Recommendation on Test Readiness Criteria for New Approach Methods in Toxicology: Exemplified for Developmental Neurotoxicity

Altex

Volumn 35, Issue 3, 2018, Pages 306-352

  Bal Price, Anna ^a   Hogberg, Helena T ^b   Crofton, Kevin M ^c   Daneshian, Mardas ^d   FitzGerald, Rex E ^e   Fritsche, Ellen ^f   Heinonen, Tuula ^g   Bennekou, Susanne Hougaard ^h   Klima, Stefanie ^d   Piersma, Aldert H ⁱ   Sachana, Magdalini ^j   Shafer, Timothy J ^c   Terron, Andrea ^k   Monnet Tschudi, Florianne ^e,l   Viviani, Barbara ^m   Waldmann, Tanja ^d   Westerink, Remco H S ⁱ   Wilks, Martin F ^e   Witters, Hilda ⁿ   Zurich, Marie Gabrielle ^e,l   Leist, Marcel ^d   more..

^a JOINT RESEARCH CENTRE   (Italy)

^b JOHNS HOPKINS UNIVERSITY   (United States)

^c U S ENVIRONMENTAL PROTECTION AGENCY   (United States)

^d UNIVERSITY OF KONSTANZ   (Germany)

^e UNIVERSITY OF BASEL   (Switzerland)

^f HEINRICH HEINE UNIVERSITY   (Germany)

^g TAMPERE UNIVERSITY OF TECHNOLOGY   (Finland)

^h The Danish Environmental Protection Agency EPA   (Denmark)

ⁱ UTRECHT UNIVERSITY   (Netherlands)

^j OECD   (France)

^k EUROPEAN FOOD SAFETY AUTHORITY   (Italy)

^l UNIVERSITY OF LAUSANNE   (Switzerland)

^m UNIVERSITY OF MILAN   (Italy)

ⁿ FLEMISH INSTITUTE FOR TECHNOLOGICAL RESEARCH VITO   (Belgium)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ANIMAL; ANIMAL TESTING ALTERNATIVE; EDUCATION; HUMAN; PRACTICE GUIDELINE; PROCEDURES; RISK ASSESSMENT; TOXICITY AND INTOXICATION; TOXICITY TESTING; TRENDS;

ANIMAL TESTING ALTERNATIVES; ANIMALS; EDUCATION; GUIDELINES AS TOPIC; HUMANS; NEUROTOXICITY SYNDROMES; RISK ASSESSMENT; TOXICITY TESTS;

EID: 85051034983     PISSN: 1868596X     EISSN: 18688551     Source Type: Journal    
DOI: 10.14573/altex.1712081     Document Type: Article

References (366)

