Division of Neuroanatomy, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan; Center for Language Education, Ritsumeikan Asia Pacific University, 1-1 Jumonjibaru, Beppu, Oita 874-8577, Japan.
Division of Neuroanatomy, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
Neuroscience. 2018 Dec 1;394:109-126. doi: 10.1016/j.neuroscience.2018.10.029. Epub 2018 Oct 24.
Huntingtin-associated protein 1 (HAP1) is a neural interactor of huntingtin in Huntington's disease and interacts with gene products in a number of other neurodegenerative diseases. In normal brains, HAP1 is expressed abundantly in the hypothalamus and limbic-associated regions. These areas tend to be spared from neurodegeneration while those with little HAP1 are frequently neurodegenerative targets, suggesting its role as a protective factor against apoptosis. In light of the relationship between neurodegenerative diseases and deterioration of higher nervous activity, it is important to definitively clarify HAP1 expression in a cognitively important brain region, the retrosplenial-retrohippocampal area. Here, HAP1 expression was evaluated immunohistochemically over the retrosplenial cortex, the subicular complex, and the entorhinal and perirhinal cortices. HAP1-immunoreactive (ir) cells were classified into five discrete groups: (1) a distinct retrosplenial cell cluster exclusive to the superficial layers of the granular cortex, (2) a conspicuous, thin line of cells in layers IV/V of the "subiculum-backing cortex," (3) a group of highly immunoreactive cells associated with the medial entorhinal-subicular corner, (4) pericallosal cells just below layer VI and adjacent to the white matter, and (5) other sporadic, widely-disseminated HAP1-immunoreactive cells. HAP1 was found to be the first marker for the complex subiculum-backing cortex and a precise marker for several subfields in the retrosplenial-retrohippocampal area, verified through comparative staining with other neurochemicals. HAP1 may play an important role in protecting these cortical structures and functions for higher nervous activity by increasing the threshold to neurodegeneration and decreasing vulnerability to stress or aging.
亨廷顿蛋白关联蛋白 1（HAP1）是亨廷顿病中亨廷顿蛋白的神经相互作用蛋白，与许多其他神经退行性疾病的基因产物相互作用。在正常大脑中，HAP1 在下丘脑和边缘相关区域表达丰富。这些区域往往免受神经退行性变的影响，而那些 HAP1 含量较少的区域则经常成为神经退行性变的靶标，这表明它作为一种对抗细胞凋亡的保护因子的作用。鉴于神经退行性疾病与高级神经活动恶化之间的关系，明确阐明认知重要的脑区，即后扣带回-后海马回区域中的 HAP1 表达非常重要。在这里，通过免疫组织化学方法评估了 HAP1 在后扣带皮层、下托复合体以及内嗅和旁嗅皮层中的表达。HAP1 免疫反应（ir）细胞分为五个离散的组：（1）颗粒皮层浅层特有的明显的后扣带回细胞簇，（2）“下托背侧皮层”IV/V 层中的一条明显的细胞线，（3）与内侧内嗅-subicular 角相关的一组高度免疫反应性细胞，（4）刚好在第六层下方的胼胝体细胞和邻近白质，以及（5）其他散在的、广泛分布的 HAP1 免疫反应性细胞。发现 HAP1 是复杂的下托背侧皮层的第一个标志物，也是后扣带回-后海马回区域中几个亚区的精确标志物，通过与其他神经化学物质的比较染色得到验证。HAP1 可能通过增加神经退行性变的阈值和降低对压力或衰老的易感性，在保护这些皮质结构和功能以进行高级神经活动方面发挥重要作用。
