Use of toxins to disrupt neurotransmitter circuitry in the developing brain

This chapter describes the use of two major groups of developmental neurotoxins. The first, mitotic disrupters (e.g., methylazoxymethanol acetate (MAM)) delete populations of rapidly dividing neuroepithelial cells. Their effects are limited to phases of rapid embryonic neurogenesis. Because of the restricted birthdays of certain groups of neurons, mitotic disruptors administered at appropriate times lead to atrophic brain regions and major imbalances in remaining neurotransmitter-specific neuronal circuitry. Many teratogens and drugs disrupt developing neuronal circuitry. The mechanisms for these effects and their relationship to neurobehavioral abnormalities are poorly understood. In contrast, synaptic disruptors destroy neurons and possibly other structures bearing specific neurotransmitter receptors. The proliferative neuroepithelium may be less vulnerable to toxins of this group, which act primarily on maturing synapses associated with postmitotic neurons. Improving understanding of the molecular nature of these events should allow a finer resolution of mechanisms of neurotoxicity.