Involvement of endocannabinoids and glucocorticoids on the modulation of astrocytic function and in vitro humoral release in response to osmotic stimulation

• Grant number: 14/07240-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2014
• End date: May 31, 2017
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: José Antunes Rodrigues
• Grantee: Fernanda Maria Veanholi Vechiato
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/09799-1 - Energy balance and body fluid homeostasis control: from cells to the physiological systems, AP.TEM

Abstract

The hidromineral homeostasis constitutes effective regulation of both the volume and the composition of the extracellular fluid (ECF) and intracellular. Detected changes, there is activation of the hypothalamic nuclei such as the paraventricular (PVN) and supraoptic (NSO), which synthesize and release oxytocin (OT) and vasopressin (AVP), important to maintenance of this balance. Thus, several groups, including ours, have been devoted to identify l the phenotypes involved on its regulation. Within these arise glucocorticoids as neuromodulators, which inhibit the secretion of OT and AVP after osmotic stimulation and / or changes in ECF volume. Also participates in the synthesis of endocannabinoid (eCBs), which in its binding to type 1 receptor (CB1R), inhibiting glutamate exocytosis of magnocellular neurons, and thus, the secretion of AVP and OT. During chronic dehydration, astrocytes undergo conformational changes and release gliotransmissores, among them cytokines (TNF - ±, IL - 1², IL - 6). These in turn, stimulate the secretion of AVP and OT. Our laboratory has shown that chronic salt load increases plasma levels of AVP, OT and the cytokines mentioned, and this effect is decreased after treatment with glucocorticoids. In these animals there was also increased expression of CB1R in NPV and NSO. Knowing that ECBs are anti-inflammatory, and also synthesized by astrocytes, this study aims to understand how glucocorticoids and ECBs interact with astrocytes and thus participate in the secretion of neurohormones and gliotransmissores. We also intend to evaluate the osmotic stimulation alters cytokine release and glutamate uptake by astrocytes in culture medium and the basal hypothalamus and neurohypophysis in vitro. (AU)