Neuronal and microglial localization of secreted phosphoprotein 1 (osteopontin) in intact and damaged motor cortex of macaques
Neuronal and microglial localization of secreted phosphoprotein 1 (osteopontin) in intact and damaged motor cortex of macaques
复制标题
DOI：
10.1016/j.brainres.2019.02.021
复制
发表时间：
2019-07
期刊：
影响因子：
2.9
通讯作者：
Yoko Sugiyama;T. Oishi;A. Yamashita;Y. Murata;Tatsuya Yamamoto;I. Takashima;T. Isa;N. Higo
中科院分区：
文献类型：
--
作者：
Yoko Sugiyama;T. Oishi;A. Yamashita;Y. Murata;Tatsuya Yamamoto;I. Takashima;T. Isa;N. Higo
我们以前报道过，mRNA编码分泌磷蛋白1（SPP1），也被称为骨桥蛋白，优先表达在大的神经元在层V的猕猴运动皮层，其中大部分被推测为皮质脊髓束神经元。作为阐明SPP1在猕猴神经元中的细胞功能的第一步，我们通过免疫组织化学方法研究了SPP1在猕猴初级运动皮层（M1）中的定位。SPP1的免疫反应被发现定位在神经元的细胞体中，但不在细胞外，表明SPP1不是从这些神经元分泌的。电镜分析和标记蛋白的双标记分析结果表明，SPP 1定位于神经元的线粒体。SPP1在神经元中的分布与整合素αV的分布相对应，整合素α V是SPP1的假定受体。SPP1的分布也进行了调查，在猕猴的M1已损坏。我们发现SPP1是由病变区增生的小胶质细胞分泌的。双标记分析表明，SPP1的免疫反应在小胶质细胞与CD44，另一个假定的受体SPP1共定位。在小物体检索任务的成功率呈正相关的SPP1免疫反应的神经元在病变周围区域。SPP1在猕猴运动皮层中具有多种作用，可能是脑损伤后手部运动恢复过程中的关键蛋白。
We previously reported that mRNA encoding secreted phosphoprotein 1 (SPP1), also known as osteopontin, is preferentially expressed in large neurons in layer V of the macaque motor cortex, most of which are presumed to be corticospinal tract neurons. As a first step to elucidating the cellular function of SPP1 in macaque neurons, we examined the localization of SPP1 in the primary motor cortex (M1) of the macaque by using immunohistochemistry. SPP1 immunoreactivity was found to be localized in the cell bodies of neurons, but not outside the cells, indicating that SPP1 was not secreted from these neurons. The results of electron microscope analysis and double-labeling analysis with marker proteins suggested that SPP1 was localized in the mitochondria of neurons. The distributions of SPP1 in the neurons corresponded to those of integrin αV, a putative receptor for SPP1. The distribution of SPP1 was also investigated in macaques whose M1 had been lesioned. We found that SPP1 was secreted by proliferated microglia in the lesioned area. Double-labeling analysis indicated that SPP1 immunoreactivity in the microglia was colocalized with CD44, another putative receptor for SPP1. Success rates in the small-object-retrieval task were positively correlated with SPP1 immunoreactivity in the neurons in the perilesional area. SPP1 has multiple roles in the macaque motor cortex, and it may be a key protein during recovery of hand movement after brain damage.