Environmental Neuroscience Advancing the Understanding of How Chemical Exposures Impact Brain Health and Disease: Proceedings of a Workshop (2020) / Chapter Skim
Currently Skimming:
3 The Exposome and Exploring the Multiple Factors That Contribute to Neurotoxicity
3 The Exposome and Exploring the Multiple Factors That Contribute to Neurotoxicity
Pages 17-28
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 17... ...
The exposomic approach has shown promise as a tool for testing hypotheses in animal models (Miller)
|
From page 18... ...
For example, it has become increasingly clear that low-level chronic exposures and windows of exposure are critically important for human health, including for neurological disorders; that there are interactions between biological pathogens and environmental exposures; and that the microbiome plays an important role in how the body deals with environmental toxicants, said Woychik. THE EXPOSOME Given the fact that disease phenotypes are the product of both genetic and environmental effects, Christopher Wild introduced the concept of the "exposome" in 2005 to capture the totality of environmental exposures that impact human health, in much the same way as the genome captures
|
From page 19... ...
. As the idea of the exposome began to take hold, Gary Miller, vice dean for research and strategy innovation and professor of environmental health sciences at the Columbia University Mailman School of Public Health, said he began thinking about it in the context of the research he was doing at Emory University.
|
From page 20... ...
Agreeing that more animal studies combining exposures and neurosciences are needed, Brenda Eskenazi, the Jennifer and Brian Maxwell Professor Emeritus of Maternal and Child Health and Epidemiology and director of the Center for Environmental Research and Children's Health at the University of California, Berkeley, noted that aligning animal and in vitro studies to human studies is also critical. The beauty of high-resolution mass spectrometry approach for studying the exposome is that it works with multiple biological matrixes as well as in dust, water, and other environmental samples, said Miller.
|
From page 21... ...
The importance of this lies in the fact that unlike inherited mutations that cannot be avoided, if a chemical exposure can be identified, there is the potential to minimize it or eliminate it during critical periods of brain development and thus to eliminate environmentally induced forms of autism. Moreover, he said many environmental toxicants target the same molecular pathways that are affected by de novo gene mutations linked to autism.
|
From page 22... ...
ABCB1 = ATP binding cassette subfamily B member 1; ALDH1 = aldehyde dehydrogenase I; APEX1 = apurinic/apyrimidinic endodeoxyribonuclease 1; DAT = dopamine active transporter; HLA-DRA = major histocompatibility complex, class II, DR alpha; MHC-II = major histocompatibility complex II; OC = organochlorine; OGG1 = 8-oxoguanine glycosylase; OP = organophosphate. SOURCE: Presented by Beate Ritz, June 25, 2020.
|
From page 23... ...
His lab is now using a collection of human neural progenitor cells, mouse cortical neurons, and other types of cells to examine how valproate and other chemicals affect signaling pathways in neural and other cells with common genetic variants associated with autism. Synaptic Function Autism-linked genes associated with synaptic function also are beginning to reveal clues about environmental risks, according to Zylka.
|
From page 24... ...
EPIGENETICS Epigenetics emerged in the early 2000s to help explain how environmental conditions can alter the expression of genes and how, for example, early life events can cause disorders with onset later in life, according to Marisa Bartolomei, Perelman Professor of Cell and Developmental Biology and co-director of the Penn Epigenetics Institute at the University of Pennsylvania. Bartolomei and colleagues have been investigating how bisphenol A (BPA)
|
From page 25... ...
The industrial solvent TCE, used in many industrial processes, is found in air, water, and soil near sites of production. Spills and surface contamination allow TCE to seep into groundwater, and through vapor intrusion it gets into drinking water.
|
From page 26... ...
; then analyzed embryonic and placental tissue from pregnant mice euthanized at two time points. Genetic analyses of the tissue revealed that maternal BPA exposure during late stages of oocyte development and early embryonic development disrupted genomic imprinting in embryos and placentas of several genes associated with human imprinting disorders.
|
From page 27... ...
Not only are they more highly exposed to neurotoxicants, but the same magnitude of exposure has a greater adverse impact on them compared to more advantaged children, he said. For more on how social stressors may impact neurological disorders, see the section on autism and ADHD in Chapter 4.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.