Application of a high-density microelectrode array assay using a 3D human iPSC-derived brain microphysiological system model for in vitro neurotoxicity screening of environmental compounds
Unraveling the associations between human exposure to environmental chemicals and potential neurotoxicity presents significant challenges. Evaluation of neurotoxicity potential using animal testing is resource-intensive (financial, labor, and animal use) and faces uncertainties regarding biological...
Gespeichert in:
| Veröffentlicht in: | Archives of toxicology Jg. 99; H. 7; S. 2917 - 2935 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Journal Article |
| Sprache: | Englisch |
| Veröffentlicht: |
Berlin/Heidelberg
Springer Berlin Heidelberg
01.07.2025
Springer Nature B.V |
| Schlagworte: | |
| ISSN: | 0340-5761, 1432-0738, 1432-0738 |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| Abstract | Unraveling the associations between human exposure to environmental chemicals and potential neurotoxicity presents significant challenges. Evaluation of neurotoxicity potential using animal testing is resource-intensive (financial, labor, and animal use) and faces uncertainties regarding biological relevance to human health outcomes. Therefore, there is a need to develop efficient and human-relevant in vitro new approach methodologies (NAMs) to screen and evaluate chemicals for neurotoxicity potential. Recording of neural network activity using microelectrode array (MEA) technology has been identified as a reliable and reproducible method for evaluating neurotoxicity. Much of this research has been performed in 2D rodent-derived cell models. The ‘BrainSpheres MEA assay’ described in this study offers a promising functional human induced pluripotent stem cell (iPSC)-derived 3D brain model comprising neurons, astrocytes, and oligodendrocytes. We demonstrate consistent spontaneous neuronal firing and network bursting parameters from 7-week-old BrainSpheres using a high-density MEA technology. The performance of this model as a human-relevant NAM was evaluated by conducting a multi-concentration, 13 day exposure study with a set of ten chemicals. Neural activity metrics were assessed and compared to results from a 2D-MEA assay using rodent cells. Loperamide and domoic acid (two assay positive controls) demonstrated similar bioactivity profiles in the BrainSphere MEA assay to the 2D-MEA assay, while acetaminophen (assay negative control) was inactive in both assays. The 2D-MEA model demonstrated more potent bioactivity for 4/7 chemicals that were active in both assays. In the future, reducing replicate variability and testing a larger set of chemicals will likely improve the accuracy and reliability of the assay. These preliminary findings suggest that the BrainSphere assay could be used alongside the rat network formation assay (rNFA) as part of a tiered strategy, where hits in the rNFA are confirmed and further characterized in the BrainSphere model, helping move toward animal-free toxicological testing. |
|---|---|
| AbstractList | Unraveling the associations between human exposure to environmental chemicals and potential neurotoxicity presents significant challenges. Evaluation of neurotoxicity potential using animal testing is resource-intensive (financial, labor, and animal use) and faces uncertainties regarding biological relevance to human health outcomes. Therefore, there is a need to develop efficient and human-relevant in vitro new approach methodologies (NAMs) to screen and evaluate chemicals for neurotoxicity potential. Recording of neural network activity using microelectrode array (MEA) technology has been identified as a reliable and reproducible method for evaluating neurotoxicity. Much of this research has been performed in 2D rodent-derived cell models. The ‘BrainSpheres MEA assay’ described in this study offers a promising functional human induced pluripotent stem cell (iPSC)-derived 3D brain model comprising neurons, astrocytes, and oligodendrocytes. We demonstrate consistent spontaneous neuronal firing and network bursting parameters from 7-week-old BrainSpheres using a high-density MEA technology. The performance of this model as a human-relevant NAM was evaluated by conducting a multi-concentration, 13 day exposure study with a set of ten chemicals. Neural activity metrics were assessed and compared to results from a 2D-MEA assay using rodent cells. Loperamide and domoic acid (two assay positive