1. Adamo, A. M., Aloise, P. A., Soto, E. F. and Pasquini, J. M. (1990). Neonatal hyperthyroidism in the rat produces an increase in the activity of microperoxisomal marker enzymes coincident with biochemical signs of accelerated myelination. J Neurosci Res 25, 353-359. doi:10.1002/jnr.490250312
2. Addae, C., Yi, X., Gernapudi, R. et al. (2012). All-trans-retinoid acid induces the differentiation of encapsulated mouse embryonic stem cells into GABAergic neurons. Differentiation 83, 233-241. doi:10.1016/j.diff.2012.03.001
3. st century (TT21C): Making safety decisions using toxicity pathways, and progress in a prototype risk assessment. Toxicology 332, 102-111. doi:10.1016/j. tox.2014.02.007
4. Alépée, N., Bahinski, A., Daneshian, M. et al. (2014). State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology. ALTEX 31, 441-477. doi:10.14573/ altex1406111
5. Ali, S., Champagne, D. L. and Richardson, M. K. (2012). Behavioral profiling of zebrafish embryos exposed to a panel of 60 water-soluble compounds. Behav Brain Res 228, 272-283. doi:10.1016/j.bbr.2011.11.020
6. Ankley, G. T., Bennett, R. S., Erickson, R. J. et al. (2010). Adverse outcome pathways: A conceptual framework to support ecotoxicology research and risk assessment. Environ Toxicol Chem 29, 730-741. doi:10.1002/etc.34
7. Aschner, M., Ceccatelli, S., Daneshian, M. et al. (2017). Reference compounds for alternative test methods to indicate developmental neurotoxicity (DNT) potential of chemicals: Example lists and criteria for their selection and use. ALTEX 34, 49-74. doi:10.14573/altex.1604201
8. Bai, X., Yan, Y., Canfield, S. et al. (2013). Ketamine enhances human neural stem cell proliferation and induces neuronal apoptosis via reactive oxygen species-mediated mitochondrial pathway. Anesth Analg 116, 869-880. doi:10.1213/ ANE.0b013e3182860fc9
9. Bal, R., Erdogan, S., Theophilidis, G. et al. (2010). Assessing the effects of the neonicotinoid insecticide imidacloprid in the cholinergic synapses of the stellate cells of the mouse cochlear nucleus using whole-cell patch-clamp recording. Neurotoxicology 31, 113-120. doi:10.1016/j.neuro.2009.10.004
10. Balmer, N. V., Weng, M., Zimmer, B. et al. (2012). Epigenetic changes and disturbed neural development in a human embryonic stem cell-based model relating to the fetal valproate syndrome. Hum Mol Genet 21, 4104-4114. doi:10.1093/hmg/ dds239
11. Balmer, N. V. and Leist, M. (2014). Epigenetics and transcriptomics to detect adverse drug effects in model systems of human development. Basic Clin Pharmacol Toxicol 115, 59-68. doi:10.1111/bcpt.12203
12. Balmer, N. V., Klima, S., Rempel, E. et al. (2014). From transient transcriptome responses to disturbed neurodevelopment: Role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol 88, 1451-1468. doi:10.1007/s00204-014-1279-6
13. Bal-Price, A. K., Hogberg, H. T. and Buzanska, L. (2010). In vitro developmental neurotoxicity (DNT) testing: Relevant models and endpoints. Neurotoxicology 31, 545-554. doi:10.1016/j. neuro.2009.11.006
14. Bal-Price, A. K., Coecke, S., Costa, L. et al. (2012). Advancing the science of developmental neurotoxicity (DNT): Testing for better safety evaluation. ALTEX 29, 202-215. doi:10.14573/ altex.2012.2.202
15. Bal-Price, A., Crofton, K. M., Leist, M. et al. (2015a). International STakeholder NETwork (ISTNET): Creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes. Arch Toxicol 89, 269-287. doi:10.1007/s00204-015-1464-2
16. Bal-Price, A., Crofton, K. M., Sachana, M. et al. (2015b). Putative adverse outcome pathways relevant to neurotoxicity. Crit Rev Toxicol 45, 83-91. doi:10.3109/10408444.2014.981331
17. Bal-Price, A. and Meek, M. E. B. (2017). Adverse outcome pathways: Application to enhance mechanistic understanding of neurotoxicity. Pharmacol Ther 179, 84-95. doi:10.1016/j. pharmthera.2017.05.006
18. Bal-Price, A., Lein, P. J., Keil, K. P. et al. (2017). Developing and applying the adverse outcome pathway concept for understanding and predicting neurotoxicity. Neurotoxicology 59, 240-255. doi:10.1016/j.neuro.2016.05.010
19. Barenys, M., Gassmann, K., Baksmeier, C. et al. (2017). Epigallocatechin gallate (EGCG) inhibits adhesion and migration of neural progenitor cells in vitro. Arch Toxicol 91, 827-837. doi:10.1007/s00204-016-1709-8
20. Baumann, J., Barenys, M., Gassmann, K. and Fritsche, E. (2014). Comparative human and rat “neurosphere assay” for developmental neurotoxicity testing. Curr Protoc Toxicol 59, 12.21.1-24. doi:10.1002/0471140856.tx1221s59
21. Baumann, J., Dach, K., Barenys, M. et al. (2015). Application of the neurosphere assay for DNT hazard assessment: Challenges and limitations. In Methods in Pharmacology and Toxicology. Humana Press. doi:10.1007/7653_2015_49
22. Baumann, J., Gassmann, K., Masjosthusmann, S. et al. (2016). Comparative human and rat neurospheres reveal species differences in chemical effects on neurodevelopmental key events. Arch Toxicol 90, 1415-1427. doi:10.1007/s00204-015-1568-8
23. Bayer, S. A. and Altman, J. (2007). Atlas of Human Central Nervous System Development. Volumes 1-5. CRC Press.
24. Begum, A. N., Guoynes, C., Cho, J. et al. (2015). Rapid generation of sub-type, region specific neurons and neural networks from human pluripotent stem cell-derived neurospheres. Stem Cell Res 15, 731-741. doi:10.1016/j.scr.2015.10.014
25. Behl, M., Hsieh, J. H., Shafer, T. J. et al. (2015). Use of alternative assays to identify and prioritize organophosphorus flame retardants for potential developmental and neurotoxicity. Neurotoxicol Teratol 52, 181-193. doi:10.1016/j.ntt.2015.09. 003
26. Behl, M., Rice, J. R., Smith, M. V. et al. (2016). Editor’s highlight: Comparative toxicity of organophosphate flame retardants and polybrominated diphenyl ethers to Caenorhabditis elegans. Toxicol Sci 154, 241-252. doi:10.1093/toxsci/kfw162 Belvindrah, R., Graus-Porta, D., Goebbels, S. et al. (2007). Beta1 integrins in radial glia but not in migrating neurons are essential for the formation of cell layers in the cerebral cortex. J Neurosci 27, 13854-13865. doi:10.1523/JNEUROSCI.4494-07.2007
27. Benninghoff, J., Grunze, H., Schindler, C. et al. (2013). Ziprasidone – not haloperidol – induces more de-novo neurogenesis of adult neural stem cells derived from murine hippocampus. Pharmacopsychiatry 46, 10-15. doi:10.1055/s-0032-1311607
28. Berbel, P., Auso, E., Garcia-Velasco, J. V. et al. (2001). Role of thyroid hormones in the maturation and organisation of rat barrel cortex. Neuroscience 107, 383-394. doi:10.1016/ S0306-4522(01)00368-2
29. Bernal, J. (2015). Thyroid hormones in brain development and function. In L. J. De Groot, G. Chrousos, K. Dungan et al. (eds.), Endotext. South Dartmouth, MA: MDText.com, Inc. https://www.ncbi.nlm.nih.gov/books/NBK285549/
30. Bond, A. M., Bhalala, O. G. and Kessler, J. A. (2012). The dynamic role of bone morphogenetic proteins in neural stem cell fate and maturation. Dev Neurobiol 72, 1068-1084. doi:10.1002/dneu.22022
31. Borrell, V. and Götz, M. (2014). Role of radial glial cells in cerebral cortex folding. Curr Opin Neurobiol 27, 39-46. doi:10.1016/j.conb.2014.02.007
32. Bradl, M. and Lassmann, H. (2010). Oligodendrocytes: Biology and pathology. Acta Neuropathol 119, 37-53. doi:10.1007/ s00401-009-0601-5
33. Bramanti, V., Tomassoni, D., Avitabile, M. et al. (2010). Bio-markers of glial cell proliferation and differentiation in culture. Front Biosci (Schol Ed) 2, 558-570. doi:10.2741/85
34. Breier, J. M., Radio, N. M., Mundy, W. R. and Shafer, T. J. (2008). Development of a high-throughput screening assay for chemical effects on proliferation and viability of immortalized human neural progenitor cells. Toxicol Sci 105, 119-133. doi:10.1093/toxsci/kfn115
35. Brinkley, J. F., Borromeo, C., Clarkson, M. et al. (2013). The ontology of craniofacial development and malformation for translational craniofacial research. Am J Med Genet C Semin Med Genet 163C, 232-245. doi:10.1002/ajmg.c.31377
36. Brown, J. P., Hall, D., Frank, C. L. et al. (2016). Evaluation of a microelectrode array-based assay for neural network ontogeny using training set chemicals. Toxicol Sci 154, 126-139. doi:10.1093/toxsci/kfw147
37. Brown, J. P., Lynch, B. S., Curry-Chisolm, I. M. et al. (2017). Assaying spontaneous network activity and cellular viability using multi-well microelectrode arrays. Methods Mol Biol 1601, 153-170. doi:10.1007/978-1-4939-6960-9_13
38. Browne, P., Judson, R. S., Casey, W. et al. (2017). Correction to screening chemicals for estrogen receptor bioactivity using a computational model. Environ Sci Technol 51, 9415-9415. doi:10.1021/acs.est.7b03317
39. Brunelli, L., Llansola, M., Felipo, V. et al. (2012). Insight into the neuroproteomics effects of the food-contaminant non-dioxin like polychlorinated biphenyls. J Proteomics 75, 2417-2430. doi:10.1016/j.jprot.2012.02.023
40. Chattopadhyay, S., Bhaumik, S., Nag Chaudhury, A. and Das Gupta, S. (2002). Arsenic induced changes in growth development and apoptosis in neonatal and adult brain cells in vivo and in tissue culture. Toxicol Lett 128, 73-84. doi:10.1016/ S0378-4274(01)00535-5
41. Chen, J., Chen, Y., Liu, W. et al. (2012a). Developmental lead acetate exposure induces embryonic toxicity and memory deficit in adult zebrafish. Neurotoxicol Teratol 34, 581-586. doi:10.1016/j.ntt.2012.09.001
42. Chen, X., Huang, C., Wang, X. et al. (2012b). BDE-47 disrupts axonal growth and motor behavior in developing zebrafish. Aquat Toxicol 120-121, 35-44. doi:10.1016/j. aquatox.2012.04.014
43. Choi, B. H. (1989). The effects of methylmercury on the developing brain. Prog Neurobiol 32, 447-470. doi:10.1016/0301-0082(89)90018-X
44. Choi, S. H., Kim, Y. H., Hebisch, M. et al. (2014). A three-dimensional human neural cell culture model of Alzheimer’s disease. Nature 515, 274-278. doi:10.1038/nature13800
45. Choi, S. H., Kim, Y. H., Quinti, L. et al. (2016). 3D culture models of Alzheimer’s disease: A road map to a “cure-in-a-dish”.
46. Mol Neurodegener 11, 75. doi:10.1186/s13024-016-0139-7 Chow, E. S., Hui, M. N., Lin, C. C. and Cheng, S. H. (2008). Cadmium inhibits neurogenesis in zebrafish embryonic brain development. Aquat Toxicol 87, 157-169. doi:10.1016/j.aquatox.2008.01.019
47. Claudio, L., Kwa, W. C., Russell, A. L. and Wallinga, D. (2000). Testing methods for developmental neurotoxicity of environmental chemicals. Toxicol Appl Pharmacol 164, 1-14. doi:10.1006/taap.2000.8890
48. Coecke, S., Goldberg, A. M., Allen, S. et al. (2007). Workgroup report: Incorporating in vitro alternative methods for developmental neurotoxicity into international hazard and risk assessment strategies. Environ Health Perspect 115, 924-931. doi:10.1289/ehp.9427
49. Cohen, M. M. Jr. and Kreiborg, S. (1990). The central nervous system in the Apert syndrome. Am J Med Genet 35, 36-45. doi:10.1002/ajmg.1320350108
50. Cohen, S. and Greenberg, M. E. (2008). Communication between the synapse and the nucleus in neuronal development, plasticity and disease. Annu Rev Cell Dev Biol 24, 183-209. doi:10.1146/annurev.cellbio.24.110707.175235
51. Colleoni, S., Galli, C., Gaspar, J. A. et al. (2011). Development of a neural teratogenicity test based on human embryonic stem cells: Response to retinoic acid exposure. Toxicol Sci 124, 370-377. doi:10.1093/toxsci/kfr245
