholipase C for the V1a and V3 types and adenylate cyclase for the V2. The vasopressin receptor subfamily also includes the receptor for oxytocin, a structurally related hormone that signals through the activation of phospholipase C. The chromosomal position of the V2 receptor gene has been assigned to Xq28-qter by PCR-based screening of somatic cell hybrids, whereas the oxytocin receptor gene has been mapped to chromosome 3q26.2 by fluorescence in situ hybridization (FISH). The chromosomal location of the V1a gene is currently unknown. We recently cloned the cDNA and the gene coding for the human pituitary-specific V3 receptor (HGMW-approved symbol AVPR3). We report here the chromosomal localization of this gene by two distinct in situ hybridization techniques using radioactive and fluorescent probes. 11 refs., 1 fig.

  15. HPG-axis hormones during puberty: A study on the association with hypothalamic and pituitary volumes.

    NARCIS (Netherlands)

    Peper, J.S.; Brouwer, R.M.; van Leeuwen, M.; Schnack, H.G.; Boomsma, D.I.; Kahn, R.S.; Hulshoff-Poll, H.E.

    2010-01-01

    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

  16. 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

  17. Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats

    National Research Council Canada - National Science Library

    Eduardo R. Ropelle; José R. Pauli; Patrícia Prada; Dennys E. Cintra; Guilherme Z. Rocha; Juliana C. Moraes; Marisa J. S. Frederico; Gabrielle da Luz; Ricardo A. Pinho; José B. C. Carvalheira; Licio A. Velloso; Mario A. Saad; Cláudio T. De Souza

    2009-01-01

    ... in insulin resistance and obesity remains unclear. Here, we identify that a high-fat diet impaired insulin-induced hypothalamic Foxo1 phosphorylation and degradation, increasing the nuclear Foxo1 activity and hyperphagic response in rats...

  18. 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.

  19. Effects of intranasal insulin application on the hypothalamic BOLD response to glucose ingestion

    DEFF Research Database (Denmark)

    Opstal, Anna M van; Akintola, Abimbola A; Elst, Marjan van der

    2017-01-01

    . In this study, we assessed whether intranasal insulin can be used to enhance neuronal hypothalamic responses to glucose ingestion. In a randomized, double-blinded, placebo-controlled 4-double cross-over experiment, hypothalamic activation was measured in young non- diabetic subjects by determining blood......The hypothalamus is a crucial structure in the brain that responds to metabolic cues and regulates energy homeostasis. Patients with type 2 diabetes demonstrate a lack of hypothalamic neuronal response after glucose ingestion, which is suggested to be an underlying cause of the disease......-oxygen-level dependent MRI signals over 30 minutes before and after ingestion of 75 g glucose dissolved in 300 ml water, under intranasal insulin or placebo condition. Glucose ingestion under placebo condition lead to an average 1.4% hypothalamic BOLD decrease, under insulin condition the average response to glucose...

  20. Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats

    National Research Council Canada - National Science Library

    Eduardo R. Ropelle; José R. Pauli; Patrícia Prada; Dennys E. Cintra; Guilherme Z. Rocha; Juliana C. Moraes; Marisa J. S. Frederico; Gabrielle da Luz; Ricardo A. Pinho; José B. C. Carvalheira; Licio A. Velloso; Mario A. Saad; Cláudio T. De Souza

    2009-01-01

    .... Foxo1 stimulates the transcription of the orexigenic neuropeptide Y and Agouti-related protein through the phosphatidylinositol-3-kinase/Akt signalling pathway, but the role of hypothalamic Foxo1...

  1. Neuropeptide Exocytosis Involving Synaptotagmin-4 and Oxytocin in Hypothalamic Programming of Body Weight and Energy Balance

    Science.gov (United States)

    Zhang, Guo; Bai, Hua; Zhang, Hai; Dean, Camin; Wu, Qiang; Li, Juxue; Guariglia, Sara; Meng, Qingyuan; Cai, Dongsheng

