Type I interferon receptor signalling is induced during demyelination while its function for myelin damage and repair is redundant

Autor: Marco Prinz, Florian Klinker, Wolfgang Brück, Doron Merkler, Hauke Schmidt, Jenni Raasch, Sandra Krauss
Rok vydání: 2008
Předmět:
Central Nervous System
medicine.medical_treatment
Cuprizone/toxicity
Receptor
Interferon alpha-beta
ddc:616.07
Myelin
Mice
0302 clinical medicine
Interferon
Receptor
Myelin Sheath
Mice
Knockout
0303 health sciences
Microglia
Glial Fibrillary Acidic Protein/metabolism
Cell biology
Specific Pathogen-Free Organisms
Gene Expression Regulation/drug effects/genetics
Cytokine
medicine.anatomical_structure
Neurology
Motor Skills
Female
Central Nervous System/metabolism/pathology/ultrastructure
medicine.drug
Signal Transduction
Biology
Motor Activity
Myelin Sheath/*metabolism/pathology
03 medical and health sciences
Cuprizone
Developmental Neuroscience
Motor Skills/physiology
Glial Fibrillary Acidic Protein
medicine
Motor Activity/drug effects/genetics
Animals
Remyelination
030304 developmental biology
Demyelinating Diseases/chemically induced/*metabolism/pathology/*physiopathology
Receptor
Interferon alpha-beta/deficiency/genetics/*metabolism
Multiple sclerosis
medicine.disease
Mice
Inbred C57BL
Disease Models
Animal
Gene Expression Regulation
Immunology
IRF7
Signal Transduction/drug effects/*physiology
030217 neurology & neurosurgery
Demyelinating Diseases
Zdroj: Experimental Neurology, Vol. 216, No 2 (2009) pp. 306-311
ISSN: 1090-2430
0014-4886
Popis: The type I interferons, interferon-beta and alpha (IFN-beta, IFN-alpha), are widely used for the treatment of autoimmune demyelination in the central nervous system (CNS). Their effects on de- and remyelination through the broadly expressed type I IFN receptor (IFNAR), however, are highly speculative. In order to elucidate the role of endogenous type I interferons for myelin damage and recovery we induced toxic demyelination in the absence of IFNAR1. We demonstrate that IFNAR signalling was induced during acute demyelination since the cytokine IFN-beta as well as the IFN-dependent genes IRF7, ISG15 and UBP43 were strongly upregulated. Myelin damage, astrocytic and microglia response, however, were not significantly reduced in the absence of IFNAR1. Furthermore, motor skills of IFNAR1-deficient animals during non-immune demyelination were unaltered. Finally, myelin recovery was found to be independent from endogenous IFNAR signalling, indicating a redundant role of this receptor for non-inflammatory myelin damage and repair.
Databáze: OpenAIRE
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