吉林大学学报(医学版)

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人α-突触核蛋白A30P突变对小鼠成体大脑吻端迁移流中神经发生的抑制作用及其机制

李玲玲1,2,孙艺学2,王爱兵2,李子义2,张学明2   

  1. 1. 吉林省前卫医院内二科,吉林  长春 130012;2. 吉林大学动物医学学院 动物胚胎工程吉林省重点实验室,吉林 长春 130062
  • 收稿日期:2013-03-02 发布日期:2013-12-12
  • 通讯作者: 张学明(Tel:0431-87836162, E-mail:zhangxuem@jlu.edu.cn);李子义(Tel : 0431-87836187,E-mail: ziyi@jlu.edu.cn) E-mail:zhangxuem@jlu.edu.cn;ziyi@jlu.edu.cn
  • 作者简介:李玲玲(1974-),女,吉林省长春市人,副主任医师,医学学士,主要从事神经疾病研究。
  • 基金资助:

    α-synuclein;rostral migratory stream;neurogenesis;brain

Inhibitory effect of human α-synuclein A30P mutation on  neurogenesis  in RMS of adult mouse brain and its mechanism

  • Received:2013-03-02 Published:2013-12-12
  • Supported by:

    吉林省科技厅科技发展计划项目资助课题(201105021)

摘要:

目的:检测表达人α-突触核蛋白(SNCA)A30P突变的小鼠大脑吻端迁移流(RMS)中的细胞增殖水平,探讨SNCA A30P突变对小鼠成体大脑神经发生的可能影响。方法:选取C57BL正常小鼠、内源性SNCA敲除小鼠(SNCA-/-)和SNCA敲除+人SNCA A30P敲入小鼠(A30P SNCA-/-)各4只作为正常对照组、SNCA-/-组和A30P SNCA-/-组,取各组小鼠脑组织冠状冰冻切片,观察各组小鼠脑组织RMS形态学;行磷酸化组蛋白(PH3)、双皮质素(Dcx)、4′,6-二脒基-2-苯基吲哚(DAPI)荧光免疫组织化学染色,统计PH3阳性细胞的数量和3组小鼠中Dcx阳性细胞的荧光强度。结果:各组小鼠RMS的形态、大小和细胞密度等无明显差异。与正常对照组比较,SNCA-/-组和A30P SNCA-/-组小鼠RMS中PH3阳性增殖性神经元数量明显减少(P<0.05)。与正常对照组比较,SNCA-/-和A30P SNCA-/-组小鼠神经母细胞的Dcx阳性细胞荧光强度轻微增加。结论:人SNCA A30P突变可能减弱成体大脑RMS中的神经细胞增殖而促进其迁移,因此对成体大脑RMS中的神经发生有一定抑制作用。

关键词: &alpha, -突触核蛋白, 吻端迁移流, 神经发生, 大脑

Abstract:

Abstract:Objective To investigate the cellular proliferation  level in the rostral migratory stream (RMS) of the adult brain in mice expressed human α-synuclein  (SNCA) A30P mutation and to explore the possible effect of SNCA A30P mutation  on  the neurogenesis in adult brain of mice. Methods 12 mice were divided into C57BL group (normal mice),SNCA-/- group (knocking out SNCA mice), and A30P SNCA-/- group (knocking out  SNCA and knocking in SNCA  A30P mice).The  mouse brains were taken out and the coronal sections were made.The  morphologies of RMS of the mice in various groups were  observed;after the free-floating fluorescent immunohistochemistry of phosphohistone 3(PH3),doublecortin(Dcx), and 4′,6-diamidino-2-phenylindole dihydrochloride(DAPI) were carried out,the number of PH3 positive cells and the fluorescence intensity of Dcx-positive neuroblasts were analyzed.Results There were no signifrcant differences of the morphology,size and cell density of mouse RMS between various groups.Compared with normal control group,the number of PH3 positive  proliferating neurons in RMS of mice in  SNCA-/- and A30P SNCA-/- groups were decreased(P<0.05);compared with normal  control group,the fluorescence intensities of Dcx-positive  neuroblasts in the other two  groups were increased slighthy.Conclusion Human SNCA A30P point mutation may  decrease the neuron proliferation,but slightly enhance its migration in RMS of adult brain of mice,which suggests that the mutation has a certain inhibitory  effect on the neurogenesis in  RMS of adult brain.

Key words: &alpha, -突触核蛋白;吻端迁移流;神经发生;大脑

中图分类号: 

  • R741