The role of leptin signaling in the dorsomedial hypothalamus in the upper airway patency during sleep

• Grant number: 19/13249-3
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: October 01, 2019
• End date: September 30, 2020
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Luiz Guilherme de Siqueira Branco
• Grantee: Mateus Ramos Amorim
• Supervisor: Vsevolod Polotsky
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Johns Hopkins University (JHU), United States
• Associated to the scholarship: 17/09878-0 - Effect of vagal stimulation during LPS immune challenge in normotensive and spontaneously hypertensive rats, BP.PD

Abstract

Obstructive sleep apnea (OSA) is a severe breathing disorder, characterized by periodic obstruction of the upper airways during sleep with eventual impact in the cardiovascular and respiratory systems as well as in the inflammatory status. OSA and its critical respiratory complications may be associated with obesity hypoventilation syndrome. Previous studies have documented the role of leptin, an adipose tissue produced hormone, as a potent respiratory stimulant. Experimental evidence has indicated that leptin may be a promising therapeutic candidate for the management of OSA. A long functional isoform of leptin receptor, LepRb, was detected in the dorsomedial hypothalamus (DMH), a critical nucleus that receives input from systems that monitor food availability. A large proportion DMH neurons express melanocortin receptor 4 (MCR4) and for this reason MCR4(+) in DMH is a highly relevant therapeutic target for OSA. In the present research project, we hypothesize that leptin regulates upper airway patency acting in the hypothalamus in an experimental model of OSA.

Scientific publications

(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)

PHO, HUY; AMORIM, MATEUS R.; QIU, QINGCHAO; SHIN, MI-KYUNG; KIM, LENISE J.; ANOKYE-DANSO, FREDERICK; JUN, JONATHAN J.; AHIMA, REXFORD S.; BRANCO, LUIZ G.; KUHN, DONALD M.; et al. The effect of brain serotonin deficiency on breathing during sleep is magnified by age. FASEB JOURNAL, v. 36, p. 1-pg., 2022-01-01. (19/13249-3)

AMORIM, MATEUS R.; WANG, XIN; PHO, HUY; BEVANS-FONTI, SHANNON; ANOKYE-DANSO, FREDERICK; ESCOBAR, JOAN; DERGACHEVA, OLGA; LUIZ, G.; BRANCO, S.; MENDELOWITZ, DAVID; et al. Activation of Leptin-Receptor-Expressing eurons in the Dorsomedial Hypothalamus Increases Hypercapcnic Ventilatory Response and Relieves Obstructive Sleep Apnea in Obese Mice. FASEB JOURNAL, v. 36, p. 2-pg., 2022-01-01. (19/13249-3)

AMORIM, MATEUS R.; DERGACHEVA, OLGA; FLEURY-CURADO, THOMAZ; PHO, HUY; FREIRE, CARLA; MENDELOWITZ, DAVID; BRANCO, LUIZ G. S.; POLOTSKY, VSEVOLOD Y.. The Effect of DREADD Activation of Leptin Receptor Positive Neurons in the Nucleus of the Solitary Tract on Sleep Disordered Breathing. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 13, JUL 2021. (19/13249-3)