LEVELS OF IEGS RESPONSIBLE FOR RECEPTOR TRAFFICKING ARE UNCHANGED IN THE AGED HIPPOCAMPUS

M.R. Penner¹*; M.K. Chawla¹; S.N. Burke¹;
H.L. Milliken¹; M.J. Schaner¹; B. Xiao²;
P.F. Worley²; C.A. Barnes¹

1. NSMA, Univ Arizona, Tucson, AZ, USA
2. Neurosci & Neurol, Johns Hopkins Univ, Baltimore, MD, USA

Among the activity-regulated genes whose expression may be affected by increasing age are Narp, a secreted neuronal pentraxin found in hippocampal axons and dendrites whose protein product functions extracellularly to aggregate AMPA receptors, and Homer1A, whose protein product interacts with many other proteins within the postsynaptic density to modify glutamatergic signalling pathways. It is these mechanisms that may lead to the lowered threshold of aged animals for LTD, a higher threshold for LTP, and ultimately memory impairment. With this in mind, we used a sensitive real-time multiplex PCR method to investigate potential age-related changes in both the basal expression and the inducibility of Narp and Homer1A in the aged hippocampus following a brief spatial experience. Behaviourally-characterized adult (9-12months) and aged (24-30 months) rats explored a novel environment for 5 minutes followed by an undisturbed rest period in their home cages for 20 or 50 minutes. These rats then explored the same environment for another 5 minutes and were sacrificed immediately following this second behavioural epoch. We found no significant differences between adult and aged rats in basal levels of Narp mRNA in the hippocampal CA region, and moreover, both the adult and aged rats showed an increase in Narp mRNA levels of ~30% following the first behavioural epoch. Similarly, Homer1A basal levels were no different between aged and adult rats, and both age groups showed an increase in mRNA levels of ~20-30% following the first behavioural epoch. These data show that the regulatory events required for transcription are preserved during aging for these two immediate early genes.

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