Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA.
Veterans Administration Palo Alto Health Care System, Palo Alto, California, USA.
J Neurosci Res. 2024 Jan;102(1):e25273. doi: 10.1002/jnr.25273.
Primary cilia are microtubule-based sensory organelles that project from the apical surface of most mammalian cells, including oligodendrocytes, which are myelinating cells of the central nervous system (CNS) that support critical axonal function. Dysfunction of CNS glia is associated with aging-related white matter diseases and neurodegeneration, and ciliopathies are known to affect CNS white matter. To investigate age-related changes in ciliary profile, we examined ciliary length and frequency in the retinogeniculate pathway, a white matter tract commonly affected by diseases of aging but in which expression of cilia has not been characterized. We found expression of Arl13b, a marker of primary cilia, in a small group of Olig2-positive oligodendrocytes in the optic nerve, optic chiasm, and optic tract in young and aged C57BL/6 wild-type mice. While the ciliary length and ciliated oligodendrocyte cells were constant in young mice in the retinogeniculate pathway, there was a significant increase in ciliary length in the anterior optic nerve as compared to the aged animals. Morphometric analysis confirmed a specific increase in the ciliation rate of CC1 /Olig2 oligodendrocytes in aged mice compared with young mice. Thus, the prevalence of primary cilia in oligodendrocytes in the visual pathway and the age-related changes in ciliation suggest that they may play important roles in white matter and age-associated optic neuropathies.
初级纤毛是从大多数哺乳动物细胞的顶表面伸出的微管基感觉细胞器,包括少突胶质细胞,少突胶质细胞是中枢神经系统 (CNS) 的髓鞘形成细胞,支持关键的轴突功能。中枢神经系统胶质细胞的功能障碍与与年龄相关的白质疾病和神经退行性变有关,并且已知纤毛病会影响中枢神经系统的白质。为了研究与年龄相关的纤毛形态变化,我们检查了视网膜-视交叉-视束(一种常见的受衰老相关疾病影响的白质束,但尚未对其纤毛表达进行特征描述)中的纤毛长度和频率。我们发现,在年轻和老年 C57BL/6 野生型小鼠的视神经、视交叉和视束中,一小部分 Olig2 阳性少突胶质细胞中表达了 Arl13b,这是初级纤毛的标志物。虽然年轻小鼠的视网膜-视交叉-视束中的纤毛长度和有纤毛的少突胶质细胞保持不变,但与老年动物相比,前视神经中的纤毛长度显著增加。形态计量学分析证实,与年轻小鼠相比,老年小鼠 CC1/Olig2 少突胶质细胞的纤毛化率有明显增加。因此,视觉通路中少突胶质细胞中初级纤毛的普遍性和纤毛化的年龄相关变化表明,它们可能在白质和与年龄相关的视神经病变中发挥重要作用。