open access

Vol 81, No 2 (2022)
Original article
Submitted: 2020-12-10
Accepted: 2021-03-03
Published online: 2021-03-22
Get Citation

Glutamate receptor antagonist suppresses the activation of nesfatin-1 neurons following refeeding or glucose administration

S. Serter Kocoglu1, C. Oy2, Z. Halk2, C. Cakır2, Z. Minbay2, O. Eyigor2
DOI: 10.5603/FM.a2021.0034
·
Pubmed: 33778937
·
Folia Morphol 2022;81(2):379-386.
Affiliations
  1. Department of Histology and Embryology, Balikesir University School of Medicine, Balikesir, Turkey
  2. Department of Histology and Embryology, Bursa Uludag University School of Medicine, Bursa, Turkey

open access

Vol 81, No 2 (2022)
ORIGINAL ARTICLES
Submitted: 2020-12-10
Accepted: 2021-03-03
Published online: 2021-03-22

Abstract

Background: Nesfatin-1 is a newly identified satiety peptide that has regulatory effects on food intake and glucose metabolism, and is located in the hypothalamic nuclei, including the supraoptic nucleus (SON). In this study, we have investigated the hypothesis that nesfatin-1 neurons are activated by refeeding and intraperitoneal glucose injection and that the glutamatergic system has regulatory influences on nesfatin-1 neurons in the SON.
Materials and methods: The first set of experiments analysed activation of nesfatin-1 neurons after refeeding as a physiological stimulus and the effectiveness of the glutamatergic system on this physiological stimulation. The subjects were randomly divided into three groups: fasting group, refeeding group and antagonist (CNQX + refeeding) group. The second set of experiments analysed activation of nesfatin-1 neurons by glucose injection as a metabolic stimulus and the effectiveness of the glutamatergic system on this metabolic stimulation. The subjects were randomly divided into three groups: saline group, glucose group and antagonist (CNQX + glucose) group.
Results: Refeeding significantly increased the number of activated nesfatin-1 neurons by approximately 66%, and intraperitoneal glucose injection activated these neurons by about 55%, compared to the fasting and saline controls. The injections of glutamate antagonist (CNQX) greatly decreased the number of activated nesfatin-1 neurons.
Conclusions: This study suggested that nesfatin-1 neurons were activated by peripheral and/or metabolic signals and that this effect was mediated through the glutamatergic system.

Abstract

Background: Nesfatin-1 is a newly identified satiety peptide that has regulatory effects on food intake and glucose metabolism, and is located in the hypothalamic nuclei, including the supraoptic nucleus (SON). In this study, we have investigated the hypothesis that nesfatin-1 neurons are activated by refeeding and intraperitoneal glucose injection and that the glutamatergic system has regulatory influences on nesfatin-1 neurons in the SON.
Materials and methods: The first set of experiments analysed activation of nesfatin-1 neurons after refeeding as a physiological stimulus and the effectiveness of the glutamatergic system on this physiological stimulation. The subjects were randomly divided into three groups: fasting group, refeeding group and antagonist (CNQX + refeeding) group. The second set of experiments analysed activation of nesfatin-1 neurons by glucose injection as a metabolic stimulus and the effectiveness of the glutamatergic system on this metabolic stimulation. The subjects were randomly divided into three groups: saline group, glucose group and antagonist (CNQX + glucose) group.
Results: Refeeding significantly increased the number of activated nesfatin-1 neurons by approximately 66%, and intraperitoneal glucose injection activated these neurons by about 55%, compared to the fasting and saline controls. The injections of glutamate antagonist (CNQX) greatly decreased the number of activated nesfatin-1 neurons.
Conclusions: This study suggested that nesfatin-1 neurons were activated by peripheral and/or metabolic signals and that this effect was mediated through the glutamatergic system.

Get Citation

Keywords

CNQX, glucose, glutamate, nesfatin-1, refeeding

About this article
Title

Glutamate receptor antagonist suppresses the activation of nesfatin-1 neurons following refeeding or glucose administration

Journal

Folia Morphologica

Issue

Vol 81, No 2 (2022)

Article type

Original article

Pages

379-386

Published online

2021-03-22

Page views

1317

Article views/downloads

474

DOI

10.5603/FM.a2021.0034

Pubmed

33778937

Bibliographic record

Folia Morphol 2022;81(2):379-386.

