Dynamics of gene expression for immediate early- and late genes after seizure activity in aged rats

The ability of the rodent brain to support plasticity-related phenomena dec lines with increasing age. A decreased coordination of genes implicated in brain plasticity may be one factor contributing to this decline. Synaptic r earrangement that occurs after seizure activity is regarded as a model of b rain plasticity. In a rat model of seizure-related brain plasticity, we fou nd that the induction of immediate-early genes: as exemplified by c-fos and tissue plasminogen activator (tPA), is not impaired in the aged rat brain. However, the aged rat brain responded more slowly to chemically induced se izure, and the levels of c-fos and tPA mRNAS induction are decreased in the cortex and in the hippocampus of 30 month old rats, as compared to the lev els expressed by 3 month old rats. In addition, at the peak induction, the TPA transcripts were restricted to certain cortical layers of the older rat s. Surprisingly, in applying the same experimental paradigm to late genes, we found that there was a shift toward earlier times in the maximum express ion of growth-related molecules, the microtubule-associated protein 1B (MAP 1B) mRNA, which was very evident in 18 month old rats. Aberrant immunolabel ing of MAP1B occurred in cortical layer VI of the aged rats where, unlike i n young rats, there was heavy staining of neuronal somata. These results su ggest that (1) one consequence of aging, besides decreases in the levels of mRNA, is a progressive loss of coordination in gene activity following the administration of a stimulus, (2) since c-fos, TPA and MAP1B have been imp licated in neuronal plasticity. these findings could explain. in part. the limited plasticity of the aging brain. (C) 2001 Elsevier Science Ireland Lt d. All rights reserved.