    2015-01-01

    Hypothalamic neuropeptides play essential roles in regulating energy and body weight balance. Energy imbalance and obesity have been linked to hypothalamic signaling defects in regulating neuropeptide genes; however, it is unknown whether dysregulation of neuropeptide exocytosis could be critically involved. This study discovered that synaptotagmin-4, an atypical modulator of synaptic exocytosis, is expressed most abundantly in oxytocin neurons of the hypothalamus. Synaptotagmin-4 negatively regulates oxytocin exocytosis, and dietary obesity is associated with increased vesicle binding of synaptotagmin-4 and thus enhanced negative regulation of oxytocin release. Overexpressing synaptotagmin-4 in hypothalamic oxytocin neurons and centrally antagonizing oxytocin in mice are similarly obesogenic. Synaptotagmin-4 inhibition prevents against dietary obesity by normalizing oxytocin release and energy balance under chronic nutritional excess. In conclusion, the negative regulation of synaptotagmin-4 on oxytocin release represents a hypothalamic basis of neuropeptide exocytosis in controlling obesity and related diseases. PMID:21315262

  2. Modification of Social Memory, Hypothalamic-Pituitary-Adrenal Axis, and Brain Asymmetry by Neonatal Novelty Exposure

    National Research Council Canada - National Science Library

    Tang, Akaysha C; Reeb, Bethany C; Romeo, Russell D; McEwen, Bruce S

    2003-01-01

    .... Using neonatal novelty exposure, a brief and transient early life stimulation method known to produce long-lasting changes in the hypothalamic-pituitary-adrenal axis, we found that social recognition...

  3. Effects of intranasal insulin application on the hypothalamic BOLD response to glucose ingestion

    DEFF Research Database (Denmark)

    van Opstal, Anna M.; Akintola, Abimbola A.; Elst, Marjan van der

    2017-01-01

    The hypothalamus is a crucial structure in the brain that responds to metabolic cues and regulates energy homeostasis. Patients with type 2 diabetes demonstrate a lack of hypothalamic neuronal response after glucose ingestion, which is suggested to be an underlying cause of the disease....... In this study, we assessed whether intranasal insulin can be used to enhance neuronal hypothalamic responses to glucose ingestion. In a randomized, double-blinded, placebo-controlled 4-double cross-over experiment, hypothalamic activation was measured in young non- diabetic subjects by determining blood......-oxygen-level dependent MRI signals over 30 minutes before and after ingestion of 75 g glucose dissolved in 300 ml water, under intranasal insulin or placebo condition. Glucose ingestion under placebo condition lead to an average 1.4% hypothalamic BOLD decrease, under insulin condition the average response to glucose...

  4. Glucose Enhances Basal or Melanocortin-Induced cAMP-Response Element Activity in Hypothalamic Cells

    Science.gov (United States)

    Wicht, Kristina; Boekhoff, Ingrid; Glas, Evi; Lauffer, Lisa; Mückter, Harald; Gudermann, Thomas

    2016-01-01

    Melanocyte-stimulating hormone (MSH)-induced activation of the cAMP-response element (CRE) via the CRE-binding protein in hypothalamic cells promotes expression of TRH and thereby restricts food intake and increases energy expenditure. Glucose also induces central anorexigenic effects by acting on hypothalamic neurons, but the underlying mechanisms are not completely understood. It has been proposed that glucose activates the CRE-binding protein-regulated transcriptional coactivator 2 (CRTC-2) in hypothalamic neurons by inhibition of AMP-activated protein kinases (AMPKs), but whether glucose directly affects hypothalamic CRE activity has not yet been shown. Hence, we dissected effects of glucose on basal and MSH-induced CRE activation in terms of kinetics, affinity, and desensitization in murine, hypothalamic mHypoA-2/10-CRE cells that stably express a CRE-dependent reporter gene construct. Physiologically relevant increases in extracellular glucose enhanced basal or MSH-induced CRE-dependent gene transcription, whereas prolonged elevated glucose concentrations reduced the sensitivity of mHypoA-2/10-CRE cells towards glucose. Glucose also induced CRCT-2 translocation into the nucleus and the AMPK activator metformin decreased basal and glucose-induced CRE activity, suggesting a role for AMPK/CRTC-2 in glucose-induced CRE activation. Accordingly, small interfering RNA-induced down-regulation of CRTC-2 expression decreased glucose-induced CRE-dependent reporter activation. Of note, glucose also induced expression of TRH, suggesting that glucose might affect the hypothalamic-pituitary-thyroid axis via the regulation of hypothalamic CRE activity. These findings significantly advance our knowledge about the impact of glucose on hypothalamic signaling and suggest that TRH release might account for the central anorexigenic effects of glucose and could represent a new molecular link between hyperglycaemia and thyroid dysfunction. PMID:27144291