controls) demonstrated similar bioactivity profiles in the BrainSphere MEA assay to the 2D-MEA assay, while acetaminophen (assay negative control) was inactive in both assays. The 2D-MEA model demonstrated more potent bioactivity for 4/7 chemicals that were active in both assays. In the future, reducing replicate variability and testing a larger set of chemicals will likely improve the accuracy and reliability of the assay. These preliminary findings suggest that the BrainSphere assay could be used alongside the rat network formation assay (rNFA) as part of a tiered strategy, where hits in the rNFA are confirmed and further characterized in the BrainSphere model, helping move toward animal-free toxicological testing. Unraveling the associations between human exposure to environmental chemicals and potential neurotoxicity presents significant challenges. Evaluation of neurotoxicity potential using animal testing is resource-intensive (financial, labor, and animal use) and faces uncertainties regarding biological relevance to human health outcomes. Therefore, there is a need to develop efficient and human-relevant in vitro new approach methodologies (NAMs) to screen and evaluate chemicals for neurotoxicity potential. Recording of neural network activity using microelectrode array (MEA) technology has been identified as a reliable and reproducible method for evaluating neurotoxicity. Much of this research has been performed in 2D rodent-derived cell models. The 'BrainSpheres MEA assay' described in this study offers a promising functional human induced pluripotent stem cell (iPSC)-derived 3D brain model comprising neurons, astrocytes, and oligodendrocytes. We demonstrate consistent spontaneous neuronal firing and network bursting parameters from 7-week-old BrainSpheres using a high-density MEA technology. The performance of this model as a human-relevant NAM was evaluated by conducting a multi-concentration, 13 day exposure study with a set of ten chemicals. Neural activity metrics were assessed and compared to results from a 2D-MEA assay using rodent cells. Loperamide and domoic acid (two assay positive controls) demonstrated similar bioactivity profiles in the BrainSphere MEA assay to the 2D-MEA assay, while acetaminophen (assay negative control) was inactive in both assays. The 2D-MEA model demonstrated more potent bioactivity for 4/7 chemicals that were active in both assays. In the future, reducing replicate variability and testing a larger set of chemicals will likely improve the accuracy and reliability of the assay. These preliminary findings suggest that the BrainSphere assay could be used alongside the rat network formation assay (rNFA) as part of a tiered strategy, where hits in the rNFA are confirmed and further characterized in the BrainSphere model, helping move toward animal-free toxicological testing.Unraveling the associations between human exposure to environmental chemicals and potential neurotoxicity presents significant challenges. Evaluation of neurotoxicity potential using animal testing is resource-intensive (financial, labor, and animal use) and faces uncertainties regarding biological relevance to human health outcomes. Therefore, there is a need to develop efficient and human-relevant in vitro new approach methodologies (NAMs) to screen and evaluate chemicals for neurotoxicity potential. Recording of neural network activity using microelectrode array (MEA) technology has been identified as a reliable and reproducible method for evaluating neurotoxicity. Much of this research has been performed in 2D rodent-derived cell models. The 'BrainSpheres MEA assay' described in this study offers a promising functional human induced pluripotent stem cell (iPSC)-derived 3D brain model comprising neurons, astrocytes, and oligodendrocytes. We demonstrate consistent spontaneous neuronal firing and network bursting parameters from 7-week-old BrainSpheres using a high-density MEA technology. The performance of this model as a human-relevant NAM was evaluated by conducting a multi-concentration, 13 day exposure study with a set of ten chemicals. Neural activity metrics were assessed and compared to results from a 2D-MEA assay using rodent cells. Loperamide and domoic acid (two assay positive controls) demonstrated similar bioactivity profiles in the BrainSphere MEA assay to the 2D-MEA assay, while acetaminophen (assay negative control) was inactive in both assays. The 2D-MEA model demonstrated more potent bioactivity for 4/7 chemicals that were active in both assays. In the future, reducing replicate variability and testing a larger set of chemicals will likely improve the accuracy and reliability of the assay. These preliminary findings suggest that the BrainSphere assay could be used alongside the rat network formation assay (rNFA) as part of a tiered strategy, where hits in the rNFA are confirmed and further characterized in the BrainSphere model, helping move toward animal-free toxicological testing. |
