Synergistic exacerbation of mitochondrial and synaptic dysfunction and resultant learning and memory deficit in a mouse model of diabetic Alzheimer's disease Journal Article
| Authors: | Wang, Y.; Wu, L.; Li, J.; Fang, D.; Zhong, C.; Chen, J. X.; Yan, S. S. |
| Article Title: | Synergistic exacerbation of mitochondrial and synaptic dysfunction and resultant learning and memory deficit in a mouse model of diabetic Alzheimer's disease |
| Abstract: | 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. |
| Keywords: | controlled study; protein expression; disease course; nonhuman; mouse; animal tissue; disease association; animal experiment; animal model; brain injury; enzyme activity; transgenic mouse; hyperglycemia; diabetes mellitus; cognitive defect; upregulation; respiratory function; insulin dependent diabetes mellitus; mitochondria; disease exacerbation; mitochondrion; alzheimer disease; diabetes; neuropathology; synapse; alzheimer's disease; amyloid beta protein; cyclophilin d; cytochrome c oxidase; reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone); learning disorder; long-term potentiation; cognitive impairment; mitochondrial dna disorder; long term potentiation; breathing rate; spatial learning; article; synaptic injury; streptozotocin-induced diabetes mellitus |
| Journal Title: | Journal of Alzheimer's Disease |
| Volume: | 43 |
| Issue: | 2 |
| ISSN: | 1387-2877 |
| Publisher: | IOS Press |
| Date Published: | 2015-01-01 |
| Start Page: | 451 |
| End Page: | 463 |
| Language: | English |
| DOI: | 10.3233/jad-140972 |
| PROVIDER: | scopus |
| PUBMED: | 25096625 |
| PMCID: | PMC4466096 |
| DOI/URL: | |
| Notes: | Export Date: 2 January 2015 -- Source: Scopus |
