Neurobehavioral abnormalities following prenatal psychosocial stress are differentially modulated by maternal environment

Zoubovsky, Sandra; Williams, Michael T.; Hoseus, Sarah; Tumukuntala, Shivani; Riesenberg, Amy N.; Schulkin, Jay; Vorhees, Charles V.; Campbell, Kenneth; Lim, Hee‐Woong; Muglia, Louis J.

doi:10.1038/s41398-022-01785-5

Cited by 11 publications

(3 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Animals exposed to PNS showed significant behavioral differences that resemble specific psychopathologic domains, with reduced sociability, increased anxiety and anhedonic behavior. These data are in line with previous reports showing the negative effects of different paradigms of prenatal stress on behavior outcomes [28][29][30][31]. It is interesting that the cluster analysis used to identify vulnerable and resilient animals revealed that the tests related to anxiety and sociability had higher predictive importance than the depressive one.…”

Section: Discussionsupporting

confidence: 91%

Vulnerability and resilience to prenatal stress exposure: behavioral and molecular characterization in adolescent rats

Creutzberg,

Begni,

Orso

et al. 2023

Transl Psychiatry

View full text Add to dashboard Cite

Exposure to stress can lead to long lasting behavioral and neurobiological consequences, which may enhance the susceptibility for the onset of mental disorders. However, there are significant individual differences in the outcome of stress exposure since only a percentage of exposed individuals may show pathological consequences, whereas others appear to be resilient. In this study, we aimed to characterize the effects of prenatal stress (PNS) exposure in rats at adolescence and to identify subgroup of animals with a differential response to the gestational manipulation. PNS adolescent offspring (regardless of sex) showed impaired emotionality in different pathological domains, such as anhedonia, anxiety, and sociability. However, using cluster analysis of the behavioral data we could identify 70% of PNS-exposed animals as vulnerable (PNS-vul), whereas the remaining 30% were considered resilient (PNS-res). At the molecular level, we found that PNS-res males show a reduced basal activation of the ventral hippocampus whereas other regions, such as amygdala and dorsal hippocampus, show significant PNS-induced changes regardless from vulnerability or resilience. Taken together, our results provide evidence of the variability in the behavioral and neurobiological effects of PNS-exposed offspring at adolescence. While these data may advance our understanding of the association between exposure to stress during gestation and the risk for psychopathology, the investigation of the mechanisms associated to stress vulnerability or resilience may be instrumental to develop novel strategies for therapeutic intervention.

show abstract

Section: Discussionsupporting

confidence: 91%

Vulnerability and resilience to prenatal stress exposure: behavioral and molecular characterization in adolescent rats

Creutzberg,

Begni,

Orso

et al. 2023

Transl Psychiatry

View full text Add to dashboard Cite

show abstract

“…The ELS used for the present studies was PD because poor paternal care or absence increases the risk of numerous negative outcomes associated with social and emotional health [ 62 ], including increased risk of psychopathology [ 63 ], substance abuse, delinquency, and susceptibility to other diseases [ 64 , 65 ]. It was robustly demonstrated that perinatal social stress, broadly, can adversely impact offspring’s behavioral development and conduct [ 66 , 67 , 68 , 69 ]. Children raised in stressful environments characterized by conflict, separation, and low attachment are more predisposed to behavioral problems [ 62 ].…”

Section: Introductionmentioning

confidence: 99%

Individual and Combined Effects of Paternal Deprivation and Developmental Exposure to Firemaster 550 on Socio-Emotional Behavior in Prairie Voles