| Author | Carstens, Kelly E. Zurich, Marie-Gabrielle Cuevas, Kelvin Ramirez Pamies, David Jäckel, David Lopez-Rodriguez, David Shafer, Timothy J. Gronskaya, Elena Bertoli, Jessica Dorier, Julien Wang, Shan |
| Author_xml | – sequence: 1 givenname: Kelly E. surname: Carstens fullname: Carstens, Kelly E. organization: Center for Computational Toxicology and Exposure, USA Environmental Protection Agency – sequence: 2 givenname: Elena surname: Gronskaya fullname: Gronskaya, Elena organization: MaxWell Biosystems AG – sequence: 3 givenname: David surname: Jäckel fullname: Jäckel, David organization: MaxWell Biosystems AG – sequence: 4 givenname: Jessica surname: Bertoli fullname: Bertoli, Jessica organization: Department of Biomedical Sciences, University of Lausanne – sequence: 5 givenname: Kelvin Ramirez surname: Cuevas fullname: Cuevas, Kelvin Ramirez organization: Department of Biomedical Sciences, University of Lausanne – sequence: 6 givenname: Julien surname: Dorier fullname: Dorier, Julien organization: Bioinformatics Competence Center, University of Lausanne, Bioinformatics Competence Center, Ecole Polytechnique Fédérale de Lausanne – sequence: 7 givenname: Shan surname: Wang fullname: Wang, Shan organization: Department of Biomedical Sciences, University of Lausanne – sequence: 8 givenname: David surname: Lopez-Rodriguez fullname: Lopez-Rodriguez, David organization: Department of Biomedical Sciences, University of Lausanne, Swiss Centre for Applied Human Toxicology (SCAHT), Institute of Earth Surface Dynamics, University of Lausanne – sequence: 9 givenname: Timothy J. surname: Shafer fullname: Shafer, Timothy J. organization: Center for Computational Toxicology and Exposure, USA Environmental Protection Agency – sequence: 10 givenname: Marie-Gabrielle surname: Zurich fullname: Zurich, Marie-Gabrielle organization: Department of Biomedical Sciences, University of Lausanne, Swiss Centre for Applied Human Toxicology (SCAHT) – sequence: 11 givenname: David orcidid: 0000-0002-1224-573X surname: Pamies fullname: Pamies, David email: David.pamies@unil.ch organization: Department of Biomedical Sciences, University of Lausanne, Swiss Centre for Applied Human Toxicology (SCAHT), Stem Cells and Organoid Facility, University of Lausanne |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/40293475$$D View this record in MEDLINE/PubMed |
| BookMark | eNp9kk1vEzEQhleoiKaFP8ABWeLCZWH8kez6hKpAAakSSMDZcryziatde7F3o-S_8eM6aVo-eujFPvh533k9M2fFSYgBi-Ilh7ccoHqXAQSoEsS8BAVKlrsnxYwrKUqoZH1SzEAqKOfVgp8WZzlfA3BRa_msOFUgtFTVfFb8vhiGzjs7-hhYbJllG7_elA2G7Mc9671LETt0Y4oNMpuS3TObM51T9mFNvPzANlNvA_Pfvi9JmPwWG7ZK1oejfNjss49dXFOZjuV9HrFnPdl1rI2JEbb1ZM8CTimOcefdoXJ2CTEcSlAqDFufYugxjGThYj_EKTT5efG0tV3GF3f3efHz8uOP5efy6uunL8uLq9KpqhpLx8FaFK7RjWgRV0JpJXhTtZa6CJxbV2u9aACF1KJu5wslqD_tClGBttrK8-L90XeYVj02jmIk25kh-d6mvYnWm_9fgt-YddwaLriuRS3I4c2dQ4q_Jsyj6X122HU2YJyykVzPa-D1QhH6-gF6HacU6H9GCqEAas45Ua_-jfQny_1kCaiPAE0g54StobbejpkS-s5wMIclMsclMrRE5naJzI6k4oH03v1RkTyKMsFhjelv7EdUN64K370 |
| CitedBy_id | crossref_primary_10_1016_j_pbiomolbio_2025_07_005 |
| Cites_doi | 10.1007/978-3-030-11135-9_12 10.1039/c5lc00133a 10.1557/s43577-022-00282-w 10.14573/altex.1712081 10.1002/jnr.10367 10.14573/altex.1609122 10.1016/j.tox.2024.153842 10.14573/altex.1604201 10.1016/j.neuro.2007.06.004 10.1177/1087057114532352 10.3390/biology10020086 10.22427/NICEATM-2 10.1016/j.taap.2004.05.003 10.1016/j.neuro.2016.03.019 10.1007/s00204-019-02636-x 10.1002/jnr.10508 10.1016/j.neuro.2010.10.007 10.3390/ijms22179473 10.1016/j.tiv.2022.105333 10.1093/toxsci/kfac018 10.3389/ftox.2023.1275980 10.1093/toxsci/kfab008 10.1038/nature12517 10.1016/j.ntt.2022.107117 10.1093/bioinformatics/btab779 10.1016/j.reprotox.2020.08.002 10.1093/toxsci/kfz052 10.1016/j.taap.2018.02.003 10.2741/2758 10.1038/mp.2011.13 10.1038/s41598-018-38130-0 10.1016/j.toxlet.2022.07.757 10.1093/toxsci/kfw147 10.1016/j.neuro.2018.06.007 10.1016/j.neuro.2012.05.001 10.1016/j.tifs.2023.02.006 