Abstract
In birds and mammals, the neuroendocrine regulation of energy balance is conserved in many aspects. Despite significant similarities between the two groups, differences in the regulatory mechanisms were detected. The present study was performed to carry out investigations of the influence of human leptin and GABAB-receptor agonist and antagonist on the firing rate of neurons of the Nucleus infundibuli hypothalami in brain slices from juvenile chickens. For the first time, we demonstrated a clear, dose-related change in the firing rate of hypothalamic neurons in juvenile chickens after the acute application of recombinant human leptin (1, 10, and 100 nM). All investigated neurons increased their subsequent firing rate. Application of GABAB-receptor agonist baclofen (1 µM) blocked, while antagonist CGP 35348 (10 µM) increased the spontaneous neuronal activity. Simultaneous application of baclofen and leptin reduced the effect observed from single leptin application. This was not found after simultaneously application of leptin and CGP. Altogether, our results indicate that in bird brain slices, and exemplarily in those of the chicken, hypothalamic neurons show mammalian-like responsiveness after acute leptin and GABA application. GABAB-mechanisms involved in GABA release play a likely important role in the leptin-mediated effects on NI neurons via functional leptin receptors.
Similar content being viewed by others
Abbreviations
- ACSF:
-
Artificial cerebrospinal fluid
- AgRP:
-
Agouti-related peptide
- Bac:
-
Baclofen
- CART:
-
Cocaine- and amphetamine-regulated transcript
- CGP 35348:
-
(3-Aminopropyl)(diethoxymethyl)phosphinie
- GABA:
-
Gamma-aminobutyric acid
- JAK:
-
Janus kinase
- mRNA:
-
Messenger ribonucleic acid
- NPY:
-
Neuropeptide Y
- POMC:
-
Proopiomelanocortin
- STAT:
-
Signal transducers and activators of the transcription
References
Adachi H, Takemoto Y, Bungo T, Ohkubo T (2008) Chicken leptin receptor is functional in activating JAK-STAT pathway in vitro. J Endocrinol 197:335–342
Arima H, Oiso Y (2010) Positive effect of baclofen on body weight reduction in obese subjects: a pilot study. Intern Med 49:2043–2047
Balthasar N, Coppari R, McMinn J, Liu SM, Lee CE, Tang V, Kenny CD, McGover, RA, Chua SC Jr, Elmquis JK, Lowell BB (2004) Leptin receptor signalling in POMC neurons is required for normal body weight homeostasis. Neuron 42:983–991
Baskin DG, Seely RJ, Kuijper JL, Lok S, Weigle DS, Erickson JC, Palmiter RD, Schwartz MW (1998) Increased expression of mRNA for the long form of the leptin receptor in the hypothalamus is associated with leptin hypersensitivity and fasting. Diabetes 47:538–544
Bettler B, Kaupmann K, Mosbacher J, Gassmann M (2004) Molecular structures and physiological functions of GABAB receptors. Physiol Rev 84:835–867
Bhumbra GS, Dyball REJ (2010) Reading between the spikes of the hypothalamic neural code. J Neuroendocrinol 22:1239–1250
Bormann J (2000) ‘ABC’ of GABA receptors. Trends Pharmacol Sci 21:16–19
Boswell T (2005) Regulation of energy balance in birds by the neuroendocrine hypothalamus. J Poult Sci 42:161–181
Boswell T, Dunn IC (2015) Regulation of the avian central melanocortin system and the role of leptin. Gen Comp Endocrinol. doi: 10.1016/j.ygcen.2014.12.009
Boswell T, Li Q, Takeuchi S (2002) Neurons expressing neuropeptide Y mRNA in the infundibular hypothalamus of Japanese quail are activated by fasting and co-express agouti-related protein mRNA. Mol. Brain Res 100:31–42
Boulant J, Silva N (1989) Multisensory hypothalamic neurons may explain interactions among regulatory systems. Physiology 4:245–248
Bühl A (2012) SPSS 20 Einführung in die moderne Datenanalyse. Pearson Deutschland GmbH
Bungo T, Shimojo M, Masuda Y, Tachibanab T, Tanaka S, Sugahara K, Furuse M (1999) Intracerebroventricular administration of mouse leptin does not reduce food intake in the chicken. Brain Res 817:196–198
