Neostigmine Attenuates Proinflammatory Cytokine Expression in Preoptic Area but Not Choroid Plexus during Lipopolysaccharide-Induced Systemic Inflammation

The study was designed to examine whether the administration of neostigmine (0.5 mg/animal), a peripheral inhibitor of acetylcholinesterase (AChE), during an immune/inflammatory challenge provoked by intravenous injection of bacterial endotoxin—lipopolysaccharide (LPS; 400 ng/kg)—attenuates the synt...

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Main Authors: Andrzej P. Herman, Dorota Tomaszewska-Zaremba, Marta Kowalewska, Aleksandra Szczepkowska, Małgorzata Oleszkiewicz, Agata Krawczyńska, Maciej Wójcik, Hanna Antushevich, Janina Skipor
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2018/9150207
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author Andrzej P. Herman
Dorota Tomaszewska-Zaremba
Marta Kowalewska
Aleksandra Szczepkowska
Małgorzata Oleszkiewicz
Agata Krawczyńska
Maciej Wójcik
Hanna Antushevich
Janina Skipor
author_facet Andrzej P. Herman
Dorota Tomaszewska-Zaremba
Marta Kowalewska
Aleksandra Szczepkowska
Małgorzata Oleszkiewicz
Agata Krawczyńska
Maciej Wójcik
Hanna Antushevich
Janina Skipor
author_sort Andrzej P. Herman
collection DOAJ
description The study was designed to examine whether the administration of neostigmine (0.5 mg/animal), a peripheral inhibitor of acetylcholinesterase (AChE), during an immune/inflammatory challenge provoked by intravenous injection of bacterial endotoxin—lipopolysaccharide (LPS; 400 ng/kg)—attenuates the synthesis of proinflammatory cytokines in the ovine preoptic area (POA), the hypothalamic structure playing an essential role in the control of the reproduction process, and in the choroid plexus (CP), a multifunctional organ sited at the interface between the blood and cerebrospinal fluid in the ewe. Neostigmine suppressed (p<0.05) LPS-stimulated synthesis of cytokines such as interleukin- (IL-) 1β, IL-6, and tumor necrosis factor (TNF) α in the POA, and this effect was similar to that induced by the treatment with systemic AChE inhibitor—donepezil (2.5 mg/animal). On the other hand, both AChE inhibitors did not influence the gene expression of these cytokines and their corresponding receptors in the CP. It was found that this structure seems to not express the neuronal acetylcholine (ACh) receptor subunit alpha-7, required for anti-inflammatory action of ACh. The mechanism of action involves inhibition of the proinflammatory cytokine synthesis on the periphery as well as inhibition of their de novo synthesis rather in brain microvessels and not in the CP. In conclusion, it is suggested that the AChE inhibitors incapable of reaching brain parenchyma might be used in the treatment of neuroinflammatory processes induced by peripheral inflammation.
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spelling doaj-art-0144370f01fd442a88ee811d2d78c9f52025-02-03T05:54:11ZengWileyMediators of Inflammation0962-93511466-18612018-01-01201810.1155/2018/91502079150207Neostigmine Attenuates Proinflammatory Cytokine Expression in Preoptic Area but Not Choroid Plexus during Lipopolysaccharide-Induced Systemic InflammationAndrzej P. Herman0Dorota Tomaszewska-Zaremba1Marta Kowalewska2Aleksandra Szczepkowska3Małgorzata Oleszkiewicz4Agata Krawczyńska5Maciej Wójcik6Hanna Antushevich7Janina Skipor8The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jabłonna, PolandThe Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jabłonna, PolandInstitute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, PolandInstitute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, PolandInstitute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, PolandThe Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jabłonna, PolandThe Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jabłonna, PolandThe Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jabłonna, PolandInstitute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, PolandThe study was designed to examine whether the administration of neostigmine (0.5 mg/animal), a peripheral inhibitor of acetylcholinesterase (AChE), during an immune/inflammatory challenge provoked by intravenous injection of bacterial endotoxin—lipopolysaccharide (LPS; 400 ng/kg)—attenuates the synthesis of proinflammatory cytokines in the ovine preoptic area (POA), the hypothalamic structure playing an essential role in the control of the reproduction process, and in the choroid plexus (CP), a multifunctional organ sited at the interface between the blood and cerebrospinal fluid in the ewe. Neostigmine suppressed (p<0.05) LPS-stimulated synthesis of cytokines such as interleukin- (IL-) 1β, IL-6, and tumor necrosis factor (TNF) α in the POA, and this effect was similar to that induced by the treatment with systemic AChE inhibitor—donepezil (2.5 mg/animal). On the other hand, both AChE inhibitors did not influence the gene expression of these cytokines and their corresponding receptors in the CP. It was found that this structure seems to not express the neuronal acetylcholine (ACh) receptor subunit alpha-7, required for anti-inflammatory action of ACh. The mechanism of action involves inhibition of the proinflammatory cytokine synthesis on the periphery as well as inhibition of their de novo synthesis rather in brain microvessels and not in the CP. In conclusion, it is suggested that the AChE inhibitors incapable of reaching brain parenchyma might be used in the treatment of neuroinflammatory processes induced by peripheral inflammation.http://dx.doi.org/10.1155/2018/9150207
spellingShingle Andrzej P. Herman
Dorota Tomaszewska-Zaremba
Marta Kowalewska
Aleksandra Szczepkowska
Małgorzata Oleszkiewicz
Agata Krawczyńska
Maciej Wójcik
Hanna Antushevich
Janina Skipor
Neostigmine Attenuates Proinflammatory Cytokine Expression in Preoptic Area but Not Choroid Plexus during Lipopolysaccharide-Induced Systemic Inflammation
Mediators of Inflammation
title Neostigmine Attenuates Proinflammatory Cytokine Expression in Preoptic Area but Not Choroid Plexus during Lipopolysaccharide-Induced Systemic Inflammation
title_full Neostigmine Attenuates Proinflammatory Cytokine Expression in Preoptic Area but Not Choroid Plexus during Lipopolysaccharide-Induced Systemic Inflammation
title_fullStr Neostigmine Attenuates Proinflammatory Cytokine Expression in Preoptic Area but Not Choroid Plexus during Lipopolysaccharide-Induced Systemic Inflammation
title_full_unstemmed Neostigmine Attenuates Proinflammatory Cytokine Expression in Preoptic Area but Not Choroid Plexus during Lipopolysaccharide-Induced Systemic Inflammation
title_short Neostigmine Attenuates Proinflammatory Cytokine Expression in Preoptic Area but Not Choroid Plexus during Lipopolysaccharide-Induced Systemic Inflammation
title_sort neostigmine attenuates proinflammatory cytokine expression in preoptic area but not choroid plexus during lipopolysaccharide induced systemic inflammation
url http://dx.doi.org/10.1155/2018/9150207
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