Looprasertkul Sasikarn, Yamazaki Reiji, Osanai Yasuyuki, Ohno Nobuhiko
Department of Anatomy, Division of Histology and Cell Biology, School of Medicine, Jichi Medical University, Shimotsuke, Japan.
Division of Ultrastructural Research, National Institute for Physiological Sciences, Okazaki, Japan.
Glia. 2025 Nov;73(11):2322-2334. doi: 10.1002/glia.70070. Epub 2025 Aug 1.
The activity of oligodendrocyte progenitor cells (OPCs) and oligodendrocytes (OLs) throughout life drives myelination, which is crucial for rapid neuronal communication. OLs in the aging brain demonstrate a reduced capacity for myelin formation and maintenance, but the underlying differentiation of individual OLs and morphological changes of their myelin in aging remain unclear. Here, we utilized Pdgfra-CreER :Tau-mGFP double transgenic mice to selectively label and visualize newly generated OLs in aged (78-week-old) mice and compared them with those in young (8-week-old) mice. We revealed a significantly lower percentage of newly generated OLs that differentiated into mature OLs and a decreased rate of myelinating OLs accumulation in aged mice compared with young mice. Additionally, newly generated myelinating mature OLs in aged mice demonstrated significantly greater height compared with those in young mice. Furthermore, myelin internodes were significantly shorter and significantly fewer in aged mice compared with young mice. Our results indicate age-related impairments in the differentiation efficiency of aged OPCs and age-related morphological changes in OLs. These alterations in newly generated OLs may contribute to impaired myelination, reduced myelin turnover, and disrupted myelin maintenance in aged mice.
少突胶质前体细胞（OPCs）和少突胶质细胞（OLs）在整个生命过程中的活动驱动着髓鞘形成，这对快速的神经元通讯至关重要。衰老大脑中的OLs表现出髓鞘形成和维持能力下降，但衰老过程中单个OLs的潜在分化及其髓鞘的形态变化仍不清楚。在这里，我们利用Pdgfra-CreER:Tau-mGFP双转基因小鼠选择性标记并可视化老年（78周龄）小鼠中新生成的OLs，并将它们与年轻（8周龄）小鼠中的OLs进行比较。我们发现，与年轻小鼠相比，老年小鼠中新生成的分化为成熟OLs的OLs百分比显著降低，且有髓鞘OLs的积累速率下降。此外，与年轻小鼠相比，老年小鼠中新生成的有髓鞘成熟OLs的高度显著更高。此外，与年轻小鼠相比，老年小鼠的髓鞘节间明显更短且数量明显更少。我们的结果表明老年OPCs的分化效率存在与年龄相关的损害，以及OLs存在与年龄相关的形态变化。新生成OLs的这些改变可能导致老年小鼠髓鞘形成受损、髓鞘更新减少以及髓鞘维持中断。