Gillera

Marinello

Nelson

et al. 2022

Toxics

View full text Add to dashboard Cite

The prevalence of neurodevelopmental disorders (NDDs) is rapidly rising, suggesting a confluence of environmental factors that are likely contributing, including developmental exposure to environmental contaminants. Unfortunately, chemical exposures and social stressors frequently occur simultaneously in many communities, yet very few studies have sought to establish the combined effects on neurodevelopment or behavior. Social deficits are common to many NDDs, and we and others have shown that exposure to the chemical flame retardant mixture, Firemaster 550 (FM 550), or paternal deprivation impairs social behavior and neural function. Here, we used a spontaneously prosocial animal model, the prairie vole (Microtus ochrogaster), to explore the effects of perinatal chemical (FM 550) exposure alone or in combination with an early life stressor (paternal absence) on prosocial behavior. Dams were exposed to vehicle (sesame oil) or 1000 µg FM 550 orally via food treats from conception through weaning and the paternal absence groups were generated by removing the sires the day after birth. Adult offspring of both sexes were then subjected to open-field, sociability, and a partner preference test. Paternal deprivation (PD)-related effects included increased anxiety, decreased sociability, and impaired pair-bonding in both sexes. FM 550 effects include heightened anxiety and partner preference in females but reduced partner preference in males. The combination of FM 550 exposure and PD did not exacerbate any behaviors in either sex except for distance traveled by females in the partner preference test and, to a lesser extent, time spent with, and the number of visits to the non-social stimulus by males in the sociability test. FM 550 ameliorated the impacts of parental deprivation on partner preference behaviors in both sexes. This study is significant because it provides evidence that chemical and social stressors can have unique behavioral effects that differ by sex but may not produce worse outcomes in combination.

show abstract

“…The identification of intrauterine stress biomarkers is fundamental in the context of early interventions targeting poor health outcomes prevention later in life. A growing body of research suggests the biological pathways, such as the glucocorticoid and pro-inflammatory pathways that could be the translators of an environmental experience into phenotypic changes mediated by the epigenome [1][2][3]. Molecular mechanisms related to cells plasticity, such as DNA methylation (DNAm) levels, may mediate the activation of pathways related to physiological stress due to its dynamic interaction with the environment [4,5].…”

Section: Introductionmentioning

confidence: 99%

Gestational age acceleration is associated with epigenetic biomarkers of prenatal physiologic stress exposure

et al. 2022

View full text Add to dashboard Cite

Background Physiological maternal stress response, such as imbalance in the glucocorticoid pathway and immune system seems to be mediated by DNA methylation (DNAm) and might translate intrauterine stress exposures into phenotypic changes in a sex-specific manner. DNAm in specific sites can also predict newborn gestational age and gestational age acceleration (GAA). GAA occurs when the predicted biological age is higher than the chronological age. In adults, poor health outcomes related to this deviance are well documented and raise questions for the interpretation and prediction in early stages of life. Boys seem to be more vulnerable to intrauterine stress exposure than girls; however, the mechanisms of adaptive sex-specific responses are still unclear. We hypothesize that intrauterine stress exposure is associated with GAA and could be different in boys and girls if inflammatory or glucocorticoid pathways exposure is considered. Results Using the Western Region Birth Cohort (ROC—São Paulo, Brazil) (n = 83), we calculated DNAm age and GAA from cord blood samples. Two epigenetic risk scores were calculated as an indirect proxy for low-grade inflammation (i-ePGS) and for glucocorticoid exposure (GES). Multivariate linear regression models were applied to investigate associations of GAA with prenatal exposures. The i-ePGS and GES were included in different models with the same co-variates considering sex interactions. The first multivariate model investigating inflammatory exposure (adj. R2 = 0.31, p = < 0.001) showed that GAA was positively associated with i-ePGS (CI, 0.26–113.87, p = 0.049) and negative pregnancy-related feelings (CI, 0.04–0.48 p = 0.019). No sex interaction was observed. The second model investigating glucocorticoid exposure (adj. R2 = 0.32, p = < 0.001) showed that the higher was the GAA was associated with a lower the lower was the GES in girls (CI, 0.04–2.55, p = 0.044). In both models, maternal self-reported mental disorder was negatively associated with GAA. Conclusion Prenatal epigenetic score of exposure to low-grade inflammatory was a predictor of GAA for both sexes. Glucocorticoid epigenetic score seems to be more important to GAA in girls. This study supports the evidence of sex-specificity in stress response, suggesting the glucocorticoid as a possible pathway adopted by girls to accelerate the maturation in an adverse condition.

show abstract

Neurobehavioral abnormalities following prenatal psychosocial stress are differentially modulated by maternal environment

Cited by 11 publications

References 67 publications

Vulnerability and resilience to prenatal stress exposure: behavioral and molecular characterization in adolescent rats

Vulnerability and resilience to prenatal stress exposure: behavioral and molecular characterization in adolescent rats

Individual and Combined Effects of Paternal Deprivation and Developmental Exposure to Firemaster 550 on Socio-Emotional Behavior in Prairie Voles

Gestational age acceleration is associated with epigenetic biomarkers of prenatal physiologic stress exposure

Contact Info

Product

Resources

About