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Cell-Based Assays for Neurotoxins

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Biological Toxins and Bioterrorism

Part of the book series: Toxinology ((TOXI))

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), APG-EA, MD, USA

    Patrick McNutt & Phillip Beske

  2. Department of Chemistry and Biochemistry, United States Food and Drug Administration, College Park, MD, USA

    Nagarajan Thirunavukkarsu

Authors
  1. Patrick McNutt
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  2. Phillip Beske
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  3. Nagarajan Thirunavukkarsu
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Corresponding author

Correspondence to Patrick McNutt .

Editor information

Editors and Affiliations

  1. Venom and Toxin Research Programme, Department of Anatomy, Yong Loo Lin School of Medicine National University of Singapore, Singapore, Singapore

    P. Gopalakrishnakone

  2. Medical Toxicology Research Centre Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Mahdi Balali-Mood

  3. Data and Technology Innovation, Australian Institute of Marine Science, Townsville, QLD, Australia

    Lyndon Llewellyn

  4. Botulinum Research Center, Institute of Advanced Sciences, Dartmouth, MA, USA

    Bal Ram Singh

  5. Prime Bio, Inc., Dartmouth, MA, USA

    Bal Ram Singh

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McNutt, P., Beske, P., Thirunavukkarsu, N. (2015). Cell-Based Assays for Neurotoxins. In: Gopalakrishnakone, P., Balali-Mood, M., Llewellyn, L., Singh, B.R. (eds) Biological Toxins and Bioterrorism. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5869-8_31

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