Alterations in polyadenylic acid-containing messenger RNA synthesis of brain polysomes after seizures of seizure-susceptible E1 mice.

Abstract

The effect of seizures on synthesis of the polyadenylic acid (poly(A]-containing messenger RNA (mRNA) isolated from brain polysomes in a genetically seizure-susceptible E1 mouse was studied in vivo. The seizure in the E1 mice was induced by tossed-up stimulation. Immediately after the seizure ceased, the labeled orotic acid was injected into the brain. The incorporation rates of labeled orotic acid into poly(A)-containing mRNA isolated from polysomes are represented as the specific radioactivity (SR) (dpm/mg RNA) and the relative specific radioactivity (RSR) (dpm/mg RNA/dpm/mumoles of acid soluble uridine-5'-monophosphate (UMP]. Both the rates were reduced to 70% in SR and 65% in RSR at 1 h after the seizures. This reduction was gradually recovered to the level of interictal E1 mice at 6 h. The seizure-induced alterations are not attributable to the difference in the uridine nucleotide pool because the SR of UMP was not significantly affected by the seizure. The peak of labeled poly(A)-containing mRNA by analysis of gel electrophoresis displaced towards a lower molecular weight at 1 h after the seizures. The RNA showed a higher ratio of AMP and UMP per GMP and CMP in nucleotide composition, implying that this RNA is identical with DNA. These results suggest that the temporary decrease found in cytoplasmic mRNA synthesis induced by the seizures of E1 mice appears to be a result of impaired transcriptional processes in heterogeneous nuclear RNA synthesis and that the smaller mRNA coding for protein associated with seizures is newly synthesized during the postictal period.