Effect of diphenylhydantoin on protein metabolism in neuron and neuroglial fractions of central nervous tissue

Abstract

The effect of diphenylhydantoin (DPH) on amino acid incorporation into proteins of rat cerebral cortex was studied after daily intraperitoneal injection of the drug for various periods and in different doses. After tritiated leucine incorporation in cerebral cortex slices, the neuronal and neuroglial fractions were prepared by ultracentrifugation in ficoll density gradients. Prompt inhibition was observed in the neuronal fraction at an early stage. During the withdrawal stage the neuronal fraction recovered rapidly, while prolonged inhibition was seen in the neuroglial fraction. These findings were compared with those from the subcellular fractions, and an attempt was made to analyze the reactions of subcellular structures from nerve and neuroglia cells. It appeared that the nerve cell perikarya, which consist predominantly of nuclei, were more sensitive to a large dose of the drug and that their reaction represented a neurosuppressive effect. A striking difference in inhibition of leucine incorporation between nerve cell perikarya and nerve endings is discussed. It is not know whether either effect is related to the specific anticonvulsant effect of DPH. The possibility that protein synthesis in the neuroglia cells, particularly in their microsomes, plays a supplementary role for recovery or maintenance of neuronal function is discussed among other possible roles.