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Impact of In-Utero Dexamethasone on Autonomic Regulation in Adulthood

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Premature babies are at risk of death from immature lung development. For this reason, pregnant mothers at risk for preterm delivery are administered dexamethasone (DEX), a synthetic glucocorticoid that promotes fetal lung development. However, exposure to DEX in utero is

Premature babies are at risk of death from immature lung development. For this reason, pregnant mothers at risk for preterm delivery are administered dexamethasone (DEX), a synthetic glucocorticoid that promotes fetal lung development. However, exposure to DEX in utero is associated with low birth weight and cardiovascular development pathologies. Moreover, our lab found that DEX administration in-utero leads to a sex-specific increase in stress-induced tachycardia in female, but not male offspring. This project seeks to expand on this preliminary finding of the heart by examining local effectors of activity from the sympathetic system (tyrosine hydroxylase and catechol-o-methyltransferase). Tyrosine hydroxylase was measured as it catalyzes the rate limiting step of norepinephrine synthesis while catechol-O- methyltransferase was studied as it catalyzes the degradation of norepinephrine. Acetylcholinesterase was used to measure parasympathetic activity as it catalyzes the degradation of the primary neurotransmitter of the parasympathetic nervous system, acetylcholine. Analyses of sympathetic as well as parasympathetic activity were done to determine influences of in-utero DEX exposure on autonomic regulation in adulthood. Pregnant rats were administered DEX (0.4 mg/kg, i.p.) or vehicle (20% w/v 2-hydroxypropyl ß- cyclodextran) at gestation days 18-21, with euthanasia of offspring occurring at around the time the offspring reached 13-15 weeks of age. Left ventricles and right atria were pulverized, processed and subjected to western blot analysis to determine expression of proteins of interest. Males exposed to DEX in-utero saw a decrease in tyrosine hydroxylase expression in left ventricle and right atrium when compared to vehicle control, a difference not seen with females. In addition, catechol-o-methyltransferase expression was increased in right atria from male, but not female rats. Acetylcholinesterase expression was reduced in the right atria of female, but not male rats. The present findings suggest reduced norepinephrine signaling in the heart of male, but not female DEX-exposed offspring. Given that we have previously found that female, but not male rats exhibit exaggerated stress-induced tachycardia, our current findings suggest that males possess a sex-specific compensatory mechanism allowing the heart to resist increased sympathetic signaling from the brain, one that females do not possess. The underlying mechanics of this proposed mechanism are unclear, and further investigation is needed in this subject to determine the significance of the findings from our study.

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2021-05

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Prenatal stress and infant regulatory capacity

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The development of self-regulation is believed to play a crucial role in predicting later psychopathology and is believed to begin in early childhood. The early postpartum period is particularly important in laying the groundwork for later self-regulation as infants' dispositional

The development of self-regulation is believed to play a crucial role in predicting later psychopathology and is believed to begin in early childhood. The early postpartum period is particularly important in laying the groundwork for later self-regulation as infants' dispositional traits interact with caregivers' co-regulatory behaviors to produce the earliest forms of self-regulation. Moreover, although emerging literature suggests that infants' exposure to maternal stress even before birth may be integral in determining children's self-regulatory capacities, the complex pathways that characterize these developmental processes remain unclear. The current study considers the complex, transactional processes in a high-risk, Mexican American sample. Data were collected from 305 Mexican American infants and their mothers during prenatal, 6- and 12-week home interviews. Mother self-reports of stress were obtained prenatally between 34-37 weeks gestation. Mother reports of infant temperamental negativity and surgency were obtained at 6-weeks as were observed global ratings of maternal sensitivity during a structured peek-a-boo task. Microcoded ratings of infants' engagement orienting and self-comforting behaviors were obtained during the 12-week peek-a-boo task. Study findings suggest that self-comforting and orienting behaviors help to modulate infants' experiences of distress, and also that prenatal stress influences infants' engagement in each of those regulatory behaviors, both directly by influence tendencies to engage in orienting behaviors and indirectly by programming higher levels of infant negativity and surgency, both of which may confer risk for later regulatory disadvantage. Advancing our understandings about the nature of these developmental pathways could have significant implications for targets of early intervention in this high-risk population.

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2013

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The Impact of Different Normalization Methods on Western Blot Results

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Reducing the amount of error and introduced data variability increases the accuracy of Western blot results. In this study, different methods of normalization for loading differences and data alignment were explored with respect to their impact on Western blot results.

Reducing the amount of error and introduced data variability increases the accuracy of Western blot results. In this study, different methods of normalization for loading differences and data alignment were explored with respect to their impact on Western blot results. GAPDH was compared to the LI-COR Revert total protein stain as a loading control. The impact of normalizing data to a control condition, which is commonly done to align Western blot data distributed over several immunoblots, was also investigated. Specifically, this study addressed whether normalization to a small subset of distinct controls on each immunoblot increases pooled data variability compared to a larger set of controls. Protein expression data for NOX-2 and SOD-2 from a study investigating the protective role of the bradykinin type 1 receptor in angiotensin-II induced left ventricle remodeling were used to address these questions but are also discussed in the context of the original study. The comparison of GAPDH and Revert total protein stain as a loading control was done by assessing their correlation and comparing how they affected protein expression results. Additionally, the impact of treatment on GAPDH was investigated. To assess how normalization to different combinations of controls influences data variability, protein data were normalized to the average of 5 controls, the average of 2 controls, or an average vehicle and the results by treatment were compared. The results of this study demonstrated that GAPDH expression is not affected by angiotensin-II or bradykinin type 1 receptor antagonist R-954 and is a less sensitive loading control compared to Revert total protein stain. Normalization to the average of 5 controls tended to reduce pooled data variability compared to 2 controls. Lastly, the results of this study provided preliminary evidence that R-954 does not alter the expression of NOX-2 or SOD-2 to an expression profile that would be expected to explain the protection it confers against Ang-II induced left ventricle remodeling.

