Role of vasopressin-producing magnocellular neurons in the development of Preeclampsia in mice

• Grant number: 22/04021-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2022
• End date: October 31, 2023
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Andre de Souza Mecawi
• Grantee: Ana Beatriz Henrique dos Santos
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 19/27581-0 - Control of vasopressin secretion in pregnancy and its implications in pathophysiology of Preeclampsia, AP.JP

Abstract

Pregnancy is a period of extreme changes in the female's physiology, adapting the mother's body to ensure the healthy development of the embryo/fetus. Pre-Eclampsia (PE) is a characteristic disease of pregnancy and is defined by the development of Hypertension in the second half of pregnancy, associated with proteinuria and/or target organ dysfunction. It affects between 3 and 5% of pregnant women in the world and 8% in the poorest regions of Brazil, being one of the main causes of maternal-fetal death. It has long been known that there is a reduction in the osmotic threshold for the Activation of Vasopressin-Producing neurons (AVP) during pregnancy, but it was only in this decade that hypersecretion of this vasoactive hormone was implicated in the induction of PE. Despite this recent finding, the mechanisms responsible for the increase in AVP secretion and consequent PE induction are not known. This project aims to study the mechanisms responsible for altering the osmosensitivity of AVP-producing neurons during pregnancy, as well as to understand the consequences of its hypersecretion for the development of PE. Using the Cre-loxP technology to produce animals that express stimulatory DREADD (Designer Receptors Exclusively Activated by Designer Drugs) in AVP-producing neurons, we intend to understand if the increased activity of AVP-producing neurons is able to induce PE in mice. We hope, therefore, to contribute to the understanding of changes in AVP secretion during pregnancy and its implication in the induction of PE, enabling the development of new strategies for the prevention, diagnosis, and treatment of this disease.(AU)