Abstract
Aim:
To observe whether an amyloid β (Aβ)-induced increase in interleukin (IL)-1β was accompanied by an increase in the p38 mitogen-activated protein kinase (MAPK) pathway and a decrease in the cell survival pathway, and whether sodium ferulate (SF) treatment was effective in preventing these Aβ-induced changes.
Methods:
Rats were injected intracerebroventricularly with Aβ25–35. Seven days after injection, immunohistochemical techniques for glial fibrillary acidic protein (GFAP) were used to determine the astrocyte infiltration and activation in hippo-campal CA1 areas. The expression of IL-1β, extracellular signal-regulated kinase (ERK), p38 MAPK, Akt/protein kinase B (PKB), Fas ligand and caspase-3 were determined by Western blotting. The caspase-3 activity was measured by cleavage of the caspase-3 substrate (Ac-DEVD-pNA). Reverse transcription-polymerase chain reaction was used to analyze the changes in IL-1βmRNA levels.
Results:
Intracerebroventricular injection of Aβ25–35 elicited astrocyte activation and infiltration and caused a strong inflammatory reaction characterized by increased IL-1β production and elevated levels of IL-1β mRNA. Increased IL-1β synthesis was accompanied by increased activation of p38 MAPK and downregulation of phospho-ERK and phospho-Akt/PKB in hippocampal CA regions prepared from Aβ-treated rats, leading to cell death as assessed by activation of caspase-3. SF significantly prevented Aβ-induced increases in IL-1β and p38 MAPK activation and also Aβ-induced changes in phospho-ERK and phospho-Akt/PKB expression levels.
Conclusion:
SF prevents Aβ-induced neurotoxicity through suppression of p38 MAPK activation and upregulation of phospho-ERK and phospho-Akt/PKB expression.
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Project supported by Natural Science Foundation of Liaoning Province (No 20042171).
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Jin, Y., Yan, Ez., Fan, Y. et al. Sodium ferulate prevents amyloid-beta-induced neurotoxicity through suppression of p38 MAPK and upregulation of ERK-1/2 and Akt/protein kinase B in rat hippocampus. Acta Pharmacol Sin 26, 943–951 (2005). https://doi.org/10.1111/j.1745-7254.2005.00158.x
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DOI: https://doi.org/10.1111/j.1745-7254.2005.00158.x
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