CHRONIC 1,25-DIHYDROXYVITAMIN D-3-MEDIATED INDUCTION OF NERVE GROWTH-FACTOR MESSENGER-RNA AND PROTEIN IN L929 FIBROBLASTS AND IN ADULT-RAT BRAIN

We have proposed that elevating levels of nerve growth factor (NGF) in the CNS is a rational strategy for treating certain neurodegenerative disorders. The present studies were conducted to determine: (1) if ph armacologically induced levels of NGF could be sustained for an extend ed time, and (2) if correlations exist between increases in NGF mRNA a nd NGF protein in L929 cells and in vivo. Short-term treatment of L929 cells with 1,25-dihydroxyvitamin D, resulted in a two-fold increase i n both NGF mRNA and NGF protein. These increases were sustained for up to 48 h with continuous exposure to 1,25-dihydroxyvitamin D-3. In rat s, 1,25-dihydroxyvitamin D-3 (2:5 nmol; i.c.v.) induced NGF mRNA trans iently, with peak two-fold increases observed 4 h post-injection. In c ontrast to L929 cells, 1,25-dihydroxyvitamin D-3 did not elicit an inc rease in NGF protein after a single adminstration in vivo. However, co nsistent with long-term exposure in L929 cells, chronic 6 day infusion of 1,25-dihydroxyvitamin D-3 resulted in induction of both NGF mRNA a nd NGF protein in the brain. These results indicate that 1,25-dihydrox yvitamin D-3-mediated NGF induction in cultured L929 cells may predict of NGF induction in vivo, suggesting that L929 cells may have utility in studying underlying mechanisms of NGF induction by 1,25-dihydroxyv itamin D-3. On the basis of NGF's ability to increase cholinergic func tion in animal models of cholinergic degeneration, these results are s upportive of a role for NGF inducers as potential drugs for neurodegen erative disorders.