  5. Differentiation of hypothalamic-like neurons from human pluripotent stem cells

    OpenAIRE

    Wang, Liheng; Meece, Kana; Damian J Williams; Lo, Kinyui Alice; Zimmer, Matthew; Heinrich, Garrett; Martin Carli, Jayne; LeDuc, Charles A.; Sun, Lei; Zeltser, Lori M.; Freeby, Matthew; Goland, Robin; Stephen H. Tsang; Wardlaw, Sharon L.; Egli, Dieter

    2015-01-01

    The hypothalamus is the central regulator of systemic energy homeostasis, and its dysfunction can result in extreme body weight alterations. Insights into the complex cellular physiology of this region are critical to the understanding of obesity pathogenesis; however, human hypothalamic cells are largely inaccessible for direct study. Here, we developed a protocol for efficient generation of hypothalamic neurons from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs...

  6. The receptive function of hypothalamic and brainstem centres to hormonal and nutrient signals affecting energy balance

    OpenAIRE

    Riediger, Thomas

    2012-01-01

    The hypothalamic arcuate nucleus (ARC) and the area postrema (AP) represent targets for hormonal and metabolic signals involved in energy homoeostasis, e.g. glucose, amylin, insulin, leptin, peptide YY (PYY), glucagon-like peptide 1 (GLP-1) and ghrelin. Orexigenic neuropeptide Y expressing ARC neurons are activated by food deprivation and inhibited by feeding in a nutrient-dependent manner. PYY and leptin also reverse or prevent fasting-induced activation of the ARC. Interestingly, hypothalam...

  7. Proliferative Hypothalamic Neurospheres Express NPY, AGRP, POMC, CART and Orexin-A and Differentiate to Functional Neurons

    Science.gov (United States)

    Sousa-Ferreira, Lígia; Álvaro, Ana Rita; Aveleira, Célia; Santana, Magda; Brandão, Inês; Kügler, Sebastian; Pereira de Almeida, Luís; Cavadas, Cláudia

    2011-01-01

    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 mitigate feeding

  8. 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

  9. Arginine-vasopressin marker copeptin is a sensitive plasma surrogate of hypoxic exposure

    Directory of Open Access Journals (Sweden)

    Ostergaard L

    2014-09-01

    Full Text Available Louise Ostergaard,1,2,* Alain Rudiger,3,* Sven Wellmann,2,4,5 Elena Gammella,6 Beatrice Beck-Schimmer,2,3 Joachim Struck,7 Marco Maggiorini,2,8 Max Gassmann,1,2,9 1Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zürich, 2Zürich Center for Integrative Human Physiology, 3Institute of Anesthesiology, 4Division of Neonatology, University Hospital Zürich, Zürich, 5Department of Neonatology, University Children's Hospital Basel, Basel, Switzerland; 6Department of Human Morphology and Biomedical Science, University of Milan, Milan, Italy; 7Research Department, B•R•A•H•M•S Biomarkers, Thermo Fisher Scientific, Hennigsdorf, Germany; 8Medical Intensive Care Unit, University Hospital Zürich, Zürich, Switzerland; 9Universidad Peruana Cayetano Heredia, Lima, Peru *These authors contributed equally to this work and share first authorship Background: A reduced oxygen supply puts patients at risk of tissue hypoxia, organ damage, and even death. In response, several changes are activated that allow for at least partial adaptation, thereby increasing the chances of survival. We aimed to investigate whether the arginine vasopressin marker, copeptin, can be used as a marker of the degree of acclimatization/adaptation in rats exposed to hypoxia. Methods: Sprague-Dawley rats were exposed to 10% oxygen for up to 48 hours. Arterial and right ventricular pressures were measured, and blood gas analysis was performed at set time points. Pulmonary changes were investigated by bronchoalveolar lavage, wet and dry weight measurements, and lung histology. Using a newly developed specific rat copeptin luminescence immunoassay, the regulation of vasopressin in response to hypoxia was studied, as was atrial natriuretic peptide (ANP by detecting mid-regional proANP. Results: With a decreasing oxygen supply, the rats rapidly became cyanotic and inactive. Despite continued exposure to 10% oxygen, all animals recuperated within 16 hours and

  10. Increasing fatty acid oxidation remodels the hypothalamic neurometabolome to mitigate stress and inflammation.

    Directory of Open Access Journals (Sweden)

    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.

  11. 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

  12. 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; Cao, Lei

    2016-03-01

    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.