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2021-05

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Links between prenatal stress and obstetrical complications and infant behavior: a twin design

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The main objective of this study was to use a genetically-informative design to examine the putative influences of maternal perceived prenatal stress, obstetrical complications, and gestational age on infant dysregulation, competence, and developmental maturity. Specifically, whether or not prenatal and

The main objective of this study was to use a genetically-informative design to examine the putative influences of maternal perceived prenatal stress, obstetrical complications, and gestational age on infant dysregulation, competence, and developmental maturity. Specifically, whether or not prenatal and obstetrical environmental conditions modified the heritability of infant outcomes was examined. A total of 291 mothers were interviewed when their twin infants were 12 months of age. Pregnancy and twin birth medical records were obtained to code obstetrical data. Utilizing behavioral genetic models, results indicated maternal perceived prenatal stress moderated genetic and environmental influences on developmental maturity whereas obstetrical complications moderated shared environmental influences on infant competence and nonshared environmental influences on developmental maturity. Gestational age moderated the heritability and nonshared environment of infant dysregulation, shared and nonshared environmental influences on competence, and nonshared environmental influences on developmental maturity. Taken together, prenatal and obstetric conditions were important nonlinear influences on infant outcomes. An evolutionary perspective may provide a framework for these findings, such that the prenatal environment programs the fetus to be adaptive to current environmental contexts. Specifically, prenatal stress governs gene expression through epigenetic processes. Findings highlight the utility of a genetically informative design for elucidating the role of prenatal and obstetric conditions in the etiology of infant developmental outcomes.

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2011

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Infant temperamental reactivity and emerging behavior problems in a Mexican American sample

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Clinically meaningful emotional and behavioral problems are thought to be present beginning in infancy, and may be reliably assessed in children as young as 12 months old. However, few studies have investigated early correlates of emotional and behavioral problems assessed

Clinically meaningful emotional and behavioral problems are thought to be present beginning in infancy, and may be reliably assessed in children as young as 12 months old. However, few studies have investigated early correlates of emotional and behavioral problems assessed in infancy. The current study investigates the direct and interactive contributions of early infant and caregiver characteristics thought to play an important role in the ontogeny of behavior problems. Specifically, the study examines: (1) the links between temperamental reactivity across the first year of life and behavior problems at 18 months, (2) whether children high in temperamental reactivity are differentially susceptible to variations in maternal sensitivity, (3) the extent to which child temperamental risk or susceptibility may further be explained by mothers’ experiences of stressful life events (SLEs) during and before pregnancy. Data were collected from 322 Mexican American families during prenatal, 6-, 12-, 18-, and 24-week home interviews, as well as during 12- and 18-month lab interviews. Mother reports of SLEs were obtained between 23-40 weeks gestation; temperamental negativity and surgency at 6 weeks and 12 months; and internalizing and externalizing behaviors at 18 months. Maternal sensitivity during structured mother-infant interaction tasks at the 6-, 12-, 18-, and 24-week visits was assessed by objective observer ratings. Study findings indicated that maternal SLEs before birth were associated with more infant negativity across the first year of life, and that negativity in turn was associated with more internalizing problems at 18 months. Ecological stressors thought to be associated with sociodemographic risk factors such as low-income and ethnic minority status may begin to exert cascades of influence on children’s developmental outcomes even before birth.

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Date Created
2016

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Prenatal Maternal Stress Exacerbates Alzheimer’s Disease Through Epigenetic Changes

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Stress and stress-related disorders increase the risk of Alzheimer’s Disease (AD) later in life. Some evidence suggests that prenatal maternal stress (PMS) can exacerbate AD. However, the effects of PMS on AD have not been as well studied. Epigenetic changes

Stress and stress-related disorders increase the risk of Alzheimer’s Disease (AD) later in life. Some evidence suggests that prenatal maternal stress (PMS) can exacerbate AD. However, the effects of PMS on AD have not been as well studied. Epigenetic changes have been shown to contribute to AD and this is a possible mechanism by which PMS could accelerate AD. Thus, the present study aimed to investigate the effects of PMS on histone modifications, which change gene expression through alterations made to chromatin structure and thereby DNA accessibility. We utilized female 3xTG-AD mice and performed spatial and learning memory assessments between 5 and 6 months of age. Tissue was analyzed for AD pathology and epigenetic markers at 6 months of age were assessed PMS was shown to influence histone modifications H3K4me3 and H3K27me3 in a manner known to promote the expression of genes associated with neurodegeneration. Further, PMS impaired spatial memory, and, interestingly, the data resembled the pattern of H3K4me3 expression across groups, suggesting that this epigenetic modification could modulate the learning and memory effects of PMS. While the presence of hallmark AD pathologies were not accelerated by PMS, PMS did increase early tau phosphorylation events. Thus, this evidence suggests that PMS impairs spatial memory through epigenetic modifications and may potentially exacerbate AD later in life.

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2022-05