Abstract
Aging is often associated with cognitive decline, but many elderly individuals maintain a high level of function throughout life. Here we studied outbred rats, which also exhibit individual differences across a spectrum of outcomes that includes both preserved and impaired spatial memory. Previous work in this model identified the CA3 subfield of the hippocampus as a region critically affected by age and integral to differing cognitive outcomes. Earlier microarray profiling revealed distinct gene expression profiles in the CA3 region, under basal conditions, for aged rats with intact memory and those with impairment. Because prominent age-related deficits within the CA3 occur during neural encoding of new information, here we used microarray analysis to gain a broad perspective of the aged CA3 transcriptome under activated conditions. Behaviorally-induced CA3 expression profiles differentiated aged rats with intact memory from those with impaired memory. In the activated profile, we observed substantial numbers of genes (greater than 1000) exhibiting increased expression in aged unimpaired rats relative to aged impaired, including many involved in synaptic plasticity and memory mechanisms. This unimpaired aged profile also overlapped significantly with a learning induced gene profile previously acquired in young adults. Alongside the increased transcripts common to both young learning and aged rats with preserved memory, many transcripts behaviorally-activated in the current study had previously been identified as repressed in the aged unimpaired phenotype in basal expression. A further distinct feature of the activated profile of aged rats with intact memory is the increased expression of an ensemble of genes involved in inhibitory synapse function, which could control the phenotype of neural hyperexcitability found in the CA3 region of aged impaired rats. These data support the conclusion that aged subjects with preserved memory recruit adaptive mechanisms to retain tight control over excitability under both basal and activated conditions.
Highlights
Significant variability characterizes cognitive outcomes in aging populations
Using principal component analysis to provide a broad perspective on individual differences among the aged rats, we found that CA3 gene expression profiles distinguished aged rats with intact memory from aged impaired subjects and distinguished the unimpaired aged rats from young
Aged rats performing within the normative range of young adults at 6 months of age (LI 240) were considered aged impaired (AI)
Summary
Significant variability characterizes cognitive outcomes in aging populations. Many individuals experience cognitive difficulties that typically emerge as mild memory deficits but can progress to greater impairment than expected for a person’s age and eventually to clinical dementia. A significant proportion of the elderly maintain a high level of cognitive function, including intact memory, well into old age [1,2]. Two concepts predominate in current views on the basis for preserved cognitive function in aging: Brain maintenance and cognitive reserve. May be susceptible to environmental influences, and results in varied aging outcomes [3]. While evidence for both of these perspectives can be found in the literature on human aging [2], direct examination of brain neurophysiology, which can be best performed in animal models, can provide significant additional insight into the basis for individual differences in aging
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
