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Study of the molecular effect of OUA treatment on the HPA axis of rats exposed to chronic unpredictable stress

Grant number: 14/10171-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): October 01, 2014
Effective date (End): September 27, 2018
Field of knowledge:Biological Sciences - Pharmacology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Cristoforo Scavone
Grantee:Jacqueline Alves Leite
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):16/21343-1 - Effects of LPS analysed in mouse models harboring disease-mutations in the 2- or ±3Na+/K+-ATPase, respectively, BE.EP.DR

Abstract

Ouabain (OUA) is a cardiotonic glycoside protein known to inhibit Na + / K +-ATPase. It is also considered an endogenous hormone and it is produced in hypothalamus and in adrenal gland, but little is known about its physiological role. However, it has been demonstrated the involvement of the OAU in the acute stress response, where physical exercise is capable of increasing its levels in rats, dogs and humans minutes after the onset of physical activity. The central effectors of the stress response are the corticotrophinreleasing hormone (CRH), which in turn stimulates the secretion of adrenocorticotropic hormone (ACTH) which acting on the adrenal cortex release glucocorticoid (GC) hormones. GCs in turn act back on the hypothalamus and pituitary (to suppress CRH and ACTH production) in a negative feedback cycle. Acute changes in HPA axis prepares the body to respond to different environmental stimuli. However, unpredictable chronic activation has been shown to affect health, making the individual more susceptible to infections, tumors, hypertension, heart attack, stroke, autoimmunity and psychopathology. Evidence has shown that OUA is release in a different time-course when compared to GC during a stress response. In addition, OUA also interferes with the CRH transport into the circulation indicating that this hormone plays an important role in the stress response. However, there is no data about the OUA effects during a chronic unpredictable stress. The present work aims to investigate the molecular effect of OUA treatment on the HPA axis of rats exposed to chronic unpredictable stress. (AU)