小鼠齿状回颗粒细胞：年龄、隔区-海马位置、品系和促凋亡基因 BAX 选择性缺失的影响。
Hilar granule cells of the mouse dentate gyrus: effects of age, septotemporal location, strain, and selective deletion of the proapoptotic gene BAX.
机构信息
New York University Langone Medical Center, 227 East 30th Street, 7th Floor, One Park Avenue, New York, NY, 10016, USA.
The Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA.
出版信息
Brain Struct Funct. 2017 Sep;222(7):3147-3161. doi: 10.1007/s00429-017-1391-5. Epub 2017 Mar 17.
The dentate gyrus (DG) principal cells are glutamatergic granule cells (GCs), and they are located in a compact cell layer. However, GCs are also present in the adjacent hilar region, but have been described in only a few studies. Therefore, we used the transcription factor prospero homeobox 1 (Prox1) to quantify GCs at postnatal day (PND) 16, 30, and 60 in a common mouse strain, C57BL/6J mice. At PND16, there was a large population of Prox1-immunoreactive (ir) hilar cells, with more in the septal than temporal hippocampus. At PND30 and 60, the size of the hilar Prox1-ir cell population was reduced. Similar numbers of hilar Prox1-expressing cells were observed in PND30 and 60 Swiss Webster mice. Prox1 is usually considered to be a marker of postmitotic GCs. However, many Prox1-ir hilar cells, especially at PND16, were not double-labeled with NeuN, a marker typically found in mature neurons. Most hilar Prox1-positive cells at PND16 co-expressed doublecortin (DCX) and calretinin, markers of immature GCs. Double-labeling with a marker of actively dividing cells, Ki67, was not detected. These results suggest that, surprisingly, a large population of cells in the hilus at PND16 are immature GCs (Type 2b and Type 3 cells). We also asked whether hilar Prox1-ir cell numbers are modifiable. To examine this issue, we conditionally deleted the proapoptotic gene BAX in Nestin-expressing cells at a time when there are numerous immature GCs in the hilus, PND2-8. When these mice were examined at PND60, the numbers of Prox1-ir hilar cells were significantly increased compared to control mice. However, deletion of BAX did not appear to change the proportion that co-expressed NeuN, suggesting that the size of the hilar Prox1-expressing population is modifiable. However, deleting BAX, a major developmental disruption, does not appear to change the proportion that ultimately becomes neurons.
齿状回（DG）的主细胞是谷氨酸能颗粒细胞（GCs），它们位于一个密集的细胞层中。然而，GCs 也存在于相邻的门区，但仅在少数研究中有所描述。因此，我们使用转录因子prospero 同源盒 1（Prox1）在常见的 C57BL/6J 小鼠中于出生后第 16、30 和 60 天定量检测门区的 GC。在 PND16 时，有大量的 Prox1 免疫反应性（ir）门区细胞，其中隔区的细胞多于颞叶海马区。在 PND30 和 60 时，门区 Prox1-ir 细胞群体的大小减小。在 PND30 和 60 的瑞士 Webster 小鼠中观察到相似数量的门区 Prox1 表达细胞。Prox1 通常被认为是有丝分裂后 GC 的标志物。然而，许多 Prox1-ir 门区细胞，尤其是在 PND16 时，没有与神经元成熟标志物 NeuN 双重标记。在 PND16 时，大多数门区 Prox1 阳性细胞共表达双皮质素（DCX）和钙结合蛋白，这是不成熟 GC 的标志物。未检测到与有丝分裂细胞标记物 Ki67 的双重标记。这些结果表明，令人惊讶的是，PND16 时门区中的一大群细胞是不成熟的 GC（类型 2b 和 3 型细胞）。我们还询问了门区 Prox1-ir 细胞数量是否可调节。为了研究这个问题，我们在 Nestin 表达细胞中条件性敲除促凋亡基因 BAX，此时门区有大量不成熟的 GC，PND2-8。当这些小鼠在 PND60 时进行检查时，与对照组小鼠相比，Prox1-ir 门区细胞的数量显著增加。然而，BAX 的缺失似乎并没有改变共表达 NeuN 的比例，这表明门区 Prox1 表达细胞群体的大小是可调节的。然而，删除 BAX（一种主要的发育中断）似乎不会改变最终成为神经元的比例。
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