Menu
×
West Ashley Library
9 a.m. - 7 p.m.
Phone: (843) 766-6635
Folly Beach Library
Closed
Phone: (843) 588-2001
Edgar Allan Poe/Sullivan's Island Library
Closed for renovations
Phone: (843) 883-3914
Wando Mount Pleasant Library
9 a.m. - 8 p.m.
Phone: (843) 805-6888
Village Library
9 a.m. - 1 p.m.
Phone: (843) 884-9741
St. Paul's/Hollywood Library
9 a.m. - 8 p.m.
Phone: (843) 889-3300
Otranto Road Library
9 a.m. - 8 p.m.
Phone: (843) 572-4094
Mt. Pleasant Library
9 a.m. - 8 p.m.
Phone: (843) 849-6161
McClellanville Library
9 a.m. - 6 p.m.
Phone: (843) 887-3699
Keith Summey North Charleston Library
9 a.m. - 8 p.m.
Phone: (843) 744-2489
John's Island Library
9 a.m. - 8 p.m.
Phone: (843) 559-1945
Hurd/St. Andrews Library
9 a.m. - 8 p.m.
Phone: (843) 766-2546
Miss Jane's Building (Edisto Library Temporary Location)
2 p.m. – 6 p.m.
Phone: (843) 869-2355
Dorchester Road Library
9 a.m. - 8 p.m.
Phone: (843) 552-6466
John L. Dart Library
9 a.m. - 7 p.m.
Phone: (843) 722-7550
Baxter-Patrick James Island
9 a.m. - 8 p.m.
Phone: (843) 795-6679
Main Library
9 a.m. - 8 p.m.
Phone: (843) 805-6930
Bees Ferry West Ashley Library
9 a.m. - 8 p.m.
Phone: (843) 805-6892
Mobile Library
9 a.m. - 5 p.m.
Phone: (843) 805-6909
Today's Hours
West Ashley Library
9 a.m. - 7 p.m.
Phone: (843) 766-6635
Folly Beach Library
Closed
Phone: (843) 588-2001
Edgar Allan Poe/Sullivan's Island Library
Closed for renovations
Phone: (843) 883-3914
Wando Mount Pleasant Library
9 a.m. - 8 p.m.
Phone: (843) 805-6888
Village Library
9 a.m. - 1 p.m.
Phone: (843) 884-9741
St. Paul's/Hollywood Library
9 a.m. - 8 p.m.
Phone: (843) 889-3300
Otranto Road Library
9 a.m. - 8 p.m.
Phone: (843) 572-4094
Mt. Pleasant Library
9 a.m. - 8 p.m.
Phone: (843) 849-6161
McClellanville Library
9 a.m. - 6 p.m.
Phone: (843) 887-3699
Keith Summey North Charleston Library
9 a.m. - 8 p.m.
Phone: (843) 744-2489
John's Island Library
9 a.m. - 8 p.m.
Phone: (843) 559-1945
Hurd/St. Andrews Library
9 a.m. - 8 p.m.
Phone: (843) 766-2546
Miss Jane's Building (Edisto Library Temporary Location)
2 p.m. – 6 p.m.
Phone: (843) 869-2355
Dorchester Road Library
9 a.m. - 8 p.m.
Phone: (843) 552-6466
John L. Dart Library
9 a.m. - 7 p.m.
Phone: (843) 722-7550
Baxter-Patrick James Island
9 a.m. - 8 p.m.
Phone: (843) 795-6679
Main Library
9 a.m. - 8 p.m.
Phone: (843) 805-6930
Bees Ferry West Ashley Library
9 a.m. - 8 p.m.
Phone: (843) 805-6892
Mobile Library
9 a.m. - 5 p.m.
Phone: (843) 805-6909
Patron Login
menu
Item request has been placed!
×
Item request cannot be made.
×
![loading](/sites/all/modules/hf_eds/images/loading.gif)
Gene-Environment Interactions in Developmental Neurotoxicity: a Case Study of Synergy between Chlorpyrifos and CHD8 Knockout in Human BrainSpheres.
