{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:08:15Z","timestamp":1790701695788,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,24]]},"group-title":"Neuroscience","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["K08 (ES038232)"],"award-info":[{"award-number":["K08 (ES038232)"]}]},{"name":"NIH","award":["K12 (TR005467)"],"award-info":[{"award-number":["K12 (TR005467)"]}]},{"name":"NIH","award":["U01 (AG08855)"],"award-info":[{"award-number":["U01 (AG08855)"]}]},{"name":"NIH","award":["R01 (7R01MH129732-04)"],"award-info":[{"award-number":["R01 (7R01MH129732-04)"]}]},{"name":"Skaggs Scholars Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Environmental microplastics and nanoplastics (MNPs) are emerging contaminants that accumulate in human tissues, including the brain, yet their mechanistic impact on the nervous system remains poorly understood. Converging postmortem evidence indicates increased MNP burden in brains from individuals with dementia, suggesting a potential link between plastic accumulation and disorders of the nervous system. However, whether MNPs directly contribute to brain aging and ensuing neurodegenerative processes, or disrupt neurodevelopment, is unknown. Here, we show that exposure to environmentally relevant MNPs induces cellular senescence and innate immune transcriptional programs in human brain organoids. Using region-specific cortical organoids, we demonstrate that synthetic polystyrene (PS), polyethylene terephthalate (PET), low-density polyethylene (LDPE), and high-density polyethylene (HDPE), as well as environmental ocean-derived MNPs (eMNPs) isolated from the coast of Hawaii, elicit a robust neuroinflammatory response. Transcriptomic analyses revealed activation of senescence-associated secretory phenotype (SASP) pathways. MNP exposure further disrupted neurodevelopmental trajectories, impairing neuroectodermal differentiation and redirecting lineage commitment toward mesoderm-like states, with concomitant enrichment of choroid plexus-like populations and a marked imbalance in neuronal and glial differentiation. These developmental alterations occurred in parallel with a pro-inflammatory and senescent microenvironment, suggesting coordinated disruption of developmental and aging programs. Importantly, high-density multielectrode array recordings revealed that MNP exposure altered electrophysiological activity and neuronal network dynamics, demonstrating that MNP-driven perturbations translate into dysfunctional neurological outcomes. Collectively, our findings identify MNPs as potent disruptors of human neurophysiology, linking plastic exposure to altered developmental trajectories, cellular senescence, neuroinflammation, and impaired neuronal network activity, providing mechanistic insights into how plastic accumulation may contribute to impaired brain dynamics.<\/jats:p>","DOI":"10.64898\/2026.09.18.752710","type":"posted-content","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:45:17Z","timestamp":1790311517000},"source":"Crossref","is-referenced-by-count":0,"title":["Micro- and nanoplastics alter electrophysiological brain patterns and reshape human neurodevelopmental trajectories"],"prefix":"10.64898","author":[{"given":"Cassidy L.","family":"Poynter","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"S\u00e1nchez-Carbonell","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebekah L.","family":"Kendall","sequence":"additional","affiliation":[{"name":"Center for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus A.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Administrative Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danilo","family":"Machado de Melo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxanne N.","family":"McPeck","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Mirita","sequence":"additional","affiliation":[{"name":"Advanced Light Microscopy Core, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared M.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Campen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrij","family":"Holian","sequence":"additional","affiliation":[{"name":"Center for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Cruz-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA"},{"name":"NeuroTechnology Center, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1841-4741","authenticated-orcid":false,"given":"Julio","family":"Aguado","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092909500611000_2026.09.18.752710v1.