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The possible role of ghrelin in AVP (arginine-vasopressin) connected psychogenic processes
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P.1.e. Basic and clinical neuroscience − Neuro-endocrinology
major depressive disorder: integrative genome-wide and candidate gene analyses. Sci Rep 6, 18776. [2] Sasayama, D., Hori, H., Nakamura, S., Miyata, R., Teraishi, T., Hattori, K., Ota, M., Yamamoto, N., Higuchi, T., Amano, N., Kunugi, H., 2013. Identification of single nucleotide polymorphisms regulating peripheral blood mRNA expression with genome-wide significance: an eQTL study in the Japanese population. PLoS One 8, e54967. [3] Hori, H., Ozeki, Y., Teraishi, T., Matsuo, J., Kawamoto, Y., Kinoshita, Y., Suto, S., Terada, S., Higuchi, T., Kunugi, H., 2010. Relationships between psychological distress, coping styles, and HPA axis reactivity in healthy adults. J Psychiatr Res 44, 865–873. Disclosure statement: One of the authors (S.N.) has been employed by the DNA Chip Research Inc. The other authors declare that they have no competing interests.
P.1.e.007 The possible role of ghrelin in AVP (argininevasopressin) connected psychogenic processes Z. Molnar1 ° , M. Radacs1 , L. Racz1 , C. Varga2 , K. Sepp3 , P. Hausinger4 , M. Galfi1 1 Institute of Applied Natural ScienceGyula Juhasz Faculty of Education- University of Szeged, Department of Environmental Biology and Education, Szeged, Hungary; 2 Faculty of Science and Informatics- University of Szeged, Department of Physiology- Anatomy and Neuroscience, Szeged, Hungary; 3 University of Szeged Medical Faculty, Endocrine Unit of First Department of Internal Medicine, Szeged, Hungary; 4 University of Szeged Medical Faculty, Invasive Cardiology Department- Second Department of Internal Medicine and Cardiology, Szeged, Hungary It is well known, that the high arginine-vasopressin (AVP) level in serum can induce the depression in mammalians. Behavior depends on secreted mediators. Brain AVP is expressed mainly by hypothalamic neurosecretory cells. It is well described that AVP affect the stress-induced activity of the hypothalamic–pituitary– adrenal axis, and AVP can affect depressive behaviors. Life exists by maintaining a complex dynamic equilibrium or homeostasis that is constantly challenged by intrinsic or extrinsic adverse forces. Ghrelin is an endogenous neuropeptide for the GH secretagogue (GHS) receptor and it stimulates GH release in rats and humans. The ghrelin receptor GHS-R is mainly expressed in the hypothalamus and pituitary, its endogenous ligand has been thought to exist mainly in the hypothalamic regions. Recent studies have reported the presence of ghrelin in previously uncharacterized hypothalamic neurons adjacent to the third ventricle between the dorsal, ventral, paraventricular, and arcuate hypothalamic nuclei. These localization patterns of ghrelin suggest a role in controlling food intake. So thus the connection between ghrelin and the induced high AVP release may be intriguing and likely important. In the present study, our aim was to investigate the possible ghrelin effects on AVP release in neurohypophysis (NH) cell cultures. We also wanted to develop a standardized in vitro research model to study the basic regulation of AVP and the effects of ghrelin on AVP release. In vitro primer NH cell cultures model systems were made (tripsine, collagenase, DNA-se I; II and mechanical dissociation) from Wistar (%) rats. The tissue cultures were standardized for cellviability (Trypan blue test), aspecific (30 mM [K+]) and specific (10−6 M norepinephrine) AVP release immune-reactive (IR) AVP content of NH cells. Control systems were used (absolute control: untreated, positive control: treatment with solvent mixture,
negative control: moved with treatment protocol) in the experimental model. The examination samples were treated with ghrelin (10−8 –10−11 M, t = 0−90 min) and/or ghrelin-antagonists ([DLys3] GHRP-6 (His-DTrp-DLys-Trp-DPhe-Lys-NH2, [10−9 M]). From the supernatant media AVP content was detected by radioimmunoassay (RIA) method. The protein content of tissue cultures was measured by modified Lowry methods. The cultured were controlled with phase contrast invertoscope. The data were analyzed by ANOVA. In our results, ghrelin has effective dose: 10−9 M, which induce significant AVP release from NH cultures (control:45.4 pg AVP/mg prot.; treatment sample: 98.9 pg AVP/mg prot.). The enhancement of AVP in supernatant media was mediated by ghrelin receptors/ghrelin antagonist + ghrelin treatment samples: 56.81 pg AVP/mg prot. In this experimental protocol it was justified that, the rat NH contains ghrelin receptors, which are connected to exocytotic cellmembrane function − to AVP release. Our results indicate that, the AVP regulate psychogenic processes can dependent from the ghrelin mediation. References [1] Aydin, S., Guzel, S.P., Kumru, S., Akin, O., Kavak, E., Sahin, I., Bozkurt, M., Halifeoglu, I., 2008. Serum leptin and ghrelin concentrations of maternal serum, arterial and venous cord blood in healthy and preeclamptic pregnant women, J Physiol Biochem, 51−60. [2] Chacko, S.K., Haymond, M.W., Sun, Y., Marini, J.C., Sauer, P.J., Ma, X. et al., 2012. Effect of ghrelin on glucose regulation in mice, Am J PhysiolEndocrinol Metab, 1055−62. [3] Ahmed, S., Harvey, S., 2002. Ghrelin: a hypothalamic GH-releasing factor in domestic fowl (Gallus domesticus), Journal of Endocrinology, 117–125. Disclosure statement: This work was supported by Institute of Applied Natural Science, Gyula Juhasz Faculty of Education, University of Szeged, Hungary.
