• acetylcholine;
  • eicosapentaenoate;
  • interleukin-1beta;
  • memory impairment;
  • microdialysis;
  • nerve growth factor

J. Neurochem. (2009) 112, 1054–1064.


Interleukin (IL)-1β may play an important role in Alzheimer’s disease. However, the relationships between glucocorticoids and acetylcholine (ACh), and between neurotrophins and ACh in IL-1-induced memory deficits are unknown. While ethyl-eicosapentaenoate (E-EPA) has recently been reported to reduce inflammation and improve memory, cholinergic and neurotrophic mechanisms by which E-EPA improves memory is unclear. This study evaluated: (i) the correlation between ACh release and memory impairment; (ii) the effect of glucocorticoids on ACh release; (iii) the relationship between nerve growth factor (NGF) and inflammation; and (iv) the effects of E-EPA treatment on IL-1β-induced changes. Intracerebroventricular IL-1β administrations produced a significant reduction in hippocampal ACh release in rats fed control diet, which was partially attenuated by mifepristone (RU 486) and completely blocked by IL-1 receptor antagonist. In eight-arm radial maze, significantly less ACh release was correlated with the memory deficits after IL-1β administrations. mRNA expression of hippocampal NGF was lower, whereas IL-1β was higher when compared with controls. E-EPA treatment significantly improved the memory, which was correlated with normalizing ACh release, and expressions of NGF and IL-1β. This study revealed important mechanisms by which IL-1β impairs, while E-EPA improves memory through IL-1-glucocorticoid-ACh release and IL-1-NGF-ACh release pathways.