Tracking CNS and systemic sources of oxidative stress during the course of chronic neuroinflammation
| Autor: | Josephine Herz, Agata Mossakowski, Helena Radbruch, Josef Priller, Michael Boschmann, Markus Bock, Leonard Viohl, Jenny Gerhard, Karolin Pollok, Moritz Radbruch, Florence Pache, Carmen Infante-Duarte, Anja Mähler, Janina Behrens, Daniel Bremer, Randall L. Lindquist, Raluca Niesner, Anja E. Hauser, Markus Bardua, Martina Füchtemeier, Julian Pohlan, Judith Bellmann-Strobl, Ronja Mothes, Jan Leo Rinnenthal, Friedemann Paul, Jason M. Millward |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
enzymology [Multiple Sclerosis]
Medizin Oxidative stress memory medicine.disease_cause physiology [Oxidative Stress] therapeutic use [Glatiramer Acetate] Antioxidants Catechin metabolism [NADPH Oxidases] Intravital imaging therapeutic use [Antioxidants] pathology [Neurons] metabolism [Calcium] therapeutic use [Catechin] Enzyme Inhibitors pathology [Astrocytes] Neurons enzymology [Neurons] NADPH oxidase CD11b Antigen biology Microglia Research Support Non-U.S. Gov't Experimental autoimmune encephalomyelitis antagonists & inhibitors [NADPH Oxidases] analogs & derivatives [Catechin] pathology [Multiple Sclerosis] Cell biology medicine.anatomical_structure therapeutic use [Enzyme Inhibitors] NOX1 Randomized Controlled Trial Disease Progression drug effects [Oxidative Stress] epigallocatechin gallate Encephalomyelitis Autoimmune Experimental Multiple Sclerosis Central nervous system Clinical Neurology drug effects [Astrocytes] Mice Transgenic methods [Microscopy Fluorescence] Pathology and Forensic Medicine enzymology [Astrocytes] Cellular and Molecular Neuroscience Oxidative enzyme Journal Article medicine metabolism [CD11b Antigen] Animals Humans drug effects [Neurons] pathology [Encephalomyelitis Autoimmune Experimental] drug therapy [Multiple Sclerosis] ddc:610 Neuroinflammation Original Paper Fluorescence lifetime microscopy Neuronal dysfunction NADPH Oxidases Glatiramer Acetate medicine.disease Mice Inbred C57BL Oxidative Stress Microscopy Fluorescence enzymology [Encephalomyelitis Autoimmune Experimental] Cardiovascular and Metabolic Diseases Astrocytes Immunology Chronic Disease biology.protein drug therapy [Encephalomyelitis Autoimmune Experimental] Calcium Neurology (clinical) Oxidative stress |
| Zdroj: | Acta neuropathologica 130(6), 799-814 (2015). doi:10.1007/s00401-015-1497-x Acta Neuropathologica Mossakowski, A A, Pohlan, J, Bremer, D, Lindquist, R, Millward, J M, Bock, M, Pollok, K, Mothes, R, Viohl, L, Radbruch, M, Gerhard, J, Bellmann-Strobl, J, Behrens, J, Infante-Duarte, C, Mähler, A, Boschmann, M, Rinnenthal, J L, Füchtemeier, M, Herz, J, Pache, F C, Bardua, M, Priller, J, Hauser, A E, Paul, F, Niesner, R & Radbruch, H 2015, ' Tracking CNS and systemic sources of oxidative stress during the course of chronic neuroinflammation ', Acta Neuropathologica, vol. 130, no. 6, pp. 799-814 . https://doi.org/10.1007/s00401-015-1497-x |
| DOI: | 10.1007/s00401-015-1497-x |
| Popis: | The functional dynamics and cellular sources of oxidative stress are central to understanding MS pathogenesis but remain elusive, due to the lack of appropriate detection methods. Here we employ NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX enzymes) in vivo to identify inflammatory monocytes, activated microglia, and astrocytes expressing NOX1 as major cellular sources of oxidative stress in the central nervous system of mice affected by experimental autoimmune encephalomyelitis (EAE). This directly affects neuronal function in vivo, indicated by sustained elevated neuronal calcium. The systemic involvement of oxidative stress is mirrored by overactivation of NOX enzymes in peripheral CD11b+ cells in later phases of both MS and EAE. This effect is antagonized by systemic intake of the NOX inhibitor and anti-oxidant epigallocatechin-3-gallate. Together, this persistent hyper-activation of oxidative enzymes suggests an “oxidative stress memory” both in the periphery and CNS compartments, in chronic neuroinflammation. Electronic supplementary material The online version of this article (doi:10.1007/s00401-015-1497-x) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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