Synergistic Exacerbation of Mitochondrial and Synaptic Dysfunction and Resultant Learning and Memory Deficit in a Mouse Model of Diabetic Alzheimer’s Disease

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Issue Date
2015Author
Wang, Yongfu
Wu, Long
Du, Fang
Zhong, Changjia
Chen, John Xi
Yan, Shirley ShiDu
Publisher
IOS Press
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
Rights
Copyright IOS Press
Metadata
Show full item recordAbstract
Diabetes is considered to be a risk factor in Alzheimer’s disease (AD) pathogenesis. Although recent evidence indicates that diabetes exaggerates pathologic features of AD, the underlying mechanisms are not well understood. To determine whether mitochondrial perturbation is associated with the contribution of diabetes to AD progression, we characterized mouse models of streptozotocin (STZ)-induced type 1 diabetes and transgenic AD mouse models with diabetes. Brains from mice with STZ-induced diabetes revealed a significant increase of cyclophilin D (CypD) expression, reduced respiratory function, and decreased hippocampal long-term potentiation (LTP); these animals had impaired spatial learning and memory. Hyperglycemia exacerbated the upregulation of CypD, mitochondrial defects, synaptic injury, and cognitive dysfunction in the brains of transgenic AD mice overexpressing amyloid-β as shown by decreased mitochondrial respiratory complex I and IV enzyme activity and greatly decreased mitochondrial respiratory rate. Concomitantly, hippocampal LTP reduction and spatial learning and memory decline, two early pathologic indicators of AD, were enhanced in the brains of diabetic AD mice. Our results suggest that the synergistic interaction between effects of diabetes and AD on mitochondria may be responsible for brain dysfunction that is in common in both diabetes and AD.
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- Pharmacy Scholarly Works [293]
Citation
Wang, Yongfu et al. “Synergistic Exacerbation of Mitochondrial and Synaptic Dysfunction and Resultant Learning and Memory Deficit in a Mouse Model of Diabetic Alzheimer’s Disease.” Journal of Alzheimer’s disease : JAD 43.2 (2015): 451–463. PMC. Web.
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