10.1007/s00204-017-2035-5 10.1186/s13024-018-0258-4 10.1289/ehp.0800168 10.1016/j.nbd.2022.105719 10.1002/cpz1.158 10.1089/ten.TEC.2015.0375 10.1016/j.celrep.2014.12.051 10.1039/b907394a 10.1111/j.1741-4520.2012.00374.x 10.1016/j.biomaterials.2013.11.028 10.3389/fneng.2011.00004 10.1016/j.amjmed.2023.03.033 10.1258/jrsm.2007.070164 10.1016/j.neuro.2010.04.001 10.1093/toxsci/kfx169 10.1007/978-1-60761-984-0_1 10.14573/altex.2206031 10.1109/BioCAS.2014.6981723 10.1523/ENEURO.0308-23.2023 10.1038/nprot.2014.020 10.1016/j.aogh.2016.01.005 10.3390/cells12091270 10.1038/s41467-022-32115-4 10.1016/j.stem.2016.07.005 10.3389/fncel.2020.00025 10.1038/s41928-023-01069-w 10.1038/nmeth.3415 10.1038/nature13716 |
| ContentType | Journal Article |
| Copyright | The Author(s) 2025 2025. The Author(s). Copyright Springer Nature B.V. Jul 2025 The Author(s) 2025 2025 |
| Copyright_xml | – notice: The Author(s) 2025 – notice: 2025. The Author(s). – notice: Copyright Springer Nature B.V. Jul 2025 – notice: The Author(s) 2025 2025 |
| DBID | C6C AAYXX CITATION CGR CUY CVF ECM EIF NPM 7T2 7TK 7U7 C1K K9. 7X8 5PM |
| DOI | 10.1007/s00204-025-04043-x |
| DatabaseName | Springer Nature OA Free Journals CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Health and Safety Science Abstracts (Full archive) Neurosciences Abstracts Toxicology Abstracts Environmental Sciences and Pollution Management ProQuest Health & Medical Complete (Alumni) MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) ProQuest Health & Medical Complete (Alumni) Health & Safety Science Abstracts Toxicology Abstracts Neurosciences Abstracts Environmental Sciences and Pollution Management MEDLINE - Academic |
| DatabaseTitleList | CrossRef ProQuest Health & Medical Complete (Alumni) MEDLINE - Academic MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Public Health |
| EISSN | 1432-0738 |
| EndPage | 2935 |
| ExternalDocumentID | PMC12198282 40293475 10_1007_s00204_025_04043_x |
| Genre | Journal Article |
| GeographicLocations | United States--US |
| GeographicLocations_xml | – name: United States--US |
| GrantInformation_xml | – fundername: Novartis funderid: http://dx.doi.org/10.13039/100004336 – fundername: Swiss Centre for Applied Human Toxicology grantid: AP20-4 funderid: http://dx.doi.org/10.13039/501100011039 – fundername: University of Lausanne – fundername: Swiss Centre for Applied Human Toxicology grantid: AP20-4 |
| GroupedDBID | --- -Y2 .55 .86 .GJ .HR .VR 06C 06D 0R~ 0VY 199 1N0 2.D 203 23N 28- 29~ 2J2 2JN 2JY 2KG 2KM 2LR 2P1 2VQ 2~H 30V 36B 3O- 3SX 4.4 406 408 409 40D 40E 4P2 53G 5QI 5RE 5VS 67N 67Z 6NX 78A 7X7 7XC 88E 88I 8AO 8C1 8FE 8FH 8FI 8FJ 8G5 8TC 8UJ 95- 95. 95~ 96X A8Z AAAVM AABHQ AACDK AAHNG AAIAL AAJBT AAJKR AANXM AANZL AAPKM AARHV AARTL AASML AATNV AATVU AAUYE AAWCG AAYIU AAYQN AAYTO AAYZH ABAKF ABBBX ABBRH ABBXA ABDBE ABDZT ABECU ABFSG ABFTV ABHLI ABHQN ABIPD ABJNI ABJOX ABKCH ABKTR ABMNI ABMQK ABNWP ABOCM ABPLI ABQBU ABQSL ABSXP ABTEG ABTHY ABTKH ABTMW ABULA ABUWG ABWNU ABXPI ACAOD ACBXY ACDTI ACGFS ACGOD ACHSB ACHXU ACKNC ACMDZ ACMLO ACOKC ACOMO ACPIV ACPRK ACSTC ACZOJ ADBBV ADHIR ADHKG ADIMF ADJJI ADKNI ADKPE ADRFC ADTPH ADURQ ADYFF ADYPR ADZKW AEBTG AEFIE AEFQL AEGAL AEGNC AEJHL AEJRE AEKMD AEMSY AENEX AEOHA AEPYU AESKC AETLH AEVLU AEXYK AEZWR AFBBN AFDZB AFEXP AFGCZ AFHIU AFKRA AFLOW AFOHR AFQWF AFRAH AFWTZ AFZKB AGAYW AGDGC AGGDS AGJBK AGMZJ AGQEE AGQMX AGQPQ AGRTI AGWIL AGWZB AGYKE AHAVH AHBYD AHIZS AHKAY AHMBA AHPBZ AHSBF AHWEU AHYZX AIAKS AIGIU AIIXL AILAN AITGF AIXLP AJBLW AJRNO AJZVZ AKMHD ALIPV ALMA_UNASSIGNED_HOLDINGS ALWAN AMKLP AMXSW AMYLF AOCGG ARMRJ ATCPS ATHPR AXYYD AYFIA AZFZN AZQEC B-. BA0 BBWZM BDATZ BENPR BGNMA BHPHI BPHCQ BSONS BVXVI C6C CAG CCPQU COF CSCUP DDRTE DL5 DNIVK DPUIP DWQXO EBD EBLON EBS EDH EIOEI EJD EMB EMOBN EN4 EPAXT ESBYG F5P FEDTE FERAY FFXSO FIGPU FINBP FNLPD FRRFC FSGXE FWDCC FYUFA G-Y G-Z GGCAI GGRSB GJIRD GNUQQ GNWQR GQ7 GQ8 GUQSH GXS H13 HCIFZ HF~ HG5 HG6 HMCUK HMJXF HQYDN HRMNR HVGLF HZ~ I09 IHE IJ- IKXTQ IMOTQ ITM IWAJR IXC IZIGR IZQ I~X I~Z J-C J0Z JBSCW JCJTX JZLTJ KDC KOV KOW KPH LAS LLZTM M1P M2O M2P M4Y MA- N2Q N9A NB0 NDZJH NPVJJ NQJWS NU0 O9- O93 O9G O9I O9J OAM OVD P19 P2P PATMY PF0 PHGZM PHGZT PQQKQ PROAC PSQYO PT4 PT5 PYCSY Q2X QOK QOR QOS R89 R9I RHV RIG RNI RNS ROL RPX RRX RSU RSV RZK S16 S1Z S26 S27 S28 S3A S3B SAP SBL SBY SCLPG SDH SDM SHX SISQX SJYHP SNE SNPRN SNX SOHCF SOJ SPISZ SRMVM SSLCW SSXJD STPWE SV3 SZN T13 T16 TEORI TSG TSK TSV TUC U2A U9L UG4 UKHRP UOJIU UTJUX UZXMN VC2 VFIZW W23 W48 WJK WK6 WK8 X7M YLTOR Z45 ZGI ZMTXR ZOVNA ~EX ~KM AAYXX ABRTQ AFFHD BANNL CITATION PJZUB PPXIY CGR CUY CVF ECM EIF NPM 7T2 7TK 7U7 C1K K9. 7X8 5PM |
