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


CONCLUSIONS
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.
Tang
Ke-Feng
KF
Hefei National Laboratory for Physical Science at Microscale and School of Life Science, University of Science and Technology of China, Hefei 230027, China.
Cai
Li
L
Zhou
Jiang-Ning
JN
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D053318:Apolipoprotein E3 / Q000172:deficiency / Q000235:genetics; D053327:Apolipoprotein E4 / Q000172:deficiency / Q000235:genetics; D001835:Body Weight / Q000235:genetics; D002561:Cerebrovascular Disorders / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein; D006624:Hippocampus / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D009929:Organ Size / Q000235:genetics; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology*; D013788:Thalamus / Q000473:pathology*
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C528900:glial fibrillary astrocytic protein, mouse