Study of mood disorders during perimenopause: possible influence of interaction between glucocorticoids and serotonergic and noradrenergic systems

• Grant number: 11/51789-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): August 01, 2012
• Effective date (End): November 30, 2014
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Janete Aparecida Anselmo Franci
• Grantee: Karin Viana Weissheimer
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Women in perimenopause are more vulnerable to depression, mainly due to fluctuations in plasma levels of sex steroids, which can affect the concentrations of neurotransmitters modulating mood in several brain regions. There is an interaction between gonadal hormones decrease and elevation of stress hormones predisposing to affective disorders in females. Evidence indicates that the deficiency in the inhibitory regulation of glucocorticoids on the hypothalamic-pituitary-adrenal axis is related to the pathogenesis of depression and anxiety. Corroborating these data, noradrenergic and serotonergic neurons, releasing neurotransmitters involved in mood disorders, also receive modulatory influence of glucocorticoids. This project aims to investigate the role of glucocorticoids in controlling depression in an experimental model of perimenopause induced by injections of 4-vinylcyclohexene diepoxide (VCD) in rats. For that, we will evaluate the immunohistochemical expression of glucocorticoid receptors in the hippocampus, medial prefrontal cortex, locus coeruleus and dorsal raphe (NDR). We will also investigate possible changes in noradrenergic and serotonergic activity by analyzing the immunohistochemical expression of tyrosine hydroxylase in the locus coeruleus and tryptophan hydroxylase in the NDR, as well as noradrenergic and serotonergic fibers in the hippocampus and medial prefrontal cortex. It is expected that this study shows neurobiological alterations occurring in perimenopause in order to clarify the mechanisms involving glucocorticoids and their interactions with the serotonergic and noradrenergic systems in the etiology of mood disorders in this period of life. (AU)