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

Exp Gerontol. 2000 Dec;35(9-10):1211-27. doi: 10.1016/s0531-5565(00)00154-6.


The ability of the rodent brain to support plasticity-related phenomena declines 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 plasticity, 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 rat brain. However, the aged rat brain responded more slowly to chemically induced seizure 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 levels expressed by 3-month-old rats. In addition, at the peak induction the TPA transcripts were restricted to certain cortical layers of the older rats. Surprisingly, in applying the same experimental paradigm to late genes we found that there was a shift toward earlier times in the maximum expression of growth-related molecule, the microtubule-associated protein 1B (MAP1B) mRNA, which was very evident in 18-month-old rats. Aberrant immunolabeling of MAP1B occurred in cortical layer VI of the aged rats where, unlike in young rats, there was heavy staining of neuronal somata. These results suggest that (i) 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; (ii) since c-fos, TPA and MAP1B have been implicated in neuronal plasticity, these findings could explain, in part, the limited plasticity of the aging brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Gene Expression Regulation, Developmental / drug effects
  • Hippocampus / chemistry
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Immunohistochemistry
  • In Situ Hybridization
  • Microtubule-Associated Proteins / genetics
  • Neuronal Plasticity / genetics*
  • Pentylenetetrazole / pharmacology
  • Proto-Oncogene Proteins c-fos / genetics
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Temporal Lobe / chemistry
  • Temporal Lobe / drug effects
  • Temporal Lobe / metabolism
  • Tissue Plasminogen Activator / genetics


  • Microtubule-Associated Proteins
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • microtubule-associated protein 1B
  • Tissue Plasminogen Activator
  • Pentylenetetrazole