Potential mechanisms underlying the destruction of dentate gyrus granule cells by colchicine

Microinjections of 1 to 6 nmol of colchicine into the hippocampal formation of rats selectively destroyed granule cells of the dentate gyrus and their axons over several days. Immediately after such microinjections, epileptiform discharges appeared in focal EEG recordings from the hippocampal formation. Vinblastine produced neuropathologic changes like colchicine, and lumicolchicine was devoid of neurotoxicity. These findings suggest that the selective cytotoxicity of colchicine for dentate gyrus granule cells may depend on its ability to bind to tubulin and is associated with an acute epileptogenic effect.