Department of Anatomy, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
Department of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea.
Cell Tissue Res. 2022 Sep;389(3):443-463. doi: 10.1007/s00441-022-03645-6. Epub 2022 Jun 11.
We previously demonstrated that osteopontin (OPN) is closely associated with calcium precipitation in response to ischemic brain insults. The present study was designed to elucidate the possible association between deposition of OPN and progressive neurodegeneration in the ischemic hippocampus. To address this, we analyzed the OPN deposits in the rat hippocampus after global cerebral ischemia in the chronic phase (4 to 12 weeks) after reperfusion using immunoelectron microscopy and correlative light and electron microscopy. We identified three different types of OPN deposits based on their morphological characteristics, numbered according to the order in which they evolved. Dark degenerative cells that retained cellular morphology were frequently observed in the pyramidal cell layer, and type I OPN deposits were degenerative mitochondria that accumulated among these cells. Type II deposits evolved into more complex amorphous structures with prominent OPN deposits within their periphery and within degenerative mitochondria-like structures. Finally, type III had large concentric laminated structures with irregularly shaped bodies in the center of the deposits. In all types, OPN expression was closely correlated with calcification, as confirmed by calcium fixation and Alizarin Red staining. Notably, type II and III deposits were highly reminiscent of corpora amylacea, glycoprotein-rich aggregates found in aged brains, or neurodegenerative disease, which was further confirmed by ubiquitin expression and periodic acid-Schiff staining. Overall, our data provide a novel link between ongoing neurodegeneration and the formation of corpora amylacea-like structures and calcium deposits in the ischemic hippocampus, suggesting that OPN may play an important role in such processes.
我们之前的研究表明，骨桥蛋白（OPN）与缺血性脑损伤后的钙沉淀密切相关。本研究旨在阐明 OPN 沉积与缺血性海马体中进行性神经退行性变之间的可能关联。为此，我们使用免疫电子显微镜和相关的光镜和电镜分析了再灌注后慢性期（4 至 12 周）全脑缺血后大鼠海马体中的 OPN 沉积。根据其形态特征，我们将 OPN 沉积分为三种不同类型，编号为按出现顺序排列。在锥体细胞层中经常观察到保留细胞形态的暗变性细胞，I 型 OPN 沉积是在这些细胞之间积累的退行性线粒体。II 型沉积物演变成更复杂的无定形结构，其外围和退行性线粒体样结构内有明显的 OPN 沉积。最后，III 型有大的同心层状结构，沉积物中心有不规则形状的体。在所有类型中，OPN 表达与钙化密切相关，这通过钙固定和茜素红染色得到证实。值得注意的是，II 型和 III 型沉积物高度类似于淀粉样小体，即老年大脑或神经退行性疾病中发现的富含糖蛋白的聚集物，这进一步通过泛素表达和过碘酸希夫染色得到证实。总体而言，我们的数据提供了缺血性海马体中持续神经退行性变与淀粉样小体样结构和钙沉积形成之间的新联系，表明 OPN 可能在这些过程中发挥重要作用。
