Developmental toxicity within the central cholinergic nervous system

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.