Brain RNA polymerase and nucleolar structure in perinatal asphyxia of the rat

Ribosomes are integral constitutens of the protein synthesis machinery. Pol ymerase I(POL I) is located in the nucleolus and transcribes the large ribo somal genes. POL I activity is decreased in ischemia but nothing is known s o far on POL I in perinatal asphyxia. We investigated the involvement of PO L I in a well-documented model of graded systemic asphyxia at the level of activity, mRNA, protein, and morphology, Caeserean section was performed at the 21st day of gestation. Rat pups still in the uterus horns were immerge d in a water bath for asphyctic periods from 5-20 min. Brain was taken for measurement of pH, nuclear POL I activity, and mRNA steady state, and prote in levels of RPA40, an essential subunit of POL I and III. Silver staining and transmission electron microscopy with morphometry when appropriate were used to examine the nucleolus. Brain pH and nuclear POL I activity decreas ed with the length of the asphyctic period while POL-I mRNA and protein lev els were unchanged. Accompanying the decrease in brain pH we found signific ant changes of nucleolar structure in the course of perinatal asphyxia at t he light and electron microscopic level. As early as ten min following the asphyctic insult, morphological disintegration of the nucleolus was observe d. The changes became more dramatic with longer duration of perinatal asphy xia. We conclude that severe acidosis may be responsible for decreased POL activity and for disintegration of nucleoli in neurons. This condition may lower the ribosome content in neonatal neurons and impair protein synthesis . (C) 2000 Academic Press.