C1型尼曼-匹克氏症小鼠嗅球胶质细胞的活性变化  

Activity of glial cells in the olfactory bulb of Niemann-Pick disease type C1 mice

作　　者：闫欣[1,2] 乔梁[1,2] 杨恩慧[1,2] 林俊堂[1,2] 

机构地区：[1]新乡医学院生命科学技术学院,新乡453003 [2]河南省医用组织再生重点实验室,新乡453003

出　　处：《生理学报》2016年第2期141-147,共7页Acta Physiologica Sinica

基　　金：supported by the National Natural Science Foundation of China(No.81400936);the Joint Foundation for Fostering Talents of NSFC-Henan Province;China(No.U1304808)

摘　　要：本文观察Npc1基因突变对于小鼠嗅球神经胶质细胞活性的影响,探讨C1型尼曼-匹克氏症的病理机制。提取鼠尾基因组DNA,采用PCR检测基因型;采用免疫荧光组织化学染色观察出生后30 d的小鼠嗅球中小胶质细胞和星形胶质细胞的活性反应;采用免疫印迹方法检测嗅球中Neu N、神经丝蛋白(neurofilament,NF)、双皮质素(Doublecortin,DCX)、CD68和GFAP的蛋白表达情况。结果显示,Npc1基因突变导致小鼠嗅球中CD68和GFAP蛋白表达显著上调,小胶质细胞和星形胶质细胞的活性明显增强;磷酸化NF的表达也明显增加,而DCX的表达量显著下调。以上结果提示,Npc1基因突变在早期能够引起小鼠嗅球发生一些变化。To study the pathological mechanisms of Niemann-Pick disease type C1, we observed the changes of activation of glial cells in the olfactory bulb of Npc1 mutant（Npc1-/-） mice. The genomic DNA was extracted from mouse tails for genotyping by PCR. Immunofluorescent histochemistry was performed to examine the activation of microglia and astrocytes in the olfactory bulb of Npc1-/- mice on postnatal day 30. Neu N, phosphorylated neurofilament（NF）, Doublecortin（DCX）, CD68 and GFAP were detected by Western blot. The results showed that Npc1 gene mutation strongly increased the activation of astrocytes and microglia in olfactory bulb associated with increased protein levels of CD68 and GFAP. Furthermore, the expression of phosphorylated NF was also significantly increased in the olfactory bulb of Npc1-/- mice compared with that in Npc1＋/＋ mice. However, DCX expression was significantly reduced. The above results suggest that there are some early changes in the olfactory bulb of Npc1-/- mice.

关 键 词：C1型尼曼-匹克氏症 嗅觉障碍 小胶质细胞 星形胶质细胞 神经胶质细胞 

分 类 号：R741[医药卫生—神经病学与精神病学]