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

Autor: Du Fang, Changjia Zhong, Yongfu Wang, Shirley ShiDu Yan, John Xi Chen, Jianping Li, Long Wu
Rok vydání: 2014
Předmět:
medicine.medical_specialty
Time Factors
Spatial Learning
Mice
Transgenic
In Vitro Techniques
Mitochondrion
Hippocampus
Article
Diabetes Mellitus
Experimental
Electron Transport Complex IV
Amyloid beta-Protein Precursor
Mice
Oxygen Consumption
Downregulation and upregulation
Alzheimer Disease
Internal medicine
Diabetes mellitus
medicine
Animals
Humans
Respiratory function
Memory Disorders
Type 1 diabetes
Learning Disabilities
General Neuroscience
Excitatory Postsynaptic Potentials
Long-term potentiation
General Medicine
medicine.disease
Streptozotocin
Mitochondria
Mice
Inbred C57BL
Disease Models
Animal
Psychiatry and Mental health
Clinical Psychology
Endocrinology
Gene Expression Regulation
Mutation
Synapses
Geriatrics and Gerontology
Alzheimer's disease
Psychology
Neuroscience
medicine.drug
Zdroj: Journal of Alzheimer's Disease. 43:451-463
ISSN: 1875-8908
1387-2877
DOI: 10.3233/jad-140972
Popis: 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.
Databáze: OpenAIRE
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