Pervasive environmental chemicals impair oligodendrocyte development.
Journal
Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671
Informations de publication
Date de publication:
25 Mar 2024
25 Mar 2024
Historique:
received:
15
11
2022
accepted:
05
02
2024
medline:
26
3
2024
pubmed:
26
3
2024
entrez:
26
3
2024
Statut:
aheadofprint
Résumé
Exposure to environmental chemicals can impair neurodevelopment, and oligodendrocytes may be particularly vulnerable, as their development extends from gestation into adulthood. However, few environmental chemicals have been assessed for potential risks to oligodendrocytes. Here, using a high-throughput developmental screen in cultured cells, we identified environmental chemicals in two classes that disrupt oligodendrocyte development through distinct mechanisms. Quaternary compounds, ubiquitous in disinfecting agents and personal care products, were potently and selectively cytotoxic to developing oligodendrocytes, whereas organophosphate flame retardants, commonly found in household items such as furniture and electronics, prematurely arrested oligodendrocyte maturation. Chemicals from each class impaired oligodendrocyte development postnatally in mice and in a human 3D organoid model of prenatal cortical development. Analysis of epidemiological data showed that adverse neurodevelopmental outcomes were associated with childhood exposure to the top organophosphate flame retardant identified by our screen. This work identifies toxicological vulnerabilities for oligodendrocyte development and highlights the need for deeper scrutiny of these compounds' impacts on human health.
Identifiants
pubmed: 38528201
doi: 10.1038/s41593-024-01599-2
pii: 10.1038/s41593-024-01599-2
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
ID : R35NS116842
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
ID : T32NS077888
Organisme : U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute (National Cancer Institute Division of Cancer Epidemiology and Genetics)
ID : P30CA043703
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : T32GM007250
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.
Références
Sanmarco, L. M. et al. Identification of environmental factors that promote intestinal inflammation. Nature 611, 801–809 (2022).
pubmed: 36266581
pmcid: 9898826
doi: 10.1038/s41586-022-05308-6
Wheeler, M. A. et al. Environmental control of astrocyte pathogenic activities in CNS inflammation. Cell 176, 581–596.e18 (2019).
pubmed: 30661753
pmcid: 6440749
doi: 10.1016/j.cell.2018.12.012
Lidsky, T. I. & Schneider, J. S. Lead neurotoxicity in children: basic mechanisms and clinical correlates. Brain 126, 5–19 (2003).
pubmed: 12477693
doi: 10.1093/brain/awg014
Grandjean, P. & Landrigan, P. J. Neurobehavioural effects of developmental toxicity. Lancet Neurol. 13, 330–338 (2014).
pubmed: 24556010
pmcid: 4418502
doi: 10.1016/S1474-4422(13)70278-3
Grandjean, P. & Landrigan, P. J. Developmental neurotoxicity of industrial chemicals. Lancet 368, 2167–2178 (2006).
pubmed: 17174709
doi: 10.1016/S0140-6736(06)69665-7
Landrigan, P. J. et al. Neuropsychological dysfunction in children with chronic low-level lead absorption. Lancet 1, 708–712 (1975).
pubmed: 47481
doi: 10.1016/S0140-6736(75)91627-X
Jacobson, J. L. & Jacobson, S. W. Intellectual impairment in children exposed to polychlorinated biphenyls in utero. N. Engl. J. Med. 335, 783–789 (1996).
pubmed: 8703183
doi: 10.1056/NEJM199609123351104
Li, Q. et al. Prevalence of autism spectrum disorder among children and adolescents in the United States from 2019 to 2020. JAMA Pediatr. 176, 943–945 (2022).
pubmed: 35789247
pmcid: 9257681
doi: 10.1001/jamapediatrics.2022.1846
Chung, W. et al. Trends in the prevalence and incidence of attention-deficit/hyperactivity disorder among adults and children of different racial and ethnic groups. JAMA Netw. Open 2, e1914344 (2019).
pubmed: 31675080
pmcid: 6826640
doi: 10.1001/jamanetworkopen.2019.14344
Zhou, T. et al. A hPSC-based platform to discover gene-environment interactions that impact human beta-cell and dopamine neuron survival. Nat. Commun. 9, 4815 (2018).
pubmed: 30446643
pmcid: 6240096
doi: 10.1038/s41467-018-07201-1
Caporale, N. et al. From cohorts to molecules: adverse impacts of endocrine disrupting mixtures. Science 375, eabe8244 (2022).
