Neurotrophins, like the nerve growth factor (NGF), trigger a variety of biological effects in their targets. Stimulating effects on antioxidant defenses have been postulated to underlie neurotrophic influence on neuron survival and maintenance. To test whether NGF is capable of inducing changes in glutathione-related enzymes in the aged cognitively impaired brain, glutathione reductase (GRD), glutathione S-transferase (GST) and total glutathione peroxidase (GPX) activities were measured in the striatum, septum, hippocampus and frontal cortex of four Sprague-Dawley rat groups: young (2 months old), aged (20 months old) untreated, aged cytochrome c-treated, and aged NGF-treated (icv delivery, 34 micrograms during 28 days). All the aged rats utilized in the study were memory impaired according to their performance in the Morris water maze test. These aged rats showed increases in the activities of septal and hippocampal GST, as well as, in the hippocampal, striatal and cortical GPX. These increases could be interpreted as compensatory responses to cope with the oxidative damage that has been accumulated by the aged brain. The increases in hippocampal and cortical GPX activity were attenuated by NGF treatment, whereas the neurotrophin induced an increase in GRD activity in the striatum of aged rats. These results point out GRD and GPX as possible targets of the neurotrophic effects.