CONICET | Buscador de Institutos y Recursos Humanos

Human and animal studies have demonstrated an age-related decline in learning and memory abilities. In previous studies, we observed a significant age-related increase in dopaminergic neuron loss in the hypothalamus and the substantia nigra in Sprague?Dawley (SD) female rats which becomes more conspicuous at extreme ages 1,2. Adittionally, in the hippocampus, we observed that doublecortin neuroblast shows a 97 % age-related reduction in the dentate gyrus of senile SD rats as compared with their young counterparts 3. Previously, our group has shown that adenoviral vector mediated-IGF-I gene therapy is effective to prevent hypothalamic DA neuron loss and reverse chronic hyperprolactinemia in senile SD rats 4. In order to extend our neuroprotective studies to treat age-related cognitive deficit, we implemented i.c.v. gene therapy on 24 months old senile SD female rats (Intact; IGF-I and DsRed). Spatial memory performance was assessed in the Barnes Maze test. The acquisition protocol was 4 trials per day during 9 consecutive days. In order to examine spatial memory retention, rats were then retested at 19, 22 and 25 days post-injection (PI); and subsequently at 62, 65 and 68 days PI. On day 19 PI, no differences were observed between all groups but, interestingly, during day 22 PI and day 25 PI, the IGF-I group showed an increase in spatial preference for the goal area compared with the intact and DsRed groups. On day 62 PI and 65 PI, no difference in spatial preference was detected among the groups. However on day 68 PI the IGF-I and DsRed groups again showed an increase in spatial preference for goal sector compared with intact rats. We conclude that long-term IGF-I gene therapy in the brain of aging rats improves their cognitive performance during the initial three weeks of treatment but the effect weakens or even disappears two months after vector injection.