Dexamethasone and Aβ₂₅-₃₅ accelerate learning and memory impairments due to elevate amyloid precursor protein expression and neuronal apoptosis in 12-month male rats.
Alzheimer's disease (AD) is an irreversible, progressive brain disorder of the elderly characterized by learning and memory impairment. Stress level glucocorticoids (GCs) and β-amyloid (Aβ) peptides deposition are found to be correlated with dementia progression in patients with AD. However, little is known about the simultaneous effects of glucocorticoids and Aβ on learning and memory impairment and its mechanism. In this study, 12-month-old male rats were chronically treated with Aβ(25-35) (10 μg/rat, hippocampal CA1 injection) and dexamethasone (DEX, 1.5mg/kg) for 14 days to investigate the effects of DEX and Aβ(25-35) treatment on learning and memory impairments, pathological changes, neuronal ultrastructure, amyloid precursor protein (APP) processing and neuronal cell apoptosis. Our results showed that DEX or Aβ(25-35) treatment alone for 14 days had caused slight damage on learning and memory impairments and hippocampal neurons, but damages were significantly increased with DEX+Aβ(25-35) treatment. And the mRNA levels of the APP, β-secretase and caspase 3 were significantly increased after DEX+Aβ(25-35) treatment. The immunohistochemistry demonstrated that APP, Aβ(1-40), caspase 3 and cytochrome c in hippocampus CA1 were significantly increased. Furthermore, Hoechst 33258 staining and Aβ(1-40) ELISA results showed that DEX+Aβ(25-35) treatment induced hippocampus CA1 neuron apoptosis and increased the level of Aβ(1-40). The results suggest that the simultaneous effects of GCs and Aβ may have important roles in the etiopathogenesis of AD, and demonstrate that stressful life events and GC therapy may increase the toxicity of Aβ and have cumulative impacts on the course of AD development and progression.
Department of Pharmacology, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Key Laboratory of Chinese Medicine Research and Development, State Administration of Traditional Chinese Medicine, Anhui Medical University, Hefei 230032, PR China., , , , , ,
MeSHAmyloid Precursor Protein Secretases
Amyloid beta-Protein Precursor
Analysis of Variance
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Gene Expression Regulation
Microscopy, Electron, Scanning
Pub Type(s)Journal Article
Research Support, Non-U.S. Gov't