Bungo T, Izumi T, Kawamura K, Takagi T, Ueda H, Furuse M (2003) Intracerebroventricular injection of muscimol, baclofen or nipecotic acid stimulates food intake in layer-type, but not meat-type, chickens. Brain Res 993:235–238
Cowley MA, Smart JL, Rubinstein M, Cerdán MG, Diano S, Horvath TL, Cone RD, Low MJ (2001) Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411:480–484
Davidowa H, Plagemann A (2000) Decreased inhibition by leptin of hypothalamic arcuate neurons in neonatally overfed young rats. NeuroReport 11:2795–2798
Denbow DM, Meade S, Robertson A, McMurtry JP, Richards M, Ashwell C (2000) Leptin-induced decrease in food intake in chickens. Physiol Behav 69:359–362
Elias CF, Lee C, Aschkenasi C, Ahima RS, Couceyro PR, Kuhar MJ, Saper CB, Elmquist JK (1998) Leptin activates hypothalamic CART Neurons projecting to the spinal cord. Neuron 21:1375–1385
Fioramonti X, Contié S, Song Z, Routh VH, Lorsignol A, Pénicaud L (2007) Characterization of glucosensing neuron subpopulations in the arcuate nucleus. Integration in neuropeptide Y and Proopiomelanocortin networks? Diabetes 56:1219–1227
Friedman-Einat M, Cogburn LA, Yosefi S, Hen G, Shinder D, Shirak A, Seroussi E (2014) Discovery and characterization of the first genuine avian leptin gene in the Rock Dove (Columba livia). Endocrinology 155:3376–3384
Fujikawa T, Berglund ED, Patel VR, Ramadori G, Vianna CR, Vong L, Thorel F, Chera S, Herrera PL, Lowell BB, Elmquist JK, Baldi P, Coppari R (2013) Leptin engages a hypothalamic neurocircuitry to permit survival in the absence of insulin. Cell Metab 18:431–444
German J, Kim F, Schwartz GJ, Havel PJ, Rhodes CJ, Schwartz MW, Morton GJ (2009) Hypothalamic leptin signaling regulates hepatic insulin sensitivity via a neurocircuit involving the vagus nerve. Endocrinology 150:4502–4511
Goodridge AG (1968) Conversion of [U-14C] glucose into carbon dioxide, glycogen, cholesterol and fatty acids in liver slices from embryonic and growing chicks. Biochem J 108:655–661
Hen G, Yosefi S, Ronin A, Einat P, Rosenblum CI, Denver RJ, Friedman-Einat M (2008) Monitoring leptin activity using the chicken leptin receptor. J Endocrinol 197:325–333
Higgins SE, Ellestad LE, Trakooljul N, McCarthy F, Saliba J, Cogburn LA, Porter TE (2010) Transcriptional and pathway analysis in the hypothalamus of newly hatched chicks during fasting and delayed feeding. BMC Genomics. doi:10.1186/1471-2164-11-162
Horev G, Einat P, Aharoni T, Eshdat Y, Friedman-Einat M (2000) Molecular cloning and properties of the chicken leptin-receptor (CLEPR) gene. Mol Cell Endocrinol 162:95–106
Hori T (1991) An update on thermosensitive neurons in the brain: from cellular biology to thermal and non-thermal homeostatic functions. Jpn J Physiol 41:1–22
Horowitz M (2014) Heat acclimation, epigenetics, and cytoprotection memory. Compr Physiol 4:199–230
Huang G, Li J, Wang H, Lan X, Wang Y (2014) Discovery of a novel functional leptin protein (LEP) in Zebra Finches: evidence for the existence of an authentic avian leptin gene predominantly expressed in the brain and pituitary. Endocrinology 155:3385–3396
Huo L, Gamber K, Greeley S, Silva J, Huntoon N, Leng X-H, Bjorbaek C (2009) Leptin-dependent control of glucose balance and locomotor activity by POMC neurons. Cell Metab 9:537–547
Jonaidi H, Babapour V, Denbow DM (2002) GABAergic control of food intake in the meat-type chickens. Physiol Behav 76:465–468
Kameda Y, Miura M, Nishimaki T (2001) Localization of neuropeptide Y mRNA and peptide in the chicken hypothalamus and their alterations after food deprivation, dehydration, and castration. J Comp Neurol 436:376–388
Kamohara S, Burcelin R, Halaas JL, Friedman JM, Charron MJ (1997) Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 389:374–377
Khan Md SI, Dodo KI, Yahata K, Nishimoto S, Ueda H, Taneike T, Kitazawa T, Hosaka Y, Bungo T (2006) Intracerebroventricular administration of growth hormone releasing peptide-6 (GHRP-6) inhibits food intake, but not food retention of crop and stomach in neonatal chicks. J Poult Sci 43:35–40
