| Cholinesterases in Neural Development: New Findings
and Toxicologic Implications Stephen Brimijoin and Carol Koenigsberger Department of Pharmacology, Mayo Clinic, Rochester, Minnesota Abstract
Developing animals are more sensitive than adults to acute cholinergic toxicity 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 permanent deficits in the architecture of the central and peripheral nervous systems. Recent observations indicate that organophosphorus exposure can affect DNA synthesis and cell survival in neonatal rat brain. New evidence that acetylcholinesterase may have a direct role in neuronal differentiation provides additional grounds for interest in the developmental toxicity of anticholinesterases. For example, correlative anatomic studies show that transient bursts of acetylcholinesterase expression often coincide with periods of axonal outgrowth in maturing avian, rodent, and primate brain. Some selective cholinesterase inhibitors effectively suppress neurite outgrowth in model systems like differentiating neuroblastoma cells and explanted sensory ganglia. When enzyme expression is altered by genetic engineering, acetylcholinesterase 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 acetylcholinesterase activity. Nonetheless, it remains possible that some pesticides interfere with important developmental functions of the cholinesterase enzyme family. -- Environ Health Perspect 107(Suppl 1) :59-64 (1999) . http://ehpnet1.niehs.nih.gov/docs/1999/Suppl-1/59-64brimijoin/abstract.html Key words: acetylcholinesterase, butyrylcholinesterase, organophosphorus, anticholinesterase, echothiophate, chlorpyrifos, neurite outgrowth, brain development, neural cell adhesion molecules, cholinergic toxicity
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