Metabolomic, Lipidomic and Proteomic Characterisation of Lipopolysaccharide-induced Inflammation Mouse Model.

Autor: Puris E; School of Pharmacy, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland; Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-University, Im Neuenheimer Feld 329, 69120 Heidelberg, Germany. Electronic address: elena.puris@uni-heidelberg.de., Kouřil Š; Institute of Molecular and Translational Medicine, Palacký University Olomouc, Hněvotínská 5, 77900 Olomouc, Czech Republic; Department of Clinical Biochemistry, University Hospital Olomouc, I.P. Pavlova 6, 77900 Olomouc, Czech Republic., Najdekr L; Institute of Molecular and Translational Medicine, Palacký University Olomouc, Hněvotínská 5, 77900 Olomouc, Czech Republic., Auriola S; School of Pharmacy, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland., Loppi S; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland; Department of Immunobiology, University of Arizona, 1656 E Mabel Street, Tucson, AZ 85724-5221, United States., Korhonen P; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland., Gómez-Budia M; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland., Fricker G; Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-University, Im Neuenheimer Feld 329, 69120 Heidelberg, Germany., Kanninen KM; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland., Malm T; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland., Friedecký D; Institute of Molecular and Translational Medicine, Palacký University Olomouc, Hněvotínská 5, 77900 Olomouc, Czech Republic; Department of Clinical Biochemistry, University Hospital Olomouc, I.P. Pavlova 6, 77900 Olomouc, Czech Republic., Gynther M; School of Pharmacy, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland; Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-University, Im Neuenheimer Feld 329, 69120 Heidelberg, Germany.
Jazyk: angličtina
Zdroj: Neuroscience [Neuroscience] 2022 Aug 01; Vol. 496, pp. 165-178. Date of Electronic Publication: 2022 May 28.
DOI: 10.1016/j.neuroscience.2022.05.030
Abstrakt: Neuroinflammation is an important feature in the pathogenesis and progression of central nervous system (CNS) diseases including Alzheimer's disease (AD). One of the widely used animal models of peripherally induced neuroinflammation and neurodegeneration is a lipopolysaccharide (LPS)-induced inflammation mouse model. An acute LPS administration has been widely used for investigation of inflammation-associated disease and testing inflammation-targeting drug candidates. In the present metabolomic, lipidomic and proteomic study, we investigated short-term effects of systemic inflammation induced by LPS administration on the mouse plasma and brain cortical and hippocampal metabolome, lipidome as well as expression of the brain cortical proteins which were shown to be involved in inflammation-associated CNS diseases. From a global perspective, the hippocampus was more vulnerable to the effects of LPS-induced systemic inflammation than the cortex. In addition, the study revealed several brain region-specific changes in metabolic pathways and lipids, such as statistically significant increase in several cortical and hippocampal phosphatidylcholines/phosphatidylethanolamines, and significantly decreased levels of brain cortical betaine after LPS treatment in mice. Moreover, LPS treatment in mice caused significantly increased protein expression of GluN1 receptor in the brain cortex. The revealed perturbations in the LPS-induced inflammation mouse model may give insight into the mechanisms underlying inflammation-associated CNS diseases. In addition, the finding of the study provide important information about the appropriate use of the model during target validation and drug candidate testing.
(Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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