P.1.e.008 The effect of serotonergic receptor activation in the paraventricular nuclei of the hypothalamus on the expression of liver cytochrome P450 E. Bromek1 ° , M. Rysz1 , A. Haduch1 , W.A. Daniel1 1 Polish Academy of Sciences Institute of Pharmacology, Pharmacokinetics and Drug Metabolism, Krakow, Poland Introduction: Cytochrome P450 (CYP) is a complex of isoenzymes, which play an important role in metabolism of endogenous substances (e.g. steroids, neurotransmitters, vitamins) and many xenobiotics including psychotropic drugs. Brain nervous system plays a significant role in the physiological and pharmacological regulation of cytochrome P450. Our previous study into the general lesion or activation of the brain serotonergic system (using the intra raphe neurotoxin 5,7-DHT or the intraventricular serotonin precursor 5-HTP, respectively) demonstrated involvement of that system in the central neuroendocrine regulation of cytochrome P450 expression in the liver [1,2]. The aim of this study was to determine the effect of activation of the 5-HT1 or 5-HT2 receptors in the paraventricular nuclei (PVN) on the expression of CYP in the liver. Methods: The experiment was carried out on male Wistar rats. Guide cannulas were implanted bilaterally into the paraventricular nuclei of the hypothalamus (PVN). The animals were given 5-carboxyamidotryptamine (5-CT), a general agonist of the 5-HT1
P.1.e. Basic and clinical neuroscience − Neuro-endocrinology
major depressive disorder: integrative genome-wide and candidate gene analyses. Sci Rep 6, 18776. [2] Sasayama, D., Hori, H., Nakamura, S., Miyata, R., Teraishi, T., Hattori, K., Ota, M., Yamamoto, N., Higuchi, T., Amano, N., Kunugi, H., 2013. Identification of single nucleotide polymorphisms regulating peripheral blood mRNA expression with genome-wide significance: an eQTL study in the Japanese population. PLoS One 8, e54967. [3] Hori, H., Ozeki, Y., Teraishi, T., Matsuo, J., Kawamoto, Y., Kinoshita, Y., Suto, S., Terada, S., Higuchi, T., Kunugi, H., 2010. Relationships between psychological distress, coping styles, and HPA axis reactivity in healthy adults. J Psychiatr Res 44, 865–873. Disclosure statement: One of the authors (S.N.) has been employed by the DNA Chip Research Inc. The other authors declare that they have no competing interests.