52. Colleoni, S., Galli, C., Gaspar, J. A. et al. (2012). Characterisation of a neural teratogenicity assay based on human ESCs differentiation following exposure to valproic acid. Curr Med Chem 19, 6065-6071. doi:10.2174/0929867311209066065
53. Coronas, V., Durand, M., Chabot, J. G. et al. (2000). Acetylcholine induces neuritic outgrowth in rat primary olfactory bulb cultures. Neuroscience 98, 213-219. doi:10.1016/S0306-4522(00)00143-3
54. Costa-Mattioli, M. and Monteggia, L. M. (2013). mTOR complexes in neurodevelopmental and neuropsychiatric disorders. Nat Neurosci 16, 1537-1543. doi:10.1038/nn.3546
55. Cotterill, E., Hall, D., Wallace, K. et al. (2016). Characterization of early cortical neural network development in multiwell microelectrode array plates. J Biomol Screen 21, 510-519. doi:10.1177/1087057116640520
56. Cowden, J., Padnos, B., Hunter, D. et al. (2012). Developmental exposure to valproate and ethanol alters locomotor activity and retino-tectal projection area in zebrafish embryos. Reprod Toxicol 33, 165-173. doi:10.1016/j.reprotox.2011.11.111
57. Crofton, K. M., Makris, S. L., Sette, W. F. et al. (2004). A qualitative retrospective analysis of positive control data in developmental neurotoxicity studies. Neurotoxicol Teratol 26, 345-352. doi:10.1016/j.ntt.2004.02.007
58. Crofton, K. M., Mundy, W. R., Lein, P. J. et al. (2011). Developmental neurotoxicity testing: Recommendations for developing alternative methods for the screening and prioritization of chemicals. ALTEX 28, 9-15. doi:10.14573/altex.2011.1.009
59. Crofton, K. M., Mundy, W. R. and Shafer, T. J. (2012). Developmental neurotoxicity testing: A path forward. Congenit Anom (Kyoto) 52, 140-146. doi:10.1111/j.1741-4520.2012.00377.x
60. Crumpton, T. L., Seidler, F. J. and Slotkin, T. A. (2000). Developmental neurotoxicity of chlorpyrifos in vivo and in vitro: Effects on nuclear transcription factors involved in cell replication and differentiation. Brain Res 857, 87-98. doi:10.1016/ S0006-8993(99)02357-4
61. Culbreth, M. E., Harrill, J. A., Freudenrich, T. M. et al. (2012). Comparison of chemical-induced changes in proliferation and apoptosis in human and mouse neuroprogenitor cells. Neurotoxicology 33, 1499-1510. doi:10.1016/j.neuro.2012.05.012
62. D’Ercole, A. J. and Ye, P. (2008). Minireview: Expanding the mind: Insulin-like growth factor I and brain development. Endocrinology 149, 5958-5962. doi:10.1210/en.2008-0920
63. Daadi, M. M., Grueter, B. A., Malenka, R. C. et al. (2012). Dopaminergic neurons from midbrain-specified human embryonic stem ceel-derived neural stem cells engrafted in a monkey model of Parkinson’s disease. PLoS One 7, e41120. doi:10.1371/journal.pone.0041120
64. Dach, K., Bendt, F., Huebenthal, U. et al. (2017). BDE-99 impairs differentiation of human and mouse NPCs into the oligodendroglial lineage by species-specific modes of action. Sci Rep 7, 44861. doi:10.1038/srep44861
65. Daneshian, M., Busquet, F., Hartung, T. et al. (2015). Animal use for science in Europe. ALTEX 32, 261-274. doi:10.14573/ altex.1509081
66. Daneshian, M., Kamp, H., Hengstler, J. et al. (2016). Launch of a large integrated European in vitro toxicology project: EU-ToxRisk. Arch Toxicol 90, 1021-1024. doi:10.1007/ s00204-016-1698-7
67. Dang, J., Tiwari, S. K., Lichinchi, G. et al. (2016). Zika virus depletes neural progenitors in human cerebral organoids through activation of the innate immune receptor TLR3. Cell Stem Cell 19, 258-265. doi:10.1016/j.stem.2016.04.014
68. de Escobar, G. M., Obregon, M. J. and del Rey, F. E. (2004). Maternal thyroid hormones early in pregnancy and fetal brain development. Best Pract Res Clin Endocrinol Metab 18, 225-248. doi:10.1016/j.beem.2004.03.012
69. Delp, J., Gutbier, S., Klima, S. et al. (2018). A high-throughput approach to identify specific neurotoxicants / developmental toxicants in human neuronal cell function assays. ALTEX 35, 235-253. doi:10.14573/altex.1712182
70. Delrue, N., Sachana, M., Sakuratani, Y. et al. (2016). The adverse outcome pathway concept: A basis for developing regulatory decision-making tools. Altern Lab Anim 44, 417-429.
71. Devakumar, D., Bamford, A., Ferreira, M. U. et al. (2018). Infectious causes of microcephaly: Epidemiology, pathogenesis, diagnosis, and management. Lancet Infect Dis 18, e1-e13. doi:10.1016/S1473-3099(17)30398-5
72. Dingemans, M. M., Schütte, M. G., Wiersma, D. M. et al. (2016). Chronic 14-day exposure to insecticides or methylmercury modulates neuronal activity in primary rat cortical cultures. Neurotoxicology 57, 194-202. doi:10.1016/j.neuro.2016.10.002
73. Dou, C. and Zhang, J. (2011). Effects of lead on neurogenesis during zebrafish embryonic brain development. J Hazard Mater 194, 277-282. doi:10.1016/j.jhazmat.2011.07.106
74. Dreser, N., Zimmer, B., Dietz, C. et al. (2015). Grouping of histone deacetylase inhibitors and other toxicants disturbing neural crest migration by transcriptional profiling. Neurotoxicology 50, 56-70. doi:10.1016/j.neuro.2015.07.008
75. Druwe, I., Freudenrich, T. M., Wallace, K. et al. (2015). Sensitivity of neuroprogenitor cells to chemical-induced apoptosis using a multiplexed assay suitable for high-throughput screening. Toxicology 333, 14-24. doi:10.1016/j.tox.2015.03.011
76. Druwe, I., Freudenrich, T. M., Wallace, K. et al. (2016). Comparison of human induced pluripotent stem cell-derived neurons and rat primary cortical neurons as in vitro models of neurite outgrowth. Appl In Vitro Toxicol 2, 26-36. doi:10.1089/ aivt.2015.0025
77. Dupin, E. and Sommer, L. (2012). Neural crest progenitors and stem cells: From early development to adulthood. Dev Biol 366, 83-95. doi:10.1016/j.ydbio.2012.02.035
78. Easton, R. M., Cho, H., Roovers, K. et al. (2005). Role for Akt3/ protein kinase bγ in attainment of normal brain size. Mol Cell Biol 25, 1869-1878. doi:10.1128/MCB.25.5.1869-1878.2005
79. Edoff, K., Raciti, M., Moors, M. et al. (2017). Gestational age and sex influence the susceptibility of human neural progenitor cells to low levels of MeHg. Neurotox Res 32, 683-693. doi:10.1007/s12640-017-9786-x
80. Efremova, L., Schildknecht, S., Adam, M. et al. (2015). Prevention of human dopaminergic neurodegeneration in an astrocytes co-culture system allowing endogenous drug metabolism. Br J Pharmacol 172, 4119-4132. doi:10.1111/bph.13193
81. Efremova, L., Chovancova, P., Adam, M. et al. (2017). Switching from astrocytic neuroprotection to neurodegeneration by cytokine stimulation. Arch Toxicol 91, 231-246. doi:10.1007/ s00204-016-1702-2
82. EFSA Panel on Plant Protection Products and their Residues. (2013). Scientific opinion on the developmental neurotoxicity potential of acetamiprid and imidacloprid. EFSA Journal 11, 3471. doi:10.2903/j.efsa.2013.3471
83. Ehrlich, D. E. and Josselyn, S. A. (2016). Plasticity-related genes in brain development and amygdala-dependent learning. Genes Brain Behav 15, 125-143. doi:10.1111/gbb.12255
84. EPA (2016). Process for Evaluating & Implementing Alternative Approaches to Traditional in vivo Acute Toxicity Studies for FIFRA Regulatory Use. US EPA Office of Pesticide Programs, 4 February 2016. https://www.epa.gov/sites/production/files/2016-03/documents/final_alternative_test_method_ guidance_2-4-16.pdf
85. Evans, R. M., Martin, O. V., Faust, M. and Kortenkamp, A. (2016). Should the scope of human mixture risk assessment span legislative/regulatory silos for chemicals? Sci Total Environ 543, 757-764. doi:10.1016/j.scitotenv.2015.10.162
86. Faivre, L., Gosset, P., Cormier-Daire, V. et al. (2002). Overgrowth and trisomy 15q26.1-qter including the IGF1 receptor gene: Report of two families and review of the literature. Eur J Hum Genet 10, 699-706. doi:10.1038/sj.ejhg.5200879
87. Falsig, J., Porzgen, P., Lund, S. et al. (2006). The inflammatory transcriptome of reactive murine astrocytes and implications for their innate immune functions. J Neurochem 96, 893-907. doi:10.1111/j.1471-4159.2005.03622.x
88. Fang, D., Hawke, D., Zheng, Y. et al. (2007). Phosphorylation of beta-catenin by AKT promotes beta-catenin transcriptional activity. J Biol Chem 282, 11221-11229. doi:10.1074/jbc. M611871200
89. Fitzpatrick, J. M. and Patlewicz, G. (2017). Application of IATA – A case study in evaluating the global and local performance of a Bayesian network model for skin sensitization. SAR QSAR Environ Res 28, 297-310. doi:10.1080/106293 6X.2017.1311941
90. Fleming, A., Diekmann, H. and Goldsmith, P. (2013). Functional characterisation of the maturation of the blood-brain barrier in larval zebrafish. PLoS One 8, e77548. doi:10.1371/journal. pone.0077548
91. Flores-Sarnat, L., Sarnat, H. B., Dávila-Gutiérrez, G. and Alvarez, A. (2003). Hemimegalencephaly: Part 2. Neuropathology suggests a disorder of cellular lineage. J Child Neurol 18, 776-785. doi:10.1177/08830738030180111101
92. Foti, S. B., Chou, A., Moll, A. D. and Roskams, A. J. (2013). HDAC inhibitors dysregulate neural stem cell activity in the postnatal mouse brain. Int J Dev Neurosci 31, 434-447. doi:10.1016/j.ijdevneu.2013.03.008
93. Frank, C. L., Brown, J. P., Wallace, K. et al. (2017). Developmental neurotoxicants disrupt formation of cortical networks on microelectrode arrays: Screening 86 compounds in the neural network formation assay. Toxicol Sci 160, 121-135. doi:10.1093/toxsci/kfx169
94. Fraser, M. M., Zhu, X., Kwon, C. H. et al. (2004). Pten loss causes hypertrophy and increased proliferation of astrocytes in vivo. Cancer Res 64, 7773-7779. doi:10.1158/0008-5472. CAN-04-2487
95. Fritsche, E., Alm, H., Baumann, J. et al. (2015). Literature review on in vitro and alternative developmental neurotoxicity (DNT) testing methods. EFSA Supporting Publications 12, 4. doi:10.2903/sp.efsa.2015.EN-778
96. Fritsche, E., Crofton, K. M., Hernandez, A. F. et al. (2017a). OECD/EFSA workshop on developmental neurotoxicity (DNT): The use of non-animal test methods for regulatory purposes. ALTEX 34, 311-315. doi:10.14573/altex.1701171
97. Fritsche, E. (2017b). Report on Integrated Testing Strategies for the identification and evaluation of chemical hazards associated with the developmental neurotoxicity (DNT), to facilitate discussions at the Joint EFSA/OECD Workshop on DNT. ENV/JM/MONO(2017)4/ANN1. https://bit.ly/2L4PPXD
98. Fuller, L. C., Cornelius, S. K., Murphy, C. W. and Wiens, D. J. (2002). Neural crest cell motility in valproic acid. Reprod Toxicol 16, 825-839. doi:10.1016/S0890-6238(02) 00059-X
99. Gantner, F., Leist, M., Küsters, S. et al. (1996). T-cell stimulus-induced crosstalk between lymphocytes and liver cells results in augmented cytokine-release. Exp Cell Res 229, 137-146. doi:10.1006/excr.1996.0351
100. st century toxicology. Pharmacol Ther 161, 11-21. doi:10.1016/j. pharmthera.2016.03.009
101. Gassmann, K., Abel, J., Bothe, H. et al. (2010). Species-specific differential AhR expression protects human neural progenitor cells against developmental neurotoxicity of PAHs. Environ Health Perspect 118, 1571-1577. doi:10.1289/ehp.0901545
102. Gassmann, K., Baumann, J., Giersiefer, S. et al. (2012). Automated neurosphere sorting and plating by the COPAS large particle sorter is a suitable method for high-throughput 3D in vitroapplications.ToxicolInVitro26,993-1000.doi:10.1016/j.tiv.2012.04.025
