Inhibition of acetylcholinesterase activity by rivastigmine decreases lipopolysaccharide-induced IL-1β expression in the hypothalamus of ewes |
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Authors: | AP Herman A Krawczyńska J Bochenek K Haziak H Antushevitch A Herman D Tomaszewska-Zaremba |
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Institution: | 1. Department of Neuroendocrinology, Polish Academy of Sciences, The Kielanowski Institute of Animal Physiology and Nutrition, 05-110 Jab?onna, Poland;2. Department of Microbiology and Cell Science, The Academy of Cosmetics and Health Care, 00-252 Warsaw, Poland |
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Abstract: | The present study was designed to determine the effect of subcutaneous rivastigmine treatment on IL-1β expression and IL-1 type I receptor (IL-1R1) gene expression in the hypothalamic structures (preoptic area POA], anterior hypothalamus AHA], and medial basal hypothalamus MBH]) of ewes after lipopolysaccharide (LPS) treatment. Endotoxin treatment increased (P ≤ 0.01) both IL-1β and IL-1R1 gene expression in the POA, AHA, and MBH compared with the control group, whereas concomitant rivastigmine and LPS injection abolished this stimulatory effect. It was also found that LPS elevated (P ≤ 0.01) IL-1β concentration in the hypothalamus (71.0 ± 2.3 pg/mg) compared with controls (16.1 ± 3.6 pg/mg). The simultaneous injection of LPS and rivastigmine did not increase IL-1β concentration in the hypothalamus (24.6 ± 13.0 pg/mg). This central change in IL-1β synthesis seems to be an effect of acetylcholinesterase (AChE) inhibition by rivastigmine, which decreases (P ≤ 0.01) the activity of this enzyme from 78.5 ± 15.0 μmol · min−1 · g−1 of total protein in the control and 68.8 ± 9.8 μmol · min−1 · g−1 of total protein in LPS-treated animals to 45.2 ± 5.6 μmol · min−1 · g−1 of total protein in the rivastigmine and LPS-treated group. Our study showed that rivastigmine could effectively reverse the stimulatory effect of immune stress induced by LPS injection on IL-1β synthesis through a decrease in AChE activity in the hypothalamic area of sheep. Our results also proved that the cholinergic anti-inflammatory pathway could directly modulate the central response to endotoxin. |
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Keywords: | Ewe Hypothalamus Immune stress IL-1β IL-1 receptors AChE |
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