Influence of phenytoin on cytoskeletal organization and cell viability of immortalized mouse hippocampal neurons

Abstract

Phenytoin (PHT) is a commonly used anticonvulsant drug; several side effects have been described, including morphological changes in brain cortex and cerebellar neurons and teratogenic lesions in infants of epileptic mothers. Evidence of other authors indicate that PHT may exert its action through the modification of phosphorylation patterns of cytoskeletal polypeptides. We have studied the influence of the anticonvulsant drug phenytoin on immortalized mouse hippocampal neurons in culture. This was done by means of MTT-assays, immunocytochemical and immunoblot 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 formation of neuronal processes, involving malfunction of an assembly-mechanism of cytoskeletal constituents. These accumulated within appendages (blebs) or cytoplasmic condensations, instead of forming normally organized processes. However, PHT did not interfere with bulk synthesis of cell proteins and specific cytoskeletal components.