Symposium
Neurobiological Signatures of Stress: Sex-Specific Trajectories from Gestation to Adulthood In Rodents and Humans
Chair
Mariela Chertoff
Department of biological chemistry, Faculty of Science, University of Buenos Aires, Argentina
Co-Chair
Lydia Kogler
Department for Psychiatry and Psychotherapy, Medical Faculty, University of Tübingen, Germany.
This symposium addressed the complex interplay between early environmental factors, sex differences, molecular mechanisms and neurobiological outcomes across developmental and hormonal stages. We will discuss the transgenerational, neurobehavioral effects of stress and maternal behavior on the offspring in a sex-dependent manner. In addition, we will address behavioral changes and molecular links between adverse factors early in life and resilience to affective disorders in adults. Complementary evidence will be presented showing that specific oxytocin receptor gene polymorphisms increase susceptibility to stress and depressive symptoms during pregnancy, suggesting a gene-environment interaction for perinatal mental health risk. Last but not least we will discuss functional neuroimaging data showing that stressor type modulates prefrontal cortex–amygdala connectivity in a sex-specific way. Taken together, these studies highlight the importance of integrating environmental, hormonal, genetic, epigenetic, and neural dimensions to better understand the mechanisms behind neurodevelopmental and sex-dependent origins of affective disorders.
Maria Angelica Rivarola
Faculty of phisics, natural and exact sciences, Universidad Nacional de Córdoba, Argentina.
From womb to adolescence: Gestational environmental enrichment shapes maternal care and sex-specific adolescent outcomes after early-life stress
Gestational environmental enrichment (EE) has emerged as a promising non pharmacological strategy to buffer the impact of perinatal stress across generations. Using two established postpartum depression/anxiety models: maternal separation (MS) and intruder male (IM), we evaluated how gestational EE modulates maternal behavior and long term offspring outcomes. EE improved maternal care and reduced anxiety like behaviors in dams exposed to MS or IM, effects associated with increased ΔFosB activity in the medial preoptic area and nucleus accumbens shell, and reduced activation in dorsal hippocampal subregions. In adolescent offspring from the same litters, anxiety like and social behaviors were assessed through elevated plus maze, open field, and social preference tests, integrating outcomes via a composite Z anxiety score. Gestational EE attenuated early life stress effects in a sex dependent manner.
Mariela Chertoff
Laboratorio de Neuroepigenetica y adversidades tempranas, Department of biological chemistry, Faculty of Science, University of Buenos Aires, Argentina
Prenatal stress and resilience: Behavioral changes and molecular correlates on a mice model
Stress is a primary risk factor for neuropsychiatric disorders like depression and anxiety. While some individuals are susceptible to these conditions, others exhibit resilience, an adaptive process for coping with adversity. Understanding the biological basis of resilience is vital for developing therapies that mimic natural adaptation.In this study, adolescent offspring of mothers subjected to gestational restraint were classified as resilient (RES) or susceptible (SUS) via the sucrose splash test. After assessing behavioral phenotypes across control, RES, and SUS groups, we performed molecular evaluations of the prefrontal cortex (PFC) in both sexes. Our findings reveal sex-specific differences in stress-coping strategies and neurobiological mechanisms, providing deeper insight into the molecular correlates of resilience in male and female mice.
Daniel Olazabal
Unidad Académica de Fisiología, Unidad Académica de Genética, Facultad de Medicina, Udelar, Asociación de Psicopatología y Psiquiatría de la Infancia y la Adolescencia, Hospital de Clínicas Manuel Quintela, Montevideo, Uruguay
Oxytocin System Polymorphism Variants increase the risk of depression and stress in pregnant women
Prenatal depression and stress are associated with early adversity, pregnancy complications, and long-term effects on child neurodevelopment. The oxytocin (OXT) system is affected by early adverse experiences and has been associated with emotional dysregulation. In the current study, we investigated risk factors for prenatal depression and stress, mainly the effects of early childhood and adolescence trauma, in combination with the presence of certain variants of polymorphism of oxytocin (OXT) and OXT receptor (OXTR) gene. We hypothesized that early trauma had higher negative effects in carriers of genetic variants of the OXTR system, increasing their risk for depression and stress. Early in pregnancy (8–14 weeks), 141 pregnant women from a Uruguayan population were asked to provide DNA samples and complete questionnaires that assessed their experience of child abuse, antecedents of psychiatric conditions, depression symptoms, perceived stress and other variables that included demographic information. Carriers of the variant allele CC of rs2740210 (OXT) or AA of rs237887 (OXTR) had significantly higher risk of experiencing depressive symptoms in abuse women, while the variant AA of the rs53576 (OXTR) had significantly higher scores of perceived stress in abused or non-abused women. Lower income and previous antecedents of depression were also correlated with higher risk of depression and perceived stress. We conclude that early detection and closer follow-up of women with child abuse and OXT/OXTR genetic variants, among other risk factors, could reduce the long-term impact of prenatal depression and stress.
Lydia Kogler
Department for Psychiatry and Psychotherapy, Medical Faculty, University of Tübingen, Germany
Social Stress and the Human Brain: A Sex-Specific Perspective on Limbic Structure and Functional Connectivity
Neural stress regulation is strongly depending on limbic regions such as the amygdala andhippocampus. How the interplay of sex and social stress is associated with structure and connectivity of these regions remains unclear. Analyzing structural brain data and self-reported chronic social stress in 83 healthy, young humans (40 females) show a reduction in hippocampus gray matter volume (GMV) in males, but not females, with higher levels of socially tense interactions.Investigating the resting-state functional connectivity of the amygdala and frontal regions in 77 healthy, young humans (40 females) also reveal sex differences in association with social stress. Females show a higher coupling of the amygdala with the ventral anterior cingulate cortex and the medial prefrontal cortex for social than for achievement stress, and compared to males. Our findings point to a complex interaction between social stress and sex and their impact on neural organization.