Królczyk G, Laskiewicz J, Sobocki J, Matyja A, Kolasinska-Kloch W, Thor PJ (2005) The effect of baclofen on the feeding behaviour and body weight of vagally stimulated rats. J Physiol Pharmacol 56:121–131
Kuenzel WJ, Masson M (1998) A Stereotaxic Atlas of the Brain of the Chick (Gallus domesticus). The John Hopkins Univ. Press, Baltimore
Kuenzel WJ, van Tienhoven A (1982) Nomenclature and location of avian hypothalamic nuclei and associated circumventricular organs. J Comp Neurol 206:293–313
Kuo AY, Cline MA, Werner E, Siegel PB, Denbow DM (2005) Leptin effects on food and water intake in lines of chickens selected for high or low body weight. Physiol Behav 84:459–464
Liu X, Dunn IC, Sharp PJ, Boswell T (2007) Molecular cloning and tissue distribution of a short form chicken leptin receptor mRNA. Domest Anim Endocrinol 32:155–166
Meister B, Gömüc B, Suarez E, Yuko I, Dürr K, Gillberg L (2006) Hypothalamic proopiomelanocortin (POMC) neurons have a cholinergic phenotype. Eur J Neurosci 24:2731–2740
Nagamori K, Ishibashi M, Shiraishi T, Oomura Y, Sasaki K (2003) Effects of leptin on hypothalamic arcuate neurons in Wistar and Zucker rats: an in vitro study. Exp Biol Med 228:1162–1167
Nakamura Y, Hinoi E, Takarada T, Takahata Y, Yamamoto T, Fujita H, Takada S, Hashizume S, Yoneda Y (2011) Positive regulation by GABABR1 subunit of leptin expression through gene transactivation in adipocytes. PloS ONE. doi:10.1371/journal.pone.0020167
Patel SM, Ebenezer IS (2004) The effect of intraperitoneal and intracerebroventricular administration of the GABAB receptor antagonist CGP 35348 on food intake in rats. Eur J Pharmacol 503:89–93
Pin J-P, Prézeau L (2007) Allosteric modulators of GABAB receptors: mechanism of action and therapeutic perspective. Curr Neuropharmacol 5:195–201
Powis JE, Bains JS, Ferguson AV (1998) Leptin depolarizes rat hypothalamic paraventricular nucleus neurons. Am J Physiol 274:R1468–R1472
Prokop JW, Schmidt C, Gasper D, Duff RJ, Milsted A, Ohkubo T, Ball HC, Shawkey MD, Mays Jr HL, Cogburn LA, Londraville RL (2014) Discovery of the elusive leptin in birds: identification of several ‘missing links’ in the evolution of leptin and its receptor. PloS ONE. doi:10.1371/journal.pone.0092751
Rancourt RC, Schellong K, Ott R, Bogatyrev S, Tzschentke B, Plagemann A (2015) Acquired alterations of hypothalamic gene expression (INSR, LEPR, GLUT1 and GLUT3) in prenatally high-glucose exposed postnatal chickens do not coincide with significantly altered promoter DNA methylation. PloS ONE. doi:10.1371/journal.pone.0119213
Richards MP, Poch SM (2003) Molecular cloning and expression of the turkey leptin receptor gene. Comp Biochem Physiol B-Biochem Mol Biol 136:833–847
Saito ES, Kaiya H, Takagi T, Yamasaki I, Denbow DM, Kangawa K, Furuse M (2002) Chicken ghrelin and growth hormone-releasing peptide-2 inhibit food intake of neonatal chicks. Eur J Pharmacol 453:75–79
Saito ES, Kaiya H, Taschibana T, Tomonaga S, Denbow DM, Kangawa K, Furuse M (2005) Inhibitory effect of ghrelin on food intake is mediated by the corticotropin-releasing factor system in neonatal chicks. Regul Pept 125:201–208
Sallagundala N, Yakimova K, Tzschentke B (2007) Effect of GABAergic substances on firing rate and thermal coefficient of hypothalamic neurons in the juvenile chicken. Comp Biochem Physiol 148:374–381
Saper CB, Chou TC, Elmquist LK (2002) The need to feed: homeostatic and hedonic control of eating. Neuron 36:199–211
Satoh N, Ogawa Y, Katsuura G, Hayase M, Tsuji T, Imagawa K, Yoshimasa Y, Nishi S, Hosoda K, Nakao K (1997) The arcuate nucleus as a primary site of satiety effect of leptin in rats. Neurosci Lett 224:149–152
Schwartz MW, Seeley RJ, Campfield LA, Burn P, Baskin DG (1996) Identification of targets of leptin action in rat hypothalamus. J Clin Invest 98:1101–1106
Scott MM, Lachey JL, Sternson SM, Lee CE, Elias CF, Friedman JM, Elmquist JK (2009) Leptin targets in the mouse brain. J Comp Neurol 514:518–532