Keywords

CNQX
glucose
glutamate
nesfatin-1
refeeding

Authors

S. Serter Kocoglu
C. Oy
Z. Halk
C. Cakır
Z. Minbay
O. Eyigor

References (52)
  1. Altarejos JY, Montminy M. CREB and the CRTC co-activators: sensors for hormonal and metabolic signals. Nat Rev Mol Cell Biol. 2011; 12(3): 141–151.
  2. Alvarsson A, Stanley SA. Remote control of glucose-sensing neurons to analyze glucose metabolism. Am J Physiol Endocrinol Metab. 2018; 315(3): E327–E339.
  3. Atsuchi K, Asakawa A, Ushikai M, et al. Centrally administered nesfatin-1 inhibits feeding behaviour and gastroduodenal motility in mice. Neuroreport. 2010; 21(15): 1008–1011.
  4. Balazs R. Trophic effect of glutamate. Curr Top Med Chem. 2006; 6(10): 961–968.
  5. Blanco AM, Velasco C, Bertucci JI, et al. Nesfatin-1 regulates feeding, glucosensing and lipid metabolism in rainbow trout. Front Endocrinol (Lausanne). 2018; 9: 484.
  6. Brailoiu GC, Dun SL, Brailoiu E, et al. Nesfatin-1: distribution and interaction with a G protein-coupled receptor in the rat brain. Endocrinology. 2007; 148(10): 5088–5094.
  7. Brann DW. Glutamate: a major excitatory transmitter in neuroendocrine regulation. Neuroendocrinology. 1995; 61(3): 213–225.
  8. Brann D, Mahesh V. Excitatory amino acids: function and significance in reproduction and neuroendocrine regulation. Front Neuroendocrinol. 1994; 15(1): 3–49.
  9. Collingridge GL, Olsen RW, Peters J, et al. A nomenclature for ligand-gated ion channels. Neuropharmacology. 2009; 56(1): 2–5.
  10. Cull-Candy S, Brickley S, Farrant M. NMDA receptor subunits: diversity, development and disease. Curr Opin Neurobiol. 2001; 11(3): 327–335.
  11. Dong J, Guan HZ, Jiang ZY, et al. Nesfatin-1 influences the excitability of glucosensing neurons in the dorsal vagal complex and inhibits food intake. PLoS One. 2014; 9(6): e98967.
  12. Eyigor O, Centers A, Jennes L. Distribution of ionotropic glutamate receptor subunit mRNAs in the rat hypothalamus. J Comp Neurol. 2001; 434(1): 101–124.
  13. Eyigor O, Minbay Z, Cavusoglu I. Activation of orexin neurons through non-NMDA glutamate receptors evidenced by c-Fos immunohistochemistry. Endocrine. 2010; 37(1): 167–172.
  14. Eyigor O, Minbay Z, Cavusoglu I, et al. Localization of kainate receptor subunit GluR5-immunoreactive cells in the rat hypothalamus. Brain Res Mol Brain Res. 2005; 136(1-2): 38–44.
  15. Fan XT, Tian Z, Li SZ, et al. Ghrelin Receptor Is Required for the Effect of Nesfatin-1 on Glucose Metabolism. Front Endocrinol (Lausanne). 2018; 9: 633.
  16. Goebel M, Stengel A, Wang L, et al. Central nesfatin-1 reduces the nocturnal food intake in mice by reducing meal size and increasing inter-meal intervals. Peptides. 2011; 32(1): 36–43.
  17. Gok-Yurtseven D, Kafa IM, Minbay Z, et al. Glutamatergic activation of A1 and A2 noradrenergic neurons in the rat brain stem. Croat Med J. 2019; 60(4): 352–360.
  18. Gok Yurtseven D, Serter Kocoglu S, Minbay Z, et al. Immunohistochemical evidence for glutamatergic regulation of nesfatin-1 neurons in the rat hypothalamus. Brain Sci. 2020; 10(9).
  19. Gonzalez R, Kerbel B, Chun A, et al. Molecular, cellular and physiological evidences for the anorexigenic actions of nesfatin-1 in goldfish. PLoS One. 2010; 5(12): e15201.
  20. Hoffman GE, Lyo D. Anatomical markers of activity in neuroendocrine systems: are we all 'fos-ed out'? J Neuroendocrinol. 2002; 14(4): 259–268.
  21. Huo L, Gamber K, Greeley S, et al. Leptin-dependent control of glucose balance and locomotor activity by POMC neurons. Cell Metab. 2009; 9(6): 537–547.
  22. Kew JNC, Kemp JA. Ionotropic and metabotropic glutamate receptor structure and pharmacology. Psychopharmacology (Berl). 2005; 179(1): 4–29.
  23. Kohno D, Nakata M, Maejima Y, et al. Nesfatin-1 neurons in paraventricular and supraoptic nuclei of the rat hypothalamus coexpress oxytocin and vasopressin and are activated by refeeding. Endocrinology. 2008; 149(3): 1295–1301.
  24. Köles L, Wirkner K, Illes P. Modulation of ionotropic glutamate receptor channels. Neurochem Res. 2001; 26(8-9): 925–932.
  25. Könczöl K, Pintér O, Ferenczi S, et al. Nesfatin-1 exerts long-term effect on food intake and body temperature. Int J Obes (Lond). 2012; 36(12): 1514–1521.
  26. Lents CA, Barb CR, Hausman GJ, et al. Effects of nesfatin-1 on food intake and LH secretion in prepubertal gilts and genomic association of the porcine NUCB2 gene with growth traits. Domest Anim Endocrinol. 2013; 45(2): 89–97.
