The Analytical core will provide state-of-the-art analyses that are of high priority to CCEH projects that link chemical exposures with clinical and epidemiological data (Project 1), epigenetic data (Project 2), immunological data (Project 3), and mechanistic data from human neurons (Project 4). Analytical Core will use its extensive experience in analytical chemistry to develop and validate highly sensitive and specific methods to quantitate target compounds in small volumes of plasma from mothers and children, in breast milk, and in urine. Specifically, the Analytical Core will serve center projects by conducting analyses on complex biological samples matrices to identify xenobiotic pollutants that are known or suspected of being developmental neurotoxicants and immunotoxicants, in human epidemiological studies and/or in animal models. Quantitative results will be provided to all CCEH Projects where they will be evaluated in the context of ASD risk, genomic and methylomic interactions, cytokine profiles and their ability to alter Ca^'^-dependent signaling pathways in human neurons and immune cells. The Core's three main objectives are: Objective 1: Provide general analytical support for efficient processing and extraction of small sample volumes archived in the CCEH biobank. Objective 2: Undertake highly sensitive and quantitative analytical chemistry techniques to determine concentrations of polybrominated diphenyl ether (PBDE), polychlorinated biphenyl (PCB), and perfluorinated compounds (PFCs) congener patterns present in maternal serum and pyrethroid pesticide metabolites in urine of women at high risk for giving birth to an autistic child participating in the MARBLES study, and those found in children and their mother participating in CHARGE Objective 3: Develop and implement new analytical techniques to measure. This will include the development of: 3.1. PBDE and PCB congener profiles in the same extracts;and 3.2. Hydroxylated PBDE and PCB (OH-PBDE and OH-PCB) metabolites in the same extracts.

Public Health Relevance

The Analytical Core will provide essential services to all Projects, which all rely on accurate exposure data. This Core will generate the first detailed congener-level assessment of xenobiotic exposures in a wellstudied longitudinal cohort at high risk for autism, accurately quantitate xenobiotics in small volume specimens by modifying extraction and detection methods, and identify lead compounds which will become instrumental to all scientific projects of the Center.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Program Projects (P01)
Project #
5P01ES011269-12
Application #
8667443
Study Section
Special Emphasis Panel (ZES1)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
12
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
DUNS #
City
Davis
State
CA
Country
United States
Zip Code
95618
Sethi, Sunjay; Keil, Kimberly P; Lein, Pamela J (2018) 3,3'-Dichlorobiphenyl (PCB 11) promotes dendritic arborization in primary rat cortical neurons via a CREB-dependent mechanism. Arch Toxicol 92:3337-3345
Stamou, Marianna; Grodzki, Ana Cristina; van Oostrum, Marc et al. (2018) Fc gamma receptors are expressed in the developing rat brain and activate downstream signaling molecules upon cross-linking with immune complex. J Neuroinflammation 15:7
Hart, Lynette A; Thigpen, Abigail P; Willits, Neil H et al. (2018) Affectionate Interactions of Cats with Children Having Autism Spectrum Disorder. Front Vet Sci 5:39
Philippat, Claire; Barkoski, Jacqueline; Tancredi, Daniel J et al. (2018) Prenatal exposure to organophosphate pesticides and risk of autism spectrum disorders and other non-typical development at 3 years in a high-risk cohort. Int J Hyg Environ Health 221:548-555
Jones, Karen L; Pride, Michael C; Edmiston, Elizabeth et al. (2018) Autism-specific maternal autoantibodies produce behavioral abnormalities in an endogenous antigen-driven mouse model of autism. Mol Psychiatry :
Rose, Destanie R; Yang, Houa; Serena, Gloria et al. (2018) Differential immune responses and microbiota profiles in children with autism spectrum disorders and co-morbid gastrointestinal symptoms. Brain Behav Immun 70:354-368
Zheng, Jing; Chen, Juan; Zou, Xiaohan et al. (2018) Saikosaponin d causes apoptotic death of cultured neocortical neurons by increasing membrane permeability and elevating intracellular Ca2+ concentration. Neurotoxicology 70:112-121
Shin, Hyeong-Moo; Schmidt, Rebecca J; Tancredi, Daniel et al. (2018) Prenatal exposure to phthalates and autism spectrum disorder in the MARBLES study. Environ Health 17:85
Keil, Kimberly P; Miller, Galen W; Chen, Hao et al. (2018) PCB 95 promotes dendritic growth in primary rat hippocampal neurons via mTOR-dependent mechanisms. Arch Toxicol 92:3163-3173
Zheng, Jing; McKinnie, Shaun M K; El Gamal, Abrahim et al. (2018) Organohalogens Naturally Biosynthesized in Marine Environments and Produced as Disinfection Byproducts Alter Sarco/Endoplasmic Reticulum Ca2+ Dynamics. Environ Sci Technol 52:5469-5478

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