  13. Protective effect of carbenoxolone on ER stress-induced cell death in hypothalamic neurons.

    Science.gov (United States)

    Kim, Jongwan; Jung, Eun Jung; Moon, Seong-Su; Seo, Minchul

    2015-12-25

    Hypothalamic endoplasmic reticulum (ER) stress is known to be increased in obesity. Induction of ER stress on hypothalamic neurons has been reported to cause hypothalamic neuronal apoptosis and malfunction of energy balance, leading to obesity. Carbenoxolone is an 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor that converts inactive glucocorticoid into an active form. In addition to its metabolic effect via enzyme inhibitory action, carbenoxolone has shown anti-apoptotic activity in several studies. In this study, the direct effects of carbenoxolone on ER stress and cell death in hypothalamic neurons were investigated. Carbenoxolone attenuated tunicamycin induced ER stress-mediated molecules such as spliced XBP1, ATF4, ATF6, CHOP, and ROS generation. In vivo study also revealed that carbenoxolone decreased tunicamycin-induced ER stress in the hypothalamus. In conclusion, the results of this study show that carbenoxolone has protective effects against tunicamycin induced-ER stress and apoptosis in hypothalamic neurons, suggesting its direct protective effects against obesity. Further study is warranted to clarify the effects of carbenoxolone on hypothalamic regulation of energy balance in obesity. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. 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

  15. Adrenalectomy stimulates hypothalamic proopiomelanocortin expression but does not correct diet-induced obesity

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    Beasley Joe

    2003-06-01

    Full Text Available Abstract Background Elevated glucocorticoid production and reduced hypothalamic POMC mRNA can cause obese phenotypes. Conversely, adrenalectomy can reverse obese phenotypes caused by the absence of leptin, a model in which glucocorticoid production is elevated. Adrenalectomy also increases hypothalamic POMC mRNA in leptin-deficient mice. However most forms of human obesity do not appear to entail elevated plasma glucocorticoids. It is therefore not clear if reducing glucocorticoid production would be useful to treat these forms of obesity. We hypothesized that adrenalectomy would increase hypothalamic POMC mRNA and reverse obese phenotypes in obesity due to a high-fat diet as it does in obesity due to leptin deficiency. Results Retired breeder male mice were placed on a high-fat diet or a low-fat diet for two weeks, then adrenalectomized or sham-adrenalectomized. The high-fat diet increased body weight, adiposity, and plasma leptin, led to impaired glucose tolerance, and slightly stimulated hypothalamic proopiomelanocortin (POMC expression. Adrenalectomy of mice on the high-fat diet significantly reduced plasma corticosterone and strikingly increased both pituitary and hypothalamic POMC mRNA, but failed to reduce body weight, adiposity or leptin, although slight improvements in glucose tolerance and metabolic rate were observed. Conclusion These data suggest that neither reduction of plasma glucocorticoid levels nor elevation of hypothalamic POMC expression is effective to significantly reverse diet-induced obesity.

  16. Hypothalamic Sirt1 regulates food intake in a rodent model system.

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    Işin Cakir

    2009-12-01

    Full Text Available Sirt1 is an evolutionarily conserved NAD(+ dependent deacetylase involved in a wide range of processes including cellular differentiation, apoptosis, as well as metabolism, and aging. In this study, we investigated the role of hypothalamic Sirt1 in energy balance. Pharmacological inhibition or siRNA mediated knock down of hypothalamic Sirt1 showed to decrease food intake and body weight gain. Central administration of a specific melanocortin antagonist, SHU9119, reversed the anorectic effect of hypothalamic Sirt1 inhibition, suggesting that Sirt1 regulates food intake through the central melanocortin signaling. We also showed that fasting increases hypothalamic Sirt1 expression and decreases FoxO1 (Forkhead transcription factor acetylation suggesting that Sirt1 regulates the central melanocortin system in a FoxO1 dependent manner. In addition, hypothalamic Sirt1 showed to regulate S6K signaling such that inhibition of the fasting induced Sirt1 activity results in up-regulation of the S6K pathway. Thus, this is the first study providing a novel role for the hypothalamic Sirt1 in the regulation of food intake and body weight. Given the role of Sirt1 in several peripheral tissues and hypothalamus, potential therapies centered on Sirt1 regulation might provide promising therapies in the treatment of metabolic diseases including obesity.

