Abstract
Aging is associated with cognitive decline in both humans and animals and of all brain regions, the hippocampus appears to be particularly vulnerable to senescence. Age-related spatial learning deficits result from alterations in hippocampal connectivity and plasticity. These changes are differentially expressed in each of the hippocampal fields known as cornu ammonis 1 (CA1), cornu ammonis 3 (CA3), and the dentate gyrus. Each sub-region displays varying degrees of susceptibility to aging. For example, the CA1 region is particularly susceptible in Alzheimer's disease while the CA3 region shows vulnerability to stress and glucocorticoids. Further, in animals, aging is the main factor associated with the decline in adult neurogenesis in the dentate gyrus. This review discusses the relationship between region-specific hippocampal connectivity, morphology, and gene expression alterations and the cognitive deficits associated with senescence. In particular, data are reviewed that illustrate how the molecular changes observed in the CA1, CA3, and dentate regions are associated with age-related learning deficits. This topic is of importance because increased understanding of how gene expression patterns reflect individual differences in cognitive performance is critical to the process of identifying new and clinically useful biomarkers for cognitive aging.
Highlights
The three main fields of the hippocampal region, cornu ammonis 1 (CA1), cornu ammonis 3 (CA3), and the dentate gyrus, possess distinctive anatomical, molecular and biophysical properties
Of the 289 probe sets identified in this analysis, the authors discuss only one functional group that includes genes involved in synaptic transmission. Their data from the CA3 region is in agreement with our findings in both the CA1 and dentate gyrus, where aged animals that had successfully learned the Morris water maze (MWM) did not show the same patterns of gene expression as trained young animals (Burger et al, 2007, 2008)
The aging hippocampus does not appear to show a major loss of cells or alterations in morphology
Summary
Age-related spatial learning deficits result from alterations in hippocampal connectivity and plasticity. These changes are differentially expressed in each of the hippocampal fields known as cornu ammonis 1 (CA1), cornu ammonis 3 (CA3), and the dentate gyrus. Data are reviewed that illustrate how the molecular changes observed in the CA1, CA3, and dentate regions are associated with age-related learning deficits. This topic is of importance because increased understanding of how gene expression patterns reflect individual differences in cognitive performance is critical to the process of identifying new and clinically useful biomarkers for cognitive aging
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