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adl2746"},{"key":"2026092909500611000_2026.09.18.752710v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03453-1"},{"key":"2026092909500611000_2026.09.18.752710v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s44360-026-00091-4"},{"key":"2026092909500611000_2026.09.18.752710v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01923-y"},{"key":"2026092909500611000_2026.09.18.752710v1.5","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13296"},{"key":"2026092909500611000_2026.09.18.752710v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-023-00519-6"},{"key":"2026092909500611000_2026.09.18.752710v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2024.04.003"},{"key":"2026092909500611000_2026.09.18.752710v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0372-9"},{"key":"2026092909500611000_2026.09.18.752710v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0543-y"},{"key":"2026092909500611000_2026.09.18.752710v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2022.11.010"},{"key":"2026092909500611000_2026.09.18.752710v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05219-6"},{"key":"2026092909500611000_2026.09.18.752710v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00804-1"},{"key":"2026092909500611000_2026.09.18.752710v1.13","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-023-00785-7"},{"key":"2026092909500611000_2026.09.18.752710v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32552-1"},{"key":"2026092909500611000_2026.09.18.752710v1.15","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl4896"},{"key":"2026092909500611000_2026.09.18.752710v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1506-7"},{"key":"2026092909500611000_2026.09.18.752710v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00497-5"},{"key":"2026092909500611000_2026.09.18.752710v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2006.08.035"},{"key":"2026092909500611000_2026.09.18.752710v1.19","doi-asserted-by":"publisher","DOI":"10.3390\/cells13211788"},{"key":"2026092909500611000_2026.09.18.752710v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2020.07.014"},{"key":"2026092909500611000_2026.09.18.752710v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.03.028"},{"key":"2026092909500611000_2026.09.18.752710v1.22","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-011-0770-y"},{"key":"2026092909500611000_2026.09.18.752710v1.23","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01794"},{"key":"2026092909500611000_2026.09.18.752710v1.24","doi-asserted-by":"publisher","DOI":"10.3390\/life12060809"},{"key":"2026092909500611000_2026.09.18.752710v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2020.01.002"},{"key":"2026092909500611000_2026.09.18.752710v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3992"},{"key":"2026092909500611000_2026.09.18.752710v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.125"},{"key":"2026092909500611000_2026.09.18.752710v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2026.106151"},{"key":"2026092909500611000_2026.09.18.752710v1.29","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16731"},{"key":"2026092909500611000_2026.09.18.752710v1.30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001664"},{"key":"2026092909500611000_2026.09.18.752710v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-024-02732-0"},{"key":"2026092909500611000_2026.09.18.752710v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2016.10.017"},{"key":"2026092909500611000_2026.09.18.752710v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.09.020"},{"key":"2026092909500611000_2026.09.18.752710v1.34","doi-asserted-by":"publisher","DOI":"10.1787\/de747aef-en"},{"key":"2026092909500611000_2026.09.18.752710v1.35","unstructured":"OECD. Plastics Use - Estimations from 1990 to 2019. (2024). OECD Data Explorer"},{"key":"2026092909500611000_2026.09.18.752710v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/protex.2018.123"},{"key":"2026092909500611000_2026.09.18.752710v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-023-02080-x"},{"key":"2026092909500611000_2026.09.18.752710v1.38","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1142"},{"key":"2026092909500611000_2026.09.18.752710v1.39","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1382-0"},{"key":"2026092909500611000_2026.09.18.752710v1.40","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01767-y"},{"key":"2026092909500611000_2026.09.18.752710v1.41","doi-asserted-by":"crossref","unstructured":"McInnes, L . UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction. arXiv 1802.03426 (2018). <https:\/\/arxiv.org\/abs\/1802.03426v3>.","DOI":"10.21105\/joss.00861"},{"key":"2026092909500611000_2026.09.18.752710v1.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2022.101121"},{"key":"2026092909500611000_2026.09.18.752710v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109229"},{"key":"2026092909500611000_2026.09.18.752710v1.44","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2026092909500611000_2026.09.18.752710v1.45","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm563"},{"key":"2026092909500611000_2026.09.18.752710v1.46","doi-asserted-by":"publisher","DOI":"10.25811\/81nc-wv41"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.18.752710","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:50:14Z","timestamp":1790700614000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.18.752710"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":46,"URL":"https:\/\/doi.org\/10.64898\/2026.09.18.752710","relation":{},"subject":[],"published":{"date-parts":[[2026,9,24]]},"subtype":"preprint"}}