  17. Syndrome of alternating hypernatremia and hyponatremia after hypothalamic hamartoma surgery.

    Science.gov (United States)

    Abla, Adib A; Wait, Scott D; Forbes, Jonathan A; Pati, Sandipan; Johnsonbaugh, Roger E; Kerrigan, John F; Ng, Yu-Tze

    2011-02-01

    In this paper, the authors' goal was to describe the occurrence of alternating hypernatremia and hyponatremia in pediatric patients who underwent resection of hypothalamic hamartomas (HHs) for epilepsy. Hypernatremia in patients after pituitary or hypothalamic surgery can be caused by diabetes insipidus (DI), whereas hyponatremia can occur due to a syndrome of inappropriate antidiuretic hormone, cerebral salt wasting, or excessive administration of desmopressin (DDAVP). The triphasic response after surgery in the pituitary region can also explain variations in sodium parameters in such cases. One hundred fifty-three patients with HH who underwent surgery were enrolled in a prospective study to monitor outcomes. Of these, 4 patients (2.6%) were noted to experience dramatic alterations in serum sodium values. The medical records of these patients were identified and evaluated. Patients' ages at surgery ranged from 1.2 to 6.0 years. All patients were girls. Two patients had Delalande Type IV lesions (of 16 total Type IV lesions surgically treated) and 2 had Type III lesions (of 39 total Type III lesions). All patients had a history of gelastic seizures refractory to medication. Seizure frequency ranged from 3 to 300 per day. After surgery, all patients experienced hypernatremia and hyponatremia. The largest fluctuation in serum sodium concentration during hospitalization in a single patient was 53 mEq/L (range 123-176 mEq/L). The mean absolute difference in maximum and minimum sodium values was 38.2 mEq/L. All patients exhibited an initial period of immediate DI (independent of treatment) after surgery followed by a period of hyponatremia (independent of treatment), with a minimum value occurring between postoperative Days 5 and 8. All patients then returned to a hypernatremic state of DI, and 3 patients still require DDAVP for DI management. A second occurrence of hyponatremia lasting several days without DDAVP administration occurred in 2 patients during their

  18. Bacteria, viruses, and hypothalamic inflammation: Potential new players in obesity

    Directory of Open Access Journals (Sweden)

    Magdalena Wierucka-Rybak

    2014-03-01

    Full Text Available Being overweight and obese has become an increasingly serious clinical and socioeconomic problem worldwide. The rapidly rising prevalence of obesity has prompted studies on modifiable, causative factors and novel treatment options for this disorder. Recent evidence indicates that excessive weight gain that leads to being overweight and obese may result from alterations in gut microflora. Studies in humans and animals demonstrated that the composition of gut microbiota may differ in lean and obese subjects, suggesting that these differences result in the increased efficiency of caloric extraction from food, enhanced lipogenesis, and impaired central and peripheral regulation of energy balance. Other studies revealed an excessive increase in body weight in a significant percentage of people infected with human adenoviruses SMAM-1 and Ad-36. Dysregulation of adipocyte function by viruses appears to be the most likely cause of excessive fat accumulation in these individuals. Studies on the pathomechanisms related to the pathogenesis of obesity indicated that a high-fat diet triggers the inflammatory response in the hypothalamus, an event that promotes weight gain and further defends elevated body weight through the initiation of central leptin and insulin resistance and impairment of regenerative capacity of hypothalamic neurons. Exposure to a high-calorie diet appears to predispose individuals to obesity not only because of excessive caloric intake but also because of the induction of microbiota- and central inflammatory response-dependent changes that lead to a dysregulation of energy balance.

  19. Hypothalamic Insulin Resistance in Obesity: Effects on Glucose Homeostasis.

    Science.gov (United States)

    Chen, Weiyi; Balland, Eglantine; Cowley, Michael A

    2017-01-01

    The central link between obesity and type 2 diabetes is the development of insulin resistance. To date, it is still not clear whether hyperinsulinemia causes insulin resistance, which underlies the pathogenesis of obesity-associated type 2 diabetes, owing to the sophisticated regulatory mechanisms that exist in the periphery and in the brain. In recent years, accumulating evidence has demonstrated the existence of insulin resistance within the hypothalamus. In this review, we have integrated the recent discoveries surrounding both central and peripheral insulin resistance to provide a comprehensive overview of insulin resistance in obesity and the regulation of systemic glucose homeostasis. In particular, this review will discuss how hyperinsulinemia and hyperleptinemia in obesity impair insulin sensitivity in tissues such as the liver, skeletal muscle, adipose tissue, and the brain. In addition, this review highlights insulin transport into the brain, signaling pathways associated with hypothalamic insulin receptor expression in the regulation of hepatic glucose production, and finally the perturbation of systemic glucose homeostasis as a consequence of central insulin resistance. We also suggest future approaches to overcome both central and peripheral insulin resistance to treat obesity and type 2 diabetes. © 2017 S. Karger AG, Basel.

