Early life adversity and fear memories: trans-generational effects and targeting the HPA axis with potentially therapeutic compounds

• Grant number: 16/21369-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: April 01, 2017
• End date: March 31, 2018
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Mario Francisco Pereira Juruena
• Grantee: Eduardo Henrique de Lima Umeoka
• Supervisor: Marian Joels
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Utrecht University (UU), Netherlands
• Associated to the scholarship: 15/18773-1 - Translational evaluation of the Hypothalamus-Pituitary-Adrenal axis and the early life stress-induced allostatic load roles on neuroprogression and vulnerability to psychopathologies, BP.PD

Abstract

The perinatal period is a unique and highly sensitive time window for the developing brain. Exposure to adversities during the early postnatal period is also an important contributing factor for the risk to develop anxiety-related disorders. These disorders are characterized by impaired abilities to use contextual information (safety cues) in a situation of potential threat and an impaired ability to inhibit fear responses. Rodent studies are essential to understand the molecular, cellular and developmental mechanisms that underlie these adverse effects of negative early life experiences. In rodents, parental care is the most important environmental factor during the first 3 weeks of their lives. In line with this, the supervisors of this project have previously found that early-life stress (ELS) enhances freezing behavior in adult male mice, and hampers the ability to recognize safety cues. Interestingly, administering an antagonist of the glucocorticoid receptor at adolescent age, i.e. after ELS (which is a therapeutically relevant time window), was able to prevent the effects of ELS on fear learning at later age. In this project we will i) evaluate novel and potentially better intervention strategies (targeting different time windows and using more specific compounds) to target the effects of ELS on adult fear learning, and ii) investigate whether ELS effects on fear learning can be trans-generationally transmitted and targeted. (AU)

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)

BUURSTEDE, JACOBUS C.; UMEOKA, EDUARDO H. L.; DA SILVA, MARCIA SANTOS; KRUGERS, HARM J.; JOELS, MARIAN; MEIJER, ONNO C.. Application of a pharmacological transcriptome filter identifies a shortlist of mouse glucocorticoid receptor target genes associated with memory consolidation. Neuropharmacology, v. 216, p. 11-pg., 2022-07-12. (16/21369-0, 15/18773-1)

GODOY, LIVEA DORNELA; ROSSIGNOLI, MATHEUS TEIXEIRA; DELFINO-PEREIRA, POLIANNA; GARCIA-CAIRASCO, NORBERTO; DE LIMA UMEOKA, EDUARDO HENRIQUE. A Comprehensive Overview on Stress Neurobiology: Basic Concepts and Clinical Implications. FRONTIERS IN BEHAVIORAL NEUROSCIENCE, v. 12, JUL 3 2018. (17/11339-0, 14/17959-1, 16/21369-0, 15/18773-1)