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基于内源性标记的立体学研究:小鼠海马体中成年神经发生的地形差异。

Topographic differences in adult neurogenesis in the mouse hippocampus: a stereology-based study using endogenous markers.

机构信息

Department of Anatomy and Neurobiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

出版信息

Hippocampus. 2011 May;21(5):467-80. doi: 10.1002/hipo.20762.

DOI:10.1002/hipo.20762
PMID:20087889
Abstract

The hippocampus plays a critical role in various cognitive and affective functions. Increasing evidence shows that these functions are topographically distributed along the dorsoventral (septotemporal) and transverse axes of the hippocampus. For instance, dorsal hippocampus is involved in spatial memory and learning whereas ventral hippocampus is related to emotion. Here, we examined the topographic differences (dorsal vs. ventral; suprapyramidal vs. infrapyramidal) in adult neurogenesis in the mouse hippocampus using endogenous markers. The optical disector was applied to estimate the numerical densities (NDs) of labeled cells in the granule cell layer. The NDs of radial glia-like progenitors labeled by brain lipid binding protein were significantly lower in the infrapyramidal blade of the ventral DG than in other subdivisions. The NDs of doublecortin-expressing cells presumed neural progenitors and immature granule cells were significantly higher in the suprapyramidal blade of the dorsal DG than in the other subdivisions. The NDs of calretinin-expressing cells presumed young granule cells at the postmitotic stage were significantly higher in the suprapyramidal blade than in the infrapyramidal blade in the dorsal DG. No significant regional differences were detected in the NDs of dividing cells identified by proliferating cell nuclear antigen. Taken together, these findings suggest that a larger pool of immature granule cells in dorsal hippocampus might be responsible for spatial learning and memory, whereas a smaller pool of radial glia-like progenitors in ventral hippocampus might be associated with the susceptibility to affective disorders. Cell number estimation using a 300-μm-thick hypothetical slice indicates that regional differences in immature cells might contribute to the formation of topographic gradients in mature granule cells in the adult hippocampus. Our data also emphasizes the importance of considering such differences when evaluating changes in adult neurogenesis in pathological conditions and following experimental procedures.

摘要

海马体在各种认知和情感功能中起着关键作用。越来越多的证据表明,这些功能沿着海马体的背腹(隔颞)和横向轴呈地形分布。例如,背侧海马体参与空间记忆和学习,而腹侧海马体与情绪有关。在这里,我们使用内源性标志物检查了成年小鼠海马体中神经发生的地形差异(背侧与腹侧;背侧齿状回的上伞突与下伞突)。光学切割器用于估计颗粒细胞层中标记细胞的数量密度(NDs)。脑脂质结合蛋白标记的放射状胶质样祖细胞的 NDs 在腹侧 DG 的下伞突明显低于其他分区。双皮质素表达细胞的 NDs 假定为神经祖细胞和未成熟的颗粒细胞,在背侧 DG 的上伞突明显高于其他分区。假定处于有丝分裂后阶段的年轻颗粒细胞的 calretinin 表达细胞的 NDs 在背侧 DG 的上伞突明显高于下伞突。增殖细胞核抗原鉴定的分裂细胞的 NDs 在各区域无显著差异。综上所述,这些发现表明,背侧海马体中未成熟颗粒细胞的数量较多可能与空间学习和记忆有关,而腹侧海马体中放射状胶质样祖细胞的数量较少可能与易感性有关。使用 300μm 厚的假设切片进行细胞数量估计表明,未成熟细胞的区域差异可能有助于成年海马体中成熟颗粒细胞的地形梯度的形成。我们的数据还强调了在评估病理性和实验性条件下成年神经发生的变化时,考虑这些差异的重要性。

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