Reductions of Acetylcholine Release and Nerve Growth Factor Expression Are Correlated With Memory Impairment Induced by interleukin-1beta Administrations: Effects of omega-3 Fatty Acid EPA Treatment

J Neurochem. 2010 Feb;112(4):1054-64. doi: 10.1111/j.1471-4159.2009.06524.x. Epub 2009 Dec 3.

Abstract

Interleukin (IL)-1beta 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-1beta-induced changes. Intracerebroventricular IL-1beta 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-1beta administrations. mRNA expression of hippocampal NGF was lower, whereas IL-1beta 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-1beta. This study revealed important mechanisms by which IL-1beta impairs, while E-EPA improves memory through IL-1-glucocorticoid-ACh release and IL-1-NGF-ACh release pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism*
  • Animals
  • Behavior, Animal
  • Chromatography, High Pressure Liquid / methods
  • Disease Models, Animal
  • Drug Administration Schedule
  • Eicosapentaenoic Acid / administration & dosage
  • Eicosapentaenoic Acid / pharmacology*
  • Electrochemical Techniques / methods
  • Gene Expression Regulation / drug effects
  • Hippocampus / metabolism
  • Hormone Antagonists / administration & dosage
  • Interleukin-1beta / genetics
  • Interleukin-1beta / pharmacology
  • Male
  • Memory Disorders* / chemically induced
  • Memory Disorders* / diet therapy
  • Memory Disorders* / metabolism
  • Microdialysis / methods
  • Mifepristone / administration & dosage
  • Nerve Growth Factor / genetics
  • Nerve Growth Factor / metabolism*
  • Rats
  • Rats, Long-Evans
  • Statistics as Topic
  • Time Factors

Substances

  • Hormone Antagonists
  • Interleukin-1beta
  • Mifepristone
  • Nerve Growth Factor
  • Eicosapentaenoic Acid
  • Acetylcholine