| ID | FETCH-LOGICAL-c477t-c10aae2cd9d2feeb249421d7fa007011ac8996d0e23928f5642029fbee409a9a3 |
| IEDL.DBID | RSV |
| ISICitedReferencesCount | 3 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=001489883500001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 0340-5761 1432-0738 |
| IngestDate | Tue Nov 04 02:05:13 EST 2025 Fri Sep 05 17:22:41 EDT 2025 Thu Nov 06 14:29:53 EST 2025 Sun Jun 29 01:31:19 EDT 2025 Tue Nov 18 22:00:53 EST 2025 Sat Nov 29 07:51:03 EST 2025 Thu Jun 26 01:51:13 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 7 |
| Keywords | MPS 3D cultures Neurotoxicology iPSC MEA High-density electrode array Microelectrode array BrainSphere Neuronal electrical activity |
| Language | English |
| License | 2025. The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c477t-c10aae2cd9d2feeb249421d7fa007011ac8996d0e23928f5642029fbee409a9a3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
| ORCID | 0000-0002-1224-573X |
| OpenAccessLink | https://link.springer.com/10.1007/s00204-025-04043-x |
| PMID | 40293475 |
| PQID | 3224008111 |
| PQPubID | 60277 |
| PageCount | 19 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_12198282 proquest_miscellaneous_3195801864 proquest_journals_3224008111 pubmed_primary_40293475 crossref_citationtrail_10_1007_s00204_025_04043_x crossref_primary_10_1007_s00204_025_04043_x springer_journals_10_1007_s00204_025_04043_x |
| PublicationCentury | 2000 |
| PublicationDate | 2025-07-01 |
| PublicationDateYYYYMMDD | 2025-07-01 |
| PublicationDate_xml | – month: 07 year: 2025 text: 2025-07-01 day: 01 |
| PublicationDecade | 2020 |
| PublicationPlace | Berlin/Heidelberg |
| PublicationPlace_xml | – name: Berlin/Heidelberg – name: Germany – name: Heidelberg |
| PublicationTitle | Archives of toxicology |
| PublicationTitleAbbrev | Arch Toxicol |
| PublicationTitleAlternate | Arch Toxicol |
| PublicationYear | 2025 |
| Publisher | Springer Berlin Heidelberg Springer Nature B.V |
| Publisher_xml | – name: Springer Berlin Heidelberg – name: Springer Nature B.V |
| References | PJ Landrigan (4043_CR68) 2016; 82 RJ McMurtrey (4043_CR37) 2016; 22 MG Zurich (4043_CR67) 2004; 201 AFM Johnstone (4043_CR29) 2010; 31 J Hartmann (4043_CR24) 2023 M Feshuk (4043_CR21) 2023; 5 ER McConnell (4043_CR36) 2012; 33 R Tsuji (4043_CR59) 2012; 52 X Zhong (4043_CR65) 2020; 14 D Pamies (4043_CR46) 2018; 354 ZX Wen (4043_CR63) 2014; 515 K Muguruma (4043_CR38) 2015; 10 MA Lancaster (4043_CR32) 2013; 501 HT Hogberg (4043_CR26) 2011; 32 AM Pasca (4043_CR49) 2015; 12 T Sheffield (4043_CR56) 2022; 38 EY Adashi (4043_CR1) 2023; 136 LS Gerber (4043_CR23) 2021; 1 T Takebe (4043_CR58) 2014; 9 L Berdondini (4043_CR5) 2009; 9 KM Crofton (4043_CR17) 2011; 28 4043_CR43 E van Vliet (4043_CR60) 2007; 28 TJ Shafer (4043_CR53) 2019; 22 MB Kosnik (4043_CR31) 2020; 94 CL Frank (4043_CR22) 2017; 160 C Nunes (4043_CR42) 2022 NRC (4043_CR41) 2007 D Pamies (4043_CR47) 2022; 169 JP Brown (4043_CR8) 2016; 154 J Jo (4043_CR28) 2016; 19 RA Matthews (4043_CR35) 2008; 101 MG Zurich (4043_CR66) 2002; 70 M Chesnut (4043_CR14) 2021 D Pamies (4043_CR44) 2017; 34 MM Martin (4043_CR33) 2022; 93 S Plummer (4043_CR50) 2019; 9 MM Martin (4043_CR34) 2024; 505 M Aschner (4043_CR2) 2017; 34 R Judson (4043_CR30) 2009; 117 J Muller (4043_CR39) 2015; 15 M Paparella (4043_CR48) 2020; 96 AM Tukker (4043_CR71) 2016; 33 JD Strickland (4043_CR57) 2018; 92 M Sachana (4043_CR51) 2021 JW Haycock (4043_CR25) 2011; 695 TJ Shafer (4043_CR54) 2019; 169 C Eskes (4043_CR19) 2003; 71 I Cattaneo (4043_CR12) 2023; 133 A Bal-Price (4043_CR3) 2018; 35 H Cai (4043_CR9) 2023; 6 D Zhang (4043_CR64) 2014; 35 KE Carstens (4043_CR10) 2022; 187 D Pamies (4043_CR45) 2018; 354 L Saavedra (4043_CR70) 2021; 180 EGZ Centeno (4043_CR13) 2018; 13 I Cattaneo (4043_CR11) 2022; 368 LG Costa (4043_CR16) 2008; 13 A Vassallo (4043_CR61) 2017; 60 M Schröter (4043_CR52) 2022; 47 T Sharf (4043_CR55) 2022; 13 4043_CR20 A Walzl (4043_CR62) 2014; 19 CH Chiang (4043_CR15) 2011; 16 A Novellino (4043_CR40) 2011; 4 K Bartmann (4043_CR4) 2023; 40 4043_CR7 4043_CR6 4043_CR27 MAT Elliott (4043_CR18) 2023 AM Tukker (4043_CR72) 2018; 67 |