  20. Dietary macronutrient composition affects hypothalamic appetite regulation in chicks.

    Science.gov (United States)

    McConn, Betty R; Matias, Justin; Wang, Guoqing; Cline, Mark A; Gilbert, Elizabeth R

    2018-01-01

    The objective was to determine the effects of high-protein and high-fat diets, and fasting and refeeding, on appetite regulation in chicks. Day of hatch chicks were fed one of four diets: basal, high protein (25% crude protein), and 15 and 30% high fat (15 and 30% metabolizable energy derived from soybean oil, respectively), and assigned to one of three treatments at 4 days: (1) access to feed, (2) 3 hours of fasting, or (3) fasting followed by 1 hour of refeeding. The hypothalamus was collected, total RNA isolated, and mRNA abundance measured. Food intake was reduced in chicks fed the high-protein and high-fat diets. Agouti-related peptide, neuropeptide Y (NPY), NPY receptors 1, 2, and 5, melanocortin receptors 3 and 4 (MC3R and 4R, respectively), mesotocin, corticotropin-releasing factor (CRF), and CRF receptor sub-type 2 (CRFR2) mRNAs were greatest in chicks that consumed the basal diet. Refeeding was associated with increased MC3R mRNA in the high-protein diet group. CRFR2 mRNA was increased by fasting and refeeding in chicks that consumed the high-protein diet. Food intake and hypothalamic gene expression of some important appetite-associated factors were reduced in chicks fed the high-protein or high-fat diets. Fasting and refeeding accentuated several differences and results suggest that the CRF and melanocortin pathways are involved.

  1. Hypothalamic hamartomas: optimal approach to clinical evaluation and diagnosis.

    Science.gov (United States)

    Wilfong, Angus A; Curry, Daniel J

    2013-12-01

    Hypothalamic hamartomas (HHs) present a difficult medical problem, manifested by gelastic seizures, which are often medically intractable. Although existing techniques offer modest surgical outcomes with the potential for significant morbidity, the relatively novel technique of magnetic resonance imaging (MRI)-guided stereotactic laser ablation (SLA) offers a potentially safer, minimally invasive method with high efficacy for the HH treatment. We report here on 14 patients with medically refractory gelastic epilepsy who underwent stereotactic frame-based placement of an MR-compatible laser catheter (1.6 mm diameter) through a 3.2-mm twist drill hole. A U.S. Food and Drug Administration (FDA)-cleared laser surgery system (Visualase, Inc.) was utilized to ablate the HH, using real-time MRI thermometry. Seizure freedom was obtained in 12 (86%) of 14 cases, with mean follow-up of 9 months. There were no permanent surgical complications, neurologic deficits, or neuroendocrine disturbances. One patient had a minor subarachnoid hemorrhage that was asymptomatic. Most patients were discharged home within 1 day. SLA was demonstrated to be a safe and effective minimally invasive tool in the ablation of epileptogenic HH. Because use of SLA for HH is being adopted by other medical centers, further data will be acquired to help treat this difficult disorder. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  2. 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.

  3. High-fat diet induces apoptosis of hypothalamic neurons.

    Directory of Open Access Journals (Sweden)

    Juliana C Moraes

    Full Text Available Consumption of dietary fats is amongst the most important environmental factors leading to obesity. In rodents, the consumption of fat-rich diets blunts leptin and insulin anorexigenic signaling in the hypothalamus by a mechanism dependent on the in situ activation of inflammation. Since inflammatory signal transduction can lead to the activation of apoptotic signaling pathways, we evaluated the effect of high-fat feeding on the induction of apoptosis of hypothalamic cells. Here, we show that consumption of dietary fats induce apoptosis of neurons and a reduction of synaptic inputs in the arcuate nucleus and lateral hypothalamus. This effect is dependent upon diet composition, and not on caloric intake, since pair-feeding is not sufficient to reduce the expression of apoptotic markers. The presence of an intact TLR4 receptor, protects cells from further apoptotic signals. In diet-induced inflammation of the hypothalamus, TLR4 exerts a dual function, on one side activating pro-inflammatory pathways that play a central role in the development of resistance to leptin and insulin, and on the other side restraining further damage by controlling the apoptotic activity.

