Glial cell line-derived neurotrophic factor (GDNF) improves spatial learning in aged Fischer 344 rats

Glial cell line-derived neurotrophic factor (GDNF) increases choline acetyltransferase (ChAT) activity in the septohippocampal system of aged rats. Since the septohippocampal system has been implicated as a neurobiological substrate for spatial learning, the effects of GDNF were tested in aged, spatial learning-impaired Fisher 344 rats. Aged rats were characterized as spatial learning “impaired” or “unimpaired” using several indices of performance in the Morris water maze, and they were then given GDNF (100-µg bolus; icv) or phosphate-buffered saline (PBS). Six days after the GDNF or PBS injection, rats returned to water maze training, which continued until a spatial bias criterion was met. Immediately after meeting the criterion, rats were tested in a cue learning version of the task. GDNF significantly improved spatial learning in aged impaired rats, but not aged unimpaired or young rats. It did not alter cue learning rate for any group, nor did it alter swim speed. These data suggest that GDNF may support the integrity of neurons in the septum and hippocampus of aged rats.