pubmed: 35175820
doi: 10.1126/science.abe8244
Bercury, K. K. & Macklin, W. B. Dynamics and mechanisms of CNS myelination. Dev. Cell 32, 447–458 (2015).
pubmed: 25710531
pmcid: 6715306
doi: 10.1016/j.devcel.2015.01.016
Nave, K. A. Myelination and the trophic support of long axons. Nat. Rev. Neurosci. 11, 275–283 (2010).
pubmed: 20216548
doi: 10.1038/nrn2797
Elitt, M. S. et al. Suppression of proteolipid protein rescues Pelizaeus-Merzbacher disease. Nature 585, 397–403 (2020).
pubmed: 32610343
pmcid: 7810164
doi: 10.1038/s41586-020-2494-3
Chang, A., Tourtellotte, W. W., Rudick, R. & Trapp, B. D. Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. N. Engl. J. Med. 346, 165–173 (2002).
pubmed: 11796850
doi: 10.1056/NEJMoa010994
Jakel, S. et al. Altered human oligodendrocyte heterogeneity in multiple sclerosis. Nature 566, 543–547 (2019).
pubmed: 30747918
pmcid: 6544546
doi: 10.1038/s41586-019-0903-2
Silbereis, J. C., Pochareddy, S., Zhu, Y., Li, M. & Sestan, N. The cellular and molecular landscapes of the developing human central nervous system. Neuron 89, 248–268 (2016).
pubmed: 26796689
pmcid: 4959909
doi: 10.1016/j.neuron.2015.12.008
Giedd, J. N. et al. Brain development during childhood and adolescence: a longitudinal MRI study. Nat. Neurosci. 2, 861–863 (1999).
pubmed: 10491603
doi: 10.1038/13158
Breinlinger, S. et al. Hunting the eagle killer: a cyanobacterial neurotoxin causes vacuolar myelinopathy. Science 371, 6536 (2021).
doi: 10.1126/science.aax9050
Klose, J. et al. Neurodevelopmental toxicity assessment of flame retardants using a human DNT in vitro testing battery. Cell Biol. Toxicol. 38, 781–807 (2022).
pubmed: 33969458
doi: 10.1007/s10565-021-09603-2
Lager, A. M. et al. Rapid functional genetics of the oligodendrocyte lineage using pluripotent stem cells. Nat. Commun. 9, 3708 (2018).
pubmed: 30213958
pmcid: 6137209
doi: 10.1038/s41467-018-06102-7
Najm, F. J. et al. Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo. Nature 522, 216–220 (2015).
pubmed: 25896324
pmcid: 4528969
doi: 10.1038/nature14335
Najm, F. J. et al. Rapid and robust generation of functional oligodendrocyte progenitor cells from epiblast stem cells. Nat. Methods 8, 957–962 (2011).
pubmed: 21946668
pmcid: 3400969
doi: 10.1038/nmeth.1712
Richard, A. M. et al. ToxCast chemical landscape: paving the road to 21st century toxicology. Chem. Res. Toxicol. 29, 1225–1251 (2016).
pubmed: 27367298
doi: 10.1021/acs.chemrestox.6b00135
Sommers, K. J. et al. Quaternary phosphonium compounds: an examination of non-nitrogenous cationic amphiphiles that evade disinfectant resistance. ACS Infect. Dis. 8, 387–397 (2022).
pubmed: 35077149
pmcid: 8996050
doi: 10.1021/acsinfecdis.1c00611
Hora, P. I., Pati, S. G., McNamara, P. J. & Arnold, W. A. Increased use of quaternary ammonium compounds during the SARS-CoV-2 pandemic and beyond: consideration of environmental implications. Environ. Sci. Tech. Let. 7, 622–631 (2020).
doi: 10.1021/acs.estlett.0c00437
Takeda, R. et al. Antiviral effect of cetylpyridinium chloride in mouthwash on SARS-CoV-2. Sci. Rep. 12, 14050 (2022).
pubmed: 35982118
pmcid: 9386671
doi: 10.1038/s41598-022-18367-6
Xiao, S., Yuan, Z. & Huang, Y. Disinfectants against SARS-CoV-2: a review. Viruses 14, 1721 (2022).
pubmed: 36016342
pmcid: 9413547
doi: 10.3390/v14081721
Costa-Mattioli, M. & Walter, P. The integrated stress response: from mechanism to disease. Science 368, eaat5314 (2020).
pubmed: 32327570
pmcid: 8997189
doi: 10.1126/science.aat5314
Madhavan, M. et al. Induction of myelinating oligodendrocytes in human cortical spheroids. Nat. Methods 15, 700–706 (2018).
