scholarly journals Maternal antioxidant treatment prevents behavioural and neural changes in offspring exposed to prenatal social stress

2019 ◽  
Author(s):  
H Scott ◽  
TJ Phillips ◽  
Y Sze ◽  
A Alfieri ◽  
MF Rogers ◽  
...  
Keyword(s):  
Conditioned Medium ◽  
Prenatal Stress ◽  
Social Stress ◽  
Maternal Stress ◽  
Later Life ◽  
Neuronal Cultures ◽  
Antioxidant Treatment ◽  
Foetal Brain ◽  
Increased Risk

AbstractMaternal exposure to social stress during pregnancy is associated with an increased risk of psychiatric disorders in the offspring in later life. However, the mechanism through which the effects of maternal stress are transmitted to the foetus is unclear. Using a rat model, we explored the mechanisms by which maternal social stress is conveyed to the foetus and the potential for targeted treatment to prevent disease in the offspring. Maternal stress increased circulating corticosterone in the mother, but not the foetuses. Maternal stress also induced oxidative stress in the placenta, but not in the foetal brain, and this was prevented by administration of a nanoparticle-bound antioxidant. Moreover, antioxidant treatment prevented prenatal stress-induced anxiety-like behaviour in the adult male offspring, along with several stress-induced neuroanatomical, neurochemical and gene expression changes in the offspring brain. Importantly, many of these neural effects were mimicked in neuronal cultures by application of placental-conditioned medium or foetal plasma from stressed pregnancies. Both placental-conditioned medium and foetal plasma contained differentially abundant extracellular microRNAs following prenatal stress. The present study highlights the crucial role of the placenta, and the molecules it secretes, in foetal brain development and provides evidence of the potential for treatment that can prevent maternal stress-induced foetal programming of neurological disease.

scholarly journals Altered cortical development and psychiatric symptom risk in adolescents exposed to maternal stress in utero

2019 ◽  
Author(s):  
Goldie A. McQuaid ◽  
Valerie L. Darcey ◽  
Melissa F. Avalos ◽  
Diana H. Fishbein ◽  
John W. VanMeter
Keyword(s):  
Gray Matter ◽  
Prenatal Stress ◽  
Brain Structure ◽  
Maternal Stress ◽  
In Utero ◽  
Brain Morphology ◽  
Maternal Report ◽  
Increased Risk ◽  
Adolescent Risk ◽  
Parietal Lobule

ABSTRACTObjectiveMaternal exposure to stress during pregnancy is associated with increased risk for cognitive and behavioral sequelae in offspring. Animal research demonstrates exposure to stress during gestation has effects on brain structure. In humans, however, little is known about the enduring effects of in utero exposure to maternal stress on brain morphology. We examine whether maternal report of stressful events during pregnancy is associated with brain structure and behavior in adolescents.MethodWe compare gray matter morphometry of typically-developing early adolescents (11-14 years of age, mean 12.7) based on presence/absence of maternal report of stressful event(s) during pregnancy: prenatal stress (PS; n=28), no prenatal stress (NS; n=55). The Drug Use Survey Index Revised (DUSI-R) assessed adolescent risk for problematic behaviors. Exclusionary criteria included pre-term birth, low birth weight, and maternal substance use during pregnancy. Groups were equivalent for demographic (age, sex, IQ, SES, race/ethnicity), and birth measures (weight, length).ResultsCompared to NS peers, adolescents in the PS group exhibited increased gray matter volume in bilateral posterior parietal cortex (PPC): bilateral intraparietal sulcus, left superior parietal lobule and inferior parietal lobule. Additionally, the PS group displayed greater risk for psychiatric symptoms and family system dysfunction, as assessed via DUSI-R subscales.ConclusionThis study provides evidence for the enduring neurodevelopmental effects of exposure to maternal stress while in utero, suggesting the dynamic alterations in brain structure that occur during the adolescent critical period may unmask the latent effects of gestational stress on brain morphology and increase subsequent risk for psychiatric symptomatology.

scholarly journals Subjective mental health, incidence of depressive symptoms in later life, and the role of epigenetics: results from two longitudinal cohort studies

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Laura Perna ◽  
Yan Zhang ◽  
Pamela R. Matias-Garcia ◽  
Karl-Heinz Ladwig ◽  
Tobias Wiechmann ◽  
...  
Keyword(s):  
Mental Health ◽  
Depressive Symptoms ◽  
Older People ◽  
Predictive Value ◽  
Meta Analysis ◽  
Later Life ◽  
Increased Risk ◽  
Mental Hrqol ◽  
Subjective Mental Health

Abstract The role of self-perceived general health in predicting morbidity and mortality among older people is established. The predictive value of self-perceived mental health and of its possible biological underpinnings for future depressive symptoms is unexplored. This study aimed to assess the role of mental health-related quality of life (HRQOL) and of its epigenetic markers in predicting depressive symptoms among older people without lifetime history of depression. Data were based on a subgroup (n = 1 492) of participants of the longitudinal ESTHER study. An epigenome-wide association study (EWAS) of mental HRQOL was conducted using DNA from baseline whole blood samples and logistic regression analyses were performed to assess the predictive value of methylation beta values of EWAS identified CpGs for incidence of depressive symptoms in later life. The methylation analyses were replicated in the independent KORA cohort (n = 890) and a meta-analysis of the two studies was conducted. Results of the meta-analysis showed that participants with beta values of cg27115863 within quartile 1 (Q1) had nearly a two-fold increased risk of developing depressive symptoms compared to participants with beta values within Q4 (ORQ1vsQ4 = 1.80; CI 1.25–2.61). In the ESTHER study the predictive value of subjective mental health for future depressive symptoms was also assessed and for 10-unit increase in mental HRQOL scores the odds for incident depressive symptoms were reduced by 54% (OR 0.46; CI 0.40–0.54). These findings suggest that subjective mental health and hypomethylation at cg27115863 are predictive of depressive symptoms, possibly through the activation of inflammatory signaling pathway.

The Role of Epigenetic Mechanisms in the Development of Obesity

2020 ◽  
Vol 62 (2) ◽  
pp. 103-108
Author(s):  
Marta Pacholczyk ◽  
Ewelina Dzwonkowska ◽  
Tomasz Ferenc
Keyword(s):  
Metabolic Disease ◽  
Body Weight ◽  
Later Life ◽  
Methylation Pattern ◽  
Targeted Prevention ◽  
Obese People ◽  
Early Postnatal Development ◽  
Exercise Interventions ◽  
Increased Risk

Obesity is an important medical and civilization problem due to health consequences and increasing incidence. The development of obesity is influenced by genetic and environmental factors. Despite intensive research the results of which allowed to identify genetic variants predisposing to the development of obesity, the knowledge about the genetic basis of this metabolic disease still remains incomplete. Furthermore, the contribution of single polymorphic gene variants to shaping the obesity phenotype is minimal and accounts for a small part of body weight variability. The need for further research in the field of obesity etiology has increased the interest in the role of epigenetics as a mediator of gene-environment interactions, underlying the development of obesity and related comorbidities. Epigenetics deals with changes in gene expression that are not related to changes of the nucleotide sequence in DNA. Epigenetic modifications include DNA methylation, post-translational modifications of histone proteins and synthesis of non-coding microRNA (miRNA). There is growing evidence indicating that environmental exposures (among others the influence of nutrients) in prenatal and early postnatal development may induce permanent changes in the epigenome, predisposing to an increased risk of obesity in later life. Epigenome-Wide Association Study (EWAS) allowed to indicate differences in the methylation pattern of genes in obese people compared to healthy subjects with normal body weight as well as to identify the first epigenetic markers of obesity in humans. EWAS also allowed to recognize epigenetic changes under the influence of nutrients, during weight loss and occurring during exercise interventions. Significant progress in epigenetic studies on the causes of obesity will allow to predict the risk for this metabolic disease already at a young age and it gives the possibility of introducing targeted prevention strategies.

Pre-Eclamptic Pregnancies: An Opportunity to Identify Women at Risk for Future Cardiovascular Disease

2008 ◽  
Vol 4 (2) ◽  
pp. 133-135 ◽  
Author(s):  
Iasmina M Craici ◽  
Steven J Wagner ◽  
Suzanne R Hayman ◽  
Vesna D Garovic
Keyword(s):  
Systematic Review ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Meta Analysis ◽  
Later Life ◽  
Future Studies ◽  
Increased Risk ◽  
All Cause Mortality ◽  
History Of

Evaluation of: Bellamy L, Casas JP, Hingorani AD, Williams DJ: Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. Br. Med. J. 335(7627), 974 (2007). Evidence has emerged over the years suggesting that women who develop hypertensive pregnancy disorders, most notably pre-eclampsia, are at an increased risk for cardiovascular disease later in life. In this study, a systematic review and meta-analysis were performed, assessing the future risks of cardiovascular disease, cancer and all-cause mortality in women with a history of pre-eclampsia and eclampsia. Women with a history of pre-eclampsia or eclampsia, compared with women without such a history, had an increased risk for cardiovascular disease, including a fourfold increased risk for hypertension, a twofold increased risk for ischemic heart disease, stroke and deep venous thrombosis, and a 1.5-times higher all-cause mortality. The study suggests that affected women may be eligible for preventive therapies at an earlier age, especially if future studies establish the role of pre-eclampsia as an independent cardiovascular risk factor.

scholarly journals Effects of maternal exposure to social stress during pregnancy: consequences for mother and offspring

Reproduction ◽  
2013 ◽  
Vol 146 (5) ◽  
pp. R175-R189 ◽  
Author(s):  
Paula J Brunton
Keyword(s):  
Hpa Axis ◽  
Prenatal Stress ◽  
Social Stress ◽  
Maternal Stress ◽  
Reproductive Potential ◽  
Maternal Behaviour ◽  
Stress Exposure ◽  
Prenatally Stressed ◽  
In Pregnancy

A suboptimalin uteroenvironment, for example, as a result of maternal stress, can have detrimental effects on the pregnancy and long-term adverse ‘programming’ effects on the offspring. This article focuses on the effects of prenatal social stress on the mother, her pregnancy and the offspring, since these issues have ethological relevance in both animals and humans. The consequences of social stress exposure depend on when during pregnancy the stress occurs, and many of the effects on the offspring are sex specific. Social stress during early pregnancy tends to result in pregnancy loss, whereas stress exposure later in pregnancy, when the mother has already invested considerable resources in the foetuses, results in programmed offspring of low birth weight: a risk factor for various adulthood diseases. Neuroendocrine and behavioural responses to stress in the offspring are particularly sensitive to foetal programming by prenatal stress, indicated by enhanced hypothalamo-pituitary–adrenal (HPA) axis responses and increased anxiety behaviour, which result from permanent changes in the offspring's brain. The dysregulation of HPA axis function may also interfere with other systems, for example, the hypothalamic–pituitary–gonadal axis, as there is evidence for alterations in steroidogenesis, reproductive potential and impaired reproductive/social behaviours in prenatally stressed offspring. Prenatal social stress also programmes future maternal behaviour, highlighting the potential for negative phenotypes to be transmitted to future generations. The possible mechanisms through which maternal stress during pregnancy is transmitted to the foetuses and the foetal brain is programmed by prenatal stress and the potential to overwrite programming of the offspring are discussed.

scholarly journals Pemanfaatan sekolah sebagai sarana pencegahan obesitas sejak dini pada remaja

2019 ◽  
Vol 1 (2) ◽  
pp. 107
Author(s):  
Harry Freitag Luglio Muhammad
Keyword(s):  
Obesity Prevention ◽  
Prevention Program ◽  
Health Workers ◽  
Later Life ◽  
Prevention Programs ◽  
School Based ◽  
Increased Risk ◽  
Obesity Prevention Programs ◽  
Obesity Prevention Program

Obesity among adolescents is a new nutritional problem in Indonesia. This is not only associated with increased risk for obesity in later life but also increased the risk for cardiovascular diseases, type 2 diabetes mellitus, hypertension, and other non-communicable diseases. Therefore an effective and integrated obesity prevention program is highly warranted. There are several community-based programs for obesity prevention that have been developed in the past few decades and school-based activity is one of the potential programs that could be implemented in the Indonesian setting. School is a strategic location for obesity prevention programs in the adolescents because school is the place where most of the adolescents spending their time outside their home. In addition, a school also a centralized community where health and nutrition promotion programs can be done at the same time. In 2012, the Indonesian Ministry of Health published a guidebook on the prevention and treatment of adolescents with obesity at school. However, this guideline only focusing on the role of health workers at puskesmas level and not detailing the role of the school in managing obesity prevention program. Thus, this review was made to provide an alternative solution for obesity prevention in adolescent via programs that can be done at school. Author aimed this review for school managers, puskesmas health workers, the local department of health, researcher and non-government organization that has the concern regarding adolescents health especially in relation to nutrition. This review can be a foundation for the development and implementation of school-based obesity prevention programs as well as a reference for the development of school policy.

scholarly journals The Role of Redox Dysregulation in the Effects of Prenatal Stress on Embryonic Interneuron Migration

2019 ◽  
Vol 29 (12) ◽  
pp. 5116-5130 ◽  
Author(s):  
Jada Bittle ◽  
Edenia C Menezes ◽  
Michael L McCormick ◽  
Douglas R Spitz ◽  
Michael Dailey ◽  
...  
Keyword(s):  
Prenatal Stress ◽  
Restraint Stress ◽  
Time Lapse ◽  
Ganglionic Eminence ◽  
Cortical Interneuron ◽  
Redox Biology ◽  
Tangential Migration ◽  
Increased Risk ◽  
Induced Changes

Abstract Maternal stress during pregnancy is associated with increased risk of psychiatric disorders in offspring, but embryonic brain mechanisms disrupted by prenatal stress are not fully understood. Our lab has shown that prenatal stress delays inhibitory neural progenitor migration. Here, we investigated redox dysregulation as a mechanism for embryonic cortical interneuron migration delay, utilizing direct manipulation of pro- and antioxidants and a mouse model of maternal repetitive restraint stress starting on embryonic day 12. Time-lapse, live-imaging of migrating GAD67GFP+ interneurons showed that normal tangential migration of inhibitory progenitor cells was disrupted by the pro-oxidant, hydrogen peroxide. Interneuron migration was also delayed by in utero intracerebroventricular rotenone. Prenatal stress altered glutathione levels and induced changes in activity of antioxidant enzymes and expression of redox-related genes in the embryonic forebrain. Assessment of dihydroethidium (DHE) fluorescence after prenatal stress in ganglionic eminence (GE), the source of migrating interneurons, showed increased levels of DHE oxidation. Maternal antioxidants (N-acetylcysteine and astaxanthin) normalized DHE oxidation levels in GE and ameliorated the migration delay caused by prenatal stress. Through convergent redox manipula-tions, delayed interneuron migration after prenatal stress was found to critically involve redox dysregulation. Redox biology during prenatal periods may be a target for protecting brain development.

Prenatal maternal stress, fetal programming, and mechanisms underlying later psychopathology—A global perspective

2018 ◽  
Vol 30 (3) ◽  
pp. 843-854 ◽  
Author(s):  
Vivette Glover ◽  
Kieran J O'Donnell ◽  
Thomas G O'Connor ◽  
Jane Fisher
Keyword(s):  
Prenatal Stress ◽  
Interpersonal Violence ◽  
Global Perspective ◽  
Wife Beating ◽  
Nutritional Deficiencies ◽  
Increased Risk ◽  
Child Neurodevelopment ◽  
The World ◽  
Underlying Mechanisms

AbstractThere is clear evidence that the mother's stress, anxiety, or depression during pregnancy can alter the development of her fetus and her child, with an increased risk for later psychopathology. We are starting to understand some of the underlying mechanisms including the role of the placenta, gene–environment interactions, epigenetics, and specific systems including the hypothalamic–pituitary–adrenal axis and cytokines. In this review we also consider how these effects may be different, and potentially exacerbated, in different parts of the world. There can be many reasons for elevated prenatal stress, as in communities at war. There may be raised pregnancy-specific anxiety with high levels of maternal and infant death. There can be raised interpersonal violence (in Afghanistan 90.2% of women thought that “wife beating” was justified compared with 2.0% in Argentina). There may be interactions with nutritional deficiencies or with extremes of temperature. Prenatal stress alters the microbiome, and this can differ in different countries. Genetic differences in different ethnic groups may make some more vulnerable or more resilient to the effects of prenatal stress on child neurodevelopment. Most research on these questions has been in predominantly Caucasian samples from high-income countries. It is now time to understand more about prenatal stress and psychopathology, and the role of both social and biological differences, in the rest of the world.

