Kimura Nobuyuki, Okabayashi Sachi, Ono Fumiko
aSection of Cell Biology and Pathology, Department of Alzheimer's Disease Research, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Aichi bTsukuba Primate Research Center, National Institute of Biomedical Innovation cThe Corporation for Production and Research of Laboratory Primates, Tsukuba, Japan.
Neuroreport. 2014 May 7;25(7):514-20. doi: 10.1097/WNR.0000000000000124.
We showed previously that aging attenuates the interaction between dynein-dynactin complexes in cynomolgus monkey brain and that dynein dysfunction reproduces age-dependent endocytic disturbances, resulting in intracellular β-amyloid (Aβ) accumulation, synaptic vesicle transport deficits, and neuritic swelling. It remains unclear whether such endocytic disturbances also occur in glial cells. Here, we show that endocytic pathology, such as intracellular accumulation of enlarged endosomes, occurs in astrocytes of aged monkey brains. Also, Aβ accumulates in these enlarged endosomes. RNA interference studies have shown that dynein dysfunction reproduces astroglial endocytic pathology and disrupts Aβ clearance in astrocytes through endocytic disturbances. These findings suggest that endocytic disturbances can alter astroglial functions and may also be involved in age-dependent Aβ pathology.
我们之前表明，衰老会减弱食蟹猴大脑中动力蛋白-动力蛋白激活蛋白复合物之间的相互作用，并且动力蛋白功能障碍会重现年龄依赖性的内吞紊乱，导致细胞内β-淀粉样蛋白（Aβ）积累、突触小泡运输缺陷和神经突肿胀。目前尚不清楚这种内吞紊乱是否也发生在神经胶质细胞中。在此，我们表明，诸如扩大的内体在细胞内积累等内吞病理现象发生在老年猴脑的星形胶质细胞中。此外，Aβ在这些扩大的内体中积累。RNA干扰研究表明，动力蛋白功能障碍会重现星形胶质细胞的内吞病理，并通过内吞紊乱破坏星形胶质细胞中的Aβ清除。这些发现表明，内吞紊乱可改变星形胶质细胞的功能，并且可能也参与了年龄依赖性的Aβ病理过程。
