Brain plasticity: to what extent do aged animals retain the capacity to coordinate gene activity in response to acute challenges

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 rearrangement that occurs after seizure activity is regarded as a model of brain plasticity. In a rat model of seizure-related brain plastici ty, we found that the induction of immediate-early genes, as exemplified by c-fos and tissue plasminogen activator (TPA) is not impaired in the aged r at brain. However, the aged rat brain responded more slowly to chemically i nduced seizure and the levels of c-fos and TPA mRNAs induction are decrease d in the cortex and in the hippocampus of 3-month-old rats, as compared to the levels expressed by 3-month-old rats. In addition, at the peak inductio n the TPA transcripts were restricted to certain cortical layers of the old er rats. Surprisingly, in applying the same experimental paradigm to late g enes we found that there was a shift toward earlier times in the maximum ex pression of growth-related molecule, the microtubule-associated protein 1B (MAP1B) mRNA, which was very evident in 18-month-old rats. Aberrant immunol abeling of MAP1B occurred in cortical layer VI of the aged rats where, unli ke in young rats, there was heavy staining of neuronal somata. These result s suggest that (i) one consequence of aging, besides decreases in the level s of mRNA, is a progressive loss of coordination in gene activity following the administration of a stimulus; (ii) since c-Sos, TPA and MAP1B have bee n implicated in neuronal plasticity, these findings could explain, in part, the limited plasticity of the aging brain. (C) 2000 Elsevier Science Inc. All rights reserved.