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 f unctional neuroanatomy of the temporal lobes in the two species is sim ilar, and since the circuits of the temporal lobes are known to be inv olved in memory function, we undertook a study of the anatomical chara cteristics of synapses in the dentate gyrus of the rhesus monkey throu ghout the adult life span, Light- and electronmicroscopic examinations were carried out on the dentate gyrus of 10 adult rhesus monkeys (4-3 5 years) to determine the effect of age on the thickness of the molecu lar layer and on axon terminals in the outer portion of the molecular layer. The thickness measurements were made on 100-mu m-thick Vibratom e sections and on 1-mu m-thick Araldite-embedded sections. A total of 100 electron micrographs covering a test area of 3,600 mu m(2) for eac h monkey were taken in the outer portion of the molecular layer. Count s of axon terminals synapsing with dendritic spines or shafts, measure ments of the cross-sectional area of these terminals, and the length o f the postsynaptic density were taken on enlarged prints. The thicknes s of the molecular layer remained unchanged throughout adulthood. Stat istical analysis revealed no overall age-associated loss of synapsing axon terminals or shrinkage of the cross-sectional areas of their prof iles, Further, there was no loss in the total number of synapses (axos pinous plus axodendritic) or any change in the lenghts of their postsy naptic membrane densities. However, when axodendritic (shaft) synapses (which constitute 13% of the total) were considered separately, a sta tistically significant age-related loss was detected. Qualitative obse rvations revealed that older monkeys had a moderate number of dystroph ic myelinated axons and corpora amylacea located in astrocytic process es in the outer portion of the molecular layer, features not present i n 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 rem ain stable throughout adulthood of rhesus monkey and there are relativ ely few other age-related changes. The small age-associated loss of ax odendritic synapses is only apparent following separate statistical tr eatment 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.