Delayed and blunted induction of mRNA for tissue plasminogen activator in the brain of old rats following pentylenetetrazole-induced seizure activity

The ability of the rodent brain to support plasticity-related phenomena dec lines with increasing age, Here we investigated the extent to which old rat s retain the rapacity to initiate transcription for immediate early genes, particularly as it relates to brain plasticity, in response to a strong sti mulus. The intraperitoneal administration of pentylenetetrazole (PTZ) to ra ts of various ages evoked tonic-clonic seizures. Using an RNA gel-blot and in situ hybridization analysis, we found that 1 hour after the onset of sei zure, messenger RNA (mRNA) for tissue plasminogen activator (TPA) was incre ased similar to 3.7-fold in the hippocampi of 3-month-old rats. The levels; of TPA mRNA in the hippocampi and cortices of 3-month-old rats returned to control levels by 3 hours after PTZ administration, The levels of TPA mRNA increased 2.5-fold in the hippocampi of 18-month-old rats and 1.8-fold in the brains of the 28-month-old-rats at 3 hours and returned to basal levels by 15 hours following PTZ treatment. Quantitatively; similar increases wer e calculated for the cortex. At peak induction the transcripts were localiz ed throughout the cortical layers of the 3-moth-old rats, whereas the TPA m RNA expression was restricted to cortical layer V of the older rats. Our re sults suggest that although the aging brain retains the capacity to respond to chemically induced seizures, the induction of TPA mRNA is temporarily d elayed and the levels are diminished with increasing age. Because TPA has b een implicated in neuronal plasticity, this finding suggests that immediate early genes are important factors in the limited plasticity of the aging b rain.