中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (24): 2249-2255.doi: 10.3969/j.issn.1673-5374.2013.24.004

• 原著:退行性病与再生 • 上一篇    下一篇

能模拟阿尔茨海默病的APP/PS1双转基因小鼠

  

  • 收稿日期:2013-04-28 修回日期:2013-06-12 出版日期:2013-08-25 发布日期:2013-08-25

Degenerative alterations in noradrenergic neurons of the locus coeruleus in Alzheimer’s disease

Lihua Liu1, 2, Saiping Luo3, Leping Zeng4, Weihong Wang2, Liming Yuan5, Xiaohong Jian5   

  1. 1 Department of Histology & Embryology, School of Basic Medical Sciences, Central South University, Changsha 410013, Hunan Province, China
    2 Department of Nursing, Medical College of Hunan Normal University, Changsha 10013, Hunan Province, China
    3 Third Department of Surgery, Agricultural Division Four Hospital, Xinjiang Production and Construction Corps, Yili 835000, Xinjiang Uygur Autonomous Region, China
    4 Department of Anatomy & Neurobiology, School of Basic Medical Sciences, Central South University, Changsha 410013, Hunan Province, China
    5 Department of Anatomy, Medical College of Hunan Normal University, Changsha 410013, Hunan Province, China
  • Received:2013-04-28 Revised:2013-06-12 Online:2013-08-25 Published:2013-08-25
  • Contact: Xiaohong Jian, Master, Lecturer, Department of Anatomy, Medical College of Hunan Normal University, Changsha 410013, Hunan Province, China, jxh1395@163.com.
  • About author:Lihua Liu, Studying for doctorate, Lecturer.

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摘要：

蓝斑神经元的死亡数目与β淀粉样蛋白沉积及阿尔茨海默病严重程度成正相关。携带有突变β-淀粉样前体蛋白基因和突变早老素1基因(APP/PS1)的双转基因阿尔茨海默病模型是目前研究阿尔茨海默病较好的动物模型，但围绕该模型的研究主要关注海马和皮质改变。鉴于此，实验选用五六月龄年轻组雌性APP/PS1双转基因小鼠与及十六七月龄老年组APP/PS1双转基因小鼠进行实验，每组均设同龄野生型小鼠作对照。免疫组织化学染色结果显示，与老年组野生型小鼠比较，老年组APP/PS1双转基因小鼠蓝斑儿茶酚胺能神经元特异性标志物-酪氨酸羟化酶阳性神经元胞体变大，细胞总数量减少23%，酪氨酸羟化酶阳性纤维少而粗短、有断裂。无偏差体视学方法定量分析结果显示，老年组APP/PS1双转基因小鼠蓝斑区酪氨酸羟化酶阳性神经元平均体积较年轻组增加，并与蓝斑总体积呈正相关。说明APP/PS1双转基因老年小鼠蓝斑去甲肾上腺素神经元和纤维较易发生退行性病理改变。

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Abstract:

Mice carrying mutant amyloid-β precursor protein and presenilin-1 genes (APP/PS1 double trans-genic mice) have frequently been used in studies of Alzheimer’s disease; however, such studies have focused mainly on hippocampal and cortical changes. The severity of Alzheimer’s disease is known to correlate with the amount of amyloid-β protein deposition and the number of dead neurons in the locus coeruleus. In the present study, we assigned APP/PS1 double transgenic mice to two groups according to age: young mice (5–6 months old) and aged mice (16–17 months old). Age-matched wild-type mice were used as controls. Immunohistochemistry for tyrosine hydroxylase (a marker of catecholaminergic neurons in the locus coeruleus) revealed that APP/PS1 mice had 23% fewer cells in the locus coeruleus compared with aged wild-type mice. APP/PS1 mice also had increased numbers of cell bodies of neurons positive for tyrosine hydroxylase, but fewer tyrosine hydroxylase-positive fibers, which were also short, thick and broken. Quantitative analysis using unbiased stereology showed a significant age-related increase in the mean volume of tyrosine hy-droxylase-positive neurons in aged APP/PS1 mice compared with young APP/PS1 mice. Moreover, the mean volume of tyrosine hydroxylase-positive neurons was positively correlated with the total volume of the locus coeruleus. These findings indicate that noradrenergic neurons and fibers in the locus coeruleus are predisposed to degenerative alterations in APP/PS1 double transgenic mice.