The role of glucocorticoids and the vagus nerve afferences on the neuronal activity and plasticity of central circuits and their implications for stress-induced anxiety in rats

• Grant number: 18/19599-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): May 01, 2019
• Effective date (End): June 30, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Carolina Demarchi Munhoz
• Grantee: Leonardo Santana Novaes
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 19/24631-6 - Gut-to-brain vagal afferences stimulation and its effects on the stress-induced depressive-like symptoms in mice, BE.EP.PD

Abstract

Stress-related disorders, such as anxiety, depression, and post-traumatic stress disorder (PTSD), are recurrent causes of occupational absence in Brazil. Both acute restraint stress and transient elevation of glucocorticoid (GC) levels induce anxiety behaviors as well as dendritic branching within the basolateral complex of the amygdala (BLA) of rodents. The BLA is one fundamental structure regulating fear- and anxious-related behaviors. We have recently shown a crucial role for glucocorticoid receptor (GR) signaling in BLA in the anxiety-like behavior, both during and after acute restraint stress. In addition to the long-lasting anxiety-like behavior, we found that the same stressor promotes a deficit in the extinction of fear memories, another PTSD-like symptom. We also observed functional alterations in BLA and medial prefrontal cortex (mPFC), another critical brain area for fear-related behavior and memory. Under stressful conditions, besides the rapid release of GC by the adrenal glands, the vagus nerve responds to elevations in epinephrine and signals the Central Nervous System (CNS), leading to the release of norepinephrine (NE) in limbic structures, such as the amygdala and mPFC. This increase of NE in the CNS may be related to behavioral effects associated to stress, such as anxiety and fear memory. Accordingly, this project aims to investigate how acute restraint stress modify the amygdalar and prefrontal circuits underlying its behavioral effects. Our central hypothesis states that endocrine signals, notably GC and norepinephrine, mediate the stress-induced modifications of these neural circuits. To achieve our goals, we will make use of tools such as optogenetics, pharmacogenetics, and virally mediated modulation of receptors expression

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NOVAES, LEONARDO SANTANA; BUENO-DE-CAMARGO, LETICIA MORAIS; MUNHOZ, CAROLINA DEMARCHI. Environmental enrichment prevents the late effect of acute stress-induced fear extinction deficit: the role of hippocampal AMPA-GluA1 phosphorylation. TRANSLATIONAL PSYCHIATRY, v. 11, n. 1, JAN 5 2021. (18/19599-3, 18/15982-7, 12/24002-0, 19/00908-9, 16/03572-3)

CAMPOS-CARDOSO, RODRIGO; NOVAES, LEONARDO SANTANA; GODOY, LIVEA DORNELA; DOS SANTOS, NILTON BARRETO; PERFETTO, JULIANO GENARO; LAZARINI-LOPES, WILLIAN; GARCIA-CAIRASCO, NORBERTO; PADOVAN, CLAUDIA MARIA; MUNHOZ, CAROLINA DEMARCHI. The resilience of adolescent male rats to acute stress-induced delayed anxiety is age-related and glucocorticoid release-dependent. Neuropharmacology, v. 226, p. 9-pg., 2023-01-16. (14/17959-1, 16/03572-3, 14/26753-8, 17/11339-0, 12/24002-0, 18/19599-3, 19/00908-9)