103. Gerhardt, E., Kügler, S., Leist, M. et al. (2001). Cascade of caspase activation in potassium-deprived cerebellar granule neurons: Targets for treatment with peptide and protein inhibitors of apoptosis. Mol Cell Neurosci 17, 717-731. doi:10.1006/ mcne.2001.0962
104. Gimenez-Llort, L., Ahlbom, E., Dare, E. et al. (2001). Prenatal exposure to methylmercury changes dopamine-modulated motor activity during early ontogeny: Age and gender-dependent effects. Environ Toxicol Pharmacol 9, 61-70. doi:10.1016/ S1382-6689(00)00060-0
105. Gomez Perdiguero, E., Schulz, C. and Geissmann, F. (2013). Development and homeostasis of “resident” myeloid cells: The case of the microglia. Glia 61, 112-120. doi:10.1002/glia.22393
106. Gordon, S., Daneshian, M., Bouwstra, J. et al. (2015). Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology. ALTEX 32, 327-378. doi:10.14573/altex.1510051
107. Grandjean, P. and Landrigan, P. J. (2006). Developmental neurotoxicity of industrial chemicals. Lancet 368, 2167-2178. doi:10.1016/S0140-6736(06)69665-7
108. Guadagnoli, T., Caltana, L., Vacotto, M. et al. (2016). Direct effects of ethanol on neuronal differentiation: An in vitro analysis of viability and morphology. Brain Res Bull 127, 177-186. doi:10.1016/j.brainresbull.2016.09.013
109. Gulisano, M., Pacini, S. Punzi, T. et al. (2009). Cadmium modulates proliferation and differentiation of human neuroblasts. J Neurosci Res 87, 228-237. doi:10.1002/jnr.21830
110. Gut, I. M., Beske, P. H., Hubbard, K. S. et al. (2013). Novel application of stem cell-derived neurons to evaluate the time- and dose-dependent progression of excitotoxic injury. PLoS One 8, e64423. doi:10.1371/journal.pone.0064423
111. Haddow, J. E., Palomaki, G. E., Allan, W. C. et al. (1999). Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med 341, 549-555. doi:10.1056/NEJM199908193410801
112. Hansen, D. V., Lui, J. H., Parker, P. R. and Kriegstein, A. R. (2010). Neurogenic radial glia in the outer subventricular zone of human neocortex. Nature 464, 554-561. doi:10.1038/ nature08845
113. Hansson, O., Castilho, R. F., Kaminski Schierle, G. S. et al. (2000). Additive effects of caspase inhibitor and lazaroid on the survival of transplanted rat and human embryonic dopamine neurons. Exp Neurol 164, 102-111. doi:10.1006/ exnr.2000.7406
114. Harrill, J. A., Freudenrich, T. M., Machacek, D. W. et al. (2010). Quantitative assessment of neurite outgrowth in human embryonic stem cell-derived hN2 cells using automated high-content image analysis. Neurotoxicology 31, 277-290. doi:10.1016/j. neuro.2010.02.003
115. Harrill, J. A., Freudenrich, T. M., Robinette, B. L. and Mundy, W. R. (2011a). Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth. Toxicol Appl Pharmacol 256, 268-280. doi:10.1016/j. taap.2011.02.013
116. Harrill, J. A., Robinette, B. L. and Mundy, W. R. (2011b). Use of high content image analysis to detect chemical-induced changes in synaptogenesis in vitro. Toxicol In Vitro 25, 368-387. doi:10.1016/j.tiv.2010.10.011
117. Harrill, J. A., Chen, H., Streifel, K. M. et al. (2015a). Ontogeny of biochemical, morphological and functional parameters of synaptogenesis in primary cultures of rat hippocampal and cortical neurons. Mol Brain 8, 10. doi:10.1186/s13041-015-0099-9
118. Harrill, J. A., Robinette, B. L., Freudenrich, T. M. and Mundy, W. R. (2015b). Media formulation influences chemical effects on neuronal growth and morphology. In Vitro Cell Dev Biol Anim 51, 612-629. doi:10.1007/s11626-015-9873-3
119. Hartung, T., Bremer, S., Casati, S. et al. (2004). A modular approach to the ECVAM principles on test validity. Altern Lab Anim 32, 467-472.
120. Hartung, T. and Leist, M. (2008). Food for thought ... on the evolution of toxicology and phasing out of animal testing. ALTEX 25, 91-96. doi:10.14573/altex.2008.2.91
121. Hartung, T., Kavlock, R. and Sturla, S. J. (2017a). Systems toxicology II: A special issue. Chem Res Toxicol 30, 869. doi:10.1021/acs.chemrestox.7b00038
122. Hartung, T., FitzGerald, R. E., Jennings, P. et al. (2017b). Systems toxicology: Real world applications and opportunities. Chem Res Toxicol 30, 870-882. doi:10.1021/acs.chemrestoz. 7b00003
123. He, X., Imanishi, S., Sone, H. et al. (2012). Effects of methylmercury exposure on neuronal differentiation of mouse and human embryonic stem cells. Toxicol Lett 212, 1-10. doi:10.1016/j.toxlet.2012.04.011
124. He, X., Gao, J., Dong, T. et al. (2016). Developmental neurotoxicity of methamidophos in the embryo-larval stages of zebrafish. Int J Environ Res Public Health 14, 23. doi:10.3390/ ijerph14010023
125. Hennessy, B. T., Smith, D. L., Ram, P. T. et al. (2005). Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov 4, 988-1004. doi:10.1038/nrd1902
126. Henrichs, J., Bongers-Schokking, J. J., Schenk, J. J. et al. (2010). Maternal thyroid function during early pregnancy and cognitive functioning in early childhood: The generation R study. J Clin Endocrinol Metab 95, 4227-4234. doi:10.1210/jc.2010-0415
127. Hevner, R. F. (2005). The cerebral cortex malformation in thanatophoric dysplasia: Neuropathology and pathogenesis. Acta Neuropathol 110, 208-221. doi:10.1007/s00401-005-1059-8
128. Hevner, R. F. (2015). Brain overgrowth in disorders of RTKPI3K-AKT signaling: A mosaic of malformations. Semin Perinatol 39, 36-43. doi:10.1053/j.semperi.2014.10.006
129. Heyer, D. B. and Meredith, R. M. (2017). Environmental toxicology: Sensitive periods of development and neurodevelopmental disorders. Neurotoxicology 58, 23-41. doi:10.1016/j. neuro.2016.10.017
130. Hirsch, C., Striegl, B., Mathes, S. et al. (2017). Multiparameter toxicity assessment of novel DOPO-derived organophosphorus flame retardants. Arch Toxicol 91, 407-425, doi:10.1007/ s00204-016-1680-4
131. Hirt, U., Gantner, F. and Leist, M. (2000). Phagocytosis of non-apoptotic cells dying by caspase-independent mechanisms. J Immunol 164, 6520-6529. doi:10.3390/ijms17122068
132. Hoareau, C., Hazane, F., Le Pen, G. and Krebs, M. O. (2006). Postnatal effect of embryonic neurogenesis disturbance on reelin level in organotypic cultures of rat hippocampus. Brain Res 1097, 43-51. doi:10.1016/j.brainres.2006.04.075
133. Hoelting, L., Scheinhardt, B., Bondarenko, O. et al. (2013). A 3-dimensional human embryonic stem cell (hESC)-derived model to detect developmental neurotoxicity of nanoparticles.
134. Arch Toxicol 87, 721-733. doi:10.1007/s00204-012-0984-2 Hoelting, L., Klima, S., Karreman, C. et al. (2016). Stem cell-derived immature human dorsal root ganglia neurons to identify peripheral neurotoxicants. Stem Cells Transl Med 5, 476-487. doi:10.5966/sctm.2015-0108
135. Hogberg, H. T. and Bal-Price, A. K. (2011). Domoic acid-induced neurotoxicity is mainly mediated by the AMPA/KA Receptor: Comparison between immature and mature primary cultures of neurons and glial cells from rat cerebellum. J Toxicol 2011, 543512. doi:10.1155/2011/543512
136. Hogberg, H. T., Sobanski, T., Novellino, A. et al. (2011). Application of micro-electrode arrays (MEAs) as an emerging technology for developmental neurotoxicity: Evaluation of domoic acid-induced effects in primary cultures of rat cortical neurons. Neurotoxicology 32, 158-168. doi:10.1016/j.neuro.2010.10.007
137. Hogberg, H. T., Bressler, J., Christian, K. M. et al. (2013). Toward a 3D model of human brain development for studying gene/environment interactions. Stem Cell Res Ther 4, Suppl 1, S4. doi:10.1186/scrt365
138. Hondebrink, L., Verboven, A. H. A., Drega, W. S. et al. (2016). Neurotoxicity screening of (illicit) drugs using novel methods for analysis of microelectrode array (MEA) recordings. Neurotoxicology 55, 1-9. doi:10.1016/j.neuro.2016.04.020
139. Hondebrink, L., Kasteel, E. E. J., Tukker, A. M. et al. (2017). Neuropharmacological characterization of the new psychoactive substance methoxetamine. Neuropharmacology 123, 1-9. doi:10.1016/j.neuropharm.2017.04.035
140. Howe, K., Clark, M. D., Torroja, C. F. et al. (2013). The zebrafish reference genome sequence and its relationship to the human genome. Nature 496, 498-503. doi:10.1038/nature12111
141. Hu, X., Yuan, Y, Wang, D. and Su, Z. (2016). Heterogeneous astrocytes: Active players in CNS. Brain Res Bull 125, 1-18. doi:10.1016/j.brainresbull.2016.03.017
142. Huang, E. J. and Reichardt, L. F. (2003). Trk receptors: Roles in neuronal signal transduction. Annu Rev Biochem 72, 609-642. doi:10.1146/annurev.biochem.72.121801.161629
143. Huang, X. and Saint-Jeannet, J. P. (2004). Induction of the neural crest and the opportunities of life on the edge. Dev Biol 275, 1-11. doi:10.1016/j.ydbio.2004.07.033
144. Huber, A. B., Kolodkin, A. L., Ginty, D. D. and Cloutier, J. F. (2003). Signaling at the growth cone: Ligand-receptor complexes and the control of axon growth and guidance. Annu Rev Neurosci 26, 509-563. doi:10.1146/annurev.neuro.26.010302.081139
145. Huber, K. M., Klann, E., Costa-Mattioli, M. et al. (2015). Dysregulation of mammalian target of rapamycin signaling in mouse models of autism. J Neurosci 35, 13836-13842. doi:10.1523/JNEUROSCI.2656-15.2015
146. Hutson, M. S., Leung, M. C. K., Baker, N. C. et al. (2017). Computational model of secondary palate fusion and disruption. Chem Res Toxicol 30, 965-979. doi:10.1021/acs.chemrestox. 6b00350
147. Iaconelli, J., Lalonde, J., Watmuff, B. et al. (2017). Lysine deacetylation by HDAC6 regulates the kinase activity of AKT in human neural progenitor cells. ACS Chem Biol 12, 2139-2148. doi:10.1021/acschembio.6b01014
148. Jarema, K. A., Hunter, D. L., Shaffer, R. M. et al. (2015). Acute and developmental behavioral effects of flame retardants and related chemicals in zebrafish. Neurotoxicol Teratol 52, 194-209. doi:10.1016/j.ntt.2015.08.010
149. Jin, Y., Zhu, Z., Wang, Y. et al. (2016). The fungicide imazalil induces developmental abnormalities and alters locomotor activity during early developmental stages in zebrafish. Chemosphere 153, 455-161. doi:10.1016/j.chemosphere.2016. 03.085
150. Kadereit, S., Zimmer, B., van Thriel, C. et al. (2012). Compound selection for in vitro modeling of developmental neurotoxicity. Front Biosci (Landmark Ed) 17, 2442-2460. doi:10.2741/4064 Kapucu, F. E., Tanskanen, J. M., Mikkonen, J. E. et al. (2012). Burst analysis tool for developing neuronal networks exhibiting highly varying action potential dynamics. Front Comput Neurosci 6, 38. doi:10.3389/fncom.2012.00038
151. Khan, K. M., Collier, A. D., Meshalkina, D. A. et al. (2017). Zebrafish models in neuropsychopharmacology and CNS drug discovery. Br J Pharmacol 174, 1925-1944. doi:10.1111/ bph.13754
152. Khor, Y. M., Soga, T. and Parhar, I. S. (2013). Caffeine neuroprotects against dexamethasone-induced anxiety-like behaviour in the Zebrafish (Danio rerio). Gen Comp Endocrinol 181, 310-315. doi:10.1016/j.ygcen.2012.09.021
153. Kiecker, C. and Lumsden, A. (2005). Compartments and their boundaries in vertebrate brain development. Nat Rev Neurosci 6, 553-564. doi:10.1038/nrn1702
154. Kigerl, K. A., Gensel, J. C., Ankeny, D. P. et al. (2009). Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci 29, 13435-13444. doi:10.1523/JNEUROSCI.3257-09.2009
155. Kiiski, H., Aänismaa, R., Tenhunen, J. et al. (2013). Healthy human CSF promotes glial differentiation of hESC-derived neural cells while retaining spontaneous activity in existing neuronal networks. Biol Open 2, 605-612. doi:10.1242/ bio.20134648
