Zeng Q, Zheng M, Zhang T, He G
Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China.
Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China.
Neuroscience. 2016 Feb 9;314:64-74. doi: 10.1016/j.neuroscience.2015.11.054. Epub 2015 Nov 27.
Alzheimer's disease (AD) is one of the most common causes of dementia. Although the exact mechanisms of AD are not entirely clear, the impairment in adult hippocampal neurogenesis has been reported to play a role in AD. To assess the relationship between AD and neurogenesis, we studied APP/PS1/nestin-green fluorescent protein (GFP) triple transgenic mice, a well-characterized mouse model of AD, which express GFP under the control of the nestin promoter. Different ages of AD mice and their wild-type littermates (WT) were used in our study. Immunofluorescent staining showed that neurogenesis occurred mainly in the subgranular zone (SGZ) of the dentate gyrus (DG) and subventricular zone (SVZ) of the lateral ventricles (LVs). The expression of neural stem cells (NSCs) (nestin) and neural precursors such as doublecortin (DCX) and GFAP in AD mice were decreased with age, as well as there being a reduction in 5-bromo-2-deoxyuridine (BrdU)-positive cells, when compared to WT. However, the number of maturate neurons (NeuN) was not significantly different between AD mice and wild-type controls, and NeuN changed only slightly with age. By Golgi-Cox staining, the morphologies of dendrites were observed, and significant differences existed between AD mice and wild-type controls. These results suggest that AD has a far-reaching influence on the regulation of adult hippocampal neurogenesis, leading to a gradual decrease in the generation of neural progenitors (NPCs), and inhibition of the differentiation and maturation of neurons.
阿尔茨海默病（AD）是痴呆最常见的病因之一。尽管AD的确切机制尚不完全清楚，但据报道，成年海马神经发生受损在AD中起作用。为了评估AD与神经发生之间的关系，我们研究了APP/PS1/巢蛋白绿色荧光蛋白（GFP）三转基因小鼠，这是一种特征明确的AD小鼠模型，其在巢蛋白启动子的控制下表达GFP。我们的研究使用了不同年龄的AD小鼠及其野生型同窝小鼠（WT）。免疫荧光染色显示，神经发生主要发生在齿状回（DG）的颗粒下区（SGZ）和侧脑室（LVs）的室下区（SVZ）。与WT相比，AD小鼠中神经干细胞（NSCs）（巢蛋白）和神经前体细胞如双皮质素（DCX）和胶质纤维酸性蛋白（GFAP）的表达随年龄下降，5-溴-2-脱氧尿苷（BrdU）阳性细胞也减少。然而，AD小鼠与野生型对照之间成熟神经元（NeuN）的数量没有显著差异，且NeuN仅随年龄略有变化。通过高尔基-考克斯染色观察树突形态，AD小鼠与野生型对照之间存在显著差异。这些结果表明，AD对成年海马神经发生的调节有深远影响，导致神经祖细胞（NPCs）生成逐渐减少，并抑制神经元的分化和成熟。
