The role of hypothalamic paraventricular nucleus GABAergic and CRHergic neurons on ghrelin's effect on energy metabolism

• Grant number: 19/01260-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2019
• End date: February 28, 2022
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: José Antunes Rodrigues
• Grantee: Raoni da Conceição dos Santos
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Ghrelin is an orexigenic hormone produced by the stomach. Our previous studies showed that ghrelin affects neurons in the hypothalamic paraventricular nucleus (PVN) and that ghrelin activates GABAergics neurons in the PVN that, in turn, inhibit anorexigenic neurons, such as the neurons that express corticotropin releasing hormone (CRH). The present study aims to assess the participation of the PVN in the response to ghrelin, by measuring the effects of ghrelin on GABAergic neurotransmission on the PVN and the modulation of PVN-CRH neurons in the responses to ghrelin. For the first set of experiment rat brain slices containing the PVN will be analyzed through whole-cell patch-clamp technique. The responses of PVN neurons to ghrelin will be assessed in the presence of biccuculine and the neurons will be characterized by the presence of the mRNA for GAD67. In a second set of experiments we will induce the decrease in GAD67 expression through infection with specific lentivirus and assess the influence of ghrelin on food intake in the absence of GABA in PVN neurons. In a third set of experiments the influence of PVN-CRH neurons in the response to ghrelin will be assessed through the DREADD (Designed Receptors Exclusively Activated by Designed Drugs). The expression of Gq and Gi receptors responsive to clozapine N-oxide will be induced specifically in PVN-CRH neurons, allowing for the evaluation of this subpopulation of neurons in the effects of ghrelin on food intake and body weight.

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FLORES, RAFAEL APPEL; DOS-SANTOS, RAONI CONCEICAO; STEINBACH, RENATA; RODRIGUES-SANTOS, ISABELLE; DE JESUS, ALINE ALVES; ANTUNES-RODRIGUES, JOSE; PASCHOALINI, MARTA APARECIDA. alpha-1 Adrenoceptor Activation in the Dorsal Raphe Nucleus Decreases Food Intake in Fasted Rats. FRONTIERS IN PHYSIOLOGY, v. 12, NOV 25 2021. (19/01260-2)

R.C. DOS-SANTOS; T. VILHENA-FRANCO; L.C. REIS; L.L.K. ELIAS; J. ANTUNES-RODRIGUES; A.S. MECAWI. AMPA and angiotensin type 1 receptors are necessary for hemorrhage-induced vasopressin secretion. Brazilian Journal of Medical and Biological Research, v. 55, 2022-02-04. (19/01260-2, 19/27581-0)

DOS-SANTOS, RAONI CONCEICAO; ISHIOKA, GABRIEL; COGNUCK, SUSANA QUIROS; MANTOVANI, MILENE; CALIMAN, IZABELA FACCO; KAGOHARA ELIAS, LUCILA LEICO; ANTUNES-RODRIGUES, JOSE. High-fat diet changes the behavioural and hormonal responses to water deprivation in male Wistar rats. Experimental Physiology, v. 107, n. 12, p. 13-pg., 2022-10-12. (13/09799-1, 16/20132-7, 18/18071-5, 19/01260-2)

DOS-SANTOS, R. C.; VILHENA-FRANCO, T.; REIS, L. C.; ELIAS, L. L. K.; ANTUNES-RODRIGUES, J.; MECAWI, A. S.. MPA and angiotensin type 1 receptors are necessary for hemorrhage-induced vasopressin secretio. Brazilian Journal of Medical and Biological Research, v. 55, n. 1, 2022. (19/01260-2)