Observation of the density and size of cells in hippocampus and vascular lesion in thalamus of GFAP-apoE transgenic mice

GFAP-apoE转基因小鼠海马细胞密度和大小以及丘脑血管损伤的观察(英文)

Objective 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. Methods 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. Results 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%）. Conclusion 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.

目的载脂蛋白E(apolipoprotein E,apoE)与衰老相关疾病的发病风险增加密切相关,如阿尔茨海默氏病和脑血管病。本研究旨在观察GFAP-apoE转基因鼠脑的一般形态随年龄的增加而发生的改变,尤以海马椎体细胞的数目大小变化和丘脑微血管损伤为主。方法雌性apoE4/4转基因鼠按年龄段分为三组:3-4月龄(青年),9-10月龄(中年),20-21月龄(老年),对照组选用对应年龄的apoE3/3转基因雌鼠(每组均为3只)。转基因鼠脑的石蜡切片经两种常规染色方法进行染色,即硫堇染色和苏木素-伊红染色。前者用来观察海马细胞,后者则用来观察脑微血管。结果apoE4/4转基因鼠大脑皮层分层的一般形态学较apoE3/3转基因鼠无差异。在各年龄段中,apoE4/4型鼠的海马CA1-CA3亚区的神经元数目相较于apoE3/3型鼠均无显著性差异(P>0.05)。然而,在海马CA1亚区,apoE3/3和apoE4/4型鼠的椎体细胞大小均随年龄的升高而显著性降低(P<0.001),并且老年apoE4/4型鼠中的细胞萎缩要比老年的apoE3/3型鼠更加明显(P<0.05)。此外,所有老年apoE4/4转基因鼠的丘脑都有不同程度微血管损伤(损伤度分别为5.24%,1.41%,3.97%);而在三只老年apoE3/3转基因鼠中仅有一只表现出丘脑微血管损伤(损伤度为0.85%)。结论本研究提示海马CA1亚区细胞大小随着衰老而减小,且不受apoE基因型影响。老年apoE4/4型鼠海马CA1区细胞萎缩及丘脑微血管损伤均强于老年apoE3/3型鼠。海马CA1亚区细胞萎缩是否与学习记忆功能损伤有关,微血管损伤增加是否预示带有人apoE4的鼠的卒中风险上升均有待进一步深入研究。