Loss of Neuronal Protein Expression in Mouse Hippocampus After Irradiation

Loss of Neuronal Protein Expression in Mouse Hippocampus After Irradiation
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DOI:
10.1097/nen.0b013e3181d1afe4
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发表时间:
2010-03-01
影响因子:
3.2
通讯作者:
Wong, C. Shun
Wong, C. Shun
中科院分区:
医学4区
文献类型:
--
作者:
Wu, Kai-Liang;Li, Yu-Qing;Wong, C. Shun

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辐射对神经元的影响还不完全清楚。我们评估了17-Gy全脑辐照后小鼠海马神经元核和其他蛋白表达的变化。采用免疫组化方法检测海马CA1、CA3和齿状回中神经元核(NeuN)、神经元特异性烯醇和prospero-related homobox 1 (Prox1)、calbindin D28k和synaptophysin 1的表达;通过基于设计的立体学估计神经元数量。照射后第7天,CA3区NeuN(+)神经元明显减少。体视学评估证实,与对照组相比,CA3在第7天、齿状回在第7天、第3周和第2个月以及CA1在第2个月的NeuN(+)神经元显著减少;CA3亚区神经元特异性烯醇化酶和与prospero相关的homobox 1阳性神经元也在第7天减少。而4′6-二氨基-2-苯基吲哚核染色检测到的颗粒细胞和锥体细胞数量保持不变,照射后calbindin D28k和synaptophysin 1的免疫反应性没有变化。我们得出结论,辐照可能导致小鼠海马神经元蛋白表达的暂时丧失。这些变化并不一定表明神经元的损失,并且表明在使用表型标记(如NeuN)来估计照射后神经元数量的变化时需要谨慎。
The effects of radiation on neurons are incompletely characterized. We evaluated changes in the expression of neuronal nuclear and other proteins in the mouse hippocampus after 17-Gy whole-brain irradiation. Expression of neuronal nuclei (NeuN), neuron-specific enolas, prospero-related homeobox 1 (Prox1), calbindin D28k, and synaptophysin 1 in the CA1, CA3, and dentate gyrus of the hippocampus was determined by immunohistochemistry; neuronal numbers were estimated by design-based stereology. At 7 days after irradiation, there was a marked reduction of NeuN(+) neurons in CA3. Stereologic estimates confirmed a significant reduction in NeuN(+) neurons in CA3 at 7 days, in the dentate gyrus at 7 days, 3 weeks and 2 months, and in CA1 at 2 months compared with controls; neuron-specific enolase and prospero-related homeobox 1-positive neurons in the CA3 subregion were also decreased at 7 days. The numbers of granule and pyramidal cells identified by 4'6-diamidino-2-phenylindole nuclear staining, however, remained unchanged, and there were no changes in calbindin D28k or synaptophysin 1 immunoreactivity after irradiation. We conclude that irradiation may result in a temporary loss of neuronal protein expression in mouse hippocampus. These changes do not necessarily indicate loss of neurons and indicate the need for caution regarding the use of phenotypic markers such as NeuN to estimate changes in neuronal numbers after irradiation.