Seroussi E, Cinnamon Y, Yosefi S, Genin O, Smith JG, Rafati N, Bornelöv S, Andersson L, Friedman-Einat M (2015) Identification of the long-sought leptin in chicken and duck: expression pattern of the highly GC-rich avian leptin fits an autocrine/paracrine rather than endocrine function. Endocrinology. doi:10.1210/en.2015-1634
Takagi T, Bungo T, Tachibana T, Saito E-S, Saito S, Yamasaki I, Tomonaga S, Denbow DM, Furuse M (2003) Intracerebroventricular administration of GABA-A and GABA-B receptor antagonists attenuate feeding and sleeping-like behavior induced by L-pipecolic acid in neonatal chicks. J Neurosci Res 73:270–275
Takahashi KA, Roger D (2005) Fasting induces a large, leptin-dependent increase in the intrinsic action potential frequency of orexigenic arcuate nucleus neuropeptide Y/Agouti-related protein neurons. Endocrinology 146:1043–1047
Tartaglia LA (1997) The leptin receptor. J Biol Chem 272:6093–6096
Tzschentke B, Nichelmann M (1999) Development of avian thermoregulatory system during the early postnatal period: development of the thermoregulatory set-point. Ornis Fenn 76:189–198
Tzschentke B, Bogatyrev S, Schellong K, Rancourt RC, Plagemann A (2015) Temporary prenatal hyperglycemia leads to postnatal neuronal ‘glucose-resistance’ in the chicken hypothalamus. Brain Res 1618:231–240
Vong L, Ye C, Yang Z, Choi B, Chua S Jr, Lowell BB (2011) Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons. Neuron 71:142–154
Wang X, Day JR, Vasilatos-Younken R (2001) The distribution of neuropeptide Y gene expression in the chicken brain. Mol Cell Endocrinol 174:129–136
Wang D, Xu C, Wang T, Li H, Li Y, Ren J, Tian Y, Li Z, Jiao Y, Kang X, Liu X (2016) Discovery and functional characterization of leptin and its receptors in Japanese quail (Coturnix japonica). Gen Comp Endocrinol 225:1–12
Williams KW, Scott MM, Elmquist JK (2009) From observation to experimentation: leptin action in the mediobasal hypothalamus. Am J Clin Nutr 89:985S–990S
Xu Y, O´Brien WG, Lee CC, Meyers MG Jr, Tong Q (2012) Role of GABA release from leptin receptor-expressing neurons in body weight regulation. Endocrinology 153:2223–2233
Yakimova K, Sann H, Schmid HA, Pierau Fr-K (1996) Effects of GABA agonists and antagonists on temperature sensitive neurons in the rat hypothalamus. J Physiol Lond 494:217–230
Yakimova K, Sallagundala N, Tzschentke B (2005) Influence of baclofen on temperature sensitive neurons in chicken hypothalamus. Methods Find Exp Clin Pharmacol 27:401–404
Yakimova KS, Nikolov RP, Todorov IG, Hristov MH (2014) Leptin and GABA interactions on thermoregulation of rats. J Biomed Clin Res 7:20–24
Yang SJ, Denbow DM (2007) Interaction of leptin and nitric oxide on food intake in broilers and Leghorns. Physiol Behav 92:651–657
Yosefi S, Hen G, Rosenblum CI, Cerasale DJ, Beaulieu M, Criscuolo F, Friedman-Einat M (2010) Lack of leptin activity in blood samples of Adélie penguin and bar-tailed godwit. J Endocrinol 207:113–122
Acknowledgements
This work was supported by a grant from the German Research Foundation (DFG: TZ 6/17-1). The guest research stay of Prof. Yakimova at the Humboldt University was supported by the German Academic Exchange Service (DAAD: 324: A/09/01589). All animal procedures were performed in accordance with the European Communities Council Directive (86/609/EEC) and were approved by the local animal welfare committee (G 0275/09; Lageso Berlin, Germany).
Author information
Authors and Affiliations
Corresponding author
Additional information
S. Bogatyrev and K. S. Yakimova have contributed equally to this work.
Rights and permissions
About this article
Cite this article
Bogatyrev, S., Yakimova, K.S. & Tzschentke, B. Influence of leptin and GABAB-receptor agonist and antagonist on neurons of the hypothalamic infundibular nucleus in the chicken. J Comp Physiol A 203, 291–299 (2017). https://doi.org/10.1007/s00359-017-1168-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00359-017-1168-6