Carbofuran induces apoptosis of rat cortical neurons and down-regulates surface alpha7 subunit of acetylcholine receptors.

Carbofuran (CF), an anticholinesterase carbamate, is one of the most widely used N-methylcarbamate esters in insect and nematode control. Despite its serious adverse health effects on wildlife and humans, cellular and molecular studies of the damage of CF to CNS neurons are very limited. We have examined the cytotoxic effects of CF on cultured rat cortical cells, and the expression of the alpha7 subunit of the nicotinic acetylcholine receptor (alpha7 nAChR) in hippocampal neurons. CF was cytotoxic with an IC50 approximately 730 and approximately 640 microm when assessed by the lactate dehydrogenase (LDH) assay and propidium iodide (PI) staining, respectively, 3 days after treatment. CF induced DNA fragmentation and exposure of phosphatidyl serine (PS) on the cell surface. Surface labeling of the alpha7 nAChR with Alexa Fluor 488-conjugated alpha-bungarotoxin (alphaBgt) revealed a significant decrease in the density of the subunits in treated (500 microm CF) hippocampal neurons. Our data indicate that CF induces neuronal death by apoptosis and down-regulates nAChRs.