156. Kim, Y. G. and Lee, Y. I. (2012). Differential expressions of synaptogenic markers between primary cultured cortical and hippocampal neurons. Exp Neurobiol 21, 61-67. doi:10.5607/ en.2012.21.2.61
157. Kindlundh-Hogberg, A. M., Pickering, C., Wicher, G. et al. (2010). MDMA (ecstasy) decreases the number of neurons and stem cells in embryonic cortical cultures. Cell Mol Neurobiol 30, 13-21. doi:10.1007/s10571-009-9426-y
158. Kleiderman, S., Gutbier, S., Tufekci, K. U. et al. (2016a). Conversion of non-proliferating astrocytes into neurogenic neural stem cells: Control by FGF2 and IFN-gamma. Stem Cells 34, 2861-2874. doi:10.1002/stem.2483
159. Kleiderman, S., Sá, J. V., Teixeira, A. P. et al. (2016b). Functional and phenotypic differences of pure populations of stem cell-derived astrocytes and neuronal precursor cells. Glia 64, 695-715. doi:10.1002/glia.22954
160. Kleinstreuer, N., Dix, D., Rountree, M. et al. (2013). A computational model predicting disruption of blood vessel development. PLoS Comput Biol 9, e1002996. doi:10.1371/journal. pcbi.1002996
161. Kolb, B. and Gibb, R. (2011). Brain plasticity and behaviour in the developing brain. J Can Acad Child Adolesc Psychiatry 20, 265-276.
162. Kriegstein, A., Noctor S. and Martinez-Cerdeno, V. (2006). Patterns of neural stem and progenitor cell division may underlie evolutionary cortical expansion. Nat Rev Neurosci 7, 883-890. doi:10.1038/nrn2008
163. Krstic, D., Madhusudan, A., Doehner, J. et al. (2012). Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice. J Neuroinflammation 9, 151. doi: 10.1186/1742-2094-9-151
164. Krstic, D. and Knuesel, I. (2013). Deciphering the mechanism underlying late-onset Alzheimer disease. Nat Rev Neurol 9, 25-34. doi:10.1038/nrneurol.2012.236
165. Krug, A. K., Balmer, N. V., Matt, F. et al. (2013). Evaluation of a human neurite growth assay as specific screen for developmental neurotoxicants. Arch Toxicol 87, 2215-2231. doi:10.1007/s00204-013-1072-y
166. 4). ALTEX 27, 17-42. doi:10.14573/altex.2010.1.16
167. Kuegler, P. B., Baumann, B. A., Zimmer, B. et al. (2012). GFAP-independent inflammatory competence and trophic functions of astrocytes generated from murine embryonic stem cells. Glia 60, 218-228. doi:10.1002/glia.21257
168. Lancaster, M. A., Renner, M., Martin, C. A. et al. (2013). Cerebral organoids model human brain development and microcephaly. Nature 501, 373-379. doi:10.1038/nature12517
169. Laurenza, I., Pallocca, G., Mennecozzi, M. et al. (2013). A human pluripotent carcinoma stem cell-based model for in vitro developmental neurotoxicity testing: Effects of methylmercury, lead and aluminum evaluated by gene expression studies. Int J Dev Neurosci 31, 679-691. doi:10.1016/j. ijdevneu.2013.03.002
170. Lee, C. T., Chen, J., Kindberg, A. A. et al. (2017). CYP3A5 mediates effects of cocaine on human neocorticogenesis: Studies using an in vitro 3D self-organized hPSC model with a single cortex-like unit. Neuropsychopharmacology 42, 774-784. doi:/10.1038/npp.2016.156
171. Lee, G., Papapetrou, E. P., Kim, H. et al. (2009). Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature 461, 402-406. doi:10.1038/ nature08320
172. Lee, J. and Freeman J. L. (2014). Zebrafish as a model for investigating developmental lead (Pb) neurotoxicity as a risk factor in adult neurodegenerative disease: A mini-review. Neurotoxicology 43, 57-64. doi:/10.1016/j.neuro.2014.03.008
173. Legradi, J., el Abdellaoui, N., van Pomeren, M. and Legler, J. (2015). Comparability of behavioural assays using zebrafish larvae to assess neurotoxicity. Environ Sci Pollut Res Int 22, 16277-16289. doi:10.1007/s11356-014-3805-8
174. Lein, P., Silbergeld, E., Locke, P. and Goldberg, A. M. (2005). In vitro and other alternative approaches to developmental neurotoxicity testing (DNT). Environ Toxicol Pharmacol 19, 735-744. doi:10.1016/j.etap.2004.12.035
175. Leist, M., Hartung, T. and Nicotera, P. (2008a). The dawning of a new age of toxicology. ALTEX 25, 103-114. doi:10.14573/ altex.2008.2.103
176. Leist, M., Bremer, S., Brundin, P. et al. (2008b). The biological and ethical basis of the use of embryonic stem cells for in vitro tests and cell therapy. ALTEX 25, 163-190. doi:10.14573/ altex.2008.3.163
177. Leist, M., Efremova, L. and Karreman, C. (2010). Food for thought on considerations and guidelines for basic test method descriptions in toxicology. ALTEX 27, 309-317. doi:10.14573/ altex.2010.4.309
178. Leist, M., Hasiwa, N., Daneshian, M. et al. (2012). Validation and quality control of replacement alternatives – Current status and future challenges. Toxicol Res 1, 8-22 doi:10.1039/ c2tx20011b
179. Leist, M., Hasiwa, N., Rovida, C. et al. (2014). Consensus report on the future of animal-free systemic toxicity testing. ALTEX 31, 341-356. doi:10.14573/altex.1406091
180. Leist, M., Ghallab, A., Graepel, R. et al. (2017). Adverse outcome pathways: Opportunities, limitations and open questions. Arch Toxicol 91, 3477-3505 doi:10.1007/s00204-017-2045-3
181. Lesiak, A., Zhu, M., Chen, H. et al. (2014). The environmental neurotoxicant PCB 95 promotes synaptogenesis via ryanodine receptor-dependent miR132 upregulation. J Neurosci 34, 717-725. doi:10.1523/JNEUROSCI.2884-13.2014
182. Leung, M. C. K., Hutson, M. S., Seifert, A. W. et al. (2016). Computational modeling and simulation of genital tubercle development. Reprod Toxicol 64, 151-161. doi:10.1016/j.reprotox.2016.05.005
183. Lewitus, E., Kelave, I. and Huttner, W. B. (2013). Conical expansion of the outer subventricular zone and the role of ceocortical folding in evolution and development. Front Hum Neurosci 7, 424. doi:10.3389/fnhum.2013.00424
184. Li, B., He, X., Sun, Y. and Li, B. (2016). Developmental exposure to paraquat and maneb can impair cognition, learning and memory in Sprague-Dawley rats. Mol Biosyst 12, 3088-3097. doi:10.1039/C6MB00284F
185. Li, L., Liu, F., Salmonsen, R. A. et al. (2002). PTEN in neural precursor cells: Regulation of migration, apoptosis, and proliferation. Mol Cell Neurosci 20, 21-29. doi:10.1006/ mcne.2002.1115
186. Liddelow, S. A., Guttenplan, K. A., Clarke, L. E. et al. (2017). Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541, 481-487. doi:10.1038/nature21029
187. Lipton, J. O. and Sahin, M. (2014). The neurology of mTOR. Neuron 84, 275-291. doi:10.1016/j.neuron.2014.09.034
188. Lonze, B. E. and Ginty, D. D. (2002). Function and regulation of CREB family transcription factors in the nervous system. Neuron 35, 605-623. doi:10.1016/S0896-6273(02)00828-0
189. López-Espíndola, D., Morales-Bastos, C., Grijota-Martínez, C. et al. (2014). Mutations of the thyroid hormone transporter MCT8 cause prenatal brain damage and persistent hypomyelination. J Clin Endocrinol Metab 99, E2799-2804. doi:10.1210/jc.2014-2162
190. Lotharius, J., Barg, S., Wiekop, P. et al. (2002). Effect of mutant alpha-synuclein on dopamine homeostasis in a new human mesencephalic cell line. J Biol Chem 277, 38884-38894. doi:10.1074/jbc.M205518200
191. Lu, Y., Christian, K. and Lu, B. (2008). BDNF: A key regulator for protein synthesis dependent LTP and long-term memory? Neurobiol Learn Mem 89, 312-323. doi:10.1016/j. nlm.2007.08.018
192. Lund, S., Porzgen, P., Mortensen, A. L. et al. (2006). The dynamics of the LPS triggered inflammatory response of murine microglia under different culture and in vivo conditions. J Neuroimmunol 180, 71-87. doi:10.1016/j.jneuroim.2006.07.007
193. Madill, M., Fitzgerald, D., O’Connell, K. E. et al. (2016). In vitro and ex vivo models of multiple sclerosis. Drug Discov Today 21, 1504-1511. doi:10.1016/j.drudis.2016.05.018
194. Manning, B. D. and Toker, A. (2017). AKT/PKB signaling: Navigating the network. Cell 169, 381-405. doi:10.1016/j. cell.2017.04.001
195. Markus, T., Hansson, S. R., Cronberg, T. et al. (2010). beta-adrenoceptor activation depresses brain inflammation and is neuroprotective in lipopolysaccharide-induced sensitization to oxygen-glucose deprivation in organotypic hippocampal slices. J Neuroinflammation 7, 94. doi:10.1186/1742-2094-7-94
196. Marx, U., Andersson, T. B., Bahinski, A. et al. (2016). Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing using animals. ALTEX 33, 272-321. doi:10.14573/altex.1603161
197. Marx-Stoelting, P., Adriaens, E., Ahr, H. J. et al. (2009). A review of the implementation of the embryonic stem cell test (EST). The report and recommendations of an ECVAM/ReProTect workshop. Altern Lab Anim 37, 313-328.
198. Mattson, M. P. (2008). Glutamate and neurotrophic factors in neuronal plasticity and disease. Ann N Y Acad Sci 1144, 97-112. doi:10.1196/annals.1418.005
199. McCarthy, D. M., Zhang, X., Darnell, S. B. et al. (2011). Cocaine alters BDNF expression and neuronal migration in the embryonic mouse forebrain. J Neurosci 31, 13400-13411. doi:10.1523/JNEUROSCI.2944-11.2011
200. McCarthy, M. M. (2008). Estradiol and the developing brain. Physiol Rev 88, 91-124. doi:10.1152/physrev.00010.2007
201. Meek, M. E. and Lipscomb, J. C. (2015). Gaining acceptance for the use of in vitro toxicity assays and QIVIVE in regulatory risk assessment. Toxicology 332, 112-123. doi:10.1016/j. tox.2015.01.010
202. Menegola, E., Broccia, M. L., Di Renzo, F. et al. (2005). Craniofacial and axial skeletal defects induced by the fungicide triadimefon in the mouse. Birth Defects Res B Dev Reprod Toxicol 74, 185-195. doi:10.1002/bdrb.20035
203. Miller, J. A., Ding, S. L., Sunkin, S. M. et al. (2014). Transcriptional landscape of the prenatal human brain. Nature 508, 199-206. doi:10.1038/nature13185
204. Molofsky, A. V. and Deneend, B. (2015). Astrocyte development: A guide for the perplexed. Glia 63, 1320-1329. doi:10.1002/ glia.22836
205. Monnet-Tschudi, F., Zurich, M. G. and Honegger, P. (1993). Evaluation of the toxicity of different metal compounds in the developing brain using aggregating cell cultures as a model. Toxicol In Vitro 7, 335-339. doi:10.1016/0887-2333(93)90024-Y
206. Monnet-Tschudi, F., Zurich, M. G. and Honegger, P. (1996). Comparison of the developmental effects of two mercury compounds on glial cells and neurons in aggregate cultures of rat telencephalon. Brain Res 741, 52-59. doi:10.1016/S0006-8993(96)00895-5
207. Monnet-Tschudi, F., Zurich, M. G., Sorg, O. et al. (1999). The naturally occurring food mycotoxin fumonisin B1 impairs myelin formation in aggregating brain cell culture. Neurotoxicology 20, 41-48.
208. Monnet-Tschudi, F., Zurich, M. G., Schilter, B. et al. (2000). Maturation-dependent effects of chlorpyrifos and parathion and their oxygen analogs on acetylcholinesterase and neuronal and glial markers in aggregating brain cell cultures. Toxicol Appl Pharmacol 165, 175-183. doi:10.1006/taap.2000.8934
209. Monteggia, L. M., Barrot, M., Powell, C. M. et al. (2004). Essential role of brain-derived neurotrophic factor in adult hippocampal function. Proc Natl Acad Sci U S A 101, 10827-10832. doi:10.1073/pnas.0402141101
210. Moors, M., Cline, J. E., Abel, J. and Fritsche, E. (2007). ERK-dependent and -independent pathways trigger human neural progenitor cell migration. Toxicol Appl Pharmacol 221, 57-67. doi:10.1016/j.taap.2007.02.018
