Role of CRF neurotransmission in the bed nucleus of the stria terminalis in control of cardiovascular function in rats: involvement in cardiovascular changes evoked by chronic variable stress?

• Grant number: 14/23082-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): September 01, 2015
• Effective date (End): January 31, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Carlos Cesar Crestani
• Grantee: Leandro Augusto de Oliveira
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated scholarship(s): 17/26566-1 - Activation of CRF neurons in the bed nucleus of stria terminalis (BNST) in male rats exposed to social defeat/witness stress, BE.EP.DR

Abstract

The bed nucleus of the stria terminalis (BNST) is a limbic structure localized in the rostral prosencephalon, which forms a continuous rostrally to the amygdala and is a constituent of the "extended amygdala." Studies have demonstrated an involvement of the BNST in the control of cardiovascular function, neuroendocrine activity and behavioral responses. However, the neurochemical mechanisms in the BNST, especially neuropeptidergics, associated with control of cardiovascular function by this nucleus are still poorly understood. It has been identified the presence of corticotropin-releasing factor (CRF) signalling in the BNST. An involvement of this signalling mechanism in the BNST in cardiovascular adjustments during exposure to acute sessions of stress was reported. Nevertheless, it has been described that CRF neurotransmission modulates other cardiovascular responses than those observed during aversive threats, including the baroreflex responses. However, the brain sites related to the influence of the CRF in baroreflex activity are unknown. Furthermore, numerous studies have shown that exposure to chronic stress, including the chronic variable stress (CVS), alters the content and the expression of CRF and CRFergic receptors in the BNST. These evidences suggest that exposure to chronic stressors can affect the control of cardiovascular function by CRF neurotransmission in the BNST, so that this neurochemical mechanism in the BNST could be involved in cardiovascular complications associated with chronic stress. Important changes in cardiovascular function has been described following exposure to CVS protocols, including changes in baroreflex activity and hyperresponsiveness to environmental stressors. Thus, this model of chronic stress has been considered useful for the investigation of the neurobiological mechanisms involved in cardiovascular complications related to stress. Thus, the present study has the following objectives: 1) to investigate the involvement of CRF neurotransmission in the BNST in cardiac baroreflex responses; 2) to evaluate the involvement of CRF signalling in the BNST in baroreflex changes evoked by exposure to CVS; 3) to study the involvement of BNST CRF neurotransmission in the alterations in cardiovascular responses to acute restraint stress evoked by CVS; and 4) to investigate if possible changes in control of baroreflex activity and cardiovascular responses to acute restraint stress by CRF signalling in the BNST following exposure to CVS are associated with changes in the expression of CRF1 and CRF2 receptors in the BNST. (AU)