Department of Histology and Neuroanatomy, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.
Institute for Advanced Bioscience Research, Hoshi University, Tokyo, Japan.
Brain Struct Funct. 2018 Jan;223(1):357-369. doi: 10.1007/s00429-017-1499-7. Epub 2017 Aug 23.
Neurogenesis occurs during the embryonic period and ceases soon after birth in the neocortex, but continues to occur in the hippocampus even in the adult. The embryonic neocortex has radial glia or progenitor cells expressing brain lipid-binding protein (BLBP), whereas the adult hippocampus has radial granule progenitor cells expressing BLBP and glial fibrillary acidic protein (GFAP) in the subgranular zone. We previously found that embryonic hippocampal granule progenitor cells express GFAP, but not BLBP, indicating that these cells are different from both embryonic neocortical and adult granule progenitor cells. In the present study, as the first step towards understanding the mechanism of persistent hippocampal neurogenesis, we aimed to determine the stage at which embryonic-type granule progenitors become adult-type progenitors using mouse Gfap-GFP transgenic mice. During the embryonic stages, Gfap-GFP-positive (Gfap-GFP+) cells were distributed in the entire developing dentate gyrus (DG), whereas BLBP-positive (BLBP+) cells were mainly present in the fimbria and subpial region, and to some extent in the DG. Up to postnatal day 0 (P0), double-positive cells were scarcely detected. However, at P1, one-third of the Gfap-GFP+ cells in the DG suddenly began to weakly express BLBP. Thereafter, Gfap-GFP+/BLBP+ cells rapidly increased in number, and extended their radial processes in the inner granular cell layer. At P14 and in the adult, two-thirds of the Gfap-GFP+ cells in the subgranular zone showed BLBP immunoreactivity. These results suggest that the properties of hippocampal granule progenitor cells are rapidly altered from an embryonic to adult type soon after birth.
神经发生发生在胚胎期，出生后不久在新皮质中停止，但在成年期仍继续在海马体中发生。胚胎新皮质具有表达脑脂质结合蛋白 (BLBP) 的放射状胶质或祖细胞，而成年海马体具有在颗粒下区表达 BLBP 和神经胶质纤维酸性蛋白 (GFAP) 的放射状颗粒祖细胞。我们之前发现胚胎海马颗粒祖细胞表达 GFAP，但不表达 BLBP，这表明这些细胞与胚胎新皮质和成年颗粒祖细胞不同。在本研究中，作为了解持续海马神经发生机制的第一步，我们旨在使用小鼠 Gfap-GFP 转基因小鼠确定胚胎型颗粒祖细胞成为成年型祖细胞的阶段。在胚胎期，Gfap-GFP 阳性 (Gfap-GFP+) 细胞分布在整个发育中的齿状回 (DG) 中，而 BLBP 阳性 (BLBP+) 细胞主要存在于穹窿和软膜下区，并且在一定程度上存在于 DG 中。直到出生后第 0 天 (P0)，几乎没有检测到双阳性细胞。然而，在 P1 时，DG 中三分之一的 Gfap-GFP+细胞突然开始弱表达 BLBP。此后，Gfap-GFP+/BLBP+ 细胞数量迅速增加，并在颗粒细胞内层延伸其放射状突起。在 P14 和成年期，颗粒下区三分之二的 Gfap-GFP+细胞显示 BLBP 免疫反应性。这些结果表明，海马颗粒祖细胞的特性在出生后不久就从胚胎型迅速转变为成年型。
