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Lifelong cortical myelin plasticity and age-related degeneration in the live mammalian brain

R. Hill,Alice M. Li,J. Grutzendler

Published 2018 in Nature Neuroscience

ABSTRACT

Axonal myelin increases neural processing speed and efficiency. It is unknown whether patterns of myelin distribution are fixed or whether myelinating oligodendrocytes are continually generated in adulthood and maintain the capacity for structural remodeling. Using high-resolution, intravital label-free and fluorescence optical imaging in mouse cortex, we demonstrate lifelong oligodendrocyte generation occurring in parallel with structural plasticity of individual myelin internodes. Continuous internode formation occurred on both partially myelinated and unmyelinated axons, and the total myelin coverage along individual axons progressed up to two years of age. After peak myelination, gradual oligodendrocyte death and myelin degeneration in aging were associated with pronounced internode loss and myelin debris accumulation within microglia. Thus, cortical myelin remodeling is protracted throughout life, potentially playing critical roles in neuronal network homeostasis. The gradual loss of internodes and myelin degeneration in aging could contribute significantly to brain pathogenesis. It is unknown if myelination patterns are fixed in adults. Using label-free & fluorescence in vivo imaging, Hill et al show lifelong internode addition to partially myelinated axons, with age-related internode loss & debris accumulation in microglia.

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