Banca de DEFESA: BRUNO PAES LEME FERREIRA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : BRUNO PAES LEME FERREIRA
DATA : 30/07/2019
HORA: 13:00
LOCAL: Sala 1 do PQ
TÍTULO:

Role of angiotensin II AT1 receptors at the subfornical organ in energetic balance control

PALAVRAS-CHAVES:

Subfornical organ, angiotensin II, Type 1 angiotensin receptor; Food deprivation; Electrophysiology;

PÁGINAS: 90
GRANDE ÁREA: Ciências Biológicas
ÁREA: Fisiologia
SUBÁREA: Fisiologia Geral
RESUMO:

Although classically involved in cardiovascular control and hydromineral balance, the renin-angiotensin system has recently been implicated in energy balance control. Angiotensin II (ANG II), the main hormone of this system, stimulating the type 1 angiotensinergic receptor (AT₁) may change body weight and food ingestion in some physiological challenges. One of the main sites of action of ANG II is the subfornical organ (SFO), a circumventricular organ related to the control of several autonomic functions and motivated behaviors. Recent studies have demonstrated that peripherical blockade of AT₁ receptors may lower body weight gain and food ingestion in high fat diet rats, and transcriptomic evaluation of rats SFO after 48h fasting suggests increase if AT₁ receptor. This thesis aims in three main goals: a) validate the transcriptome with RT-qPCR; b) test chronic and acute manipulations of central RAS during food deprivation; c) investigate if there’s any association with electrophysiological response of SFO neurons to ANG II and glucose sensitivity. Male Wistar and Sprague-Dawley rats were used and all procedures have been approved by ethics committees in experimental animal use, respectively: FMRP-USP 229/18 and Queen’s University 2017-1735. RT-qPCR of SFO in rats food-deprived for 48h have shown a 5-fold increase in expression of mRNA for AT_1a receptors (One-way ANOVA, P<0.0001). Also, intracerebroventricular (i.c.v.) injections of losartan, an AT₁ blocker, shows significant decrease in food intake after 12 hours in basal conditions (Two-way ANOVA, P<0.0001) but not after 48h of food restriction. Administration of lentiviral vector for knock-down of AT₁ receptor at the SFO shows no difference in food ingestion neither in spontaneous basal conditions, neither after 48h food deprivation, although after 24h fasting the food ingestion lowered cumulative food intake after 4 hours representation (Two-way ANOVA, P=0.024). Electrophysiological studies of SFO neurons have shown that approximately 31% (n=4/13) of tested cells didn’t responded to ANG II at 5mM glucose medium but depolarized to ANG II at 10mM, suggesting that metabolic state of the organism may change the way the central nervous system respond to ANG II. We might conclude that, although ANG II may control weight gain and food ingestion in highly caloric diets, it might not influence those parameters the same way in food deprivation. Nevertheless, the way energetic balance influence SFO response to ANG II is an interesting clue to link metabolic alterations to cardiovascular problems.

MEMBROS DA BANCA:
Presidente - 103.378.127-48 - ANDRE DE SOUZA MECAWI - UNIFESP
Interno - 3000663 - DAVID DO CARMO MALVAR
Interno - 2225596 - EMERSON LOPES OLIVARES
Interno - 387295 - LUIS CARLOS REIS
Interno - 2479104 - NORMA APARECIDA DOS SANTOS ALMEIDA
Externo à Instituição - FABRICIA VIANA FONSECA - IFRJ
Externo à Instituição - RODRIGO CESAR RORATO - URP
Externo à Instituição - EDUARDO REBELATO L. DE OLIVEIRA - UNIFESP
Externo à Instituição - CLAUDIO DA SILVA ALMEIDA - UES