Anterior commissure anomalies in APP/PS1 transgenic mouse models of Alzheimer’s disease
- VernacularTitle:APP/PS1阿尔茨海默病转基因动物模型前联合异常改变(英文)
- Author:
Han CHEN
;
Ronghua TANG
;
Zhouping TANG
- Publication Type:Journal Article
- From:
Chinese Journal of Tissue Engineering Research
2007;0(41):-
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND: Much research focuses on the link between ?-amyloid peptide and neuron death, but there is little work about white matter alterations in the Alzheimer’s disease. OBJECTIVE: To investigate the anterior commissure pathological alteration in the APP/PS1 transgenic mice which model brain amyloidosis of Alzheimer’s disease. DESIGN, TIME AND SETTING: A grouping observational study based on the histology was performed in the Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology between September 2007 and September 2008. MATERIALS: Female transgenic APP/PS1 mice [Thy1 APP751 SL (Swedish mutation KM670/671NL, London mutation V717I introduced in human sequence APP751) ? human mutation gene PS1 M146L], control animals were amyloid-deposit free female PS1 mice. A total of 28 mice were divided into young group (2 months, 8 APP/PS1, 7 PS1) and old group (24 months, 6 APP/PS1, 7 PS1). METHODS: The slides of brain tissue were stained with Congo red and antibody against amyloid beta (4G8) to detect brain amyloidosis in Alzheimer’s disease transgenic model. Myelin was stained with gold chloride and axon was stained with anti-neurofilament M antibody. The anterior commissure axonal density and myelination were quantitatively analyzed with the relative optical density value of staining with densitometry. MAIN OUTCOME MEASURES: The staining of intracellular and extracellular amyloid beta; ②the average area of anterior commissure in the coronal brain tissue sections; ③the relative optical density value of myelin and axon staining in the anterior commissure. RESULTS: A lot of Congo red positive amyloid beta plaques were observed in the cortex, hippocampus, thalamus, and anterior commissure of aged APP/PS1 mice, while intracellular amyloid beta was only present in the cortex of young APP/PS1 mice. A prominent increase in the surface area of the anterior commissure was observed in aged PS1 mice compared with young PS1 mice and aged APP/PS1 mice. The neurofilament staining remarkably decreased, both in aged APP/PS1 and aged PS1 mice; an increase trend of myelination in the anterior commissure was observed both the forementioned groups. Different phenotype analysis demonstrated that axonal density and myelination was comparative in the young APP/PS1 and young PS1 mice; axonal density of aged APP/PS1 mice decreased remarkably compared with aged PS1 control mice, while myelination of aged APP/PS1 mice had no significant difference with aged PS1 mice. CONCLUSION: There exists an axon loss in the anterior commissure in the aged APP/PS1 mice with a complete myelin sheath. The amyloid beta shows a direct toxicity on the axon.
