Neurobiologic mechanisms involved in the long-term emotional effects of maternal deprivation

• Grant number: 15/26364-4
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2016
• End date: February 28, 2019
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Deborah Suchecki
• Grantee: Deborah Suchecki
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Carlos Eduardo Neves Girardi
• Associated research grant(s): 17/50378-0 - Infantile stress and neuropeptide Y (NPY) role in vulnerability of adolescent rats to development of PTSD, AP.R SPRINT

Abstract

Worldwide and national epidemiological studies indicate a high prevalence of emotional disorders in the general population, from adolescence to adulthood. Exposure to daily stressors may represent an important risk factor for development of affective disorders in vulnerable individuals. This vulnerability stems from the interplay between genetic background and exposure to adversity during critical periods of maturation of the central nervous system, such as the stress hyporesponsive period, a developmental phase that lasts from postnatal day 4 to 14. Pre-clinical and clinical studies demonstrate that peri-natal stress can alter the activity of the hypothalamic-pituitary-adrenal axis, resulting in mal-adaptive hormonal responses (either hypo- or hyperresponsiveness). The paradigm used by our research group is the 24 h maternal deprivation (MD), specifically on postnatal days 3, 9 and 11. Previous studies have shown that male and female adult rats submitted to MD at 3 (DEP3) or 11 days of age (DEP11) are more anxious, due to reduction of taurine (in males) and GABA (in females) hippocampal levels. These results, however, appear to depend on the housing conditions that precedes the behavioral testing, since DEP3 and DEP11 male rats housed individually displayed less anxiety and reduced serotonin and noradrenaline levels in the amygdala. DEP3 male and female adolescent rats displayed a clear anxious and depressive phenotype, whereas DEP11 rats exhibited a depressive phenotype. These behavioral results are in consonance with reduced neuropeptide Y immunoreactivity in the basolateral amygdala and dorsal hippocampus. Recently we published a paper showing that adolescent male rats submitted to MD at 9 days of age and challenged with a saline injection 2 h before the end of the deprivation period showed behavioral changes related to MD or to the stress challenge, but not to the association of both neonatal stressors, indicating that different neuromodulator systems were recruited in response to each stressor. Thus, our previous results demonstrate that maternal deprivation induces vulnerability for the development of affective disorders and that neurotransmitter and neuropeptide systems participate of these behavioral alterations. The purpose of this umbrella project is to investigate the neurobiological underpinnings of MD-induced behavioral changes, using neurochemical, pharmacological and molecular approaches, which, at the end of this project, will allow us to propose novel therapeutic strategies to treat affective disorders and/or to understand how traditional therapies alter brain systems in order to produce the expected beneficial effects. (AU)

Scientific publications

(8)

(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)

SUCHECKI, D.. Maternal regulation of the infant's hypothalamic-pituitary-adrenal axis stress response: Seymour ``Gig' Levine's legacy to neuroendocrinology. Journal of Neuroendocrinology, v. 30, n. 7, SI, JUL 2018. (15/26364-4)

MIRAGAIA, ALEXANDRA S.; DE OLIVEIRA WERTHEIMER, GUILHERME S.; CONSOLI, AMANDA C.; CABBIA, RAFAEL; LONGO, BEATRIZ M.; GIRARDI, CARLOS E. N.; SUCHECKI, DEBORAH. Maternal Deprivation Increases Anxiety- and Depressive-Like Behaviors in an Age-Dependent Fashion and Reduces Neuropeptide Y Expression in the Amygdala and Hippocampus of Male and Female Young Adult Rats. FRONTIERS IN BEHAVIORAL NEUROSCIENCE, v. 12, AUG 7 2018. (15/26364-4)

HENN, LORENA; ZANTA, NATALIA C.; GIRARDI, CARLOS EDUARDO N.; SUCHECKI, DEBORAH. Chronic Escitalopram Treatment Does Not Alter the Effects of Neonatal Stress on Hippocampal BDNF Levels, 5-HT(1A)Expression and Emotional Behaviour of Male and Female Adolescent Rats. Molecular Neurobiology, v. 58, n. 3, p. 926-943, MAR 2021. (15/24745-0, 15/26364-4)

SUCHECKI, D.. Maternal regulation of the infant's hypothalamic-pituitary-adrenal axis stress response: Seymour "Gig' Levine's legacy to neuroendocrinology. Journal of Neuroendocrinology, v. 30, n. 7, p. 17-pg., 2018-07-01. (15/26364-4)

ZANTA, NATALIA CRISTINA; ASSAD, NADYME; SUCHECKI, DEBORAH. Neurobiological mechanisms involved in maternal deprivation-induced behaviours relevant to psychiatric disorders. FRONTIERS IN MOLECULAR NEUROSCIENCE, v. 16, p. 8-pg., 2023-04-13. (15/26364-4, 06/06415-4, 19/21980-0)

CABBIA, RAFAEL; CONSOLI, AMANDA; SUCHECKI, DEBORAH. Association of 24h maternal deprivation with a saline injection in the neonatal period alters adult stress response and brain monoamines in a sex-dependent fashion. STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS, v. 21, n. 4, p. 333-346, 2018. (14/22395-0, 15/26364-4)

CESCHIM, VIVIANE C.; SUMARAN, PAULA; BORGES, ANDREA A.; GIRARDI, CARLOS EDUARDO N.; SUCHECKI, DEBORAH. Maternal deprivation during early infancy in rats increases oxytocin immunoreactivity in females and corticosterone reactivity to a social test in both sexes without changing emotional behaviour. Hormones and Behavior, v. 129, MAR 2021. (14/13454-2, 08/07448-9, 15/26364-4)

MACHADO, RICARDO BORGES; SUCHECKI, DEBORAH. Neuroendocrine and Peptidergic Regulation of Stress-Induced REM Sleep Rebound. FRONTIERS IN ENDOCRINOLOGY, v. 7, DEC 23 2016. (98/14303-3, 15/26364-4)