Cholinesterases in neural development: New findings and toxicologic implications

Developing animals are more sensitive than adults to acute cholinergic toxi city from anticholinesterases, including organophosphorus pesticides, when administered in a laboratory setting. it is also possible that these agents adversely affect the process of neural development itself, leading to perm anent deficits in the architecture oi the central and peripheral nervous sy stems. Recent observations indicate that organophosphorus exposure can affe ct DNA synthesis and cell survival in neonatal rat brain. New evidence that acetylcholinesterase may have a direct role in neuronal differentiation pr ovides additional grounds for interest in the developmental toxicity of ant icholinesterases. For example, correlative anatomic studies show that trans ient bursts of acetylcholinesterase expression often coincide with periods of axonal outgrowth in maturing avian, rodent, and primate brain. Some sele ctive cholinesterase inhibitors effectively suppress neurite outgrowth in m odel systems like differentiating neuroblastoma cells and explanted sensory ganglia. When enzyme expression is altered by genetic engineering, acetylc holinesterase levels on the outer surface of transfected neurons correlate with ability to extend neurites. Certain of these "morphogenic" effects may depend on protein-protein interactions rather than catalytic acetylcholine sterase activity. Nonetheless, it remains possible that some pesticides int erfere with important developmental functions of the cholinesterase enzyme family.