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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. 2009 Dec 3;
Authors: Taepavarapruk P, Song C
J. Neurochem. (2009) 10.1111/j.1471-4159.2009.06524.x
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.
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In other words:
IL-1Beta – a pro-inflammatory cytokine – impairs memory and may play a role in Alzheimer’s disease.
IL-1beta reduces hippocampal acetylcholine release and reduces nerve growth factor production. These lead to memory impairment.
Omega-3 Fatty Acid EPA (not DHA in this study) improves hippocampal ACh release, improves nerve growth factor production, and reduces IL-1beta production, leading to an improvement in memory.
Mifepristone (RU 486, the abortion pill) is a glucocorticoid receptor blocker (with 10 times more affinitiy for the glucocorticoid receptor than Cortisol). It is a progesterone receptor blocker and partial agonist (binding to the progesterone receptor twice as strong as progesterone, and acting as an agonist if progesterone is not present). This is why it is used as an abortion pill. It is also an androgen receptor blocker (binding to the receptor 1/3rd as strong as testosterone).
Mifepristone partially blocks IL-1beta’s reduction in hippocampal ACh release.
The question I have is whether or not this indicates that cortisol is involved in reducing hippocampal ACh release and whether or not this causes memory problems. This is particularly so since all of Mifepristone’s pharmacological effects are not clear. Given Mifepristone’s multiple mechanisms of action, correlating it with glucocorticoid signaling alone is imprecise.