211. Moors, M., Rockel, T. D., Abel, J. et al. (2009). Human neurospheres as three-dimensional cellular systems for developmental neurotoxicity testing. Environ Health Perspect 117, 1131-1138. doi:10.1289/ehp.0800207
212. Moors, M., Vudattu, N. K., Abel, J. et al. (2010). Interleukin-7 (IL-7) and IL-7 splice variants affect differentiation of human neural progenitor cells. Genes Immun 11, 11-20. doi:10.1038/ gene.2009.77
213. Moors, M., Bose, R., Johansson-Hague, K. et al. (2012). Dickkopf 1 mediates glucocorticoid-induced changes in human neural progenitor cell proliferation and differentiation. Toxicol Sci 125, 488-495. doi:10.1093/toxsci/kfr304
214. 2+/calmodulin-dependent protein kinase IV pathway. Endocrinology 151, 810-820. doi:10.1210/en.2009-0958
215. nd edition. Academic Press. doi:10.1016/B978-0-12-418669-9.09987-6
216. Mundy, W. R., Radio, N. M. and Freudenrich, T. M. (2010). Neuronal models for evaluation of proliferation in vitro using high content screening. Toxicology 270, 121-130. doi:10.1016/j. tox.2010.02.004
217. Mundy, W. R., Padilla, S., Breier, J. M. et al. (2015). Expanding the test set: Chemicals with potential to disrupt mammalian brain development. Neurotoxicol Teratol 52, 25-35. doi:10.1016/j.ntt.2015.10.001
218. Nagappan, G. and Lu, B. (2005). Activity-dependent modulation of the BDNF receptor TrkB: Mechanisms and implications. Trends Neurosci 28, 464-471. doi:10.1016/j.tins.2005.07.003
219. Nash, R., Krishnamoorthy, M., Jenkins, A. and Csete, M. (2012). Human embryonic stem cell model of ethanol-mediated early developmental toxicity. Exp Neurol 234, 127-135. doi:10.1016/j.expneurol.2011.12.022
220. 2+): Effect on synaptic function. Mol Neurobiol 42, 151-160. doi:10.1007/s00210-008-0344-1
221. Nelson, T. J. and Alkon, D. L. (2015). Molecular regulation of synaptogenesis during associative learning and memory. Brain Res 1621, 239-251 doi:10.1016/j.brainres.2014.11.054
222. Ninomiya, E., Hattori, T., Toyoda, M. et al. (2014). Glucocorticoids promote neural progenitor cell proliferation derived from human induced pluripotent stem cells. Springerplus 3, 527. doi:10.1186/2193-1801-3-527
223. Nishimura, Y., Murakami, S., Ashikawa, Y. et al. (2015). Zebrafish as a systems toxicology model for developmental neurotoxicity testing. Congenit Anom (Kyoto) 55, 1-16. doi:10.1111/ cga.12079
224. Noyes, P. D., Haggard, D. E., Gonnerman, G. D. and Tanguay, R. L. (2015). Advanced morphological – Behavioral test platform reveals neurodevelopmental defects in embryonic zebrafish exposed to comprehensive suite of halogenated and organophosphate flame retardants. Toxicol Sci 145, 177-195. doi:10.1093/toxsci/kfv044
225. Nyffeler, J., Karreman, C., Leisner, H. et al. (2017a). Design of a high-throughput human neural crest cell migration assay to indicate potential developmental toxicants. ALTEX 34, 75-94. doi:10.14573/altex.1605031
226. Nyffeler, J., Dolde, X., Krebs, A. et al. (2017b). Combination of multiple neural crest migration assay to identify environmental toxicants from a proof-of-concept chemical library. Arch Toxicol 91, 3613-3632. doi:10.1007/s00204-017-1977-y
227. Nygard, M., Wahlstrom, G. M., Gustafsson, M. V. et al. (2003). Hormone-dependent repression of the E2F-1 gene by thyroid hormone receptors. Mol Endocrinol 17, 79-92. doi:10.1210/ me.2002-0107
228. rd edition. John Wiley & Sons, Inc. doi:10.1002/0471973084
229. nd edition. ENV/JM/MONO(2013)6. Series on Testing and Assessment No. 184, OECD Publishing, Paris. https://bit.ly/1RJXOEx
230. OECD (2014a). New Scoping Document on In Vitro and Ex Vivo Assays for the Identification of Modulators of Thyroid Hormone Signalling. ENV/JM/MONO(2014)23. Series on Testing and Assessment No. 207, OECD Publishing, Paris. doi:10.1787/20777876
231. OECD (2014b). Guidance Document for Describing Non-Guideline In Vitro Test Methods. ENV/JM/MONO(2014)35. Series on Testing and Assessment No. 211, OECD Publishing, Paris. doi:10.1787/20777876
232. OECD (2016a). Guidance Document for the Use of Adverse Outcome Pathways in Developing Integrated Approaches to Testing and Assessment (IATA). ENV/JM/MONO(2016)67. Series on Testing and Assessment No. 260, OECD Publishing, Paris. https://bit.ly/2IJNOC3
233. OECD (2016b). Guidance Document on the Reporting of Defined Approaches and Individual Information Sources to be used within Integrated Approaches to Testing and Assessment for Skin Sensitisation. ENV/JM/MONO(2016)29. Series on Testing and Assessment No. 256, OECD Publishing, Paris. doi:10.1787/20777876
234. OECD (2016c). Guidance Document on the Reporting of Defined Approaches to be Used Within Integrated Approaches to Testing and Assessment. ENV/JM/MONO(2016)28. Series on Testing and Assessment No. 255, OECD Publishing, Paris. doi:10.1787/20777876
235. OECD (2017). Draft Guidance Document on Good In Vitro Method Practices (GIVIMP) for the Development and Implementation of In Vitro Methods for Regulatory Use in Human Safety Assessment. OECD Paris. https://bit.ly/2LaoZgU
236. Orsolits, B., Borsy, A., Madarasz, E. et al. (2013). Retinoid machinery in distinct neural stem cell populations with different retinoid responsiveness. Stem Cells Dev 22, 2777-2793. doi:10.1089/scd.2012.0422
237. Padilla, S., Hunter, D. L., Padnos, B. et al. (2011). Assessing locomotor activity in larval zebrafish: Influence of extrinsic and intrinsic variables. Neurotoxicol Teratol 33, 624-630. doi:10.1016/j.ntt.2011.08.005
238. Pal, R., Mamidi, M. K., Das, A. K. and Bhonde, R. (2011). Human embryonic stem cell proliferation and differentiation as parameters to evaluate developmental toxicity. J Cell Physiol 226, 1583-1595. doi:10.1002/jcp.22484
239. Pallocca, G., Fabbri, M., Sacco, M. G. et al. (2013). miRNA expression profiling in a human stem cell-based model as a tool for developmental neurotoxicity testing. Cell Biol Toxicol 29, 239-257, doi:10.1007/s10565-013-9250-5
240. Pallocca, G., Grinberg, M., Henry, M. et al. (2016). Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol 90, 159-180. doi:10.1007/ s00204-015-1658-7
241. Palmer, J. A., Poenitzsch, A. M., Smith, S. M. et al. (2012). Metabolic biomarkers of prenatal alcohol exposure in human embryonic stem cell-derived neural lineages. Alcohol Clin Exp Res 36, 1314-1324. doi:10.1111/j.1530-0277.2011.01732.x
242. Pamies, D., Barreras, P., Block, K. et al. (2017a). A human brain microphysiological system derived from induced pluripotent stem cells to study neurological diseases and toxicity. ALTEX 34, 362-376. doi:10.14573/altex.1609122
243. Pamies, D., Bal-Price, A., Simeonov, A. et al. (2017b). Good cell culture practice for stem cells and stem-cell-derived models. ALTEX 34, 95-132. doi:10.14573/altex.1607121
244. st century toxicology. Chem Res Toxicol 30, 43-52. doi:10.1021/acs.chemrestox.6b00269
245. Panula, P., Chen, Y. C., Priyadarshini, M. et al. (2010). The comparative neuroanatomy and neurochemistry of zebrafish CNS systems of relevance to human neuropsychiatric diseases. Neurobiol Dis 40, 46-57. doi:10.1016/j.nbd.2010.05.010
246. Park, H. and Poo, M. M. (2013). Neurotrophin regulation of neural circuit development and function. Nat Rev Neurosci 14, 7-23. doi:10.1038/nrn3379
247. Parker, M. O., Brock, A. J., Walton, R. T. et al. (2013). The role of zebrafish (Danio rerio) in dissecting the genetics and neural circuits of executive function. Front Neural Circuits 7, 63. doi:10.3389/fncir.2013.00063
248. Parker, M. O., Annan, L. V., Kanellopoulos, A. H. et al. (2014). The utility of zebrafish to study the mechanisms by which ethanol affects social behavior and anxiety during early brain development. Prog Neuropsychopharmacol Biol Psychiatry 55, 94-100, doi:10.1016/j.pnpbp.2014.03.011
249. Patlewicz, G., Kuseva, C., Kesova, A. et al. (2014). Towards AOP application – Implementation of an integrated approach to testing and assessment (IATA) into a pipeline tool for skin sensitization. Regul Toxicol Pharmacol 69, 529-545. doi:10.1016/j.yrtph.2014.06.001
250. Pearce, R. G., Setzer, R. W., Davis, J. L. and Wambaugh, J. F. (2017). Evaluation and calibration of high-throughput predictions of chemical distribution to tissues. J Pharmacokinet Pharmacodyn 44, 549-565. doi:10.1007/s10928-017-9548-7
251. Perez-Gomez, A. and Tasker, R. A. (2012). Enhanced neurogenesis in organotypic cultures of rat hippocampus after transient subfield-selective excitotoxic insult induced by domoic acid. Neuroscience 208, 97-108. doi:10.1016/j. neuroscience.2012.02.003
252. Piersma, A. H., Bosgra, S., van Duursen, M. B. et al. (2013). Evaluation of an alternative in vitro test battery for detecting reproductive toxicants. Reprod Toxicol 38, 53-64. doi:10.1016/j.reprotox.2013.03.002
253. Piersma, A. H., Ezendam, J., Luijten, M. et al. (2014). A critical appraisal of the process of regulatory implementation of novel in vivo and in vitro methods for chemical hazard and risk assessment. Crit Rev Toxicol 44, 876-894. doi:10.3109/104084 44.2014.940445
254. Pistollato, F., Louisse, J., Scelfo, B. et al. (2014). Development of a pluripotent stem cell derived neuronal model to identify chemically induced pathway perturbations in relation to neurotoxicity: Effects of CREB pathway inhibition. Toxicol Appl Pharmacol 280, 378-388. doi:10.1016/j.taap.2014.08.007
255. Pistollato, F., Canovas-Jorda, D., Zagoura, D. and Price, A. (2017). Protocol for the differentiation of human induced pluripotent stem cells into mixed cultures of neurons and glia for neurotoxicity testing. J Vis Exp 124, e55702. doi:10.3791/55702
256. Planchart, A., Mattingly, C., Allen, D. et al. (2016). Advancing toxicology research using in vivo high throughput toxicology with small fish models. ALTEX 33, 435-452. doi:10.14573/ altex.1601281
257. Popova, D. and Jacobsson, S. O. (2014). A fluorescence micro-plate screen assay for the detection of neurite outgrowth and neurotoxicity using an antibody against betaIII-tubulin. Toxicol In Vitro 28, 411-418. doi:10.1016/j.tiv.2013.12.009
258. Puehringer, D., Orel, N., Lüningschrör, P. et al. (2013). EGF transactivation of Trk receptors regulates the migration of newborn cortical neurons. Nat Neurosci 16, 407-415. doi:10.1038/nn.3333
259. Quasthoff, S. and Hartung, H. P. (2002). Chemotherapy-induced peripheral neuropathy. J Neurol 249, 9-17. doi:10.1007/ PL00007853
260. Qian, X., Nguyen, H. N., Song, M. M. et al. (2016). Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell 165, 1238-1254. doi:10.1016/j. cell.2016.04.032
261. Radio, N. M., Breier, J. M., Reif, D. M. et al. (2015). Use of neural models of proliferation and neurite outgrowth to screen environmental chemicals in the ToxCast phase I library. Appl In Vitro Toxicol 1, 131-139. doi:10.1089/aivt.2014.0009
262. Raffaele, K. C., Rowland, J., May, B. et al. (2010). The use of developmental neurotoxicity data in pesticide risk assessments. Neurotoxicol Teratol 32, 563-572. doi:10.1016/j. ntt.2010.04.053
263. Ryan, K. R., Sirenko, O., Parham, F. et al. (2016). Neurite outgrowth in human induced pluripotent stem cell-derived neurons as a high-throughput screen for developmental neurotoxicity or neurotoxicity. Neurotoxicology 53, 271-281. doi:10.1016/j.neuro.2016.02.003
264. Reif, D. M., Martin, M. T., Tan, S. W. et al. (2010). Endocrine profiling and prioritization of environmental chemicals using ToxCast data. Environ Health Perspect 118, 1714-1720. doi:10.1289/ehp.1002180
