Age-related morphologic alterations in the brain of macaque monkey: Dendritic morphology, spine density, and catecholaminergic innervation

Cognitive functions, including working memory, decline during normal aging. However neuronal death does not appear to underlie this decline. Thus, these cognitive deficits are likely due mainly to subtle cellular or neurochemical changes in still relatively intact neural circuits. Dendritic arbors and the dendritic spines of cortical pyramidal neurons, as the postsynaptic structures, have been observed to undergo age-related changes in specific regions and layers in the primate neocortex. Furthermore, the cortically projecting brainstem dopaminergic system has been implicated as a major modulator of the prefrontal cortex (PFC) functions and the dopamine (DA) levels in the PFC undergo age-related decrease in macaque monkeys. In this thesis, we explored the projection type-specific differences and age-related alterations in the dendrites, dendritic spines of corticocortical pyramidal cells in the association cortex, as well as age-related change in the catecholaminergic innervation of the PFC in macaque monkeys.; One of our hypotheses was that the dendritic arbor, especially dendritic spines of long corticocortical projection neurons, should be compromised with aging. We tested this hypothesis in a distinct subpopulation of pyramidal neurons furnishing a projection directly linked to cognitive processing, from the superior temporal cortex to the dorsolateral prefrontal area 46. We have demonstrated that the dendritic arbors of these pyramidal neurons are generally stable in aged monkeys. However, significant loss of spines was found in old animals in both the apical and basal dendrites of these neurons. We also tested the hypothesis that the catecholaminergic innervation of the PFC is compromised during normal aging. We used an antibody to tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis to examine TH-immunoreactive axons in prefrontal area 46 in young and old macaque monkeys. Our results show that the total length TH-immunoreactive fibers in area 46 decreases significantly in old animals compared with young animals. Thus, we have identified two systems projecting to the PFC that are impaired in the aging brain, namely, long corticocortical projection neurons that exhibit a significant loss of spine numbers and a reduction in the catecholaminergic innervations of the PFC, which may contribute to the cognitive deficits that accompany normal aging.