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Effects of environmental enrichment in long-lasting anxiety symptoms triggered by acute stress: implications in the emotional memory acquisition

Grant number: 12/24002-0
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2013
Effective date (End): January 31, 2018
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
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):15/15169-6 - Restraint stress-induced long-lasting anxiety and contextual fear extinction impairment in rats: role of glucocorticoid and ghrelin receptors on BLA neuronal excitability, BE.EP.DR


The consequences of stressful events on human health, especially related to psychiatric disorders, has gained notoriety in recent years due to the increasing number of comorbidities associated to stress registered in large cities. Emotional disorders related to anxiety symptoms are common among the psychiatric patients and have increasing in importance in scientific papers devoted to stress, which use different approaches to understanding the neurobiological mechanisms underlying the process of emotional memory as a strategy to unravel the persistence of anxiety symptoms caused by a stressful event. The use of the classical paradigm of fear conditioning in several studies have helped to understand the modulatory mechanisms of the emotional arousal on memory processes, reporting the basolateral complex of the amygdala (BLA) as a key brain structure in this process. Among the main findings, changes in local signaling mediated by stress hormones (corticosterone and norepinephrine), as well as CREB signaling, including epigenetic mechanisms, figure as central mechanisms occurring in the BLA. Approaches interested in assess environmental influences on susceptibility and resistance of the organism to stress also grow in number and importance. In a previous study (in preparation) we have found that rats housed in enriched environments are resistant to anxiogenic effects of acute stress, and this process is related to changes in corticosterone signaling process (by glucocorticoid receptor - GR) and CREB in the BLA. As a general objective of this project we are proposing to study the modulatory effects of anxiety, triggered by an acute stressor stimulus, on the mechanism of acquisition of emotional memory. Based on our previous findings and on published data, we are interested in verify the effects of environmental enrichment, and its consequences over GR and CREB signaling in BLA, on the body's response to stress and its implications in the acquisition process of aversive memory in a state of high emotional arousal, as manifested by symptoms of anxiety. We have special interest in epigenetic mechanisms of gene expression control modulated by CREB and GR. (AU)

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Scientific publications (7)
(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)
MALTA, MARILIA B.; MARTINS, JOELCIMAR; NOVAES, LEONARDO S.; DOS SANTOS, NILTON B.; SITA, LUCIANE; CAMARINI, ROSANA; SCAVONE, CRISTOFORO; BITTENCOURT, JACKSON; MUNHOZ, CAROLINA D.. Norepinephrine and Glucocorticoids Modulate Chronic Unpredictable Stress-Induced Increase in the Type 2 CRF and Glucocorticoid Receptors in Brain Structures Related to the HPA Axis Activation. Molecular Neurobiology, v. 58, n. 10, . (12/24002-0, 16/02224-1, 12/24727-4, 10/52068-0, 10/13843-8, 16/03572-3)
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, . (18/19599-3, 18/15982-7, 12/24002-0, 19/00908-9, 16/03572-3)
SZRIBER, SHIRLEY JAQUELINE; NOVAES, LEONARDO SANTANA; DOS SANTOS, NILTON BARRETO; MUNHOZ, CAROLINA DEMARCHI; ALMEIDA LEITE-DELLOVA, DEISE CARLA. Imbalance in the ratio between mineralocorticoid and glucocorticoid receptors and neurodegeneration in the dentate gyrus of aged dogs. VETERINARY WORLD, v. 15, n. 11, p. 8-pg., . (12/24002-0, 16/03572-3)
DOS SANTOS, NILTON; NOVAES, LEONARDO S.; DRAGUNAS, GUILHERME; RODRIGUES, JENNIFER R.; BRANDAO, WESLEY; CAMARINI, ROSANA; SCHATZMANN PERON, JEAN PIERRE; DEMARCHI MUNHOZ, CAROLINA. High dose of dexamethasone protects against EAE-induced motor deficits but impairs learning/memory in C57BL/6 mice. SCIENTIFIC REPORTS, v. 9, . (12/24002-0, 16/03572-3, 12/24727-4, 11/18703-2)
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., . (14/17959-1, 16/03572-3, 14/26753-8, 17/11339-0, 12/24002-0, 18/19599-3, 19/00908-9)
NOVAES, LEONARDO SANTANA; DOS SANTOS, NILTON BARRETO; PERFETTO, JULIANO GENARO; GOOSENS, KI ANN; MUNHOZ, CAROLINA DEMARCHI. Environmental enrichment prevents acute restraint stress-induced anxiety-related behavior but not changes in basolateral amygdala spine density. PSYCHONEUROENDOCRINOLOGY, v. 98, p. 6-10, . (16/03572-3, 12/24727-4, 12/24002-0)
NOVAES, LEONARDO SANTANA; DOS SANTOS, NILTON BARRETO; DRAGUNAS, GUILHERME; PERFETTO, JULIANO GENARO; CARLOS LEZA, JUAN; SCAVONE, CRISTOFORO; MUNHOZ, CAROLINA DEMARCHI. Repeated Restraint Stress Decreases Na,K-ATPase Activity via Oxidative and Nitrosative Damage in the Frontal Cortex of Rats. Neuroscience, v. 393, p. 273-283, . (12/24002-0, 12/24727-4, 10/13843-8, 16/03572-3)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
NOVAES, Leonardo Santana. Environmental enrichment protection on acute stress-induced late anxiety-like behavior and fear extinction impairment in rats: role of glucocorticoid receptor signaling in the basolateral nucleus of amygdala.. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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