REDUCTION OF NEURITE EXTENSION BY PIPERINE, EXAMINED ON HIPPOCAMPAL AND SEPTAL NEURONS IN SERUM-FREE CULTURES

The presence of piperine in a serum-free medium for 72 h markedly inhi bited the neurite extension of cultured hippocampal and septal neurons under both high and low density cell culture conditions (initial cell density was 10(5) cells/cm2 and 2.5-5 x 10(3) cells/cm2, respectively ). The average length of neurites decreased over a concentration range of piperine (12.5-100 muM, and the distribution of neurite population shifted towards the shorter neurite lengths whereas an increase in th e soma size was observed only with high piperine concentrations (75 an d 100 muM in a high density cell culture). This indicates that the pip erine effect was relatively selective to the neurite extension. The ne urite extension in low density cell cultures was considerably, more su sceptible to piperine than that in high density cell cultures (hippoca mpus: EC50 = 39 versus 113 muM, septum: EC50 = 48 versus 101 muM, in t he low and high density cell cultures, respectively). This difference may be due to a lack of neurotrophic supports from non-neuronal cells under the low density cell culture condition. These findings suggest t hat piperine, in addition to its cytotoxic effect on the neuronal surv ival, suppresses the neurite extension in developing neurons.