Basal levels of several immediate-early genes are lower in the aged rat hippocampus versus the adult rat hippocampus.
1. ARL NSMA
2. Evelyn F. McKnight Brain Inst., Univ. Arizona, Tucson, AZ
3. Neurosci. and Neurol., Johns Hopkins Univ., Baltimore, MD
Long-term memory and long-term potentiation are two examples of long-lasting changes in neuronal function that result from changes in gene expression. Neuronal immediate-early genes (IEGs), which are the first group of genes expressed following synaptic activity, encode transcription factors, cytoskeletal proteins, growth factors, metabolic enzymes, and proteins involved in signal transduction. Although many of this particular class of genes are considered ‘activity-dependent’, these genes also demonstrate relatively low levels of ‘constitutive’ or ‘basal’ expression. Consideration of basal levels of IEG transcription is crucial, since these levels may ultimately affect, not only the levels induced following some treatment, but also the functional changes that result. For example, it has been demonstrated that the basal level of Arc, an IEG critically involved in neuronal plasticity, is lower in the aged hippocampus compared to the adult hippocampus and as a result, Arc transcription following spatial behavior must be comparatively increased in aged rats to reach mRNA levels equivalent to adult rats. In the current study we extended our analysis to analyze the basal levels of several IEGs involved in neuronal plasticity using methods that allowed us to determine: 1) how much mRNA was present within a particular CA1 sample, and 2) the proportion of CA1 pyramidal neurons that expressed a particular mRNA. We found basal levels of Arc, zif268, and Homer1a were significantly lower in the aged versus adult hippocampus, whereas basal levels of c-fos are not significantly different between aged and adult rats. Despite the significantly lower levels of Arc, zif268, and Homer1a, the proportion of neurons that expressed these IEGs were not different between aged and adult rats. This finding indicates that while aged neurons maintain their ability to transcribe these IEGs under ‘basal’ conditions, some or all of the aged neurons are transcribing less mRNA. An inability to maintain equivalent basal levels of plasticity-associated IEGs in the hippocampus may contribute to the memory deficits observed in the aged rat.
Grant/Other Support: AG009219; McKnight Brain Research Foundation; state of Arizona and ADHS
Keyword (Complete): Arc; gene expression; memory impairment; plasticity