pubmed: 30046099
pmcid: 6508550
doi: 10.1038/s41592-018-0081-4
Pașca, S. P. et al. A nomenclature consensus for nervous system organoids and assembloids. Nature 609, 907–910 (2022).
pubmed: 36171373
pmcid: 10571504
doi: 10.1038/s41586-022-05219-6
Paul-Friedman, K. et al. Limited chemical structural diversity found to modulate thyroid hormone receptor in the Tox21 chemical library. Environ. Health Perspect. 127, 97009 (2019).
pubmed: 31566444
doi: 10.1289/EHP5314
Liu, W. et al. Prenatal exposure to halogenated, aryl, and alkyl organophosphate esters and child neurodevelopment at two years of age. J. Hazard. Mater. 408, 124856 (2021).
pubmed: 33383451
doi: 10.1016/j.jhazmat.2020.124856
Hoffman, K., Gearhart-Serna, L., Lorber, M., Webster, T. F. & Stapleton, H. M. Estimated tris(1,3-dichloro-2-propyl) phosphate exposure levels for US infants suggest potential health risks. Environ. Sci. Technol. Lett. 4, 334–338 (2017).
pubmed: 34853794
pmcid: 8630826
doi: 10.1021/acs.estlett.7b00196
Ciesielski, T. et al. Cadmium exposure and neurodevelopmental outcomes in U.S. children. Environ. Health Perspect. 120, 758–763 (2012).
pubmed: 22289429
pmcid: 3346779
doi: 10.1289/ehp.1104152
Kwon, S. & O’Neill, M. Socioeconomic and familial factors associated with gross motor skills among US children aged 3–5 years: the 2012 NHANES National Youth Fitness Survey. Int J. Environ. Res Public Health 17, 4491 (2020).
Steadman, P. E. et al. Disruption of oligodendrogenesis impairs memory consolidation in adult mice. Neuron 105, 150–164.e6 (2020).
pubmed: 31753579
doi: 10.1016/j.neuron.2019.10.013
McKenzie, I. A. et al. Motor skill learning requires active central myelination. Science 346, 318–322 (2014).
pubmed: 25324381
pmcid: 6324726
doi: 10.1126/science.1254960
Xiao, L. et al. Rapid production of new oligodendrocytes is required in the earliest stages of motor-skill learning. Nat. Neurosci. 19, 1210–1217 (2016).
pubmed: 27455109
pmcid: 5008443
doi: 10.1038/nn.4351
Kleinstreuer, N. C. et al. Phenotypic screening of the ToxCast chemical library to classify toxic and therapeutic mechanisms. Nat. Biotechnol. 32, 583–591 (2014).
pubmed: 24837663
doi: 10.1038/nbt.2914
Hogberg, H. T. et al. Organophosphorus flame retardants are developmental neurotoxicants in a rat primary brainsphere in vitro model. Arch. Toxicol. 95, 207–228 (2021).
pubmed: 33078273
doi: 10.1007/s00204-020-02903-2
Renner, H. et al. Cell-type-specific high throughput toxicity testing in human midbrain organoids. Front Mol. Neurosci. 14, 715054 (2021).
pubmed: 34335182
pmcid: 8321240
doi: 10.3389/fnmol.2021.715054
Chesnut, M., Hartung, T., Hogberg, H. & Pamies, D. Human oligodendrocytes and myelin in vitro to evaluate developmental neurotoxicity. Int. J. Mol. Sci. 22, 7929 (2021).
pubmed: 34360696
pmcid: 8347131
doi: 10.3390/ijms22157929
About List N: Disinfectants for Coronavirus (COVID-19) (United States Environmental Protection Agency, 2023); https://www.epa.gov/coronavirus/about-list-n-disinfectants-coronavirus-covid-19-0
Zheng, G., Webster, T. F. & Salamova, A. Quaternary ammonium compounds: bioaccumulation potentials in humans and levels in blood before and during the Covid-19 pandemic. Environ. Sci. Technol. 55, 14689–14698 (2021).
pubmed: 34662096
pmcid: 8547165
doi: 10.1021/acs.est.1c01654
Lin, W. & Popko, B. Endoplasmic reticulum stress in disorders of myelinating cells. Nat. Neurosci. 12, 379–385 (2009).
pubmed: 19287390
pmcid: 2697061
doi: 10.1038/nn.2273
Li, D., Sangion, A. & Li, L. Evaluating consumer exposure to disinfecting chemicals against coronavirus disease 2019 (COVID-19) and associated health risks. Environ. Int. 145, 106108 (2020).
