The effects of normal aging on myelinated nerve fibers in monkey central nervous system

Abstract

The effects of aging on myelinated nerve fibers of the central nervous system are complex. Many myelinated nerve fibers in white matter degenerate and are lost, leading to some disconnections between various parts of the central nervous system. Other myelinated nerve fibers are affected differently, because only their sheaths degenerate, leaving the axons intact. Such axons are remyelinated by a series of internodes that are much shorter than the original ones and are composed of thinner sheaths. Thus the myelin-forming cells of the central nervous system, the oligodendrocytes, remain active during aging. Indeed, not only do these neuroglial cell remyelinate axons, with age they also continue to add lamellae to the myelin sheaths of intact nerve fibers, so that sheaths become thicker. It is presumed that the degeneration of myelin sheaths is due to the degeneration of the parent oligodendrocyte, and that the production of increased numbers of internodes as a consequence of remyelination requires additional oligodendrocytes. Whether there is a turnover of oligodendrocytes during life has not been studied in primates, but it has been established that over the life span of the monkey, there is a substantial increase in the numbers of oligodendrocytes. While the loss of some myelinated nerve fibers leads to some disconnections, the degeneration of other myelin sheaths and the subsequent remyelination of axons by shorter internodes slow down the rate conduction along nerve fibers. These changes affect the integrity and timing in neuronal circuits, and there is evidence that they contribute to cognitive decline.

Keywords: axons; degeneration; myelin sheaths; oligodendrocytes; remyelination; rhesus monkey.

Figure 1

A longitudinal section of a myelinated nerve fiber in primary visual cortex of a rhesus monkey. The section passes through a node of Ranvier (N) where the axolemma has a characteristic undercoating. On each side of the node are the paranodes (p). The sheath on the right has 8 lamellae, while the one on the left is thicker with 15 lamellae, so that it has a longer paranode. Scale bar = 1 micron. (From Peters and Sethares, 2003).

Figure 2

In the field is a normal nerve fiber (N) and another nerve fiber (E) in which the axon has degenerated, leaving an empty sheath. Layer 4 from area 46 of a 27-year-old rhesus monkey. Scale bar = 1 micron.

Figure 3

A cross-sectioned nerve fiber bundle in primary visual cortex of a 29-year-old rhesus monkey. In this bundle some of the nerve fibers (N) have normal sheaths and are sectioned through internodes, and others (P) are sectioned through paranodes. Three nerve fibers (D) have degenerating sheaths, as shown by the accumulation of dense cytoplasm in splits between lamellae. Scale bar = 1 micron.

Figure 4

Electron micrograph of an oligodendrocyte in layer 6 of area 17 of a 35-year-old rhesus monkey. Three processes, p1–p3, extend from the cell body. One of the processes, p1, has a swelling that contains dense inclusions, which are similar to the dense inclusions in the cell body. Scale bar = 1 micron. The insert shows a light microscopic image of an oligodendrocyte stained with Perl's reaction for iron compounds. Note the large swelling (arrow) on one of the processes. It is similar to the one seen on process p1 in the accompanying electron micrograph. Area 46 of a 28-year-old monkey. Scale bar = 10 microns.

Figure 5

Diagrammatic representation of the degeneration of sheaths with age, and the subsequent remyelination of axons. (A) Normal state. (B) Some sheaths become altered by the presence of dense cytoplasm and the formation of balloons. This is believed to occur when the oligodendrocyte accumulates dense inclusions within its cell body and within swellings along its processes. (C) The degeneration of myelin sheaths leaves axons bare. (D) The bare axons are remyelinated by newly generated oligodendrocytes that form short internodal lengths with thin sheaths.