  27. Lerma J, Paternain AV, Rodríguez-Moreno A, et al. Molecular physiology of kainate receptors. Physiol Rev. 2001; 81(3): 971–998.
  28. Li Z, Gao L, Tang H, et al. Peripheral effects of nesfatin-1 on glucose homeostasis. PLoS One. 2013; 8(8): e71513.
  29. Maejima Y, Sedbazar U, Suyama S, et al. Nesfatin-1-regulated oxytocinergic signaling in the paraventricular nucleus causes anorexia through a leptin-independent melanocortin pathway. Cell Metab. 2009; 10(5): 355–365.
  30. Mayer ML. Structural biology of glutamate receptor ion channel complexes. Curr Opin Struct Biol. 2016; 41: 119–127.
  31. Meeker RB, Greenwood RS, Hayward JN. Glutamate is the major excitatory transmitter in the supraoptic nuclei. Ann N Y Acad Sci. 1993; 689: 636–639.
  32. Meeker RB, McGinnis S, Greenwood RS, et al. Increased hypothalamic glutamate receptors induced by water deprivation. Neuroendocrinology. 1994; 60(5): 477–485.
  33. Miñana-Solis MD, Angeles-Castellanos M, Buijs RM, et al. Altered Fos immunoreactivity in the hypothalamus after glucose administration in pre- and post-weaning malnourished rats. Nutr Neurosci. 2010; 13(4): 152–160.
  34. Minbay FZ, Eyigor O, Cavusoglu I. Kainic acid activates oxytocinergic neurons through non-nmda glutamate receptors. Int J Neurosci. 2006; 116(5): 587–600.
  35. Oh-I S, Shimizu H, Satoh T, et al. Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature. 2006; 443(7112): 709–712.
  36. Ozawa S, Kamiya H, Tsuzuki K. Glutamate receptors in the mammalian central nervous system. Prog Neurobiol. 1998; 54(5): 581–618.
  37. Pachernegg S, Strutz-Seebohm N, Hollmann M. GluN3 subunit-containing NMDA receptors: not just one-trick ponies. Trends Neurosci. 2012; 35(4): 240–249.
  38. Paoletti P. Molecular basis of NMDA receptor functional diversity. Eur J Neurosci. 2011; 33(8): 1351–1365.
  39. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. Acad Press, London 2009.
  40. Samson WK, Zhang JV, Avsian-Kretchmer O, et al. Neuronostatin encoded by the somatostatin gene regulates neuronal, cardiovascular, and metabolic functions. J Biol Chem. 2008; 283(46): 31949–31959.
  41. Schalla MA, Stengel A. Current understanding of the role of nesfatin-1. J Endocr Soc. 2018; 2(10): 1188–1206.
  42. Serter Kocoglu S, Gok Yurtseven D, Cakir C, et al. Glutamatergic activation of neuronostatin neurons in the periventricular nucleus of the hypothalamus. Brain Sci. 2020; 10(4).
  43. Stengel A, Goebel M, Taché Y. Nesfatin-1: a novel inhibitory regulator of food intake and body weight. Obes Rev. 2011; 12(4): 261–271.
  44. Stengel A, Goebel M, Wang L, et al. Central nesfatin-1 reduces dark-phase food intake and gastric emptying in rats: differential role of corticotropin-releasing factor2 receptor. Endocrinology. 2009; 150(11): 4911–4919.
  45. Tse YC, Yung KK. Cellular expression of ionotropic glutamate receptor subunits in subpopulations of neurons in the rat substantia nigra pars reticulata. Brain Res. 2000; 854(1-2): 57–69.
  46. Üner A, Gonçalves GHM, Li W, et al. The role of GluN2A and GluN2B NMDA receptor subunits in AgRP and POMC neurons on body weight and glucose homeostasis. Mol Metab. 2015; 4(10): 678–691.
  47. Üner AG, Keçik O, Quaresma PGF, et al. Role of POMC and AgRP neuronal activities on glycaemia in mice. Sci Rep. 2019; 9(1): 13068.
  48. Yosten GLC, Redlinger L, Samson WK. Evidence for a role of endogenous nesfatin-1 in the control of water drinking. J Neuroendocrinol. 2012; 24(7): 1078–1084.
  49. Yosten GLC, Samson WK. Nesfatin-1 exerts cardiovascular actions in brain: possible interaction with the central melanocortin system. Am J Physiol Regul Integr Comp Physiol. 2009; 297(2): R330–R336.
  50. Yosten GLC, Samson WK. The anorexigenic and hypertensive effects of nesfatin-1 are reversed by pretreatment with an oxytocin receptor antagonist. Am J Physiol Regul Integr Comp Physiol. 2010; 298(6): R1642–R1647.
  51. Yuan JH, Chen Xi, Dong J, et al. Nesfatin-1 in the lateral parabrachial nucleus inhibits food intake, modulates excitability of glucosensing neurons, and enhances UCP1 expression in brown adipose tissue. Front Physiol. 2017; 8: 235.
  52. Zhao JB, Zhang Y, Li GZ, et al. Activation of JAK2/STAT pathway in cerebral cortex after experimental traumatic brain injury of rats. Neurosci Lett. 2011; 498(2): 147–152.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By  "Via Medica sp. z o.o." sp.k., Świętokrzyska 73, 80–180 Gdańsk, Poland

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl