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Prenatal stress unmasks neurotoxic consequences of developmental exposures to lead and to methylmercury
80
Platform presentations
rural cohort. In both cohorts the Mexican Farmworker questionnaire was related to the Perceived Stress Scale. This study builds tools for the integration and optimization of maternal stress assessment. Understanding the relationship between and within biological and questionnaire based stress measurements is important to the cohesive characterization of maternal stress exposure. This work was supported the National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (Contract No. HHSN267200700023C), by National Institute of Environmental Health Sciences (Award #5P01ES009601), by National Institute of Diabetes and Digestive and Kidney Diseases (Award # R01 DK079042) and by USEPA (grant #RD8345140). doi:10.1016/j.ntt.2014.04.014
NBTS 12 Systems medicine and proactive P4 medicine: A revolution in healthcare L. Hood Institute for Systems Biology, Seattle, WA, United States The challenge for biology in the 21st century is the need to deal with its incredible complexity. One powerful way to think of biology is to view it as an informational science. This view leads to the conclusion that biological information is captured, mined, integrated by biological networks, and finally passed off to molecular machines for execution. Hence the challenge in understanding biological complexity is that of deciphering the operation of dynamic biological networks across the three time scales of life-evolution, development, and physiological responses. Systems approaches to biology are focused on delineating and deciphering dynamic biological networks and their interactions with simple and complex molecular machines. I will define our contemporary view of systems biology and then focus on our efforts at a systems approach to disease-looking at prion disease in mice. We have just published a study that has taken more than 5 years — that lays out the principles of a systems approach to disease including dealing with the striking signal to noise problems of high throughput biological measurements and biology itself (e.g. polymorphisms). I will also discuss the emerging technologies (measurement and visualization) that will transform biology and medicine over the next 10 years — including next generation DNA sequencing, microfluidic protein chips and single-cell analyses. I will as well discuss some of the computational and mathematical challenges that are fundamental to the revolution in biology and medicine. It appears that systems medicine, together with emerging technologies, Big Data and patient-activated social networks will transform medicine over the next 5–20 years from its currently reactive state to a mode that is predictive, personalized, preventive, and participatory (P4) medicine. I will discuss the impact P4 medicine has on society and several ISB-strategic partnerships that have been established to attack the technical and societal barriers to the realization of P4 medicine. doi:10.1016/j.ntt.2014.04.015
Developmental exposure to methylmercury (MeHg) may be unmasked later in life. In animal models, signs of poisoning may not appear for weeks or months after exposure, and in humans the effects may be masked for months or years, perhaps even decades. Mechanisms that govern the protracted unmasking of MeHg neurotoxicity have yet to be fully uncovered. Potential mechanisms include (1) the slow production and accumulation of a toxic metabolite/s, (2) compounding of the normal age-related cell loss by developmental MeHg exposure, (3) exhaustion of inherent compensatory mechanisms, and (4) later-life exposure to Hg or other compounds may unmask the developmental effects of MeHg. The talk will discuss molecular mechanisms and genetic interactions associated with the unmasking of silent MeHg neurotoxicity drawing parallels from other diseases, which are known to affect the central nervous system, such as Parkinson disease. doi:10.1016/j.ntt.2014.04.016
NBTS 14 Prenatal stress unmasks neurotoxic consequences of developmental exposures to lead and to methylmercury D.A. Cory-Slechta University of Rochester Medical School, Rochester, NY, USA In addition to serving as co-occurring risk factors, particularly for low socioeconomic status communities, neurotoxic metals such as lead and methylmercury also share biological substrates and produce common adverse outcomes, including deficits in cognitive functions with prenatal stress. Such observations suggest the possibility of interactive, even enhanced effects of combined exposures to lead or methylmercury with prenatal stress. A series of studies in rodents has now confirmed both enhanced and unmasked effects of lead or methylmercury in combination with prenatal stress, with such effects being highly sex-dependent In the case of Pb exposures, combined Pb and prenatal stress in females result in increased response rates on fixed interval (FI) schedules of food reward and increases in levels of brain monoamines in regions known to control FI performance; the combination likewise unmasked sequence-specific learning impairments. In males, lead and prenatal stress results in enhanced delays in glucocorticoid negative feedback. Similarly, prenatal stress further reduced FI response rates at the highest dose of MeHg tested, and unmasked deficits in novel object recognition in females, while neurochemical effects of MeHg were seen only in the presence of prenatal stress in both sexes. Collectively these findings underscore the critical need to evaluate the neurotoxic hazards/risk of chemicals in contexts that are more relevant to the human environment. doi:10.1016/j.ntt.2014.04.017
NBTS 15 Neuroimmune interactions in early development and the biological embedding of health disparities S. Bilbo Duke University, Durham, NC, USA
NBTS 13 Unmasking silent neurotoxicity following developmental exposure to methylmercury M. Aschner Albert Einstein School of Medicine, Bronx, NY, USA
Although low socioeconomic status (SES) has been repeatedly associated with a higher rate of chronic health problems and mental disorders, explicit characterization of the factors that underlie this phenomenon remains elusive. A growing body of research suggests that maternal well-being during pregnancy is a crucial determinant
Platform presentations
rural cohort. In both cohorts the Mexican Farmworker questionnaire was related to the Perceived Stress Scale. This study builds tools for the integration and optimization of maternal stress assessment. Understanding the relationship between and within biological and questionnaire based stress measurements is important to the cohesive characterization of maternal stress exposure. This work was supported the National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (Contract No. HHSN267200700023C), by National Institute of Environmental Health Sciences (Award #5P01ES009601), by National Institute of Diabetes and Digestive and Kidney Diseases (Award # R01 DK079042) and by USEPA (grant #RD8345140). doi:10.1016/j.ntt.2014.04.014
NBTS 12 Systems medicine and proactive P4 medicine: A revolution in healthcare L. Hood Institute for Systems Biology, Seattle, WA, United States The challenge for biology in the 21st century is the need to deal with its incredible complexity. One powerful way to think of biology is to view it as an informational science. This view leads to the conclusion that biological information is captured, mined, integrated by biological networks, and finally passed off to molecular machines for execution. Hence the challenge in understanding biological complexity is that of deciphering the operation of dynamic biological networks across the three time scales of life-evolution, development, and physiological responses. Systems approaches to biology are focused on delineating and deciphering dynamic biological networks and their interactions with simple and complex molecular machines. I will define our contemporary view of systems biology and then focus on our efforts at a systems approach to disease-looking at prion disease in mice. We have just published a study that has taken more than 5 years — that lays out the principles of a systems approach to disease including dealing with the striking signal to noise problems of high throughput biological measurements and biology itself (e.g. polymorphisms). I will also discuss the emerging technologies (measurement and visualization) that will transform biology and medicine over the next 10 years — including next generation DNA sequencing, microfluidic protein chips and single-cell analyses. I will as well discuss some of the computational and mathematical challenges that are fundamental to the revolution in biology and medicine. It appears that systems medicine, together with emerging technologies, Big Data and patient-activated social networks will transform medicine over the next 5–20 years from its currently reactive state to a mode that is predictive, personalized, preventive, and participatory (P4) medicine. I will discuss the impact P4 medicine has on society and several ISB-strategic partnerships that have been established to attack the technical and societal barriers to the realization of P4 medicine. doi:10.1016/j.ntt.2014.04.015
Developmental exposure to methylmercury (MeHg) may be unmasked later in life. In animal models, signs of poisoning may not appear for weeks or months after exposure, and in humans the effects may be masked for months or years, perhaps even decades. Mechanisms that govern the protracted unmasking of MeHg neurotoxicity have yet to be fully uncovered. Potential mechanisms include (1) the slow production and accumulation of a toxic metabolite/s, (2) compounding of the normal age-related cell loss by developmental MeHg exposure, (3) exhaustion of inherent compensatory mechanisms, and (4) later-life exposure to Hg or other compounds may unmask the developmental effects of MeHg. The talk will discuss molecular mechanisms and genetic interactions associated with the unmasking of silent MeHg neurotoxicity drawing parallels from other diseases, which are known to affect the central nervous system, such as Parkinson disease. doi:10.1016/j.ntt.2014.04.016
NBTS 14 Prenatal stress unmasks neurotoxic consequences of developmental exposures to lead and to methylmercury D.A. Cory-Slechta University of Rochester Medical School, Rochester, NY, USA In addition to serving as co-occurring risk factors, particularly for low socioeconomic status communities, neurotoxic metals such as lead and methylmercury also share biological substrates and produce common adverse outcomes, including deficits in cognitive functions with prenatal stress. Such observations suggest the possibility of interactive, even enhanced effects of combined exposures to lead or methylmercury with prenatal stress. A series of studies in rodents has now confirmed both enhanced and unmasked effects of lead or methylmercury in combination with prenatal stress, with such effects being highly sex-dependent In the case of Pb exposures, combined Pb and prenatal stress in females result in increased response rates on fixed interval (FI) schedules of food reward and increases in levels of brain monoamines in regions known to control FI performance; the combination likewise unmasked sequence-specific learning impairments. In males, lead and prenatal stress results in enhanced delays in glucocorticoid negative feedback. Similarly, prenatal stress further reduced FI response rates at the highest dose of MeHg tested, and unmasked deficits in novel object recognition in females, while neurochemical effects of MeHg were seen only in the presence of prenatal stress in both sexes. Collectively these findings underscore the critical need to evaluate the neurotoxic hazards/risk of chemicals in contexts that are more relevant to the human environment. doi:10.1016/j.ntt.2014.04.017
NBTS 15 Neuroimmune interactions in early development and the biological embedding of health disparities S. Bilbo Duke University, Durham, NC, USA
NBTS 13 Unmasking silent neurotoxicity following developmental exposure to methylmercury M. Aschner Albert Einstein School of Medicine, Bronx, NY, USA
Although low socioeconomic status (SES) has been repeatedly associated with a higher rate of chronic health problems and mental disorders, explicit characterization of the factors that underlie this phenomenon remains elusive. A growing body of research suggests that maternal well-being during pregnancy is a crucial determinant