265. Reif, D. M., Sypa, M., Lock, E. F. et al. (2013). ToxPi GUI: An interactive visualization tool for transparent integration of data from diverse sources of evidence. Bioinformatics 29, 402-403. doi:10.1093/bioinformatics/bts686
266. Reif, D., Truong, L., Mandrell, D. et al. (2016). High-throughput characterization of chemical-associated embryonic behavioral changes predicts teratogenic outcomes. Arch Toxicol 90, 1459-1470. doi:10.1007/s00204-015-1554-1
267. Rempel, E., Hölting, L., Waldmann, T. et al. (2015). A transcriptome-based classifier to identify developmental toxicants by stem cell testing: Design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol 89, 1599-1618. doi:10.1007/s00204-015-1573-y
268. st century toxicology. Chem Res Toxicol 29, 1225-1251. doi:10.1021/acs. chemrestox.6b00135
269. Rigamonti, A., Repetti, G., Sun, C. et al. (2016). Large-scale production of mature neurons from human pluripotent stem cells in a three-dimensional suspension culture system. Stem Cell Reports 6, 93-1008. doi:10.1016/j.stemcr.2016.05.010
270. Robinette, B. L., Harrill, J. A., Mundy, W. R. and Shafer, T. J. (2011). In vitro assessment of developmental neurotoxicity: Use of microelectrode arrays to measure functional changes in neuronal network ontogeny. Front Neuroeng 4, 1. doi:10.3389/ fneng.2011.00001
271. st century beyond environmental chemicals. ALTEX 32, 171-181. doi:10.14573/altex.1506201
272. Rowitch, D. H. (2004). Glial specification in the vertebrate neural tube. Nat Rev Neurosci 5, 409-419. doi:10.1038/nrn1389
273. Sachana, M., Munn, S. and Bal-Price, A. (2016). Adverse outcome pathway on chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities. OECD Series on Adverse Outcome Pathways No. 5, OECD Publishing, Paris. doi:10.1787/5jlsqs5hcrmq-en
274. Salamon, N., Andres, M., Chute, D. J. et al. (2006). Contralateral hemimicrencephaly and clinical-pathological correlations in children with hemimegalencephaly. Brain 129, 352-365. doi:10.1093/brain/awh681
275. Sànchez-Màrtin, F. J., Fan, X., Lindquist, D. M. et al. (2013). Lead induces similar gene expression changes in brains of gestationally exposed adult mice and in neurons differentiated from mouse embryonic stem cells. PLoS One 8, e80558. doi:10.1371/journal.pone.0080558
276. Sandström von Tobel, J., Zoia, D., Althaus, J. et al. (2014). Immediate and delayed effects of subchronic Paraquat exposure during an early differentiation stage in 3D-rat brain cell cultures. Toxicol Lett 230, 188-197. doi:10.1016/j. toxlet.2014.02.001
277. Sandström, J., Broyer, A., Zoia, D. et al. (2017a). Potential mechanisms of development-dependent adverse effects of the herbicide paraquat in 3D rat brain cell cultures. Neurotoxicology 60, 116-124. doi:10.1016/j.neuro.2017.04.010
278. Sandström, J., Eggermann, E., Charvet, I. et al. (2017b). Development and characterization of a human embryonic stem cell-derived 3D neural tissue model for neurotoxicity testing. Toxicol In Vitro 38, 124-135. doi:10.1016/j.tiv.2016.10.001
279. Santos-Fandila, A., Vasquez, E., Barranco, A. et al. (2015). Analysis of 17 neurotransmitters, metabolites and precursors in zebrafish through the life cycle using ultrahigh performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 1001, 191-201. doi:10.1016/j.jchromb.2015.07.040
280. +. Antioxid Redox Signal 23, 1001-1016. doi:10.1089/ ars.2015.6297
281. Schildknecht, S., Di Monte, D. A., Pape, R. et al. (2017). Tipping points and endogenous determinants of nigrostriatal degeneration by MPTP. Trends Pharmacol Sci 38, 541-555. doi:10.1016/j.tips.2017.03.010
282. Schmidt, B. Z., Lehmann, M., Gutbier, S. et al. (2017). In vitro acute and developmental neurotoxicity screening: An overview of cellular platforms and high-throughput technical possibilities. Arch Toxicol 91, 1-33. doi:10.1007/s00204-016-1805-9
283. Schmidt, R., Strähle, U. and Scholpp, S. (2013). Neurogenesis in zebrafish – From embryo to adult. Neural Dev 8, 3. doi:10.1186/1749-8104-8-3
284. Schmuck, M. R., Temme, T., Dach, K. et al. (2017). Omnisphero: A high-content image analysis (HCA) approach for phenotypic developmental neurotoxicity (DNT) screenings of organoid neurosphere cultures in vitro. Arch Toxicol 91, 2017-2028. doi:10.1007/s00204-016-1852-2
285. Scholz, D., Pöltl, D., Genewsky, A. et al. (2011). Rapid, complete and large-scale generation of post-mitotic neurons from the human LUHMES cell line. J Neurochem 119, 957-971. doi:10.1111/j.1471-4159.2011.07255.x
286. Schreiber, T., Gassmann, K., Götz, C. et al. (2010). Polybrominated diphenyl ethers induce developmental neurotoxicity in a human in vitro model: Evidence for endocrine disruption. Environ Health Perspect 118, 572-578. doi:10.1289/ehp. 0901435
287. 2+/cAMP response element binding protein in cultured neurons. Toxicol Appl Pharmacol 182, 176-185. doi:10.1006/taap.2002.9445
288. Schultz, L., Zurich, M. G., Culot, M. et al. (2015). Evaluation of drug-induced neurotoxicity based on metabolomics, proteomics and electrical activity measurements in complementary CNS in vitro models. Toxicol In Vitro 30, 138-165. doi:10.1016/j.tiv.2015.05.016
289. Schwartz, M. P., Hou, Z., Propson, N. E. et al. (2015). Human pluripotent stem cell-derived neural constructs for predicting neural toxicity. Proc Natl Acad Sci U S A 112, 12516-12521. doi:10.1073/pnas.1516645112
290. Selderslaghs, I. W., Hooyberghs, J., De Coen, W. and Witters, H. E. (2010). Locomotor activity in zebrafish embryos: A new method to assess developmental neurotoxicity. Neurotoxicol Teratol 32, 460-471. doi:10.1016/j.ntt.2010.03.002
291. Selderslaghs, I. W., Hooyberghs, J., Blust, R. and Witters, H. E. (2013). Assessment of the developmental neurotoxicity of compounds by measuring locomotor activity in zebrafish embryos and larvae. Neurotoxicol Teratol 37, 44-56. doi:10.1016/j.ntt.2013.01.003
292. Senut, M. C., Sen, A., Cingolani, P. et al. (2014). Lead exposure disrupts global DNA methylation in human embryonic stem cells and alters their neuronal differentiation. Toxicol Sci 139, 142-161. doi:10.1093/toxsci/kfu028
293. Shang, E. H. and Zhdanova, I. V. (2007). The circadian system is a target and modulator of prenatal cocaine effects. PLoS One 2, e587, doi:10.1371/journal.pone.0000587
294. Shi, P., Scott, M. A., Ghosh, B. et al. (2011). Synapse microarray identification of small molecules that enhance synaptogenesis. Nat Commun 2, 510-519. doi:10.1038/ncomms1518
295. Shinde, V., Klima, S., Sureshkumar, P. S. et al. (2015). Human pluripotent stem cell based developmental toxicity assays for chemical safety screening and systems biology data generation. J Vis Exp 100, e52333. doi:10.3791/52333
296. Shinde, V., Hoelting, L., Perumal, S. S. et al. (2016). Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development – Introduction of the STOP-Toxukn and STOP-Toxukk. Arch Toxicol 91, 839-864. doi:10.1007/s00204-016-1741-8
297. Shinozaki, Y., Shibata, K., Yoshida, K. et al. (2017). Transformation of astrocytes to a neuroprotective phenotype by microglia via P2Y1 receptor downregulation. Cell Rep 19, 1151-1164. doi:10.1016/j.celrep.2017.04.047
298. Silbereis, J. C., Pochareddy, S., Zhu, Y. et al. (2016). The cellular and molecular landscapes of the developing human central nervous system. Neuron 89, 248-268. doi:10.1016/j. neuron.2015.12.008
299. Simão, D., Terrasso, A. P., Teixeira, A. P. et al. (2016). Functional metabolic interactions of human neuron-astrocyte 3D in vitro networks. Sci Rep 6, 33285. doi:10.1038/srep33285
300. Slikker, W. Jr., Liu, F., Rainosek, S. W. et al. (2015). Ketamine-induced toxicity in neurons differentiated from neural stem cells. Mol Neurobiol 52, 959-969. doi:10.1007/s12035-015-9248-5
301. Slotkin, T. A. and Seidler, F. J. (2012). Developmental neurotoxicity of organophosphates targets cell cycle and apoptosis, revealed by transcriptional profiles in vivo and in vitro. Neurotoxicol Teratol 34, 232-241. doi:10.1016/j.ntt.2011.12.001
302. Smart, I. H., Dehay, C., Giroud, P. et al. (2002). Unique morphological features of the proliferative zones and postmitotic compartments of the neural epithelium giving rise to striate and extrastriate cortex in the monkey. Cereb Cortex 12, 37-53. doi:10.1093/cercor/12.1.37
303. st century and in vitro opportunities. ALTEX 31, 129-156. doi:10.14573/ altex.1403271
304. Smirnova, L., Harris, G., Delp, J. et al. (2016). A LUHMES 3D dopaminergic neuronal model for neurotoxicity testing allowing long-term exposure and cellular resilience analysis. Arch Toxicol 90, 2725-2743. doi:10.1007/s00204-015-1637-z
305. Soulé, J., Messaoudi, E. and Bramham, C. R. (2006). Brain-derived neurotrophic factor and control of synaptic consolidation in the adult brain. Biochem Soc Trans 34, 600-604. doi:10.1042/BST0340600
306. Souza, B. S., Sampaio, G. L., Pereira, C. S. et al. (2016). Zika virus infection induces mitosis abnormalities and apoptotic cell death of human neural progenitor cells. Sci Rep 6, 39775. doi:10.1038/srep39775
307. Stiegler, N. V., Krug, A. K., Matt, F. and Leist, M. (2011). Assessment of chemical-induced impairment of human neurite outgrowth by multiparametric live cell imaging in high-density cultures. Toxicol Sci 121, 73-87. doi:10.1093/ toxsci/kfr034
308. Strickland, J. D., Martin, M., Houck, T. et al. (2017). Screening the ToxCast phase II libraries for neuroactivity using cortical neurons grown on multi-well microelectrode array (mwMEA) plates. Arch Toxicol 92, 487-500. doi:10.1007/s00204-017-2035-5
309. Stummann, T. C., Hareng, L. and Bremer, S. (2009). Hazard assessment of methylmercury toxicity to neuronal induction in embryogenesis using human embryonic stem cells. Toxicology 257, 117-126. doi:10.1016/j.tox.2008.12.018
310. Suarez-Isla, B. A., Pelto, D. J., Thompson, J. M. and Rapoport, S. I. (1984). Blockers of calcium permeability inhibit neurite extension and formation of neuromuscular synapses in cell culture. Brain Res 316, 263-270. doi:10.1016/0165-3806(84)90311-0
311. Talens-Visconti, R., Sanchez-Vera, I., Kostic, J. et al. (2011). Neural differentiation from human embryonic stem cells as a tool to study early brain development and the neuroteratogenic effects of ethanol. Stem Cells Dev 20, 327-339. doi:10.1089/ scd.2010.0037
312. Tamm, C. and Ceccatelli, S. (2017). Mechanistic insight into neurotoxicity induced by developmental insults. Biochem Biophys Res Commun 482, 408-418. doi:10.1016/j. bbrc.2016.10.087
313. Tang, H., Hammack, C., Ogden, S. C. et al. (2016). Zika virus infects human cortical neural progenitors and attenuates their growth. Cell Stem Cell 18, 587-590. doi:10.1016/j. stem.2016.02.016
314. Tasneem, S., Farrell, K., Lee, M. Y. and Kothapalli, C. R. (2016). Sensitivity of neural stem cell survival, differentiation and neurite outgrowth within 3D hydrogels to environmental heavy metals. Toxicol Lett 242, 9-22. doi:10.1016/j. toxlet.2015.11.021
315. Terron, A., Bal-Price, A., Paini, A. et al. (2018). An adverse outcome pathway for parkinsonian motor deficits associated with mitochondrial complex I inhibition. Arch Toxicol 92, 41-82. doi:10.1007/s00204-017-2133-4
316. Tiedeken, J. A., Ramsdell, J. S. and Ramsdell, A. F. (2005). Developmental toxicity of domoic acid in zebrafish (Danio rerio). Neurotoxicol Teratol 27, 711-717. doi:10.1016/j. ntt.2005.06.013
