Research article
Insulin deficiency exacerbates cerebral amyloidosis and behavioral deficits in an Alzheimer transgenic mouse model
-
* Corresponding authors: Wei-Ping Teng twpendocrine@yahoo.com.cn - Zhan-You Wang wangzy@mail.cmu.edu.cn
1 Key Laboratory of Medical Cell Biology of Ministry of Education, and Key Laboratory of Endocrine Diseases of Liaoning Province, China Medical University, Shenyang, PR China
2 Department of Histology and Embryology, Liaoning University of Traditional Chinese Medicine, Shenyang, PR China
3 Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, PR China
Molecular Neurodegeneration 2010, 5:46 doi:10.1186/1750-1326-5-46
Published: 2 November 2010Abstract
Background
Although increasing evidence has indicated that brain insulin dysfunction is a risk factor for Alzheimer disease (AD), the underlying mechanisms by which insulin deficiency may impact the development of AD are still obscure. Using a streptozotocin (STZ)-induced insulin deficient diabetic AD transgenic mouse model, we evaluated the effect of insulin deficiency on AD-like behavior and neuropathology.
Results
Our data showed that administration of STZ increased the level of blood glucose and reduced the level of serum insulin, and further decreased the phosphorylation levels of insulin receptors, and increased the activities of glycogen synthase kinase-3α/β and c-Jun N-terminal kinase in the APP/PS1 mouse brain. We further showed that STZ treatment promoted the processing of amyloid-β (Aβ) precursor protein resulting in increased Aβ generation, neuritic plaque formation, and spatial memory deficits in transgenic mice.
Conclusions
Our present data indicate that there is a close link between insulin deficient diabetes and cerebral amyloidosis in the pathogenesis of AD.