Hilar granule cells of the mouse dentate gyrus: effects of age, septotemporal location, strain, and selective deletion of the proapoptotic gene BAX.

Hilar granule cells of the mouse dentate gyrus: effects of age, septotemporal location, strain, and selective deletion of the proapoptotic gene BAX.
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DOI:
10.1007/s00429-017-1391-5
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发表时间:
2017-09
影响因子:
3.1
通讯作者:
Scharfman HE
Scharfman HE
中科院分区:
医学3区
文献类型:
--
作者:
Bermudez-Hernandez K;Lu YL;Moretto J;Jain S;LaFrancois JJ;Duffy AM;Scharfman HE

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齿状回(DG)的主要细胞是谷氨酸能颗粒细胞(GCs),它们位于致密的细胞层。然而,GCs也存在于邻近的肺门区域,但只有少数研究描述了这一现象。因此,我们使用转录因子Propero Homeobox 1(Prox1)对普通小鼠品系C57BL/6J小鼠在出生后16、30和60天的GCs进行了定量。在PND16,有大量的Prox1免疫反应(Ir)细胞,在隔区多于颞叶海马区。在PND30和60时,肺门Prox1-ir细胞群的大小减小。在PND30和60只瑞士Webster小鼠中观察到类似数量的肺门Prox1表达细胞。PROX1通常被认为是有丝分裂后GC的标志。然而,许多Prox1-ir肺门细胞,特别是在PND16处,并没有被Neun双重标记,Neun是一种通常在成熟神经元中发现的标记。在PND16处,大多数肺门Prox1阳性细胞共同表达未成熟GC的标记物双皮质素(DCX)和钙维A(Calretinin)。没有检测到与活跃分裂细胞的标记Ki67的双重标记。这些结果表明,令人惊讶的是,在PND16的门部有大量的细胞是未成熟的GC(2b型和3型细胞)。我们还询问了肺门Prox1-ir细胞数量是否可以修改。为了研究这个问题,我们有条件地删除了表达Nestin的细胞中的促凋亡基因Bax,而此时在PND2-8门中有许多未成熟的GC。当这些小鼠在PND60被检查时,Prox1-ir肺门细胞的数量与对照小鼠相比显著增加。然而,Bax的缺失似乎并没有改变共表达NeuN的比例,这表明肺门Prox1表达群体的大小是可以改变的。然而,删除Bax这一主要的发育障碍似乎并不会改变最终成为神经元的比例。
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 cellss 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 become neurons.
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