  4. Dopamine Autoreceptor Regulation of a Hypothalamic Dopaminergic Network

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    Stefanos Stagkourakis

    2016-04-01

    Full Text Available How autoreceptors contribute to maintaining a stable output of rhythmically active neuronal circuits is poorly understood. Here, we examine this issue in a dopamine population, spontaneously oscillating hypothalamic rat (TIDA neurons, that underlie neuroendocrine control of reproduction and neuroleptic side effects. Activation of dopamine receptors of the type 2 family (D2Rs at the cell-body level slowed TIDA oscillations through two mechanisms. First, they prolonged the depolarizing phase through a combination of presynaptic increases in inhibition and postsynaptic hyperpolarization. Second, they extended the discharge phase through presynaptic attenuation of calcium currents and decreased synaptic inhibition. Dopamine reuptake blockade similarly reconfigured the oscillation, indicating that ambient somatodendritic transmitter concentration determines electrical behavior. In the absence of D2R feedback, however, discharge was abolished by depolarization block. These results indicate the existence of an ultra-short feedback loop whereby neuroendocrine dopamine neurons tune network behavior to echoes of their own activity, reflected in ambient somatodendritic dopamine, and also suggest a mechanism for antipsychotic side effects.

  5. Hypothalamic eIF2α Signaling Regulates Food Intake

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    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.

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

    Science.gov (United States)

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

    2009-02-01

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

  7. Hypothalamic pituitary adrenal axis and prolactin abnormalities in suicidal behavior.

    Science.gov (United States)

    Pompili, Maurizio; Serafini, Gianluca; Palermo, Mario; Seretti, Maria Elena; Stefani, Henry; Angeletti, Gloria; Lester, David; Amore, Mario; Girardi, Paolo

    2013-11-01

    Hypothalamic-Pituitary-Adrenal (HPA) axis hyperactivity measured with the dexamethasone suppression test and the dexamethesone/CRH test may have some predictive power for suicidal behavior in patients with mood disorders. Increased prolactin (PRL) levels may be related both to physiological and pathological conditions. HPA-axis abnormalities and increased levels of PRL may coexist, and common neuroendocrine changes may activate both HPA axis and PRL release. HPA-axis hyperactivity is presumably present in a large subpopulation of depressed subjects. Suicidal behavior is considered to be a form of inward-directed aggression, and aggressive behavior has been connected to high androgen levels. However, lower plasma total testosterone levels have also been reported in subjects with depression and higher suicidality. Lipid/immune dysregulations, the increased ratio of blood fatty acids, and increased PRL levels may each be associated with the increased production of pro-inflammatory cytokines, which have been reported in patients with major depression and patients engaging in suicidal behavior. Although no studies have been done to determine whether ante-mortem physical stress may be detected by raised post-mortem PRL, this would be of great interest for physicians.

  8. 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

  9. Hypothalamic regulation of brown adipose tissue thermogenesis and energy homeostasis

    Directory of Open Access Journals (Sweden)

    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.

  10. Hypothalamic-pituitary-adrenal (HPA) axis and aging.

    Science.gov (United States)

    Gupta, Deepashree; Morley, John E

    2014-10-01

    Human aging is associated with increasing frailty and morbidity which can result in significant disability. Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis may contribute to aging-related diseases like depression, cognitive deficits, and Alzheimer's disease in some older individuals. In addition to neuro-cognitive dysfunction, it has also been associated with declining physical performance possibly due to sarcopenia. This article reviews the pathophysiology of HPA dysfunction with respect to increased basal adrenocorticotropic hormone (ACTH) and cortisol secretion, decreased glucocorticoid (GC) negative feedback at the level of the paraventricular nucleus (PVN) of the hypothalamus, hippocampus (HC), and prefrontal cortex (PFC), and flattening of diurnal pattern of cortisol release. It is possible that the increased cortisol secretion is secondary to peripheral conversion from cortisone. There is a decline in pregnolone secretion and C-19 steroids (DHEA) with aging. There is a small decrease in aldosterone with aging, but a subset of the older population have a genetic predisposition to develop hyperaldosteronism due to the increased ACTH stimulation. The understanding of the HPA axis and aging remains a complex area with conflicting studies leading to controversial interpretations.

