CELL MOTILITY IS INHIBITED BY THE ANTIEPILEPTIC COMPOUND, VALPROIC ACID AND ITS TERATOGENIC ANALOGS

Valproic acid (VPA) is an established human teratogen that causes neur al tube defects in 1-2 % of human foetuses exposed to the drug during early pregnancy. in this study, individual cell motility was evaluated using short- and long-term time-lapse video-recording and computer as sisted image analysis, and it was found that VPA and selected VPA-anal ogues inhibited individual cell motility of L-cells in a dose-dependen t manner. The compounds caused a decrease in the root-mean-square spee d, S, and in the rate of diffusion, R, but an increase in the time of persistence in direction, P, Using short-term recordings and measureme nts of mean-cell speed, the reduction in the motile behaviour was show n to correlate with the teratogenic potency of the tested compounds. T he observed effects of VPA on cell motility was independent of the emp loyed L-cell clone, and could be reproduced in cells containing the ne uronal marker NCAM and in the neuronal cell line N2a. Furthermore, the observed effect was independent of culture substratum, being observed for L-cells grown on fibronectin as well as on plastic. Immunofluores cence microscopy revealed that VPA-treatment of mouse L-ceIls caused a redistribution of F-actin and of a series of focal adhesion proteins, indicating that the effect of VPA on cell motility may be causally re lated to increased cell-substratum interactions or to alterations in t he organisation or dynamics of the actin cytoskeleton. Cell Motil. Cyt oskeleton 40:220-237, 1998. (C) 1998 Wiley-Liss, Inc.