Lifelong oligodendrogenesis and myelination is critical for healthy brain aging. Using cumulative labelling with thymidine analogue, 5-ethynyl-2'-deoxyuridine (EdU) for 6-weeks commencing at 2-, 12- and 18-months of age in C57BL/6 mice, we found that oligodendrocyte progenitor cell (OPC) proliferation and oligodendroglial densities are relatively stable in the adult mouse optic nerve, corpus callosum and somatosensory cortex. We also found that more proliferative adult OPCs differentiate into oligodendrocytes in the somatosensory cortex than the corpus callosum during aging. To determine the role of neuronal TrkB in adult oligodendrogenesis in the older brain, we generated Thy1-CreERT2-EYFP::TrkBfl/fl mice and administered tamoxifen at 12-months of age, before cumulative EdU labelling. This resulted in TrkB deletion from 10 % of layer V projection neurons in the somatosensory cortex and reduced the level of TrkB in the remaining Thy1-YFP+ neurons by approximately half. Neuronal TrkB reduction had no effect on OPC proliferation in the optic nerve, corpus callosum or somatosensory cortex. However, there was a significant decrease in the proportion of proliferative OPCs that contributed to the post-mitotic oligodendrocyte population in the somatosensory cortex 5-months later. These findings provide insight into regional and age-related changes in oligodendroglial population dynamics and identify that neuronal TrkB supports cortical oligodendrogenesis during healthy brain aging.
Keywords: Aging; Cortex; Neurotrophin receptor; Oligodendrogenesis; TrkB.
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