Item request has been placed!
×
Item request cannot be made.
×
![loading](/sites/all/modules/hf_eds/images/loading.gif)
- Author(s): Modafferi, Sergio1,2; Xiali Zhong1,3; Kleensang, Andre1; Murata, Yohei1,4; Fagiani, Francesca1,5,6; Pamies, David1,7; Hogberg, Helena T.1; Calabrese, Vittorio2; Lachman, Herbert8,9; Hartung, Thomas1,10; Smirnova, Lena1
- Source:
Environmental Health Perspectives. Jul2021, Vol. 129 Issue 7, p1-21. 21p. 2 Color Photographs, 1 Diagram, 2 Charts, 4 Graphs.- Subject Terms:
*Biomarkers; *Liquid chromatography; *Toxicity testing; *Mass spectrometry; *Environmental exposure; Genetics of autism; Autism risk factors; Neurotoxicology; Brain; In vitro studies; Reverse transcriptase polymerase chain reaction; Acetylcholinesterase; Statistics; Nerve growth factor; Energy metabolism; Syndromes; Genetic mutation; Analysis of variance; Structural models; Western immunoblotting; One-way analysis of variance; Metabolomics; Organothiophosphorus compounds; Neurotransmitters; Risk assessment; Cell survival; Oxidative stress; Gene expression; DNA-binding proteins; Fluorescent antibody technique; CRISPRs; Reactive oxygen species; Polymerase chain reaction; Data analysis - Source:
- Additional Information
- Abstract: BACKGROUND: Autism spectrum disorder (ASD) is a major public health concern caused by complex genetic and environmental components. Mechanisms of gene–environment (G × E) interactions and reliable biomarkers associated with ASD are mostly unknown or controversial. Induced pluripotent stem cells (iPSCs) from patients or with clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9)-introduced mutations in candidate ASD genes provide an opportunity to study (G × E) interactions. OBJECTIVES: In this study, we aimed to identify a potential synergy between mutation in the high-risk autism gene encoding chromodomain helicase DNA binding protein 8 (CHD8) and environmental exposure to an organophosphate pesticide (chlorpyrifos; CPF) in an iPSC-derived human threedimensional (3D) brain model. METHODS: This study employed human iPSC-derived 3D brain organoids (BrainSpheres) carrying a heterozygote CRISPR/Cas9-introduced inactivating mutation in CHD8 and exposed to CPF or its oxon-metabolite (CPO). Neural differentiation, viability, oxidative stress, and neurite outgrowth were assessed, and levels of main neurotransmitters and selected metabolites were validated against human data on ASD metabolic derangements. RESULTS: Expression of CHD8 protein was significantly lower in CHD8 heterozygous knockout (CHD8+/-) BrainSpheres compared with CHD8+/+ ones. Exposure to CPF/CPO treatment further reduced CHD8 protein levels, showing the potential (G×E) interaction synergy. A novel approach for validation of the model was chosen: from the literature, we identified a panel of metabolic biomarkers in patients and assessed them by targeted metabolomics in vitro. A synergistic effect was observed on the cholinergic system, S-adenosylmethionine, S-adenosylhomocysteine, lactic acid, tryptophan, kynurenic acid, and a-hydroxyglutaric acid levels. Neurite outgrowth was perturbed by CPF/CPO exposure. Heterozygous knockout of CHD8 in BrainSpheres led to an imbalance of excitatory/inhibitory neurotransmitters and lower levels of dopamine. DISCUSSION: This study pioneered (G × E) interaction in iPSC-derived organoids. The experimental strategy enables biomonitoring and environmental risk assessment for ASD. Our findings reflected some metabolic perturbations and disruption of neurotransmitter systems involved in ASD. The increased susceptibility of CHD8+/- BrainSpheres to chemical insult establishes a possibly broader role of (G × E) interaction in ASD [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Abstract:
Contact CCPL
Copyright 2022 Charleston County Public Library Powered By EBSCO Stacks 3.3.0 [350.3] | Staff Login
No Comments.