Novel neuronal effects of midkine on embryonic cerebellar neurons examined using a defined culture system.

1. Midkine (MK) is known to be a member of a family of heparin-binding neurotrophic factors. We used a chemically defined culture system to examine neuronal activities of MK on embryonic rat cerebellar cells. 2. In the culture system, a substrate surface was chemically modified either 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 survivability (1.3-fold) and accelerated neurite outgrowth (1.4-fold) of cerebellar cells, putatively granule neurons, grown on an amine-modified surface. 4. Higher dosages (10 ng/ml or more) of MK, however, caused cellular fragmentation and detachment. Such degenerative effects were diminished by increasing the surface adhesiveness using laminin peptide, suggesting that the cellular 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 that MK may be involved in the developmental events of the cerebellum.