Effect of cycloheximide administered to rats in early postnatal life: prolonged inhibition of DNA synthesis in the developing brain

Abstract

Administration of cycloheximide in a single dose of 0.6 mg/kg to 7-day-old rats was used to induce short-term inhibition of protein synthesis at the period of brain 'growth spurt'. Measurement of the rate of [14C]lysine incorporation indicated that the initial inhibition of protein synthesis in the brain (by 75%) was released within about 12 h. The normal rate of protein synthesis was attained by 48 h after cycloheximide administration; there was no sign of protein synthesis stimulation. The estimation of [14C]thymidine incorporation into brain DNA showed that inhibition of DNA synthesis was greater and longer lasting in the forebrain and olfactory bulbs (by about 80%) than in the cerebellum (by about 40%). Similar differential inhibition of thymidine kinase activity was observed in the olfactory bulbs (by 75%) and cerebellum (by 30%) at 24 h after cycloheximide, suggesting that the formation of [14C]thymidine nucleotides may have been impaired. However, a retardation of DNA accumulation was found in the forebrain and cerebellum at 72 h after cycloheximide. Thus, the short-term inhibition of protein synthesis produced prolonged inhibition of DNA synthesis and altered cell proliferation in the developing brain.