Neurotoxicity refers to the direct or indirect effect of chemicals that disrupt the nervous system of humans or animals. Numerous chemicals can produce neurotoxic diseases in humans, and many more are used as experimental tools to disturb or damage the nervous system of animals. Some act directly on neural cells, others interfere with metabolic processes on which the nervous system is especially dependent. Some disrupt neural function, others induce maldevelopment or damage to the adult nervous system. Perturbations may appear and disappear rapidly, evolve slowly over days or weeks and regress over months or years, or cause permanent deficits. Neurotoxicity is usually self-limiting after exposure ceases and rarely progressive in the absence of continued exposure, although there may be a significant delay between exposure and manifestation of neurotoxic effects.

© 2016 Elsevier Inc. All rights reserved. Sympathetic cell culture is widely used for mechanistic studies of neurodevelopment, plasticity and neurotransmission. Other than chick ciliary ganglia, parasympathetic and enteric cultures are not as widely used, and have largely focused on electrophysiological and pharmacological properties of these cells. New procedures for culturing primary human autonomic neurons, and for co-culturing autonomic neurons with target tissue cells will increase the power of these models for addressing significant gaps in understanding of the cell biology and pharmacology of these neurons, the impact of which is underscored by the importance of autonomic nervous systems in regulating all major organ systems in vertebrates.

Neurotoxicity refers to the direct or indirect effect of chemicals that disrupt the nervous system of humans or animals. Numerous chemicals can produce neurotoxic diseases in humans, and many more are used as experimental tools to probe molecular and cellular mechanisms of physiology and pathophysiology in the nervous system of animal tissues in vivo and in vitro, and in human neural progenitor cell lines. Some chemicals act directly on neural cells, others interfere with metabolic processes on which the nervous system is especially dependent. Emerging evidence suggests that toxic effects on physiological systems outside the brain, in particular the endocrine system, immune system and gut microbiome, may also adversely impact the nervous system. Some neurotoxic chemicals disrupt neural function, others alter normal developmental trajectories of the brain or cause damage to the adult nervous system. Perturbations may appear and disappear rapidly, evolve slowly over days or weeks and regress over months or years, or cause permanent deficits. Neurotoxicity is usually self-limiting after exposure ceases and rarely progressive in the absence of continued exposure, although there may be a significant delay between exposure and manifestation of neurotoxic effects.

Sympathetic cell culture is widely used for mechanistic studies of neurodevelopment, plasticity and neurotransmission. Other than chick ciliary ganglia, parasympathetic and enteric cultures are not as widely used, and have largely focused on electrophysiological and pharmacological properties of these cells. New procedures for culturing primary human autonomic neurons, and for co-culturing autonomic neurons with target tissue cells will increase the power of these models for addressing significant gaps in understanding of the cell biology and pharmacology of these neurons, the impact of which is underscored by the importance of autonomic nervous systems in regulating all major organ systems in vertebrates.

Apoptosis is a tightly controlled physiological process in which individual cells die without damaging neighboring healthy cells. Apoptosis is crucial for normal neurodevelopment, and altered patterns of apoptotic cell death of neurons and glial cells during development are associated with functional deficits. Experimental and clinical evidence has established that neurological insults, including chemical exposures, can induce aberrant apoptosis in the developing nervous system. This chapter will discuss chemical-induced apoptosis as a mechanism of developmental neurotoxicity. The goals are as follows: (1) provide an overview of the molecular mechanisms of apoptosis and its role in the normally developing nervous system, (2) discuss the evidence implicating inappropriate apoptosis in adverse neurodevelopmental outcomes, and (3) illustrate mechanisms by which neurotoxic chemicals modulate apoptosis using pediatric anesthesia, developmental exposures to polychlorinated biphenyls, and zinc dyshomeostasis as examples.

Neurons that use acetylcholine in the developing brain make up an extremely important network that helps guide other systems during critical time periods of cell proliferation and differentiation. This important function and the variety of molecular targets for developmental neurotoxicants makes the central cholinergic system vulnerable to neurodevelopmental abnormalities that can result in functional deficits later in life. The alteration of brain development by toxicants, such as anticholinesterase pesticides, lead (Pb), nicotine, and others is supported by many studies that demonstrate concomitant changes in a variety of cholinergic targets, which provide clues to potential underlying mechanisms for their neurodevelopmental toxicity. This chapter discusses the role of the cholinergic system in brain development, special vulnerabilities related to brain region and developmental time periods, and human, animal, and mechanistic data on the neurodevelopmental toxicity of pesticides and other environmental chemicals.