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Cell-Based Assays for Neurotoxins

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Biological Toxins and Bioterrorism

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Abstract

The implementation of cell-based assays in basic research, disease modeling, and drug discovery has dramatically increased over the past 10 years. One field which has suffered from the lack of physiologically relevant cell-based models that are compatible with moderate-throughput applications is neurotoxicology. The development of next-generation stem cell-derived neurons for neurotoxicology research has the potential to resolve this limitation; however, derived neurons have to be demonstrated to exhibit the same physiological responses as primary neuron populations. In particular, derived neurons must demonstrate appropriate electrical behaviors, transsynaptic signaling, and network activity to be considered relevant models. This chapter reviews the state of the art in cell-based assays (CBAs) predicated on the use of stem cell-derived neurons, describes the different pluripotent populations that are currently used, discusses advantages and limitations of differentiation methods, and reviews some initial applications. Finally, developing techniques are presented that are anticipated to increase throughput, sensitivity, and relevance. While the transition to moderate-throughput assays is still under way, it is clear that stem cell-derived neurons offer a potent combination of physiological relevance with scalability and genetic tractability, and therefore, CBAs based on derived neurons are poised to revolutionize neurotoxicology research and drug discovery.

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Authors and Affiliations

  1. US Army Medical Research Institute of Chemical Defense (USAMRICD), 3100 Ricketts Point Road, APG-EA, MD, 21010, USA

    Dr. Patrick McNutt & Dr. Phillip Beske

  2. Department of Chemistry and Biochemistry, United States Food and Drug Administration, 5100 Paint Branch Pkwy, CPK1 Room # 4E026 (Mail Stop: HFS-712), College Park, 20740, MD, USA

    Dr. Nagarajan Thirunavukkarasu

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  1. Dr. Patrick McNutt
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  3. Dr. Nagarajan Thirunavukkarasu
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  1. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    P. Gopalakrishnakone

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McNutt, P., Beske, P., Thirunavukkarasu, N. (2014). Cell-Based Assays for Neurotoxins. In: Gopalakrishnakone, P. (eds) Biological Toxins and Bioterrorism. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6645-7_31-2

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    Cell-Based Assays for Neurotoxins
    Published:
    17 August 2015

    DOI: https://doi.org/10.1007/978-94-007-6645-7_31-2

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    DOI: https://doi.org/10.1007/978-94-007-6645-7_31-1

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