Acta Anatomica Sinica

AAS ›› 2013, Vol. 44 ›› Issue (4 ): 451-455.doi: 10.3969/j.issn.0529-1356.2013.04.002

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Gene knockout of amyloid precursor protein promotes aluminum-induced cognitive impairment in mice

WANG Dong-mei 1,2  YUAN Shu-min2  ZHANG Xu2  ZHANG Lian-feng2   

  1. 1. Department of Microbiology, Henan University of Science and Technology, Henan Luoyang 471000, China;2. Key Laboratory of Human Disease Comparative Medicine, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Comparative Medical Center, Peking Union Medical College, Beijing 100021，China
  • Received:2012-11-22 Revised:2013-05-20 Online:2013-08-06 Published:2013-09-04

Abstract:

Objective Amyloid precursor protein (APP) is involved in dementia, however, little is known about its role in the development of dementia. The APP knockout mice were used to investigate the effects of amyloid precursor protein on
aluminum-induced cognitive impairment in mice. Methods  APP knockout mice and the littermates of no-negative mice aged 3 months were selected randomly and performed Morris water-maze tests after administration for 8 weeks. Aluminum was administrated in the diet. One group of APP knockout mice was used for vehicle group. One group of the littermates of no-negative mice was used as normal control (WT). The pathological changes in brain were detected by HE staining. The activities of glycogen synthase kinase 3β(GSK-3β)and Caspase-3 were also examined by Western blotting.  Results Compared with WT mice, Al-treated WT mice exhibited a decrease in the target-quadrant abidance by 28.1% and the crossing-target number by 18.8% in the probe test; APP knockout mice administrated showed a significant decrease in the target-quadrant abidance by 44.1% and the crossing-target number by 51% in the probe test. Compared with that of WT mice, the level of p-GSK-3β was decreased by 17.4% in Al-treated WT mice and by 46.4% in Al-treated APP knockout mice. Conclusion Gene knockout of APP promotes aluminum-induced neurotoxicity and cognitive impairment in mice. APP knockout leads to a significant increase of the activity of GSK-3β, which can accelerate the processing of dementia. Thus the protective effect of APP may be through inhibiting the activity of GSK-3β.

Key words: Amyloid ecursor protein, Aluminum, Morris water maze, Cognitive impairment, Glycogen synthase kinase 3β, Mouse