Cu(II) Attenuates Oligomeric and Fibrillar Abeta-Induced Activation of BV-2 Microglia Cells

• Published in: Alzheimer's & dementia Vol. 6; no. 4S1; p. S20
• Main Authors: Jiang, Zhao-Feng, Huang, Han-Chang, Dai, Xue-Ling, Yang, Xiao-Hui, Lin, Chang-Jun
• Format: Journal Article
• Language: English
• Published: 01.07.2010
• Subjects: Aggregation; Alzheimer's disease; Concentration; Nitrites; Signals; Vehicles
• ISSN: 1552-5260
• DOI: 10.1016/j.jalz.2010.05.056

Background: ABeta is one of the main components of senile plaques, a pathological hallmark of Alzheimer's disease. Activated microglia represents a major source of inflammatory factors in Alzheimer's disease and a possible source of cytotoxic factors. ABeta has been shown to activate microglia and stimulate to produce inflammatory factors. Mounting evidence has shown that Cu(II) can modulate the physiochemical properties of A. This article is aim to evaluate the effect of Cu(II) on the oligomeric and fibrillar A in microglia activation. Methods: Oligomeric and fibrilliar A were prepared by incubate at 4 degrees C for 24h and at 37 degrees C for 7 days, respectively. A assemblies were extensively characterized by CD, TH-T fluorescence and sedimentation assay. For the A-Cu(II) complex preparation, the above oligomeric and fibrillar A were incubated with Cu(II) for 1h to form the A-Cu(II) complexes, respectively. The immortalized murine BV-2 cells were grown and maintained in Dulbecco's Modified Eagles Medium (DMEM) (supplemented with 10% fetal bovine serum and 100 mg/mL streptomycin and 10 U/mL penicillin) at 37 DGC in a humidified incubator with 5% CO2. 1M concentration of oligomeric or fillbrillar A was chosen. LPS was chosen as positive control and PBS as Vehicle control. Cell viability was quantitively determined using the MTT assay.After BV-2 cells co-incubated with different forms of A or their A-Cu(II) complexes for 24 h, real-time PCR detected TNF and iNOS mRNA expression levels of BV-2 cells. The production of nitric oxide (NO) was quantified by measuring the released NO metabolites(nitrate and nitrite) with Griess reagent. Results: Cu(II) has an important effect on the oligomeric and filbrillar ABeta secondary structure and aggregation, and will disrupts Beta-sheet structure and converts Beta aggregates into non- aggregates. Both oligomeric and filbrillar ABeta can induce microglial activation, however the cellular signal ways are different due to the TNF and iNOS mRNA expression levels, and NO metabolites activity are different when the BV2 cells were co-incubated with oligomeric and filbrillar A40, respectively. ABeta-Cu(II) complexes play less roles on the activation of microglial than both oligomeric and fibrillar ABeta. Conclusions: These results indicated that oligomeric and fibrillar ABeta induce differentially activation of BV-2 cells and which were dramatically attenuated by Cu(II). [Copyright Elsevier B.V.]