The relationship between glucocorticoid receptor activation and the neuronal hyperexcitability in the basolateral amygdala in the restraint stress-induced long-lasting anxiety and their implications in the impaired contextual fear extinction

• Grant number: 16/03572-3
• Support Opportunities: Regular Research Grants
• Duration: August 01, 2016 - October 31, 2018
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Carolina Demarchi Munhoz
• Grantee: Carolina Demarchi Munhoz
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Ki Ann Goosens

Abstract

Anxiety-related disorders are common among psychiatric patients and are widely present in studies devoted to stress. In addition to the long-lasting anxiety behavior, impaired extinction of learned fear is associated with the development of post-traumatic stress disorder, one of the most debilitating anxiety-related disorder. The amygdala is a key brain structure essential for behavioral manifestations of emotional content and electrical stimulation of the basolateral amygdala (BLA) promotes anxiety-like behavior in rats. Because the complexity of such phenomena, it is urgent the need to understand the correlation among stress, BLA neuronal excitability, and anxiety; and how the activation of glucocorticoid receptors intracellular signaling coordinates these events and modulates the extinction of learned fear. These mechanisms are particularly relevant to the understanding of pathologies related to fear and anxiety. Thus, the objective of this project is, using viral vectors to modulate GR activity (HSV-GR and dnGR-HSV) and the neuronal excitability in BLA (SK2-HSV), to verify whether both restraint stress-induced long-lasting anxiety and the impairment in contextual fear extinction are dependent on the increase of neuronal excitability in the BLA and/or nuclear activity of GR. We feel that this project brings major advances in the understanding of stress-associated disorders, and can offer structural and molecular substrates as therapeutic targets that will serve as basis for the cure of such malady, such as the posttraumatic stress disorder. (AU)

Scientific publications

(15)

(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 S.; DOS SANTOS, NILTON BARRETO; BATALHOTE, RAFAELA F. P.; MALTA, MARILIA BRINATI; CAMARINI, ROSANA; SCAVONE, CRISTOFORO; MUNHOZ, CAROLINA DEMARCHI. Environmental enrichment protects against stress-induced anxiety: Role of glucocorticoid receptor, ERK, and CREB signaling in the basolateral amygdala. Neuropharmacology, v. 113, n. A, p. 457-466, FEB 2017. (12/24727-4, 10/13843-8, 16/03572-3)

REIS, FERNANDO MIDEA CUCCOVIA, V; NOVAES, LEONARDO SANTANA; SANTOS, NILTON BARRETO DOS; FERREIRA-ROSA, KELVIA CAROLINA; PERFETTO, JULIANO GENARO; BALDO, MARCUS VINICIUS C.; MUNHOZ, CAROLINA DEMARCHI; CANTERAS, NEWTON SABINO. Predator fear memory depends on glucocorticoid receptors and protein synthesis in the basolateral amygdala and ventral hippocampus. PSYCHONEUROENDOCRINOLOGY, v. 141, p. 11-pg., 2022-07-01. (19/00908-9, 17/08668-1, 16/03572-3, 14/05432-9, 15/23092-3)

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, JUL 2021. (12/24002-0, 16/02224-1, 12/24727-4, 10/52068-0, 10/13843-8, 16/03572-3)

ALBERNAZ-MARIANO, KAIRO ALAN; MUNHOZ, CAROLINA DEMARCHI. The infralimbic mineralocorticoid blockage prevents the stress-induced impairment of aversive memory extinction in rats. TRANSLATIONAL PSYCHIATRY, v. 12, n. 1, p. 11-pg., 2022-08-24. (16/03572-3, 19/00908-9)

RUSSELL, ASHLEY L.; TASKER, JEFFREY G.; LUCION, ALDO B.; FIEDLER, JENNY; MUNHOZ, CAROLINA D.; WU, TAO-YIAO JOHN; DEAK, TERRENCE. Factors promoting vulnerability to dysregulated stress reactivity and stress-related disease. Journal of Neuroendocrinology, v. 30, n. 10, p. 13-pg., 2018-10-01. (12/24727-4, 16/03572-3)

NOVAES, LEONARDO S.; DOS SANTOS, NILTON BARRETO; BATALHOTE, RAFAELA F. P.; MALTA, MARILIA BRINATI; CAMARINI, ROSANA; SCAVONE, CRISTOFORO; MUNHOZ, CAROLINA DEMARCHI. Environmental enrichment protects against stress-induced anxiety: Role of glucocorticoid receptor, ERK, and CREB signaling in the basolateral amygdala. Neuropharmacology, v. 113, p. 10-pg., 2017-02-01. (16/03572-3, 10/13843-8, 12/24727-4)

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., 2022-11-01. (12/24002-0, 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, JAN 5 2021. (18/19599-3, 18/15982-7, 12/24002-0, 19/00908-9, 16/03572-3)

RUSSELL, ASHLEY L.; TASKER, JEFFREY G.; LUCION, ALDO B.; FIEDLER, JENNY; MUNHOZ, CAROLINA D.; WU, TAO-YIAO JOHN; DEAK, TERRENCE. Factors promoting vulnerability to dysregulated stress reactivity and stress-related disease. Journal of Neuroendocrinology, v. 30, n. 10, SI, OCT 2018. (12/24727-4, 16/03572-3)

FALQUETTO, BARBARA; THIEME, KARINA; MALTA, MARILIA B.; ROCHA, KARINA C. E.; TUPPY, MARINA; POTJE, SIMONE R.; ANTONIALI, CRISTINA; RODRIGUES, ALICE C.; MUNHOZ, CAROLINA D.; MOREIRA, THIAGO S.; et al. Oxidative stress in the medullary respiratory neurons contributes to respiratory dysfunction in the 6-OHDA model of Parkinson's disease. JOURNAL OF PHYSIOLOGY-LONDON, v. 598, n. 22, SEP 2020. (19/01236-4, 18/05426-0, 19/00065-1, 18/07087-8, 16/03572-3, 15/23376-1, 15/11268-0)

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, DEC 2018. (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, NOV 21 2018. (12/24002-0, 12/24727-4, 10/13843-8, 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, APR 30 2019. (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., 2023-01-16. (14/17959-1, 16/03572-3, 14/26753-8, 17/11339-0, 12/24002-0, 18/19599-3, 19/00908-9)

NASCIMENTO, ANDRE L. F.; MEDEIROS, PAMELA O. S.; PEDRAO, LUIZ F. A. T.; QUEIROZ, VITORIA C.; OLIVEIRA, LUIZ M.; NOVAES, LEONARDO S.; CAETANO, ARIADINY L.; MUNHOZ, CAROLINA D.; TAKAKURA, ANA C.; FALQUETTO, BARBARA. Oxidative Stress Inhibition Via Apocynin Prevents Medullary Respiratory Neurodegeneration and Respiratory Pattern Dysfunction in a 6-Hydroxydopamine Animal Model of Parkinson's Disease. Neuroscience, v. 502, p. 16-pg., 2022-10-15. (15/23376-1, 19/00065-1, 16/03572-3, 19/01236-4)