Age‐related myelin dynamics revealed by increased oligodendrogenesis and short internodes

Abstract

SummaryAging is associated with many functional and morphological central nervous system changes. It is important to distinguish between changes created by normal aging and those caused by disease. In the present study we characterized myelin changes within the murine rubrospinal tract and found that internode lengths significantly decrease as a function of age which suggests active remyelination. We also analyzed the proliferation, distribution and phenotypic fate of dividing cells with Bromodeoxyuridine (5-bromo-2-deoxyuridine, BrdU). The data reveal a decrease in glial cell proliferation from 1 to 6, 14 and 21 months of age in gray matter 4 weeks post-BrdU injections. However, we found an increase in gliogenesis at 21st month in white matter of the spinal cord. Half of newly generated cells expressed NG2. Most cells were positive for the early oligodendrocyte marker Olig2 and a few also expressed CC1. Very few cells ever became positive for the astrocytic markers S100β β β β or GFAP. These data demonstrate ongoing oligodendrogenesis and myelinogenesis as a function of age in the spinal cord.

Oligodendrocyte Development and Plasticity

“…3D) (Young et al 2013). This is consistent with previous observations that average internode length decreases (Lasiene et al 2009) and the number of nodes per unit volume increases (Peters and Kemper 2012) with the age of the animal, and suggests that late-forming OLs might intercalate new internodes among the earlier-formed internodes, perhaps initiating myelination from nodes of Ranvier to create two nodes from one. The functional or behavioral consequences of remodeling myelin in this way are unknown and difficult to predict.…”

Fractionation Spares Mice From Radiation-Induced Reductions in Weight Gain But Does Not Prevent Late Oligodendrocyte Lineage Side Effects

“…In addition to an increased g-ratio, we observed reduced density of Ankyrin G+ nodes of Ranvier at 18 months following both radiation protocols. Internode length has been shown to decrease with normal aging, suggesting myelin turnover and remyelination (38). Therefore, the reduced density of nodes seen after radiation exposure may also represent a decrease in adult myelination.…”

Glial Progenitors as Targets for Transformation in Glioma

“…In fact, approximately 70% of 5-bromo-2′-deoxyuridine (BrdU)-incorporating cells in the adult rat brain co-expressed NG2 (Dawson, Polito, Levine, & Reynolds, 2003; Lasiene, Matsui, Sawa, Wong, & Horner, 2009). An elegant study by Hughes et al (2013) show that OPCs are under homeostatic control to ensure generation of appropriate numbers of myelin-producing oligodendrocytes (Hughes, Kang, Fukaya, & Bergles, 2013).…”