Selective working memory impairments following intradentate injection of colchicine: attenuation of the behavioral but not the neuropathological effects by gangliosides GM1 and AGF2.

Bilateral injection of 3.5 micrograms of colchicine into the dentate gyrus produced specific learning and memory impairments together with a selective pattern of neuropathology. Animals injected with colchicine exhibited a significant impairment in their ability to perform the working memory, but not the reference memory, component of a multiple component T-maze task. These deficits were transient and over time all animals were able to reaquire the task to preoperative levels of performance. Histological analyses revealed that intradentate injection of colchicine produced 1) a significant decrease in the width of both the superior and inferior blades of the dentate gyrus reflecting the extensive loss of granule cells, 2) a related decrease in the size of the dentate molecular layer, and 3) a decrease in the number of cholinergic neurons in the medial septum. The second phase of the experiment demonstrated that gangliosides GM1 and AGF2 did not prevent the initial impairments in working memory performance induced by colchicine but rather accelerated the rate at which it recovered. The gangliosides did not decrease the extent of neuronal damage; there was no sparing of granule cells in the dentate gyrus or cholinergic neurons in the medial septum. These data further support a role for the hippocampus in working memory processes and they also indicate that gangliosides GM1 and AGF2 might be useful for treating the behavioral deficits induced by hippocampal damage.