317. Tofighi, R., Wan Ibrahim, W. N., Rebellato, P. et al. (2011). Non-dioxin-like polychlorinated biphenyls interfere with neuronal differentiation of embryonic neural stem cells. Toxicol Sci 124, 192-201. doi:10.1093/toxsci/kfr221
318. Tokuda, S., Mahaffey C. L, Monks, B. et al. (2011). A novel Akt3 mutation associated with enhanced kinase activity and seizure susceptibility in mice. Hum Mol Genet 20, 988-999. doi:10.1093/hmg/ddq544
319. Tollefsen, K. E., Scholz, S., Cronin, M. T. et al. (2014). Applying adverse outcome pathways (AOPs) to support Integrated approaches to testing and assessment (IATA). Regul Toxicol Pharmacol 70, 629-640. doi:10.1016/j.yrtph.2014.09.009
320. Tonduti, D., Vanderver, A., Berardinelli, A. et al. (2013). MCT8 deficiency: Extrapyramidal symptoms and delayed myelination as prominent features. J Child Neurol 28, 795-800. doi:10.1177/0883073812450944
321. Tonk, E. C., Pennings, J. L. and Piersma, A. H. (2015). An adverse outcome pathway framework for neural tube and axial defects mediated by modulation of retinoic acid homeostasis. Reprod Toxicol 55, 104-113. doi:10.1016/j.reprotox.2014.10.008
322. 2+ exposure alters NMDAR subtypes and reduces CREB phosphorylation in the rat brain. Dev Brain Res 139, 217-226. doi:10.1016/S0165-3806(02)00569-2
323. Tschopp, O., Yang, Z. Z. and Brodbeck, D. (2005). Essential role of protein kinase B gamma (PKB gamma/Akt3) in postnatal brain development but not in glucose homeostasis. Development 132, 2943-2954. doi:10.1242/dev.01864
324. Tsuji, R. and Crofton K. M. (2012). Developmental neurotoxicity guideline study: Issues with methodology, evaluation and regulation. Congenit Anom (Kyoto) 52, 122-128. doi:10.1111/ j.1741-4520.2012.00374.x
325. Tukker, A. M., de Groot, M. W., Wijnolts, F. M. et al. (2016). Is the time right for in vitro neurotoxicity testing using human iPSC-derived neurons? ALTEX 33, 261-271. doi:10.14573/ altex.1510091
326. Tyler, W. J., Alonso, M., Bramham, C. R. and Pozzo-Miller, L. D. (2002). From acquisition to consolidation: On the role of brain-derived neurotrophic factor signaling in hippocampal-dependent learning. Learn Mem 9, 224-237. doi:10.1101/ lm.51202
327. Urbisch, D., Mehling, A., Guth, K. et al. (2015). Assessing skin sensitization hazard in mice and men using non-animal test methods. Regul Toxicol Pharmacol 71, 337-351. doi:10.1016/j. yrtph.2014.12.008
328. van Thriel, C., Westerink, R. H., Beste, C. et al. (2012). Translating neurobehavioural endpoints of developmental neurotoxicity tests into in vitro assays and readouts. Neurotoxicology 33, 911-924. doi:10.1016/j.neuro.2011.10.002
329. Vassallo, A., Chiappalone, M., De Camargos, L. R. et al. (2017). A multi-laboratory evaluation of microelectrode array-based measurements of neural network activity for acute neurotoxicity testing. Neurotoxicology 60, 280-292. doi:10.1016/j. neuro.2016.03.019
330. Viberg, H. (2009). Neonatal ontogeny and neurotoxic effect of decabrominated diphenyl ether (PBDE 209) on levels of synaptophysin and tau. Int J Dev Neurosci 27, 423-429. doi:10.1016/j.ijdevneu.2009.05.007
331. Vinken, M. (2013). The adverse outcome pathway concept: A pragmatic tool in toxicology. Toxicology 312, 158-165. doi:10.1016/j.tox.2013.08.011
332. Visan, A., Hayess, K., Sittner, D. et al. (2012). Neural differentiation of mouse embryonic stem cells as a tool to assess developmental neurotoxicity in vitro. Neurotoxicology 33, 1135-1146. doi:/10.1016/j.neuro.2012.06.006
333. Volbracht, C., Leist, M. and Nicotera, P. (1999). ATP controls neuronal apoptosis triggered by microtubule breakdown or potassium deprivation. Mol Med 5, 477-489.
334. Vorhees, C. V. and Makris, S. L. (2015). Assessment of learning, memory, and attention in developmental neurotoxicity regulatory studies: Synthesis, commentary, and recommendations. Neurotoxicol Teratol 52, 109-115. doi:10.1016/j. ntt.2015.10.004
335. Wagenaar, D. A., Pine, J. and Potter, S. M. (2006). An extremely rich repertoire of bursting patterns during the development of cortical cultures. BMC Neurosci 7, 11. doi:10.1186/1471-2202-7-11
336. Waldmann, T., Rempel, E., Balmer, N. V. et al. (2014). Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol 27, 408-420. doi:10.1021/tx400402j
337. Waldmann, T., Grinberg, M., König, A. et al. (2017). Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol 30, 905-922. doi:10.1021/acs.chemrestox. 6b00259
338. Wallace, K., Strickland, J. D., Valdivia, P. et al. (2015). A multiplexed assay for determination of neurotoxicant effects on spontaneous network activity and viability from microelectrode arrays. Neurotoxicology 49, 79-85. doi:10.1016/j. neuro.2015.05.007
339. Wang, L., Liu, Y., Li, S. et al. (2015). Wnt signaling pathway participates in valproic acid-induced neuronal differentiation of neural stem cells. Int J Clin Exp Pathol 8, 578-585.
340. Wang, L., Zhou, K., Fu, Z. et al. (2017). Brain development and Akt signaling: The crossroads of signaling pathway and neurodevelopmental diseases. J Mol Neurosci 61, 379-384. doi:10.1007/s12031-016-0872-y
341. Weng, M., Zimmer, B., Pöltl, D. et al. (2012). Extensive transcriptional regulation of chromatin modifiers during human neurodevelopment. PLoS One 7, e36708. doi:10.1371/journal. pone.0036708
342. Weng, M. K., Nataraj, K., Scholz, D. et al. (2014). Lineage-specific regulation of epigenetic modifier genes in human liver and brain. PLoS One 9, e102035. doi:10.1371/journal. pone.0102035
343. Wetmore, B. A. (2015). Quantitative in vitro-to-in vivo extrapolation in a high-throughput environment. Toxicology 332, 94-101. doi:10.1016/j.tox.2014.05.012
344. Wilson, M. S., Graham, J. R. and Ball, A. J. (2014). Multiparametric high content analysis for assessment of neurotoxicity in differentiated neuronal cell lines and human embryonic stem cell-derived neurons. Neurotoxicology 42, 33-48. doi:10.1016/j.neuro.2014.03.013
345. Workman, A. D., Charvet, C. J., Clancy, B. et al. (2013). Modeling transformations of neurodevelopmental sequences across mammalian species. J Neurosci 33, 7368-7383. doi:10.1523/ JNEUROSCI.5746-12.2013
346. Worth, A. P. and Patlewicz, G. (2016). Integrated approaches to testing and assessment. Adv Exp Med Biol 856, 317-342. doi:10.1007/978-3-319-33826-2_13
347. Wu, C., Orozco, C., Boyer, J. et al. (2009). BioGPS: An extensible and customizable portal for querying and organizing gene annotation resources. Genome Biol 10, R130. doi:10.1186/ gb-2009-10-11-r130
348. Xiong, Y., Ibhazehiebo, K., Iwasaki, T. and Koibuchi, N. (2012). An in vitro method to study the effects of thyroid hormone-disrupting chemicals on neuronal development. Neurotoxicology 33, 753-757. doi:10.1016/j.neuro.2012.04.021
349. Yang, D., Kania-Korwel, I., Ghogha, A. et al. (2014). PCB 136 atropselectively alters morphometric and functional parameters of neuronal connectivity in cultured rat hippocampal neurons via ryanodine receptor-dependent mechanisms. Toxicol Sci 138, 379-392. doi:10.1093/toxsci/kft334
350. Yao, L., Peng, S. X., Xu, Y. D. et al. (2017). Unexpected neuroprotective effects of loganin on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity and cell death in zebrafish. J Cell Biochem 118, 615-628. doi:10.1002/jcb.25749 Yoon, M., Campbell, J. L., Andersen, M. E. and Clewell, H. J. (2012). Quantitative in vitro to in vivo extrapolation of cell-based toxicity assay results. Crit Rev Toxicol 42, 633-652. doi: 10.3109/10408444.2012.692115
351. York, R. G., Barnett, J., Girard, M. F. et al. (2005). Refining the effects observed in a developmental neurobehavioral study of ammonium perchlorate administered orally in drinking water to rats. II. Behavioral and neurodevelopment effects. Int J Toxicol 24, 451-467. doi:10.1080/10915810500367094
352. Yu, J. S. and Cui, W. (2016). Proliferation, survival and metabolism: The role of PI3K/AKT/mTOR signalling in pluripotency and cell fate determination. Development 143, 3050-3060. doi:10.1242/dev.137075
353. Zagoura, D., Canovas-Jorda, D., Pistollato, F. et al. (2017). Evaluation of the rotenone-induced activation of the Nrf2 pathway in a neuronal model derived from human induced pluripotent stem cells. Neurochem Int 106, 62-73. doi:10.1016/j.neuint.2016.09.004
354. Zheng, J., Feng, X., Hou, L. et al. (2011). Latanoprost promotes neurite outgrowth in differentiated RGC-5 cells via the PI3KAkt-mTOR signaling pathway. Cell Mol Neurobiol 31, 597-604. doi:10.1007/s10571-011-9653-x
355. Zhou, H., Liu, Y., Tan, X. J. et al. (2015). Inhibitory effect of arsenic trioxide on neuronal migration in vitro and its potential molecular mechanism. Environ Toxicol Pharmacol 40, 671-677. doi:10.1016/j.etap.2015.08.026
356. Zhou, J. and Parada L. F. (2012). PTEN signaling in autism spectrum disorders. Curr Opin Neurobiol 22, 873-879. doi:10.1016/j.conb.2012.05.004
357. Zhu, Y. P., Xi, S. H., Li, M. Y. et al. (2017). Fluoride and arsenic exposure affects spatial memory and activates the ERK/CREB signaling pathway in offspring rats. Neurotoxicology 59, 56-64. doi:10.1016/j.neuro.2017.01.006
358. Zimmer, B., Kuegler, P. B., Baudis, B. et al. (2011a). Coordinated waves of gene expression during neuronal differentiation of embryonic stem cells as basis for novel approaches to developmental neurotoxicity testing. Cell Death Differ 18, 383-395. doi:10.1038/cdd.2010.109
359. Zimmer, B., Schildknecht, S., Kuegler, P. B. et al. (2011b). Sensitivity of dopaminergic neuron differentiation from stem cells to chronic low-dose methylmercury exposure. Toxicol Sci 12, 357-367. doi:10.1093/toxsci/kfr054
360. Zimmer, B., Lee, G., Balmer, N. V. et al. (2012). Evaluation of developmental toxicants and signaling pathways in a functional test based on the migration of human neural crest cells. Environ Health Perspect 120, 1116-1122. doi:10.1289/ ehp.1104489
361. Zimmer, B., Pallocca, G., Dreser, N. et al. (2014). Profiling of drugs and environmental chemicals for functional impairment of neural crest migration in a novel stem cell-based test battery. Arch Toxicol 88, 1109-1126. doi:10.1007/s00204-014-1231-9
362. Zimmermann, F. F., Gaspary, K. V., Leite, C. E. et al. (2015). Embryological exposure to valproic acid induces social interaction deficits in zebrafish (Danio rerio): A developmental behavior analysis. Neurotoxicol Teratol 52, 36-41. doi:10.1016/j. ntt.2015.10.002
363. Zuo, Z., Cai, J., Wang, X. et al. (2009). Acute administration of tributyltin and trimethyltin modulate glutamate and N-methyl-D-aspartate receptor signalling pathway in Sebastiscus marmoratus. Aquat Toxicol 92, 44-49. doi:10.1016/j. aquatox.2009.01.008
364. Zurich, M. G., Honegger, P., Schilter, B. et al. (2000). Use of aggregating brain cell cultures to study developmental effects of organophosphorus insecticides. Neurotoxicology 21, 599-605.
365. Zurich, M. G., Eskes, C., Honegger, P. et al. (2002). Maturation-dependent neurotoxicity of lead aceate in vitro: Implication of glial reactions. J Neurosc Res 70, 108-116. doi:10.1002/ jnr.10367
366. Zurich, M. G., Stanzel, S., Kopp-Schneuder, A. et al. (2012). Evaluation of aggregating brain cell cultures for the detection of acute organ-specific toxicity. Toxicol In Vitro 27, 1416-1424. doi:10.1016/j.tiv.2012.06.018