Novel neuronal effects of midkine on embryonic cerebellar neurons examinedusing a defined culture system

1. Midkine (MK) is known to be a member of a family of heparin-binding neur otrophic factors. We used a chemically defined culture system to examine ne uronal activities of MK on embryonic rat cerebellar cells. 2. In the culture system, a substrate surface was chemically modified eithe r with amine or with laminin peptide to homogenize substrate conditions for culturing neurons. 3. At the optimal concentration (2.5 ng/ml), MK moderately promoted surviva bility (1.3-fold) and accelerated neurite outgrowth (3.4-fold) of cerebella r cells, putatively granule neurons, grown on an amine-modified surface. 4. Higher dosages (10 ng/ml or more) of MK, however, caused cellular fragme ntation and detachment. Such degenerative effects were diminished by increa sing the surface adhesiveness using laminin peptide, suggesting that the ce llular degeneration might be caused by changes in the adhesive property of the neuron. 5. Using this culture system, we have found that MK has a novel modulatory activity of neuronal adhesiveness on the cultured cerebellar granule cells. Together with the expression pattern of MK, our study supports the idea th at MK may be involved in the developmental events of the cerebellum.