Age-related changes in the rhesus monkey cerebral cortex: A molecular biology approach with anatomical correlations

In humans and non-human primates, cognitive ability declines with advancing age. It was once widely believed that large numbers of cortical neurons are lost with age, but recent studies have demonstrated that this does not occur. The goal of the present study was to search for other biological changes associated with aging in the cerebral cortex that may be related to cognitive impairment. Specifically, an effort was made to identify molecular changes in the aging brain, and to evaluate the effect of these molecular changes on anatomical structures. The first objective was to detect and identify age-related alterations in mRNA levels between samples of cerebral cortex taken from young and aged rhesus monkeys, and to determine if translation levels of specific gene products were affected by altered transcription. The second objective was to localize the protein expression of the gene in question, and the third objective was to perform a morphometric analysis of the relevant anatomical structures in young and aged brains.;The mRNA differential display (DD-PCR) method was performed on samples of primary visual cortex, revealing that mRNA levels of a number of genes may change in the brain with advanced age. One of these genes was identified as the monkey homologue of the laminin gamma-1 chain gene. The DD-PCR studies indicated that mRNA levels for this gene appear to be decreased in the aged brain. Western blot analysis indicated that laminin gamma-1 chain protein expression is reduced in aged occipital cortex as compared to young adult controls. Subsequent immunohistochemical staining with a monoclonal antibody directed against the laminin gamma-1 chain revealed that, in young and aged occipital cortex, this laminin chain is found predominantly in blood vessel walls. Based on this finding, a morphometric analysis of cortical microvasculature was carried out using samples from cortical area 17 in occipital cortex and area 46 in frontal cortex. Regional differences were found in microvascular density, and in the effect of age on microvascular density. In area 17, an age-related decline in the microvascular density of layer I correlated with declining performance on behavioral tests of cognitive function.