scholarly journals Role of the kidney in the prenatal and early postnatal programming of hypertension

2010 ◽  
Vol 298 (2) ◽  
pp. F235-F247 ◽  
Author(s):  
Michel Baum
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Animal Models ◽  
Adverse Events ◽  
Renin Angiotensin System ◽  
Later Life ◽  
Low Birth Weight Infants ◽  
Increased Risk

Epidemiologic studies from several different populations have demonstrated that prenatal insults, which adversely affect fetal growth, result in an increased incidence of hypertension when the offspring reaches adulthood. It is now becoming evident that low-birth-weight infants are also at increased risk for chronic kidney disease. To determine how prenatal insults result in hypertension and chronic kidney disease, investigators have used animal models that mimic the adverse events that occur in pregnant women, such as dietary protein or total caloric deprivation, uteroplacental insufficiency, and prenatal administration of glucocorticoids. This review examines the role of the kidney in generating and maintaining an increase in blood pressure in these animal models. This review also discusses how early postnatal adverse events may have repercussions in later life. Causes for the increase in blood pressure by perinatal insults are likely multifactorial and involve a reduction in nephron number, dysregulation of the systemic and intrarenal renin-angiotensin system, increased renal sympathetic nerve activity, and increased tubular sodium transport. Understanding the mechanism for the increase in blood pressure and renal injury resulting from prenatal insults may lead to therapies that prevent hypertension and the development of chronic kidney and cardiovascular disease.

scholarly journals Preeclamptic placentae release factors that damage neurons: implications for foetal programming of disease

2018 ◽  
Vol 2 (4) ◽  
Author(s):  
Hannah Scott ◽  
Tom J. Phillips ◽  
Greer C. Stuart ◽  
Mark F. Rogers ◽  
Bruno R. Steinkraus ◽  
...  
Keyword(s):  
Placental Tissue ◽  
Later Life ◽  
Prenatal Development ◽  
Autism Spectrum ◽  
Antioxidant Treatment ◽  
Cortical Cells ◽  
Release Factors ◽  
Foetal Programming ◽  
Signalling Molecules ◽  
Increased Risk

Prenatal development is a critical period for programming of neurological disease. Preeclampsia, a pregnancy complication involving oxidative stress in the placenta, has been associated with long-term health implications for the child, including an increased risk of developing schizophrenia and autism spectrum disorders in later life. To investigate if molecules released by the placenta may be important mediators in foetal programming of the brain, we analysed if placental tissue delivered from patients with preeclampsia secreted molecules that could affect cortical cells in culture. Application of culture medium conditioned by preeclamptic placentae to mixed cortical cultures caused changes in neurons and astrocytes that were related to key changes observed in brains of patients with schizophrenia and autism, including effects on dendrite lengths, astrocyte number as well as on levels of glutamate and γ-aminobutyric acid receptors. Treatment of the placental explants with an antioxidant prevented neuronal abnormalities. Furthermore, we identified that bidirectional communication between neurons and astrocytes, potentially via glutamate, is required to produce the effects of preeclamptic placenta medium on cortical cells. Analysis of possible signalling molecules in the placenta-conditioned medium showed that the secretion profile of extracellular microRNAs, small post-transcriptional regulators, was altered in preeclampsia and partially rescued by antioxidant treatment of the placental explants. Predicted targets of these differentially abundant microRNAs were linked to neurodevelopment and the placenta. The present study provides further evidence that the diseased placenta may release factors that damage cortical cells and suggests the possibility of targeted antioxidant treatment of the placenta to prevent neurodevelopmental disorders.

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