Mild age-related changes in the dentate gyrus of adult rhesus monkeys.

Memory and cognitive performance decline with advancing age in humans. Rhesus monkeys show a similar age-related memory deficit. Since the functional neuroanatomy of the temporal lobes in the two species is similar, and since the circuits of the temporal lobes are known to be involved in memory function, we undertook a study of the anatomical characteristics of synapses in the dentate gyrus of the rhesus monkey throughout the adult life span. Light- and electron-microscopic examinations were carried out on the dentate gyrus of 10 adult rhesus monkeys (4-35 years) to determine the effect of age on the thickness of the molecular layer and on axon terminals in the outer portion of the molecular layer. The thickness measurements were made on 100-microns-thick Vibratome sections and on 1 micron-thick Araldite-embedded sections. A total of 100 electron micrographs covering a test area of 3,600 microns2 for each monkey were taken in the outer portion of the molecular layer. Counts of axon terminals synapsing with dendritic spines or shafts, measurements of the cross-sectional area of these terminals, and the length of the postsynaptic density were taken on enlarged prints. The thickness of the molecular layer remained unchanged throughout adulthood. Statistical analysis revealed no overall age-associated loss of synapsing axon terminals or shrinkage of the cross-sectional areas of their profiles. Further, there was no loss in the total number of synapses (axospinous plus axodendritic) or any change in the lengths of their postsynaptic membrane densities. However, when axodendritic (shaft) synapses (which constitute 13% of the total) were considered separately, a statistically significant age-related loss was detected. Qualitative observations revealed that older monkeys had a moderate number of dystrophic myelinated axons and corpora amylacea located in astrocytic processes in the outer portion of the molecular layer, features not present in young monkeys. Also, glial cells and pericytes showed age-associated accumulation of lipofuscin-like inclusions. A single occurrence of a structured inclusion body in a dendrite was observed in a 10-year-old monkey. In conclusion, most synaptic measures in the dentate gyrus remain stable throughout adulthood of rhesus monkey and there are relatively few other age-related changes. The small age-associated loss of axodendritic synapses is only apparent following separate statistical treatment of these synapses. The functional significance of this loss is unclear since it would result in only 3% reduction in total synapses (shaft plus spinous) from 4 to 35 years of age, the maximal life span of the rhesus monkey.