P.1.e.007 The possible role of ghrelin in AVP (argininevasopressin) connected psychogenic processes Z. Molnar1 ° , M. Radacs1 , L. Racz1 , C. Varga2 , K. Sepp3 , P. Hausinger4 , M. Galfi1 1 Institute of Applied Natural ScienceGyula Juhasz Faculty of Education- University of Szeged, Department of Environmental Biology and Education, Szeged, Hungary; 2 Faculty of Science and Informatics- University of Szeged, Department of Physiology- Anatomy and Neuroscience, Szeged, Hungary; 3 University of Szeged Medical Faculty, Endocrine Unit of First Department of Internal Medicine, Szeged, Hungary; 4 University of Szeged Medical Faculty, Invasive Cardiology Department- Second Department of Internal Medicine and Cardiology, Szeged, Hungary It is well known, that the high arginine-vasopressin (AVP) level in serum can induce the depression in mammalians. Behavior depends on secreted mediators. Brain AVP is expressed mainly by hypothalamic neurosecretory cells. It is well described that AVP affect the stress-induced activity of the hypothalamic–pituitary– adrenal axis, and AVP can affect depressive behaviors. Life exists by maintaining a complex dynamic equilibrium or homeostasis that is constantly challenged by intrinsic or extrinsic adverse forces. Ghrelin is an endogenous neuropeptide for the GH secretagogue (GHS) receptor and it stimulates GH release in rats and humans. The ghrelin receptor GHS-R is mainly expressed in the hypothalamus and pituitary, its endogenous ligand has been thought to exist mainly in the hypothalamic regions. Recent studies have reported the presence of ghrelin in previously uncharacterized hypothalamic neurons adjacent to the third ventricle between the dorsal, ventral, paraventricular, and arcuate hypothalamic nuclei. These localization patterns of ghrelin suggest a role in controlling food intake. So thus the connection between ghrelin and the induced high AVP release may be intriguing and likely important. In the present study, our aim was to investigate the possible ghrelin effects on AVP release in neurohypophysis (NH) cell cultures. We also wanted to develop a standardized in vitro research model to study the basic regulation of AVP and the effects of ghrelin on AVP release. In vitro primer NH cell cultures model systems were made (tripsine, collagenase, DNA-se I; II and mechanical dissociation) from Wistar (%) rats. The tissue cultures were standardized for cellviability (Trypan blue test), aspecific (30 mM [K+]) and specific (10−6 M norepinephrine) AVP release immune-reactive (IR) AVP content of NH cells. Control systems were used (absolute control: untreated, positive control: treatment with solvent mixture,
negative control: moved with treatment protocol) in the experimental model. The examination samples were treated with ghrelin (10−8 –10−11 M, t = 0−90 min) and/or ghrelin-antagonists ([DLys3] GHRP-6 (His-DTrp-DLys-Trp-DPhe-Lys-NH2, [10−9 M]). From the supernatant media AVP content was detected by radioimmunoassay (RIA) method. The protein content of tissue cultures was measured by modified Lowry methods. The cultured were controlled with phase contrast invertoscope. The data were analyzed by ANOVA. In our results, ghrelin has effective dose: 10−9 M, which induce significant AVP release from NH cultures (control:45.4 pg AVP/mg prot.; treatment sample: 98.9 pg AVP/mg prot.). The enhancement of AVP in supernatant media was mediated by ghrelin receptors/ghrelin antagonist + ghrelin treatment samples: 56.81 pg AVP/mg prot. In this experimental protocol it was justified that, the rat NH contains ghrelin receptors, which are connected to exocytotic cellmembrane function − to AVP release. Our results indicate that, the AVP regulate psychogenic processes can dependent from the ghrelin mediation. References [1] Aydin, S., Guzel, S.P., Kumru, S., Akin, O., Kavak, E., Sahin, I., Bozkurt, M., Halifeoglu, I., 2008. Serum leptin and ghrelin concentrations of maternal serum, arterial and venous cord blood in healthy and preeclamptic pregnant women, J Physiol Biochem, 51−60. [2] Chacko, S.K., Haymond, M.W., Sun, Y., Marini, J.C., Sauer, P.J., Ma, X. et al., 2012. Effect of ghrelin on glucose regulation in mice, Am J PhysiolEndocrinol Metab, 1055−62. [3] Ahmed, S., Harvey, S., 2002. Ghrelin: a hypothalamic GH-releasing factor in domestic fowl (Gallus domesticus), Journal of Endocrinology, 117–125. Disclosure statement: This work was supported by Institute of Applied Natural Science, Gyula Juhasz Faculty of Education, University of Szeged, Hungary.
P.1.e.008 The effect of serotonergic receptor activation in the paraventricular nuclei of the hypothalamus on the expression of liver cytochrome P450 E. Bromek1 ° , M. Rysz1 , A. Haduch1 , W.A. Daniel1 1 Polish Academy of Sciences Institute of Pharmacology, Pharmacokinetics and Drug Metabolism, Krakow, Poland Introduction: Cytochrome P450 (CYP) is a complex of isoenzymes, which play an important role in metabolism of endogenous substances (e.g. steroids, neurotransmitters, vitamins) and many xenobiotics including psychotropic drugs. Brain nervous system plays a significant role in the physiological and pharmacological regulation of cytochrome P450. Our previous study into the general lesion or activation of the brain serotonergic system (using the intra raphe neurotoxin 5,7-DHT or the intraventricular serotonin precursor 5-HTP, respectively) demonstrated involvement of that system in the central neuroendocrine regulation of cytochrome P450 expression in the liver [1,2]. The aim of this study was to determine the effect of activation of the 5-HT1 or 5-HT2 receptors in the paraventricular nuclei (PVN) on the expression of CYP in the liver. Methods: The experiment was carried out on male Wistar rats. Guide cannulas were implanted bilaterally into the paraventricular nuclei of the hypothalamus (PVN). The animals were given 5-carboxyamidotryptamine (5-CT), a general agonist of the 5-HT1