| References_xml | – volume: 22 start-page: 275 year: 2019 ident: 4043_CR53 publication-title: Adv Neurobiol doi: 10.1007/978-3-030-11135-9_12 – volume: 15 start-page: 2767 issue: 13 year: 2015 ident: 4043_CR39 publication-title: Lab Chip doi: 10.1039/c5lc00133a – volume: 47 start-page: 530 issue: 6 year: 2022 ident: 4043_CR52 publication-title: MRS Bull doi: 10.1557/s43577-022-00282-w – volume: 35 start-page: 306 issue: 3 year: 2018 ident: 4043_CR3 publication-title: Altex doi: 10.14573/altex.1712081 – volume: 70 start-page: 108 issue: 1 year: 2002 ident: 4043_CR66 publication-title: J Neurosci Res doi: 10.1002/jnr.10367 – volume: 34 start-page: 362 issue: 3 year: 2017 ident: 4043_CR44 publication-title: Altex doi: 10.14573/altex.1609122 – volume: 505 year: 2024 ident: 4043_CR34 publication-title: Toxicology doi: 10.1016/j.tox.2024.153842 – volume: 34 start-page: 49 issue: 1 year: 2017 ident: 4043_CR2 publication-title: Altex doi: 10.14573/altex.1604201 – volume: 28 start-page: 1136 issue: 6 year: 2007 ident: 4043_CR60 publication-title: Neurotoxicology doi: 10.1016/j.neuro.2007.06.004 – volume: 19 start-page: 1047 issue: 7 year: 2014 ident: 4043_CR62 publication-title: J Biomol Screen doi: 10.1177/1087057114532352 – year: 2021 ident: 4043_CR51 publication-title: Biology (Basel) doi: 10.3390/biology10020086 – ident: 4043_CR27 doi: 10.22427/NICEATM-2 – volume: 201 start-page: 97 issue: 2 year: 2004 ident: 4043_CR67 publication-title: Toxicol Appl Pharmacol doi: 10.1016/j.taap.2004.05.003 – volume: 60 start-page: 280 year: 2017 ident: 4043_CR61 publication-title: Neurotoxicology doi: 10.1016/j.neuro.2016.03.019 – volume-title: Toxicity testing in the twenty-first century: a vision and a strategy year: 2007 ident: 4043_CR41 – volume: 94 start-page: 469 issue: 2 year: 2020 ident: 4043_CR31 publication-title: Arch Toxicol doi: 10.1007/s00204-019-02636-x – volume: 71 start-page: 583 issue: 4 year: 2003 ident: 4043_CR19 publication-title: J Neurosci Res doi: 10.1002/jnr.10508 – volume: 32 start-page: 158 issue: 1 year: 2011 ident: 4043_CR26 publication-title: Neurotoxicology doi: 10.1016/j.neuro.2010.10.007 – year: 2021 ident: 4043_CR14 publication-title: Int J Mol Sci doi: 10.3390/ijms22179473 – year: 2022 ident: 4043_CR42 publication-title: Toxicol in Vitro doi: 10.1016/j.tiv.2022.105333 – volume: 187 start-page: 62 issue: 1 year: 2022 ident: 4043_CR10 publication-title: Toxicol Sci doi: 10.1093/toxsci/kfac018 – volume: 5 start-page: 1275980 year: 2023 ident: 4043_CR21 publication-title: Front Toxicol doi: 10.3389/ftox.2023.1275980 – volume: 180 start-page: 295 issue: 2 year: 2021 ident: 4043_CR70 publication-title: Toxicol Sci doi: 10.1093/toxsci/kfab008 – volume: 501 start-page: 373 issue: 7467 year: 2013 ident: 4043_CR32 publication-title: Nature doi: 10.1038/nature12517 – volume: 93 year: 2022 ident: 4043_CR33 publication-title: Neurotoxicol Teratol doi: 10.1016/j.ntt.2022.107117 – volume: 38 start-page: 1157 issue: 4 year: 2022 ident: 4043_CR56 publication-title: Bioinformatics doi: 10.1093/bioinformatics/btab779 – volume: 96 start-page: 327 year: 2020 ident: 4043_CR48 publication-title: Reprod Toxicol (Elmsford, NY) doi: 10.1016/j.reprotox.2020.08.002 – volume: 169 start-page: 436 issue: 2 year: 2019 ident: 4043_CR54 publication-title: Toxicol Sci doi: 10.1093/toxsci/kfz052 – volume: 354 start-page: 101 year: 2018 ident: 4043_CR45 publication-title: Toxicol Appl Pharm doi: 10.1016/j.taap.2018.02.003 – ident: 4043_CR20 – volume: 13 start-page: 1240 year: 2008 ident: 4043_CR16 publication-title: Front Biosci doi: 10.2741/2758 – volume: 16 start-page: 358 issue: 4 year: 2011 ident: 4043_CR15 publication-title: Mol Psychiatr doi: 10.1038/mp.2011.13 – volume: 9 start-page: 1407 year: 2019 ident: 4043_CR50 publication-title: Sci Rep-Uk doi: 10.1038/s41598-018-38130-0 – volume: 368 start-page: S288 year: 2022 ident: 4043_CR11 publication-title: Toxicol Lett doi: 10.1016/j.toxlet.2022.07.757 – volume: 154 start-page: 126 issue: 1 year: 2016 ident: 4043_CR8 publication-title: Toxicol Sci doi: 10.1093/toxsci/kfw147 – volume: 67 start-page: 215 year: 2018 ident: 4043_CR72 publication-title: Neurotoxicol doi: 10.1016/j.neuro.2018.06.007 – volume: 33 start-page: 1048 issue: 5 year: 2012 ident: 4043_CR36 publication-title: Neurotoxicology doi: 10.1016/j.neuro.2012.05.001 – volume: 133 start-page: 277 year: 2023 ident: 4043_CR12 publication-title: Trends Food Sci Tech doi: 10.1016/j.tifs.2023.02.006 – volume: 92 start-page: 487 issue: 1 year: 2018 ident: 4043_CR57 publication-title: Arch Toxicol doi: 10.1007/s00204-017-2035-5 – volume: 13 start-page: 27 issue: 1 year: 2018 ident: 