Remarkable Stability of Myelinating Oligodendrocytes in Mice

Abstract

Summary: New myelin-forming oligodendrocytes (OLs) are generated in the mouse central nervous system during adulthood. These adult-born OLs might augment the existing population, contributing to neural plasticity, or else replace OLs that die in use (turnover). To distinguish between these alternatives, we induced genetic labeling of mature myelinating OLs in young adult mice and tracked their subsequent survival. OL survival rates were region dependent, being higher in corpus callosum (∼90% survival over 20 months) and motor cortex (∼70% survival) than in corticospinal tract or optic nerve (50%–60% survival). Survival rates over the first 8 months were 90%–100% in all regions except the optic nerve. In the corpus callosum, new OLs accumulate during young adulthood and are therefore likely to participate in adaptive myelination. We also found that the number of myelin internodes maintained by individual cortical OLs is stable for at least 8 months but declines ∼12% in the following year. : Tripathi et al. estimate the lifetime of myelinating oligodendrocytes (OLs) by fate-mapping in Opalin-CreERT2: Tau-mGFP mice. In the corpus callosum, >90% of OLs survived for >1.5 years and probably outlive the mouse. Therefore, adult-born OLs are not needed for myelin homeostasis but potentially contribute to experience-dependent, adaptive myelination. Keywords: myelin, internode, cell survival, cell turnover, transgenic mouse, Opalin-CreER, corpus callosum, cerebral cortex, spinal cord, optic nerve