pubmed: 32927283
pmcid: 7470762
doi: 10.1016/j.envint.2020.106108
Herron, J. M. et al. Multiomics investigation reveals benzalkonium chloride disinfectants alter sterol and lipid homeostasis in the mouse neonatal brain. Toxicol. Sci. 171, 32–45 (2019).
pubmed: 31199489
pmcid: 6736422
doi: 10.1093/toxsci/kfz139
Patisaul, H. B. et al. Beyond cholinesterase inhibition: developmental neurotoxicity of organophosphate ester flame retardants and plasticizers. Environ. Health Perspect. 129, 105001 (2021).
pubmed: 34612677
pmcid: 8493874
doi: 10.1289/EHP9285
Hou, M., Zhang, B., Fu, S., Cai, Y. & Shi, Y. Penetration of organophosphate triesters and diesters across the blood–cerebrospinal fluid barrier: efficiencies, impact factors, and mechanisms. Environ. Sci. Technol. 56, 8221–8230 (2022).
pubmed: 35658413
doi: 10.1021/acs.est.2c01850
Blum, A. et al. Organophosphate ester flame retardants: are they a regrettable substitution for polybrominated diphenyl ethers? Environ. Sci. Technol. Lett. 6, 638–649 (2019).
pubmed: 32494578
pmcid: 7269169
doi: 10.1021/acs.estlett.9b00582
Gibson, E. A. et al. Flame retardant exposure assessment: findings from a behavioral intervention study. J. Expo. Sci. Environ. Epidemiol. 29, 33–48 (2019).
pubmed: 29950671
doi: 10.1038/s41370-018-0049-6
Najm, F. J. et al. Isolation of epiblast stem cells from preimplantation mouse embryos. Cell Stem Cell 8, 318–325 (2011).
pubmed: 21362571
pmcid: 3073125
doi: 10.1016/j.stem.2011.01.016
Najm, F. J. et al. Transcription factor-mediated reprogramming of fibroblasts to expandable, myelinogenic oligodendrocyte progenitor cells. Nat. Biotechnol. 31, 426–433 (2013).
pubmed: 23584611
pmcid: 3678540
doi: 10.1038/nbt.2561
Allan, K. C. et al. Non-canonical targets of HIF1a impair oligodendrocyte progenitor cell function. Cell Stem Cell 28, 257–272.e11 (2021).
pubmed: 33091368
doi: 10.1016/j.stem.2020.09.019
Hubler, Z. et al. Accumulation of 8,9-unsaturated sterols drives oligodendrocyte formation and remyelination. Nature 560, 372–376 (2018).
pubmed: 30046109
pmcid: 6423962
doi: 10.1038/s41586-018-0360-3
Bankhead, P. et al. QuPath: open source software for digital pathology image analysis. Sci. Rep. 7, 16878 (2017).
pubmed: 29203879
pmcid: 5715110
doi: 10.1038/s41598-017-17204-5
Patro, R., Duggal, G., Love, M. I., Irizarry, R. A. & Kingsford, C. Salmon provides fast and bias-aware quantification of transcript expression. Nat. Methods 14, 417–419 (2017).
pubmed: 28263959
pmcid: 5600148
doi: 10.1038/nmeth.4197
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
pubmed: 25516281
pmcid: 4302049
doi: 10.1186/s13059-014-0550-8
Adamson, B. et al. A multiplexed single-cell CRISPR screening platform enables systematic dissection of the unfolded protein response. Cell 167, 1867–1882.e21 (2016).
pubmed: 27984733
pmcid: 5315571
doi: 10.1016/j.cell.2016.11.048
Wong, Y. L. et al. eIF2B activator prevents neurological defects caused by a chronic integrated stress response. eLife 8, e42940 (2019).
pubmed: 30624206
pmcid: 6326728
doi: 10.7554/eLife.42940
Judson, R. et al. Analysis of the effects of cell stress and cytotoxicity on in vitro assay activity across a diverse chemical and assay space. Toxicol. Sci. 153, 409 (2016).
pubmed: 27605417
pmcid: 7297301
doi: 10.1093/toxsci/kfw148
Paul Friedman, K. et al. Utility of in vitro bioactivity as a lower bound estimate of in vivo adverse effect levels and in risk-based prioritization. Toxicol. Sci. 173, 202–225 (2020).
pubmed: 31532525
doi: 10.1093/toxsci/kfz201