INFLUENCE OF PHENYTOIN ON CYTOSKELETAL ORGANIZATION AND CELL VIABILITY OF IMMORTALIZED MOUSE HIPPOCAMPAL-NEURONS

Phenytoin (PHT) is a commonly used anticonvulsant drug; several side e ffects have been described, including morphological changes in brain c ortex and cerebellar neurons and teratogenic lesions in infants of epi leptic mothers. Evidence of other authors indicate that PHT may exert its action through the modification of phosphorylation patterns of cyt oskeletal polypeptides. We have studied the influence of the anticonvu lsant drug phenytoin on immortalized mouse hippocampal neurons in cult ure. This was done by means of MTT-assays, immunocytochemical and immu noblot analyses, measurements of cell metabolism, measurements of the length of neuronal processes, and electron microscopy. A distinct and pronounced effect of PHT could be characterized with regard to the for mation of neuronal processes, involving malfunction of an assembly-mec hanism of cytoskeletal constituents. These accumulated within appendag es (blebs) or cytoplasmic condensations, instead of forming normally o rganized processes. However, PHT did not interfere with bulk synthesis of cell proteins and specific cytoskeletal components.