SYNAPTIC LOSS IN COGNITIVELY IMPAIRED AGED RATS IS AMELIORATED BY CHRONIC HUMAN NERVE GROWTH-FACTOR INFUSION

In the present study, we assessed the synaptic changes in aged impaire d and unimpaired rats, and the effect of exogenous human nerve growth factor administration on behavioral activity and synaptic density. Hum an nerve growth factor was administered into the rat ventricles with a cannula connected to an osmotic pump in adult, aged impaired and unim paired rats. Behavioral performance was evaluated in the Morris water maze. Aged impaired rats had an 18 +/- 4% decrease in the number of sy naptophysin-immunoreactive presynaptic terminals as compared to aged u nimpaired rats. After a continuous four-week human nerve growth factor , the aged impaired rats displayed a significant 16 +/- 3% increase in the number of synaptophysin-immunoreactive presynaptic terminals in t he frontal cortex, as compared to aged impaired rats treated with vehi cle. This increase correlated with an improvement in water maze perfor mance (r = -0.74, P < 0.001). Measurements of synaptophysin-immunoreac tive presynaptic terminals in other cortical and subcortical regions d id not show any statistically significant difference or correlations a mong the various groups. These results support the possibility that ne rve growth factor mediates the induction of other trophic factors whic h, in turn, might potentially produce a sprouting response of non-chol inergic fibers that ameliorate the cognitive deficits in impaired, age d rats.