Is there remyelination during aging of the primate central nervous system?

Abstract

The effect of aging on myelin sheaths in the rhesus monkey was studied in the vertical bundles of nerve fibers that traverse monkey cerebral cortex in primary visual area 17 and prefrontal area 46. As shown previously, with age the internodes of many of these myelin sheaths show structural changes, the most common of which is an accumulation of electron-dense cytoplasm within some sheaths, a change which is considered to indicate that breakdown of myelin is taking place. Supporting the suggestion that myelin is breaking down with age, astrocytes in the cortices of old monkeys contain phagocytosed myelin and some of the inclusion bodies in astrocytes label with antibodies to myelin basic protein. There is also evidence that remyelination is taking place. Thus, we have found an increase in the frequency of profiles of paranodes when transverse sections of the nerve fibers are examined. The increase in paranodal frequency with age is 57% in area 17 and 90% in area 46. This increase cannot all be attributed to lengthening of paranodes with age, because in area 17 the 11% increase in mean paranodal length with age is insufficient to account for an age-related increase in paranodal profile frequency. Consequently, there must be an increase in the number of internodal lengths of myelin with age, as would occur if shorter lengths of myelin are produced by remyelination. In support of the proposal that remyelination is occurring, short internodal lengths of myelin have been found in the nerve bundles passing through the cortices of old monkeys and inappropriately thin sheaths occur around some axons. Both of these features are generally considered to be the hallmarks of remyelination. Consequently, it is proposed that in the aging cerebral cortex of the monkey there is some breakdown of internodes of myelin with subsequent remyelination that leads to the formation of some new and shorter internodal lengths of myelin.