›› 2016, Vol. 47 ›› Issue (1): 2-6.

• 神经生物学 •    下一篇

C1型尼曼-匹克氏症小鼠嗅球细胞的病理变化

闫欣1,乔梁1,林俊堂2   

  1. 1. 新乡医学院生命科学技术学院
    2. 新乡医学院
  • 收稿日期:2015-06-16 修回日期:2015-07-19 出版日期:2016-02-06 发布日期:2016-02-06
  • 通讯作者: 林俊堂 E-mail:juntang.lin@googlemail.com
  • 基金资助:
    C1型尼曼-匹克氏症轴突发育异常的病理机制;C1型尼曼-匹克氏症的神经发育基础研究

The pathological changes of the olfactory bulbs in the Niemann-pick type C1 mice

Xin YAN1,Liang QIAOLin Juntang   

  • Received:2015-06-16 Revised:2015-07-19 Online:2016-02-06 Published:2016-02-06
  • Contact: Lin Juntang E-mail:juntang.lin@googlemail.com

摘要: 目的 通过观察NPC1基因突变型小鼠嗅球的形态学变化,探讨C1型尼曼-匹克氏症对嗅觉系统的影响。方法 提取小鼠尾部组织DNA进行聚合酶链式反应(PCR)检测种系基因型;选取出生后第30 d的野生型和突变型小鼠,采用免疫组织化学方法观察对比嗅球系统中神经元轴突的形态结构和髓鞘形成,以及SMI31和MBP的表达情况;TUNEL方法染色检测嗅球神经细胞的凋亡情况。结果 NPC1基因突变型小鼠嗅球中NPC1蛋白表达明显降低,神经细胞凋亡增加;SMI31免疫荧光显示嗅球内神经丝蛋白发生变性聚集,导致神经纤维缠结;同时,MBP蛋白表达量明显降低,髓鞘形成受到抑制。结论 NPC1基因突变能够引起嗅球神经细胞发生病理性变化,影响嗅觉系统的正常功能。

关键词: C1型尼曼-匹克氏症, 嗅觉障碍, 神经元, 髓鞘障碍, 小鼠

Abstract: Objective To examine the impact of Niemann-pick type C1 disease on the olfactory system, we investigated the morphological changes of the olfactory bulbs in NPC1 mutant mouse. Methods The genomic DNA was extracted from mice tails for genotyping by PCR;30-day-old mice including wild type and NPC1 gene mutation were selected, and immunohistochemistry was performed to examine and compare the axonal structure, the myelination process, as well as the expression of SMI31 and MBP in the olfactory bulbs;The cell apoptosis were analyzed by TUNEL assay. Results In NPC1-/- mice, the expression of NPC1 protein is rarely detected, but TUNEL-positive cells are increased. Immunofluorescence using SMI31 antibody indicates accumulation of neurofilament and formation of axonal spheroids in the NPC1-/- olfactory bulbs. Furthermore, the decreased expression of MBP protein is also found in NPC1-/- olfactory system, which is associated with perturbed myelination. Conclusion Our data show pathological changes in the olfactory bulbs of NPC1 mutant mice, which is accompanied by olfactory defects.

Key words: Niemann-pick type C1 disease, olfactory defects, neuron, perturbed myelination, mouse