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Increased Expression and Activity of Brain Cortical cPLA2 Due to Chronic Lipopolysaccharide Administration in Mouse Model of Familial Alzheimer’s Disease

Cytosolic phospholipase A2 (cPLA2) is an enzyme regulating membrane phospholipid homeostasis and the release of arachidonic acid utilized in inflammatory responses. It represents an attractive target for the treatment of Alzheimer’s disease (AD). Previously, we showed that lipopolysaccharide (LPS)-i...

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Autores principales: Gynther, Mikko, Estrada, Mariana Leal, Loppi, Sanna, Korhonen, Paula, Kanninen, Katja M., Malm, Tarja, Koistinaho, Jari, Auriola, Seppo, Fricker, Gert, Puris, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695895/
https://www.ncbi.nlm.nih.gov/pubmed/36365256
http://dx.doi.org/10.3390/pharmaceutics14112438
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author Gynther, Mikko
Estrada, Mariana Leal
Loppi, Sanna
Korhonen, Paula
Kanninen, Katja M.
Malm, Tarja
Koistinaho, Jari
Auriola, Seppo
Fricker, Gert
Puris, Elena
author_facet Gynther, Mikko
Estrada, Mariana Leal
Loppi, Sanna
Korhonen, Paula
Kanninen, Katja M.
Malm, Tarja
Koistinaho, Jari
Auriola, Seppo
Fricker, Gert
Puris, Elena
author_sort Gynther, Mikko
collection PubMed
description Cytosolic phospholipase A2 (cPLA2) is an enzyme regulating membrane phospholipid homeostasis and the release of arachidonic acid utilized in inflammatory responses. It represents an attractive target for the treatment of Alzheimer’s disease (AD). Previously, we showed that lipopolysaccharide (LPS)-induced systemic inflammation caused abnormal lipid metabolism in the brain of a transgenic AD mouse model (APdE9), which might be associated with potential changes in cPLA2 activity. Here, we investigated changes in cPLA2 expression and activity, as well as the molecular mechanisms underlying these alterations due to chronic LPS administration in the cerebral cortex of female APdE9 mice as compared to saline- and LPS-treated female wild-type mice and saline-treated APdE9 mice. The study revealed the significant effects of genotype LPS treatment on cortical cPLA2 protein expression and activity in APdE9 mice. LPS treatment resulted in nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) activation in the cortex of APdE9 mice. The gene expressions of inflammation markers Il1b and Tnfa were significantly elevated in the cortex of both APdE9 groups compared to the wild-type groups. The study provides evidence of the elevated expression and activity of cPLA2 in the brain cortex of APdE9 mice after chronic LPS treatment, which could be associated with NFkB activation.
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spelling pubmed-96958952022-11-26 Increased Expression and Activity of Brain Cortical cPLA2 Due to Chronic Lipopolysaccharide Administration in Mouse Model of Familial Alzheimer’s Disease Gynther, Mikko Estrada, Mariana Leal Loppi, Sanna Korhonen, Paula Kanninen, Katja M. Malm, Tarja Koistinaho, Jari Auriola, Seppo Fricker, Gert Puris, Elena Pharmaceutics Article Cytosolic phospholipase A2 (cPLA2) is an enzyme regulating membrane phospholipid homeostasis and the release of arachidonic acid utilized in inflammatory responses. It represents an attractive target for the treatment of Alzheimer’s disease (AD). Previously, we showed that lipopolysaccharide (LPS)-induced systemic inflammation caused abnormal lipid metabolism in the brain of a transgenic AD mouse model (APdE9), which might be associated with potential changes in cPLA2 activity. Here, we investigated changes in cPLA2 expression and activity, as well as the molecular mechanisms underlying these alterations due to chronic LPS administration in the cerebral cortex of female APdE9 mice as compared to saline- and LPS-treated female wild-type mice and saline-treated APdE9 mice. The study revealed the significant effects of genotype LPS treatment on cortical cPLA2 protein expression and activity in APdE9 mice. LPS treatment resulted in nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) activation in the cortex of APdE9 mice. The gene expressions of inflammation markers Il1b and Tnfa were significantly elevated in the cortex of both APdE9 groups compared to the wild-type groups. The study provides evidence of the elevated expression and activity of cPLA2 in the brain cortex of APdE9 mice after chronic LPS treatment, which could be associated with NFkB activation. MDPI 2022-11-10 /pmc/articles/PMC9695895/ /pubmed/36365256 http://dx.doi.org/10.3390/pharmaceutics14112438 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gynther, Mikko
Estrada, Mariana Leal
Loppi, Sanna
Korhonen, Paula
Kanninen, Katja M.
Malm, Tarja
Koistinaho, Jari
Auriola, Seppo
Fricker, Gert
Puris, Elena
Increased Expression and Activity of Brain Cortical cPLA2 Due to Chronic Lipopolysaccharide Administration in Mouse Model of Familial Alzheimer’s Disease
title Increased Expression and Activity of Brain Cortical cPLA2 Due to Chronic Lipopolysaccharide Administration in Mouse Model of Familial Alzheimer’s Disease
title_full Increased Expression and Activity of Brain Cortical cPLA2 Due to Chronic Lipopolysaccharide Administration in Mouse Model of Familial Alzheimer’s Disease
title_fullStr Increased Expression and Activity of Brain Cortical cPLA2 Due to Chronic Lipopolysaccharide Administration in Mouse Model of Familial Alzheimer’s Disease
title_full_unstemmed Increased Expression and Activity of Brain Cortical cPLA2 Due to Chronic Lipopolysaccharide Administration in Mouse Model of Familial Alzheimer’s Disease
title_short Increased Expression and Activity of Brain Cortical cPLA2 Due to Chronic Lipopolysaccharide Administration in Mouse Model of Familial Alzheimer’s Disease
title_sort increased expression and activity of brain cortical cpla2 due to chronic lipopolysaccharide administration in mouse model of familial alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695895/
https://www.ncbi.nlm.nih.gov/pubmed/36365256
http://dx.doi.org/10.3390/pharmaceutics14112438
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