| Abstract: | Ganglioside AGF2 attenuated both the cognitive impairments and the cholinergic hypofunction induced by ethylcholine aziridinium ion (AF64A). Adult male rats were initially trained to perform a standard radial arm maze (RAM) task. Following training, they were injected intraperitoneally with 10 mg/kg AGF2 (AF/AGF2, CSF/AGF2) or the saline vehicle (AF/SAL, CSF/SAL) for 3 days prior to and for 14 days following bilateral injection of AF64A (3 nmol/side) or artificial CSF into the lateral ventricles. AF64A (AF/SAL) impaired performance of the standard RAM task and a working memory version of the task in which various delays were imposed between the fourth and fifth arm choices. In contrast, animals that received AGF2 and AF64A (AF/AGF2) were initially impaired on the standard RAM task but rapidly recovered and were performing as well as the control groups (CSF/SAL, CSF/AGF2) by the end of training. The AF/AGF2 group, however, exhibited persistent deficits on the working memory version of the RAM task. These data demonstrate that AGF2 promotes behavioral recovery in a task-dependent manner in this model system. Neurochemical analysis revealed that AF64A produced a significant 37% decrease in hippocampal ChAT activity that was significantly attenuated, but not prevented, by prior treatment with AGF2. Thus the behavioral recovery afforded by AGF2 might be related to increased cholinergic activity in the hippocampus that is sufficient for the performance of tasks which either lack or have a minimal working memory component. An analysis of the temporal profile of AGF2-induced neurochemical recovery revealed that ChAT activity was enhanced at 20, but not 2 or 11, weeks following AF64A. Since AGF2 did not attenuate the cholinergic cell loss (35%) induced by AF64A in the medial septum these data indicate that AGF2 might have (1) enhanced sprouting of cholinergic terminals following the initial insult, (2) directly increased ChAT activity in surviving neurons, or (3) induced behavioral and neurochemical recovery through a combination of these or other mechanisms. |