4043_CR13 publication-title: Mol Neurodegener doi: 10.1186/s13024-018-0258-4 – volume: 117 start-page: 685 issue: 5 year: 2009 ident: 4043_CR30 publication-title: Environ Health Perspect doi: 10.1289/ehp.0800168 – volume: 169 year: 2022 ident: 4043_CR47 publication-title: Neurobiol Dis doi: 10.1016/j.nbd.2022.105719 – volume: 1 issue: 6 year: 2021 ident: 4043_CR23 publication-title: Curr Protoc doi: 10.1002/cpz1.158 – volume: 22 start-page: 221 issue: 3 year: 2016 ident: 4043_CR37 publication-title: Tissue Eng Part C Methods doi: 10.1089/ten.TEC.2015.0375 – volume: 354 start-page: 101 year: 2018 ident: 4043_CR46 publication-title: Toxicol Appl Pharmacol doi: 10.1016/j.taap.2018.02.003 – volume: 10 start-page: 537 issue: 4 year: 2015 ident: 4043_CR38 publication-title: Cell Rep doi: 10.1016/j.celrep.2014.12.051 – volume: 9 start-page: 2644 issue: 18 year: 2009 ident: 4043_CR5 publication-title: Lab Chip doi: 10.1039/b907394a – volume: 52 start-page: 122 issue: 3 year: 2012 ident: 4043_CR59 publication-title: Congenit Anom (Kyoto) doi: 10.1111/j.1741-4520.2012.00374.x – volume: 35 start-page: 1420 issue: 5 year: 2014 ident: 4043_CR64 publication-title: Biomaterials doi: 10.1016/j.biomaterials.2013.11.028 – volume: 28 start-page: 9 issue: 1 year: 2011 ident: 4043_CR17 publication-title: Altex – volume: 4 start-page: 4 year: 2011 ident: 4043_CR40 publication-title: Front Neuroeng doi: 10.3389/fneng.2011.00004 – ident: 4043_CR7 – volume: 136 start-page: 853 issue: 9 year: 2023 ident: 4043_CR1 publication-title: Am J Med doi: 10.1016/j.amjmed.2023.03.033 – volume: 101 start-page: 95 issue: 2 year: 2008 ident: 4043_CR35 publication-title: J R Soc Med doi: 10.1258/jrsm.2007.070164 – volume: 31 start-page: 331 issue: 4 year: 2010 ident: 4043_CR29 publication-title: Neurotoxicology doi: 10.1016/j.neuro.2010.04.001 – volume: 160 start-page: 121 issue: 1 year: 2017 ident: 4043_CR22 publication-title: Toxicol Sci doi: 10.1093/toxsci/kfx169 – volume: 695 start-page: 1 year: 2011 ident: 4043_CR25 publication-title: Methods Mol Biol (Clifton, NJ) doi: 10.1007/978-1-60761-984-0_1 – volume: 33 start-page: 261 issue: 3 year: 2016 ident: 4043_CR71 publication-title: ALTEX – volume: 40 start-page: 452 issue: 3 year: 2023 ident: 4043_CR4 publication-title: Altex doi: 10.14573/altex.2206031 – ident: 4043_CR6 doi: 10.1109/BioCAS.2014.6981723 – year: 2023 ident: 4043_CR18 publication-title: eNeuro doi: 10.1523/ENEURO.0308-23.2023 – volume: 9 start-page: 396 issue: 2 year: 2014 ident: 4043_CR58 publication-title: Nat Protoc doi: 10.1038/nprot.2014.020 – volume: 82 start-page: 10 issue: 1 year: 2016 ident: 4043_CR68 publication-title: Ann Glob Health doi: 10.1016/j.aogh.2016.01.005 – year: 2023 ident: 4043_CR24 publication-title: Cells doi: 10.3390/cells12091270 – volume: 13 start-page: 4403 issue: 1 year: 2022 ident: 4043_CR55 publication-title: Nat Commun doi: 10.1038/s41467-022-32115-4 – volume: 19 start-page: 248 issue: 2 year: 2016 ident: 4043_CR28 publication-title: Cell Stem Cell doi: 10.1016/j.stem.2016.07.005 – volume: 14 start-page: 25 year: 2020 ident: 4043_CR65 publication-title: Front Cell Neurosci doi: 10.3389/fncel.2020.00025 – volume: 6 start-page: 1032 issue: 12 year: 2023 ident: 4043_CR9 publication-title: Nature Electronics doi: 10.1038/s41928-023-01069-w – volume: 12 start-page: 671 issue: 7 year: 2015 ident: 4043_CR49 publication-title: Nat Methods doi: 10.1038/nmeth.3415 – volume: 515 start-page: 414 issue: 7527 year: 2014 ident: 4043_CR63 publication-title: Nature doi: 10.1038/nature13716 – ident: 4043_CR43 |
| SSID | ssj0012893 |
| Score | 2.45522 |
| Snippet | Unraveling the associations between human exposure to environmental chemicals and potential neurotoxicity presents significant challenges. Evaluation of... |
| SourceID | pubmedcentral proquest pubmed crossref springer |
| SourceType | Open Access Repository Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 2917 |
| SubjectTerms | Acetaminophen Animal models Animal research Arrays Assaying Astrocytes Astrocytes - drug effects Biological activity Biomedical and Life Sciences Biomedicine Brain Brain - cytology Brain - drug effects Cell culture Cells, Cultured Chemical activity Chemicals Cosmetics Domoic acid Electrodes Environmental Health Environmental Pollutants - toxicity High density Humans In vitro methods and tests In Vitro Systems Induced Pluripotent Stem Cells - drug effects Microelectrodes Microphysiological Systems Morphology Network formation Neural networks Neurons - drug effects Neurotoxicity Neurotoxicity Syndromes - etiology Occupational Medicine/Industrial Medicine Oligodendrocytes Oligodendroglia - drug effects Pharmacology/Toxicology Pluripotency Reproducibility Rodents Stem cells Toxicity Toxicity Tests - methods |
