Hefei National Laboratory for Physical Science at Microscale and School of Life Science, University of Science and Technology of China, Hefei 230027, China.
Neurosci Bull. 2009 Aug;25(4):167-78. doi: 10.1007/s12264-009-0324-6.
Apolipoprotein E (apoE) is associated with increased risk of age-related diseases, such as Alzheimer's disease (AD) and cerebrovascular disease (CVD). The present study aims to investigate the age-related general morphological changes of the brain in GFAP-apoE transgenic mice, especially the alterations in number and size of hippocampal pyramidal cells and the microvascular lesions in the thalamus.
Nine female apoE4/4 mice were divided into 3 groups (n=3 in each group): 3-4 months (young group), 9-10 months (middle-aged group) and 20-21 months (old group). Age-matched apoE3/3 mice were employed as control group (n=3 in each group). The paraffin sections of brain tissue were stained by 2 conventional staining methods, thionin staining and hematoxylin-esion(HE) staining, the former of which was to observe the hippocampal cells, while the latter was used to examine the brain microvasculature.
There was no apparent difference in the cortical layer between apoE3/3 and apoE4/4 mice, neither any significant difference in the number of cells in hippocampal CA1-CA3 subfields between apoE3/3 and apoE4/4 mice at various age points (P>0.05). However, the mean size of pyramidal cells in CA1 subfield in apoE3/3 and apoE4/4 mice decreased as mice were getting older (P<0.001). At the age of 20-21 months, this cellular atrophy in apoE4/4 mice was more severe than that in old apoE3/3 mice (P<0.05). Furthermore, microvascular lesion in the thalamus was detected in all the 3 old apoE4/4 mice, at varying degrees (5.24%, 1.41% and 3.97%, respectively), while only one apoE3/3 mouse exhibited microvascular lesion in the thalamus, at a low level (0.85%).
The current study suggests that the cell size in hippocampal CA1 subfield decreases with aging, irrespective of apoE genotype. Cellular atrophy in CA1 subfield and the microvascular lesion in the thalamus are both more severe in old apoE4/4 mice as compared with those in age-matched apoE3/3 mice. Doubts still exist on whether the decreased cell size in hippocampal CA1 subfield in old apoE4/4 mice is associated with dysfunction in learning and memory and whether the microvascular lesions indicate a higher risk of stroke in human apoE4 allele mice. To clarify these issues, further investigations are needed.
载脂蛋白 E（apoE）与年龄相关性疾病（如阿尔茨海默病（AD）和脑血管疾病（CVD））的风险增加有关。本研究旨在探讨 GFAP-apoE 转基因小鼠大脑与年龄相关的一般形态变化，特别是海马锥体细胞数量和大小的变化以及丘脑的微血管病变。
将 9 只雌性 apoE4/4 小鼠分为 3 组（每组 3 只）：3-4 个月（年轻组）、9-10 个月（中年组）和 20-21 个月（老年组）。年龄匹配的 apoE3/3 小鼠作为对照组（每组 3 只）。脑组织石蜡切片分别用 2 种常规染色方法，即硫堇染色和苏木精伊红（HE）染色进行染色，前者用于观察海马细胞，后者用于检查脑微血管。
apoE3/3 和 apoE4/4 小鼠皮质层无明显差异，apoE3/3 和 apoE4/4 小鼠在不同年龄点海马 CA1-CA3 亚区的细胞数量也无显著差异（P>0.05）。然而，apoE3/3 和 apoE4/4 小鼠 CA1 亚区锥体细胞的平均大小随着年龄的增长而减小（P<0.001）。在 20-21 个月时，apoE4/4 小鼠的这种细胞萎缩比老年 apoE3/3 小鼠更严重（P<0.05）。此外，3 只老年 apoE4/4 小鼠的丘脑均存在不同程度的微血管病变（分别为 5.24%、1.41%和 3.97%），而只有 1 只 apoE3/3 小鼠的丘脑存在低水平的微血管病变（0.85%）。
本研究表明，海马 CA1 亚区的细胞大小随年龄增长而减小，与 apoE 基因型无关。与年龄匹配的 apoE3/3 小鼠相比，老年 apoE4/4 小鼠 CA1 亚区的细胞萎缩和丘脑的微血管病变更为严重。apoE4/4 老年小鼠海马 CA1 亚区细胞体积减小是否与学习记忆功能障碍有关，apoE4 等位基因小鼠的微血管病变是否提示中风风险增加，仍存在疑问。需要进一步研究来阐明这些问题。
