In Vitro Neurotoxicology: Principles and Challenges (Methods in Pharmacology and Toxicology)

Neurotoxicity assessment with in vitro systems offers not only a means to better understand mechanisms of action of toxicants and decrease reliance on laboratory animals, but also provides a basis for reliable, high throughput screening of new and untested chemicals. In In Vitro Neurotoxicology: Principles and Challenges, well-respected leaders in the field take a fresh look at their own and others' work, critically and comparatively analyzing it across experimental systems and toxicants, and synthesizing essential principles for in vitro neurotoxicity testing. In thematically organized chapters, the authors employ examples comprised of multiple experimental systems and endpoints, and discuss the use of complementary in vivo/in vitro strategies. Neurotoxicants of significance to human health are emphasized, especially those for which metabolism and dose-responses are well studied both in vivo and in vitro: lead, mercury, organophosphorus insecticides, polychlorinated biphenyls and dioxin, ethanol, and endogenous proteins. Several neurotoxicology topics covered provide insight into neurodevelopmental and neurodegenerative diseases, including the concept of astroglia as depots for lead and other metals in the central nervous system, the elucidation of factors involved in the onset of puberty in females, and the exploration of endogenous proteins as neurotoxicants. Authoritative and forward-looking, In Vitro Neurotoxicology: Principles and Challenges sets out new concepts and research directions that will facilitate significant improvement in today's methods and systems for in vitro neurotoxicity testing. In Vitro Neurotoxicology......Page 2 Cover......Page 1 Copyright......Page 5 Dedication......Page 6 Foreword......Page 7 Preface......Page 8 Contents......Page 10 1 In Vitro Neurotoxicology: Introduction to Concepts......Page 15 2 Predictive Value of In Vitro Systems for Neurotoxicity Risk Assessment......Page 43 3 Exposure–Dose–Response Paradigm as It Relates to Toxicogenomics......Page 55 4 In Vitro Studies of Neurotoxicant Effects on Cellular Homeostasis......Page 72 5 Role of Apoptosis in Neurotoxicology......Page 107 6 Impairment of Neurotransmitter Metabolism and Function by Neurotoxicants......Page 145 7 Cell-Type-Specific Responses of the Nervous System to Lead......Page 163 8 Effects of Toxicants on Neural Differentiation......Page 199 9 Impairment of Synaptic Function by Exposure to Lead......Page 228 10 Aggregating Brain Cell Cultures for Neurotoxicological Studies......Page 253 11 Use of Complimentary In Vitro and In Vivo Methods for Assessing Neuroendocrine Disruptors......Page 277 12 Establishing In Vitro Models to Study Endogenous Neurotoxicants......Page 300 Appendix: Annotated Reading List......Page 324 Index......Page 333 In Vitro Neurotoxicology 2 Cover 1 Copyright 5 Dedication 6 Foreword 7 Preface 8 Contents 10 1 In Vitro Neurotoxicology: Introduction to Concepts 15 2 Predictive Value of In Vitro Systems for Neurotoxicity Risk Assessment 43 3 Exposure–Dose–Response Paradigm as It Relates to Toxicogenomics 55 4 In Vitro Studies of Neurotoxicant Effects on Cellular Homeostasis 72 5 Role of Apoptosis in Neurotoxicology 107 6 Impairment of Neurotransmitter Metabolism and Function by Neurotoxicants 145 7 Cell-Type-Specific Responses of the Nervous System to Lead 163 8 Effects of Toxicants on Neural Differentiation 199 9 Impairment of Synaptic Function by Exposure to Lead 228 10 Aggregating Brain Cell Cultures for Neurotoxicological Studies 253 11 Use of Complimentary In Vitro and In Vivo Methods for Assessing Neuroendocrine Disruptors 277 12 Establishing In Vitro Models to Study Endogenous Neurotoxicants 300 Appendix: Annotated Reading List 324 Index 333 1588290476,9781588290472 Well-respected leaders in the field of in vitro neurotoxicology take a fresh look at their own and other's work, critically and comparatively analyzing it across experimental systems and toxicants, and synthesizing essential principles for in vitro neurotoxicity testing. Neurotoxicants of significance to human health are emphasized, especially those for which metabolism and dose-responses are well well studied both in vivo and in vitro: lead, mercury, organophosphorous insecticides, polychlorinated biphenyls and dioxin, ethanol, and endogenous proteins. The goal is to set out new concepts and research directions that will hasten significant improvement in the methods and systems for in vitro neurotoxicity testing. Provides new concepts and directions for in vitro assessment of neurotoxicity; functional assays for evaluation of neruotoxicity; interactions of neurons and glia in neurotoxicity; review of endogenous neurotoxic proteins; complementary in vivo/in vitro strategies in neurotoxicology; validation of in vitro models in neurotoxicology; interdisciplinary approach utilizing cell biology, neurophysiology, and risk assessment; annotated bibliography of important review articles, books, and methods manuals; and explorations of emerging frontiers in genomic toxicology Edited By Evelyn Tiffany-castiglioni ; Foreword By Mannfred A. Hollinger. Includes Bibliographical References And Index. The history of neuroscience is punctuated by oracular disclosures from in vitro systems.