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 Aβ25–35 (10 μg/rat, hippocampal CA1 injection) and dexamethasone (DEX, 1.5 mg/kg) for 14 days to investigate the effects of DEX and Aβ25–35 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 Aβ25–35 treatment alone for 14 days had caused slight damage on learning and memory impairments and hippocampal neurons, but damages were significantly increased with DEX + Aβ25–35 treatment. And the mRNA levels of the APP, β-secretase and caspase 3 were significantly increased after DEX + Aβ25–35 treatment. The immunohistochemistry demonstrated that APP, Aβ1–40, caspase 3 and cytochrome c in hippocampus CA1 were significantly increased. Furthermore, Hoechst 33258 staining and Aβ1–40 ELISA results showed that DEX + Aβ25–35 treatment induced hippocampus CA1 neuron apoptosis and increased the level of Aβ1–40. 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.

► Stress level glucocorticoids (GCs) and β-amyloid (Aβ) peptides deposition are correlated with dementia progression in patients with AD. But little is known about the simultaneous effects of glucocorticoids and Aβ on learning and memory impairment and its mechanism. ► In this study, 12 months male rats were chronically treated with Aβ25–35 (10 μg/rat, hippocampal CA1 injection) and dexamethasone (DEX, 1.5 mg/kg) for 14 days. DEX or Aβ25–35 treatment alone for 14 days had little damage on learning and memory impairments and hippocampal neurons. But DEX + Aβ25–35 could accelerate learning and memory impairments, increase APP processing and neuronal cell apoptosis. ► The results suggest that the simultaneous effects of GCs and Aβ may have important roles in the pathogenesis of AD.