  11. Androgen manipulation and vasopressin binding in the rat brain and peripheral organs

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Xin; Phillips, P.; Oldfield, B.; Trinder, D.; Risvanis, J.; Stephenson, J.; Johnston, C. (Univ. of Melbourne, Parkville, Victoria (Australia))

    1994-03-01

    It is now widely recognized that there is a sexual dimorphism in the development of arginine vasopressin (AVP) immunoreactivity in certain parts of the brain, and that changes in brain AVP immunoreactivity change with manipulation of androgen status. The aim of the present experiment was to determine specifically any AVP receptor changes in response to manipulation of androgen levels using a selective V[sub 1] antagonist radioligand. Following castration, plasma testosterone levels fell and AVP immunoreactivity was reduced in the lateral septum and bed nucleus of the stria terminalis. With testosterone supplementation in castrated animals, the immunoreactivity in these regions was restored to a higher degree than in sham-operated animals. Central and peripheral V[sub 1] AVP receptor binding (as determined using the selective AVP V)[sub 1] antagonist radioligand [[sup 125]I](d(CH[sub 2])[sub 5],sarcosine[sup 7]) AVP was not changed in any of the brain regions studied or in liver or kidney membranes from the three groups. The study demonstrates that there is no change in brain AVP receptor binding despite changes in regional AVP immunoreactivity in the brain, and excludes any confounding interaction with changes in oxytocin receptors. 23 refs., 1 fig., 2 tabs.

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

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Jensen, B.

    1983-01-01

    Three groups of weanling male rats were fed on a fat-free diet for 13 weeks. One group received only the fat-free diet (FF rats), the other 2 groups received the fat-free diet and a daily supplement of 2 energy% ethyl linoleate ([n-6] rats), or 2 energy% ethyl linolenate ([n-3] rats). Urinary...... 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...... significantly in the FF rats and the (n-3) rats compared with the (n-6) rats. Urinary PGE excretion was the same for all 3 groups during the first 10 weeks; thereafter it decreased in FF rats and (n-3) rats compared with the (n-6) rats. There was no difference in urinary PGE excretion between the FF rats...

  13. Aptamer based surface enhanced Raman scattering detection of vasopressin using multilayer nanotube arrays.

    Science.gov (United States)

    Huh, Yun Suk; Erickson, David

    2010-01-15

    Here we present an optofluidic surface enhanced Raman spectroscopy (SERS) device for on-chip detection of vasopressin using an aptamer based binding assay. To create the SERS-active substrate, densely packed, 200 nm diameter, metal nanotube arrays were fabricated using an anodized alumina nanoporous membrane as a template for shadow evaporation. We explore the use of both single layer Au structures and multilayer Au/Ag/Au structures and also demonstrate a facile technique for integrating the membranes with all polydimethylsiloxane (PDMS) microfluidic devices. Using the integrated device, we demonstrate a linear response in the main detection peak intensity to solution phase concentration and a limit of detection on the order of 5.2 microU/mL. This low limit of detection is obtained with device containing the multilayer SERS substrate which we show exhibits a stronger Raman enhancement while maintaining biocompatibility and ease or surface reactivity with the capture probe. Copyright 2009 Elsevier B.V. All rights reserved.

  14. 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).

  15. Arginine vasopressin, copeptin, and the development of relative AVP deficiency in hemorrhagic shock.

    Science.gov (United States)

    Sims, Carrie A; Guan, Yuxia; Bergey, Meredith; Jaffe, Rebecca; Holmes-Maguire, Lilias; Martin, Niels; Reilly, Patrick

    2017-10-01

    Arginine vasopressin (AVP) is critical for maintaining vasomotor tone and low levels have been associated with the development of irreversible shock. We investigated the clinical relationship between AVP, copeptin (the C-terminal fragment of the AVP precursor), and the development of relative AVP deficiency following hemorrhagic shock. A prospective, observational study of 21 hypotensive (SBPcopeptin were measured post hoc. AVP and copeptin levels were markedly elevated on admission, but decreased rapidly over time (p copeptin levels were positively correlated on admission (r = 0.769, p copeptin levels predicted the need for ≥10 unit blood product transfusion (AUC = 81% and 87%, respectively). The development of a relative AVP deficiency occurred frequently and was associated with an increased need for blood product transfusion. Copeptin correlates well with AVP and initial values predict the need for massive transfusion in trauma patients. Copeptin demonstrates promise as a clinical biomarker in hemorrhagic shock. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Copeptin in the diagnosis of vasopressin-dependent disorders of fluid homeostasi