Stereological quantification of age-related changes in myelinated fibers of rat white matter.

We investigated changes in myelin sheaths in the myelinated fibers of subcortical white matter in young (6-8 months old), middle-aged (18 months old), and elderly (27-28 months old) female Long-Evans rats using transmission electron microscopy and unbiased stereological techniques. We observed three age-related changes in myelin sheaths in the white matter of elderly rats: local splitting of the major dense line, myelin ballooning, and the formation of abundant myelin sheaths. Stereological analysis showed that the total length of myelinated fibers in white matter was 115±12 km (mean±SD) in young rats, 135±21 km in middle-aged rats, and 62±11 km in elderly rats. Myelinated fibers with diameters less than 1.0 μm and myelin sheath thicknesses less than 0.1 μm were significantly shorter in middle-aged and elderly rats compared with young rats. Age-related changes in myelin sheaths were evident in aged white matter. The loss of myelinated fibers with both small diameters and thin myelin sheaths is a potentially important change in aged white matter. Our results suggest that the myelin sheath changes in aged white matter may have important implications for age-related cognitive impairments.