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.
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.
Taepavarapruk
Pornnarin
P
Department of Biomedical Sciences, AVC, University of Prince Edward Island, Charlottetown PEC1A4P3, Canada.
Song
Cai
C
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D055664:Electrochemical Techniques / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism; D006727:Hormone Antagonists / Q000008:administration & dosage; D053583:Interleukin-1beta / Q000235:genetics / Q000494:pharmacology; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000178:diet therapy / Q000378:metabolism; D017551:Microdialysis / Q000379:methods; D015735:Mifepristone / Q000008:administration & dosage; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D013223:Statistics as Topic; D013997:Time Factors
D006727:Hormone Antagonists; D053583:Interleukin-1beta; D015735:Mifepristone; D020932:Nerve Growth Factor; D015118:Eicosapentaenoic Acid; D000109:Acetylcholine