Muramatsu R, Ikegaya Y, Matsuki N, Koyama R
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Neuroscience. 2007 Sep 7;148(3):593-8. doi: 10.1016/j.neuroscience.2007.06.040. Epub 2007 Jul 17.
Hippocampal granule cells (GCs) are continuously generated in the subgranular zone of the dentate gyrus (DG) and functionally incorporated to dentate neural circuits even in adulthood. This raises a question about the fate of neonatally born GCs in adult DG. Do they exist until adulthood or are they largely superseded by adult-born GCs? To investigate this question, we examined the contributions of postnatally born GCs to the adult mouse DG. C57BL/6 mice were grouped in three different postnatal (P) ages (group 1: P0, group 2: P7, and group 3: P35) and received a daily bromodeoxyuridine (BrdU) injection for three consecutive days (P0/1/2, P7/8/9, and P35/36/37, respectively) to label dividing cells. At 6 months old, hippocampal sections were prepared from the animals and immunostained with anti-BrdU antibody and an antibody against the homeobox prospero-like protein Prox1, a marker of GCs. We defined BrdU- and Prox1-double positive cells as newborn GCs and analyzed their density and distribution in the granule cell layer (gcl), revealing that newborn GCs of each group still existed 6 months after BrdU injections and that the density of GCs born during P0-2 (group 1) was significantly higher compared with the other groups. Although the density of newborn GCs in the each group did not differ between male and female, the radial distribution of them in gcl showed some differences, that is, male newborn GCs localized toward the molecular layer compared with female ones in group 1, while to the hilus in group 2. These results suggest that GCs born in early postnatal days numerically dominate adult DG and that there exist sex differences in GC localizations which depend on the time when they were born.
海马颗粒细胞（GCs）在齿状回（DG）的颗粒下区持续生成，即使在成年期也能功能性地整合到齿状神经回路中。这就引出了一个关于成年DG中新生GCs命运的问题。它们会一直存在到成年期，还是在很大程度上被成年新生的GCs所取代？为了研究这个问题，我们检测了出生后生成的GCs对成年小鼠DG的贡献。将C57BL/6小鼠分为三个不同的出生后（P）年龄组（第1组：P0，第2组：P7，第3组：P35），并连续三天每天注射溴脱氧尿苷（BrdU）（分别为P0/1/2、P7/8/9和P35/36/37）以标记分裂细胞。在6个月大时，从这些动物身上制备海马切片，并用抗BrdU抗体和一种针对同源框类prospero蛋白Prox1（一种GCs标志物）的抗体进行免疫染色。我们将BrdU和Prox1双阳性细胞定义为新生GCs，并分析它们在颗粒细胞层（gcl）中的密度和分布，结果显示每组新生GCs在BrdU注射后6个月仍然存在，并且P0 - 2（第1组）期间生成的GCs密度显著高于其他组。尽管每组新生GCs的密度在雄性和雌性之间没有差异，但它们在gcl中的径向分布存在一些差异，也就是说，第1组中雄性新生GCs比雌性更靠近分子层，而第2组中则更靠近门区。这些结果表明，出生后早期生成的GCs在数量上主导成年DG，并且GCs的定位存在性别差异，这取决于它们出生的时间。
