解剖学报

解剖学报 ›› 2015, Vol. ›› Issue (3): 317-323.doi: 10.16098/j.issn.0529-1356.2015.03.005

• 神经生物学 • 上一篇    下一篇

别孕烯醇酮对APPswe/PSEN1小鼠黑质多巴胺能神经元的影响

张鹏1,2 戚双双3 谢明琦1,2廖敏2,4刘芬2,4周鹏1,,2崔怀瑞1,2孙臣友1,2*   

  1. 1.温州医科大学基础医学院人体解剖学教研室，浙江 温州 325035; 2.温州医科大学基础医学院神经科学研究所，浙江 温州 325035; 3.温州医科大学附属第二医院育英儿童医院药剂科，浙江 温州 325000; 4.温州医科大学基础医学院组织学胚胎学教研室，浙江 温州 325035
  • 收稿日期:2014-09-28 修回日期:2014-12-02 出版日期:2015-06-06 发布日期:2015-06-06
  • 通讯作者: 孙臣友 E-mail:sunchenyou1972@aliyun.com
  • 基金资助:

    浙江省自然科学基金;浙江省钱江人才计划

Effect of allopregnanolone on the dopaminergic neurons in the substantia nigra of APPswe/PSEN1 mice

ZHANG Peng 1,2 QI Shuang-shuang3 XIE Ming-qi 1,2 LIAO Min 2,4 LIU Fen 2,4 ZHOU Peng 1,2CUI Huai-rui 1,2 SUN Chen-you 1,2*   

  1. 1.Department of Anatomy, School of Basic Medical Sciences of Wenzhou Medical University, Zhejiang Wenzhou 325035, China; 2.Institute of Neuroscience, School of Basic Medical Sciences of Wenzhou Medical University, Zhejiang Wenzho 325035, China; 3.Department of Pharmacy, the 2nd Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Zhejiang Wenzhou 325035, China; 4.Department of Histology and Embryology, School of Basic Medical Sciences of Wenzhou Medical University, Zhejiang Wenzhou 325035, China

  • Received:2014-09-28 Revised:2014-12-02 Online:2015-06-06 Published:2015-06-06
  • Contact: SUN Chen-you E-mail:sunchenyou1972@aliyun.com

摘要：

目的 评估别孕烯醇酮（APα）对阿尔茨海默病（AD）小鼠黑质（SN）酪氨酸羟化酶（TH）神经元数目的影响。方法 31只4月龄雄性小鼠采用免疫荧光染色观察和计算各种免疫阳性细胞的数目。结果 双转基因AD小鼠（2×TgAD）APα水平和TH神经元数目均明显减少，且出现在β淀粉样斑块形成之前。给予APα处理可预防2×TgAD小鼠SN总神经元、TH神经元和TH/5溴脱氧尿嘧啶核苷（BrdU）神经元数目的下降，但对纹状体TH神经纤维吸光度下降无影响。此外，APα能增加2×TgAD小鼠新生成熟神经元的数目，但对新生胶质细胞数目无影响。结论 2×TgAD小鼠体内低水平APα与多巴胺能神经元下降相关，外源性APα能够通过增加新生TH神经元的形成来恢复2×TgAD小鼠TH神经元的下降。

Abstract:

Objective To evaluate the effect of allopregnanolone (APα) on the tyrosine hydroxylase (TH)-positive neuron in the substantia nigra (SN) of the transgenic mouse of Alzheimer’s disease (AD). Methods Immunopositive cells were observed and measured in the 4-month-old male mice (n=31) using an immuno-staining technique.
Results The APα level and the number of TH-positive neurons were reduced in the double-transgenic AD mouse (2×TgAD), and these reductions were present prior to the appearance of β-amyloid positive plaques. APα treatment prevented the decrease of the total number of neurons, TH-positive neurons and TH/bromodeoxyuridine (BrdU)-double positive neurons in the SN of 2×TgAD mice although the decreased intensities of TH-positive neural fibers were not rescued in the striatum. In addition, APα administration had an apparent increase in the number of new-born mature neurons without affecting the new-generating astrocytes in the SN of 2×TgAD mice. Conclusion A lower level of endogenous APα is implicated in the loss of dopaminergic neurons in the 2×TgAD mice. Exogenous APα can recover the reducing TH-positive neurons by promoting their neurogenesis in the 2×TgAD mice.