| Title | Application of a high-density microelectrode array assay using a 3D human iPSC-derived brain microphysiological system model for in vitro neurotoxicity screening of environmental compounds |
| URI | https://link.springer.com/article/10.1007/s00204-025-04043-x https://www.ncbi.nlm.nih.gov/pubmed/40293475 https://www.proquest.com/docview/3224008111 https://www.proquest.com/docview/3195801864 https://pubmed.ncbi.nlm.nih.gov/PMC12198282 |
| Volume | 99 |
| WOSCitedRecordID | wos001489883500001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| journalDatabaseRights | – providerCode: PRVAVX databaseName: Springer LINK customDbUrl: eissn: 1432-0738 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0012893 issn: 0340-5761 databaseCode: RSV dateStart: 19970101 isFulltext: true titleUrlDefault: https://link.springer.com/search?facet-content-type=%22Journal%22 providerName: Springer Nature |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LT9wwEB61tIdKiD6BAEWu1FtrKc6G2D4iKOJQIVRatLfIcew2UsmibEDw3_hxzDgPutBWai-RooztRB7PIzPzDcD7zBXKoFnLM20tTzNDZw5vhVOZd9r7OFR4n36WR0dqOtXHfVHYfMh2H0KSQVKPxW6hjpNT-9WYIGE4Wo5PUN0pOo5fTk7H2AG6EF1T5DTmaE2LvlTm93MsqqMHNubDVMl78dKghg6e_98HvICV3uxkux2fvIRHrn4Fy90_O9aVIr2Gm927aDabeWYYgRnzknLc22t2Rrl7fduc0jHTNOaaoe2NV8qe_470k30Wmv6x6vhkDwc2KEtLVlAbim54-JEyyFvWwUiz0I2HofXMkOyywulZgNlsZ1eVpZVRtKG7TUvgW_1SmodTUEo8dYaav4FvB5--7h3yvrsDt6mULbciNsYlttRl4h06-KlOE1FKbwiCSAhj0RXMytglaMIpv4OOUpxoXziHLqnRZrIKS_WsduvATOaFEVK6Ar1JI7TyLtGE_I7WjSxsEYEYNjm3PfQ5deD4mY-gzWFvctybPOxNfhXBh3HMeQf88VfqrYF38l4IzPNJSNBVqE0ieDc-xuNLMRlTu9kF0hDYTyxUlkaw1rHauBy69nqSyp0I1AITjgQEDb74pK5-BIhwgYoIfekkgo8DL969158_Y-PfyDfhWRLYmbKXt2CpbS7cW3hqL9tq3mzDYzlV2-Fs3gJgOjgq |
| linkProvider | Springer Nature |
| linkToHtml | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1ba9VAEB6kCgri3RqtOoJvupDNSZPsY-mFisdDsbX0LWw2uzbQ5khOWtr_5o9zZnOpx6qgL4GQ2d2EmZ2dycx8A_A2sUWmyawViTJGxInmPUe30maJs8q50Fd4H07T2Sw7OlJ7fVHYYsh2H0KSXlOPxW6-jlNw-9WQIWEEWY43YzqxOJHv8_7hGDsgF6JrihyHgqxp2ZfK_H6O5ePomo15PVXyl3ipP4Z27v_fBzyAe73ZiRudnDyEG7Z-BHe7f3bYlSI9hu8bV9FsnDvUyGDGouQc9_YSTzl3r2-bU1rUTaMvkWxvunL2_Fein2yhb_qH1d7-Jg1sSJeWWHAbim64_5Ey6FvsYKTRd-NBsp6RyM4rmh49zGY7v6gMr0yqjdxtXoLe6qfSPJqCU-K5M9TiCXzZ2T7Y3BV9dwdh4jRthZGh1jYypSojZ8nBjxVxs0ydZggiKbUhVzApQxuRCZe5dXKUwki5wlpySbXSk6ewUs9r-wxQJ05qmaa2IG9SS5U5GylGfifrJi1MEYAcmJybHvqcO3Cc5CNos-dNTrzJPW_yiwDejWO-dcAff6VeG2Qn75XAIp_4BN2MTpMA3oyPaftyTEbXdn5GNAz2E8osiQNY7URtXI5cezWJ0_UAsiUhHAkYGnz5SV0de4hwSQcR-dJRAO8HWbx6rz9_xvN_I38Nt3cPPk3z6YfZxxdwJ_KizZnMa7DSNmf2Jdwy5221aF75HfoDrOU6Jg |
| linkToPdf | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3ha9UwED9kigjDOXWzbroM_KZhTV_XNh_H5kNxPB5sjn0raZpsBe0bfd3Y_jf_OO-StttzKohfCqWXpCWX5K539_sBvEtMkSk0a3kiteZxomjN4a0wWWKNtDZ0Fd4nh-lkkp2eyumdKn6X7d6HJH1NA6E01e3ORWl3hsI3V9PJiYo1JHgYjlbkw5hIg8hfPzoZ4gjoTniC5DjkaFmLrmzm930sHk337M37aZO_xE7dkTRe-f-PeQZPO3OU7Xn9WYUHpn4Oy_5fHvMlSi_gx95tlJvNLFOMQI55Sbnv7Q37Tjl9HZ1OaZhqGnXD0CbHK2XVn6H86IA5MkBWTY_2sWGDe2zJCqKn8M3dD5Z-H2YeXpo5lh6GVjVDsasKu2cOfrOdXVeaRsYtD91wGgLf6k7JHnZBqfLEGDV_CV_HH4_3P_GO9YHrOE1brkWolIl0KcvIGnT8YxlHokytImgiIZRGFzEpQxOhaZfZXXSgwkjawhh0VZVUozVYqme1eQVMJVYokaamQC9TCZlZE0lChEerJy10EYDoJzzXHSQ6MXN8ywcwZzc3Oc5N7uYmvw7g_dDmwgOC_FV6s9ejvNsc5vnIJe5meMoEsD08xmVNsRpVm9klyhAIUCiyJA5g3avdMBy6_HIUp7sBZAsKOQgQZPjik7o6d9DhAg8o9LGjAD70enn7Xn_-jNf_Jr4Fj6cH4_zw8-TLBjyJnGZTgvMmLLXNpXkDj_RVW82bt26x_gS_QkMK |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Application+of+a+high-density+microelectrode+array+assay+using+a+3D+human+iPSC-derived+brain+microphysiological+system+model+for+in+vitro+neurotoxicity+screening+of+environmental+compounds&rft.jtitle=Archives+of+toxicology&rft.au=Carstens%2C+Kelly+E.&rft.au=Gronskaya%2C+Elena&rft.au=J%C3%A4ckel%2C+David&rft.au=Bertoli%2C+Jessica&rft.date=2025-07-01&rft.pub=Springer+Berlin+Heidelberg&rft.issn=0340-5761&rft.eissn=1432-0738&rft.volume=99&rft.issue=7&rft.spage=2917&rft.epage=2935&rft_id=info:doi/10.1007%2Fs00204-025-04043-x&rft_id=info%3Apmid%2F40293475&rft.externalDocID=PMC12198282 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0340-5761&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0340-5761&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0340-5761&client=summon |