Neurotrophic effects of simplified mastigophorene analogs on mesencephalicdopaminergic cells in primary culture

Mastigophorenes are dimeric isocuparane-type sesquiterpenes of plant origin which have been found to exhibit neurotrophic properties. In this study, a simplified synthetically produced analog (1) and its dimethylether (2) wer e screened for potential neurotrophic effects on primary dopaminergic cell cultures in vitro. Dopaminergic cultures were prepared from embryonic mouse mesencephalon and 6-day serum-free cultures were exposed to low concentrat ions (0.05-5.0 mu M) of these compounds for 6 days. Although differing by o nly two O-methyl groups, the two substances differed in their effects on do paminergic cells. 1 promoted growth of individual cells at low concentratio ns, whereas the more lipophilic 2 prevented cell death in culture and also clearly stimulated the growth of neuronal processes, although effects on gr owth of the total cell area were less pronounced. Effects on mitochondrial respiratory enzymes appear unlikely as 1 and 2 showed inhibitory effects on ly at concentrations 10-100-fold higher than those used in cell culture. Th e results obtained show that synthetically produced substances analogous to neuron-supportive mastigophorenes of plant origin can serve as neurotrophi c substances. (C) 2000 Wiley-Liss, Inc.